Occupational Exposure to Beryllium and Beryllium Compounds, 47565-47828 [2015-17596]
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Vol. 80
Friday,
No. 152
August 7, 2015
Part II
Department of Labor
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Occupational Safety and Health Administration
29 CFR Part 1910
Occupational Exposure to Beryllium and Beryllium Compounds; Proposed
Rule
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Federal Register / Vol. 80, No. 152 / Friday, August 7, 2015 / Proposed Rules
DEPARTMENT OF LABOR
Occupational Safety and Health
Administration
29 CFR Part 1910
[Docket No. OSHA–H005C–2006–0870]
RIN 1218–AB76
Occupational Exposure to Beryllium
and Beryllium Compounds
Occupational Safety and Health
Administration (OSHA), Department of
Labor.
ACTION: Proposed rule; request for
comments.
AGENCY:
The Occupational Safety and
Health Administration (OSHA) proposes
to amend its existing exposure limits for
occupational exposure in general
industry to beryllium and beryllium
compounds and promulgate a
substance-specific standard for general
industry regulating occupational
exposure to beryllium and beryllium
compounds. This document proposes a
new permissible exposure limit (PEL),
as well as ancillary provisions for
employee protection such as methods
for controlling exposure, respiratory
protection, medical surveillance, hazard
communication, and recordkeeping. In
addition, OSHA seeks comment on a
number of alternatives, including a
lower PEL, that could affect
construction and maritime, as well as
general industry.
DATES: Written comments. Written
comments, including comments on the
information collection determination
described in Section IX of the preamble
(OMB Review under the Paperwork
Reduction Act of 1995), must be
submitted (postmarked, sent, or
received) by November 5, 2015.
Informal public hearings. The Agency
will schedule an informal public
hearing on the proposed rule if
requested during the comment period.
The location and date of the hearing,
procedures for interested parties to
notify the Agency of their intention to
participate, and procedures for
participants to submit their testimony
and documentary evidence will be
announced in the Federal Register if a
hearing is requested.
ADDRESSES: Written comments. You may
submit comments, identified by Docket
No. OSHA–H005C–2006–0870, by any
of the following methods:
Electronically: You may submit
comments and attachments
electronically at https://
www.regulations.gov, which is the
Federal e-Rulemaking Portal. Follow the
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SUMMARY:
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instructions on-line for making
electronic submissions. When
uploading multiple attachments into
Regulations.gov, please number all of
your attachments because
www.Regulations.gov will not
automatically number the attachments.
This will be very useful in identifying
all attachments in the beryllium rule.
For example, Attachment 1—title of
your document, Attachment 2—title of
your document, Attachment 3—title of
your document, etc. Specific
instructions on uploading all documents
are found in the Facts, Answer,
Questions portion and the commenter
check list on Regulations.gov Web page.
Fax: If your submissions, including
attachments, are not longer than 10
pages, you may fax them to the OSHA
Docket Office at (202) 693–1648.
Mail, hand delivery, express mail,
messenger, or courier service: You may
submit your comments to the OSHA
Docket Office, Docket No. OSHA–
H005C–2006–0870, U.S. Department of
Labor, Room N–2625, 200 Constitution
Avenue NW., Washington, DC 20210,
telephone (202) 693–2350 (OSHA’s TTY
number is (877) 889–5627). Deliveries
(hand, express mail, messenger, or
courier service) are accepted during the
Docket Office’s normal business hours,
8:15 a.m.–4:45 p.m., E.S.T.
Instructions: All submissions must
include the Agency name and the
docket number for this rulemaking
(Docket No. OSHA–H005C–2006–0870).
All comments, including any personal
information you provide, are placed in
the public docket without change and
may be made available online at https://
www.regulations.gov. Therefore, OSHA
cautions you about submitting personal
information such as Social Security
numbers and birthdates.
If you submit scientific or technical
studies or other results of scientific
research, OSHA requests (but is not
requiring) that you also provide the
following information where it is
available: (1) Identification of the
funding source(s) and sponsoring
organization(s) of the research; (2) the
extent to which the research findings
were reviewed by a potentially affected
party prior to publication or submission
to the docket, and identification of any
such parties; and (3) the nature of any
financial relationships (e.g., consulting
agreements, expert witness support, or
research funding) between investigators
who conducted the research and any
organization(s) or entities having an
interest in the rulemaking. If you are
submitting comments or testimony on
the Agency’s scientific or technical
analyses, OSHA requests that you
disclose: (1) The nature of any financial
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relationships you may have with any
organization(s) or entities having an
interest in the rulemaking; and (2) the
extent to which your comments or
testimony were reviewed by an
interested party before you submitted
them. Disclosure of such information is
intended to promote transparency and
scientific integrity of data and technical
information submitted to the record.
This request is consistent with
Executive Order 13563, issued on
January 18, 2011, which instructs
agencies to ensure the objectivity of any
scientific and technological information
used to support their regulatory actions.
OSHA emphasizes that all material
submitted to the rulemaking record will
be considered by the Agency to develop
the final rule and supporting analyses.
Docket: To read or download
comments and materials submitted in
response to this Federal Register notice,
go to Docket No. OSHA–H005C–2006–
0870 at https://www.regulations.gov, or
to the OSHA Docket Office at the
address above. All comments and
submissions are listed in the https://
www.regulations.gov index; however,
some information (e.g., copyrighted
material) is not publicly available to
read or download through that Web site.
All comments and submissions are
available for inspection at the OSHA
Docket Office.
Electronic copies of this Federal
Register document are available at
https://www.regulations.gov. Copies also
are available from the OSHA Office of
Publications, Room N–3101, U.S.
Department of Labor, 200 Constitution
Avenue NW., Washington, DC 20210;
telephone (202) 693–1888. This
document, as well as news releases and
other relevant information, is also
available at OSHA’s Web site at https://
www.osha.gov.
OSHA has not provided the document
ID numbers for all submissions in the
record for this beryllium proposal. The
proposal only contains a reference list
for all submissions relied upon. The
public can find all document ID
numbers in an Excel spreadsheet that is
posted on OSHA’s rulemaking Web page
(see www.osha.gov/
berylliumrulemaking). The public will
be able to locate submissions in the
record in the public docked Web page:
https://www.regulations.gov. To locate a
particular submission contained in
https://www.regulations.gov, the public
should enter the full document ID
number in the search bar.
FOR FURTHER INFORMATION CONTACT: For
general information and press inquiries,
contact Frank Meilinger, Director, Office
of Communications, Room N–3647,
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OSHA, U.S. Department of Labor,
200 Constitution Avenue NW.,
Washington, DC 20210; telephone: (202)
693–1999; email: meilinger.francis2@
dol.gov . For technical inquiries,
contact: William Perry or Maureen
Ruskin, Directorate of Standards and
Guidance, Room N–3718, OSHA, U.S.
Department of Labor, 200 Constitution
Avenue NW., Washington, DC 20210;
telephone (202) 693–1955 or fax (202)
693–1678; email: perry.bill@dol.gov.
SUPPLEMENTARY INFORMATION:
The preamble to the proposed
standard on occupational exposure to
beryllium and beryllium compounds
follows this outline:
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Executive Summary
I. Issues and Alternatives
II. Pertinent Legal Authority
III. Events Leading to the Proposed Standards
IV. Chemical Properties and Industrial Uses
V. Health Effects
VI. Preliminary Risk Assessment
VII. Response to Peer Review
VIII. Significance of Risk
IX. Summary of the Preliminary Economic
Analysis and Initial Regulatory
Flexibility Analysis
X. OMB Review under the Paperwork
Reduction Act of 1995
XI. Federalism
XII. State-Plan States
XIII. Unfunded Mandates Reform Act
XIV. Protecting Children from Environmental
Health and Safety Risks
XV. Environmental Impacts
XVI. Consultation and Coordination with
Indian Tribal Governments
XVII. Public Participation
XVIII. Summary and Explanation of the
Proposed Standard
(a) Scope and Application
(b) Definitions
(c) Permissible Exposure Limits (PELs)
(d) Exposure Assessment
(e) Beryllium Work Areas and Regulated
Areas
(f) Methods of Compliance
(g) Respiratory Protection
(h) Personal Protective Clothing and
Equipment
(i) Hygiene Areas and Practices
(j) Housekeeping
(k) Medical Surveillance
(l) Medical Removal
(m) Communication of Hazards to
Employees
(n) Recordkeeping
(o) Dates
XIX. References
Executive Summary
OSHA currently enforces permissible
exposure limits (PELs) for beryllium in
general industry, construction, and
shipyards. These PELs were adopted in
1971, shortly after the Agency was
created, and have not been updated
since then. The time-weighted average
(TWA) PEL for beryllium is 2
micrograms per cubic meter of air (mg/
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m3) as an 8-hour time-weighted average.
OSHA is proposing a new TWA PEL of
0.2 mg/m3 in general industry. OSHA is
also proposing other elements of a
comprehensive health standard,
including requirements for exposure
assessment, preferred methods for
controlling exposure, respiratory
protection, personal protective clothing
and equipment (PPE), medical
surveillance, medical removal, hazard
communication, and recordkeeping.
OSHA’s proposal is based on the
requirements of the Occupational Safety
and Health Act (OSH Act) and court
interpretations of the Act. For health
standards issued under section 6(b)(5) of
the OSH Act, OSHA is required to
promulgate a standard that reduces
significant risk to the extent that it is
technologically and economically
feasible to do so. See Section II of this
preamble, Pertinent Legal Authority, for
a full discussion of OSHA legal
requirements.
OSHA has conducted an extensive
review of the literature on adverse
health effects associated with exposure
to beryllium. The Agency has also
assessed the risk of beryllium-related
diseases at the current TWA PEL, the
proposed TWA PEL and the alternative
TWA PELs. These analyses are
presented in this preamble at Section V,
Health Effects, Section VI, Preliminary
Risk Assessment, and Section VIII,
Significance of Risk. As discussed in
Section VIII of this preamble,
Significance of Risk, the available
evidence indicates that worker exposure
to beryllium at the current PEL poses a
significant risk of chronic beryllium
disease (CBD) and lung cancer, and that
the proposed standard will substantially
reduce this risk.
Section 6(b) of the OSH Act requires
OSHA to determine that its standards
are technologically and economically
feasible. OSHA’s examination of the
technological and economic feasibility
of the proposed rule is presented in the
Preliminary Economic Analysis and
Initial Regulatory Flexibility Analysis
(PEA) (OSHA, 2014), and is summarized
in Section IX of this preamble,
Summary of the Preliminary Economic
Analysis and Initial Regulatory
Flexibility Analysis. OSHA has
preliminarily concluded that the
proposed PEL of 0.2 mg/m3 is
technologically feasible for all affected
industries and application groups. Thus,
OSHA preliminarily concludes that
engineering and work practices will be
sufficient to reduce and maintain
beryllium exposures to the proposed
PEL of 0.2 mg/m3 or below in most
operations most of the time in the
affected industries. For those few
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operations within an industry or
application group where compliance
with the proposed PEL cannot be
achieved even when employers
implement all feasible engineering and
work practice controls, the proposed
standard would require employers to
supplement controls with respirators.
OSHA developed quantitative
estimates of the compliance costs of the
proposed rule for each of the affected
industry sectors. The estimated
compliance costs were compared with
industry revenues and profits to provide
a screening analysis of the economic
feasibility of complying with the revised
standard and an evaluation of the
potential economic impacts. Industries
with unusually high costs as a
percentage of revenues or profits were
further analyzed for possible economic
feasibility issues. After performing these
analyses, OSHA has preliminarily
concluded that compliance with the
requirements of the proposed rule
would be economically feasible in every
affected industry sector.
The Regulatory Flexibility Act, as
amended by the Small Business
Regulatory Enforcement Fairness Act
(SBREFA), requires that OSHA either
certify that a rule would not have a
significant economic impact on a
substantial number of small entities or
prepare a regulatory flexibility analysis
and hold a Small Business Advocacy
Review (SBAR) Panel prior to proposing
the rule. OSHA has determined that a
regulatory flexibility analysis is needed
and has provided this analysis in
Chapter IX of the PEA (OSHA, 2014). A
summary is provided in Section IX of
this preamble, Summary of the
Preliminary Economic Analysis and
Initial Regulatory Flexibility Analysis.
OSHA also previously held a SBAR
Panel for this rule. The
recommendations of the Panel and
OSHA’s response to them are
summarized in Section IX of this
preamble.
Executive Orders 13563 and 12866
direct agencies to assess all costs and
benefits of available regulatory
alternatives. Executive Order 13563
emphasizes the importance of
quantifying both costs and benefits, of
reducing costs, of harmonizing rules,
and of promoting flexibility. This rule
has been designated an economically
significant regulatory action under
section 3(f)(1) of Executive Order 12866.
Accordingly, this proposed rule has
been reviewed by the Office of
Management and Budget. The
remainder of this section summarizes
the key findings of the analysis with
respect to costs and benefits of the
proposed standard, presents alternatives
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to the proposed standard, and requests
comments on a number of issues.
Table I–1, which is derived from
material presented in the PEA, provides
a summary of OSHA’s best estimate of
the costs and benefits of this proposed
rule. As shown, this proposed rule is
estimated to prevent 96 fatalities and 50
non-fatal beryllium-related illnesses
annually once it is fully effective, and
the monetized annualized benefits of
the proposed rule are estimated to be
$576 million using a 3-percent discount
rate and $255 million using a 7-percent
discount rate. Also as shown in Table
I–1, the estimated annualized cost of the
rule is $37.6 million using a
3-percent discount rate and $39.1
million using a 7-percent discount rate.
This proposed rule is estimated to
generate net benefits of $538 million
annually using a 3-percent discount rate
and $216 million annually using a 7percent discount rate. These estimates
are for informational purposes only and
have not been used by OSHA as the
basis for its decision concerning the
choice of a PEL or of other ancillary
requirements for this proposed
beryllium rule. The courts have ruled
that OSHA may not use benefit-cost
analysis or a criterion of maximizing net
benefits as a basis for setting OSHA
health standards.1
TABLE I–1—ANNUALIZED COSTS, BENEFITS AND NET BENEFITS OF OSHA’S PROPOSED BERYLLIUM STANDARD OF 0.2 μG/
M3
Discount rate
3%
Annualized Costs
Engineering Controls ................................................................................
Respirators ...............................................................................................
Exposure Assessment ..............................................................................
Regulated Areas and Beryllium Work Areas ...........................................
Medical Surveillance .................................................................................
Medical Removal ......................................................................................
Exposure Control Plan .............................................................................
Protective Clothing and Equipment ..........................................................
Hygiene Areas and Practices ...................................................................
Housekeeping ...........................................................................................
Training .....................................................................................................
Total Annualized Costs (Point Estimate) .........................................................
Annual Benefits: Number of Cases Prevented
Fatal Lung Cancer ....................................................................................
CBD-Related Mortality ..............................................................................
Total Beryllium Related Mortality .............................................................
Morbidity ..........................................................................................................
Monetized Annual Benefits (midpoint estimate) ..............................................
Net Benefits .......................................................................................
7%
$9,540,189
249,684
2,208,950
629,031
2,882,076
148,826
1,769,506
1,407,365
389,241
12,574,921
5,797,535
37,597,325
572,981,864
2,844,770
575,826,633
538,229,308
4.0
92.0
96.0
49.5
$10,334,036
252,281
2,411,851
652,823
2,959,448
166,054
1,828,766
1,407,365
389,891
12,917,944
5,826,975
39,147,434
253,743,368
1,590,927
255,334,295
216,186,861
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Source: OSHA, Directorate of Standards and Guidance, Office of Regulatory Analysis.
Both the costs and benefits of Table I–
1 reflect the incremental costs and
benefits associated with achieving full
compliance with the proposed standard.
They do not include costs and benefits
associated with employers’ current
exposure control measures or other
aspects of the proposed standard they
have already implemented. For
example, for employers whose
exposures are already below the
proposed PEL, OSHA’s estimated costs
and benefits for the proposed standard
do not include the costs of their
exposure control measures or the
benefits of these employers’ compliance
with the proposed PEL. The costs and
benefits of Table I–1 also do not include
costs and benefits associated with
achieving compliance with existing
requirements, to the extent that some
employers may currently not be fully
complying with applicable regulatory
requirements.
1 Am. Textile Mfrs. Inst., Inc. v. Nat’l Cotton
Council of Am., 452 U.S. 490, 513 (1981); Pub.
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I. Issues and Alternatives
Regulatory Alternatives
In addition to the proposed standard
itself, this preamble discusses more than
two dozen regulatory alternatives,
including various sub-alternatives, to
the proposed standard and requests
comments and information on a variety
of topics pertinent to the proposed
standard. The regulatory alternatives
OSHA is considering include
alternatives to the proposed scope of the
standard, regulatory alternatives to the
proposed TWA PEL of 0.2 mg/m3 and
proposed STEL of 2 mg/m3, a regulatory
alternative that would modify the
proposed methods of compliance, and
regulatory alternatives that affect
proposed ancillary provisions. The
Agency solicits comment on the
proposed phase-in schedule for the
various provisions of the standard.
Additional requests for comments and
information follow the summaries of
regulatory alternatives, under the
‘‘Issues’’ heading.
OSHA believes that inclusion of
regulatory alternatives serves two
important functions. The first is to
explore the possibility of less costly
ways (than the proposed standard) to
provide an adequate level of worker
protection from exposure to beryllium.
The second is tied to the Agency’s
statutory requirement, which underlies
the proposed standard, to reduce
significant risk to the extent feasible.
Each regulatory alternative presented
here is described and analyzed more
fully elsewhere in this preamble or in
the PEA. Where appropriate, the
alternative is included in this preamble
at the end of the relevant section of
Section XVIII, Summary and
Explanation of the Proposed Standard,
to facilitate comparison of the
alternative to the proposed standard.
For example, alternative PELs under
consideration by the Agency are
presented in the discussion of paragraph
(c) in Section XVIII. In addition, all
Citizen Health Research Group v. U.S. Dep’t of
Labor, 557 F.3d 165, 177 (3d Cir. 2009).
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alternatives are discussed in the PEA,
Chapter VIII: Regulatory Alternatives
(OSHA, 2014). The costs and benefits of
each regulatory alternative are presented
both in Section IX of this preamble and
in Chapter VIII of the PEA.
The more than two dozen regulatory
alternatives, including various subalternatives regulatory alternatives
under consideration are summarized
below, and are organized into the
following categories: alternatives to the
proposed scope of the standard;
alternatives to the proposed PELs;
alternatives to the proposed methods of
compliance; alternatives to the proposed
ancillary provisions; and the timing of
the standard.
Scope
OSHA has examined three
alternatives that would alter the groups
of employers and employees covered by
this rulemaking. Regulatory Alternative
#1a would expand the scope of the
proposed standard to include all
operations in general industry where
beryllium exists only as a trace
contaminant; that is, where the
materials used contain no more than
0.1% beryllium by weight. Regulatory
Alternative #1b is similar to Regulatory
Alternative #1a, but exempts operations
where the employer can show that
employees’ exposures will not meet or
exceed the action level or exceed the
STEL. Where the employer has objective
data demonstrating that a material
containing beryllium or a specific
process, operation, or activity involving
beryllium cannot release beryllium in
concentrations at or above the proposed
action level or above the proposed STEL
under any expected conditions of use,
that employer would be exempt from
the proposed standard except for
recordkeeping requirements pertaining
to the objective data. Alternative #1a
and Alternative #1b, like the proposed
rule, would not cover employers or
employees in construction or shipyards.
Regulatory Alternative #2a would
expand the scope of the proposed
standard to also include employers in
construction and maritime. For
example, this alternative would cover
abrasive blasters, pot tenders, and
cleanup staff working in construction
and shipyards who have the potential
for airborne beryllium exposure during
blasting operations and during cleanup
of spent media. Regulatory Alternative
#2b would update §§ 1910.1000 Tables
Z–1 and Z–2, 1915.1000 Table Z, and
1926.55 Appendix A so that the
proposed TWA PEL and STEL would
apply to all employers and employees in
general industry, shipyards, and
construction, including occupations
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where beryllium exists only as a trace
contaminant. However, all other
provisions of the standard would be in
effect only for employers and employees
that fall within the scope of the
proposed rule. More detailed discussion
of Regulatory Alternatives #1a, #1b, #2a,
and #2b appears in Section IX of this
preamble and in Chapter VIII of the PEA
(OSHA, 2014). In addition, Section
XVIII of this preamble, Summary and
Explanation, includes a discussion of
paragraph (a) that describes the scope of
the proposed rule, issues with the
proposed scope, and Regulatory
Alternatives #1a, #1b, #2a, and #2b.
Another regulatory alternative that
would impact the scope of affected
industries, extending eligibility for
medical surveillance to employees in
shipyards, construction, and parts of
general industry excluded from the
scope of the proposed standard, is
discussed along with other medical
surveillance alternatives later in this
section (Regulatory Alternative #21) and
in the discussion of paragraph (k) in this
preamble at Section XVIII, Summary
and Explanation of the Proposed
Standard.
Permissible Exposure Limits
OSHA has examined several
regulatory alternatives that would
modify the TWA PEL or STEL for the
proposed rule. Under Regulatory
Alternative #3, OSHA would adopt a
STEL of 5 times the proposed PEL.
Thus, this alternative STEL would be
1.0 mg/m3 if OSHA adopts a PEL of 0.2
mg/m3; it would be 0.5 mg/m3 if OSHA
adopts a PEL of 0.1 mg/m3; and it would
be 2.5 mg/m3 if OSHA adopts a PEL of
0.5 mg/m3 (see Regulatory Alternatives
#4 and #5). Under Regulatory
Alternative #4, the proposed PEL would
be lowered from 0.2 mg/m3 to 0.1 mg/m3.
Under Regulatory Alternative #5, the
proposed PEL would be raised from 0.2
mg/m3 to 0.5 mg/m3. In addition, for
informational purposes, OSHA
examined a regulatory alternative that
would maintain the TWA PEL at 2.0 mg/
m3, but all of the other proposed
provisions would be required with their
triggers remaining the same as in the
proposed rule. This alternative is not
one OSHA could legally adopt because
the absence of a more protective
requirement for engineering controls
would not be consistent with section
6(b)(5) of the OSH Act. More detailed
discussion of these alternatives to the
proposed PEL appears in Section IX of
this preamble and in Chapter VIII of the
PEA (OSHA, 2014). In addition, in
Section XVIII of this preamble,
Summary and Explanation of the
Proposed Standard, the discussion of
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proposed paragraph (c) describes the
proposed TWA PEL and STEL, issues
with the proposed exposure limits, and
Regulatory Alternatives #3, #4, and #5.
Methods of Compliance
The proposed standard would require
employers to implement engineering
and work practice controls to reduce
employees’ exposures to or below the
TWA PEL and STEL. Where engineering
and work practice controls are
insufficient to reduce exposures to or
below the TWA PEL and STEL,
employers would still be required to
implement them to reduce exposure as
much as possible, and to supplement
them with a respiratory protection
program. In addition, for each operation
where there is airborne beryllium
exposure, the employer must ensure
that one or more of the engineering and
work practice controls listed in
paragraph (f)(2) are in place, unless all
of the listed controls are infeasible, or
the employer can demonstrate that
exposures are below the action level
based on two samples taken seven days
apart. Regulatory Alternative #6 would
eliminate the engineering and work
practice controls provision currently
specified in paragraph (f)(2). This
regulatory alternative does not eliminate
the need for engineering controls to
lower exposure levels to or below the
TWA PEL and STEL; rather, it dispenses
with the mandatory use of certain
engineering controls that must be
installed above the action level but at or
below the TWA PEL.
More detailed discussion of
Regulatory Alternative #6 appears in
Section IX of this preamble and in
Chapter VIII of the PEA (OSHA, 2014).
In addition, the discussion of paragraph
(f) in Section XVIII of this preamble,
Summary and Explanation, provides a
more detailed explanation of the
proposed methods of compliance, issues
with the proposed methods of
compliance, and Regulatory Alternative
#6.
Ancillary Provisions
The proposed rule contains several
ancillary provisions, including
requirements for exposure assessment,
personal protective clothing and
equipment (PPE), medical surveillance,
medical removal, training, and regulated
areas or access control. OSHA has
examined a variety of regulatory
alternatives involving changes to one or
more of these ancillary provisions.
OSHA has preliminarily determined
that several of these ancillary provisions
will increase the benefits of the
proposed rule, for example, by helping
to ensure the TWA PEL is not exceeded
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or by lowering the risks to workers
given the significant risk remaining at
the proposed TWA PEL. However,
except for Regulatory Alternative #7
(involving the elimination of all
ancillary provisions), OSHA did not
estimate changes in monetized benefits
for the regulatory alternatives that affect
ancillary provisions. Two regulatory
alternatives that involve all ancillary
provisions are presented below (#7 and
#8), followed by regulatory alternatives
for exposure monitoring (#9, #10, and
#11), for regulated areas (#12), for
personal protective clothing and
equipment (#13), for medical
surveillance (#14 through #21), and for
medical removal (#22).
All Ancillary Provisions
During the Small Business Regulatory
Fairness Act (SBREFA) process
conducted in 2007, the SBAR Panel
recommended that OSHA analyze a
PEL-only standard as a regulatory
alternative. The Panel also
recommended that OSHA consider
applying ancillary provisions of the
standard so as to minimize costs for
small businesses where exposure levels
are low (OSHA, 2008b). In response to
these recommendations, OSHA
analyzed Regulatory Alternative #7, a
PEL-only standard, and Regulatory
Alternative #8, which would only apply
ancillary provisions of the beryllium
standard at exposures above the
proposed PEL of 0.2 mg/m3 or the
proposed STEL of 2 mg/m3. Regulatory
Alternative #7 would update the Z
tables for § 1910.1000, so that the
proposed TWA PEL and STEL would
apply to all workers in general industry.
All other provisions of the proposed
standard would be dropped.
As indicated previously, OSHA has
preliminarily determined that there is
significant risk remaining at the
proposed PEL of 0.2 mg/m3. However,
the available evidence on feasibility
suggests that 0.2 mg/m3 may be the
lowest feasible PEL (see Chapter IV of
the PEA, OSHA 2014). Therefore, the
Agency believes that it is necessary to
include ancillary provisions in the
proposed rule to further reduce the
remaining risk. In addition, the
recommended standard provided to
OSHA by representatives of the primary
beryllium manufacturing industry and
the Steelworkers Union further supports
the importance of ancillary provisions
in protecting workers from the harmful
effects of beryllium exposure (Materion
and USW, 2012).
Under Regulatory Alternative #8,
several ancillary provisions that the
current proposal would require under a
variety of exposure conditions (e.g.,
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dermal contact; any airborne exposure;
exposure at or above the action level)
would instead only apply where
exposure levels exceed the TWA PEL or
STEL. Regulatory Alternative #8 affects
the following provisions of the proposed
standard:
—Exposure monitoring. Whereas the
proposed standard requires annual
monitoring where exposure levels are
at or above the action level and at or
below the TWA PEL, Alternative #8
would require annual exposure
monitoring only where exposure
levels exceed the TWA PEL or STEL;
— Written exposure control plan.
Whereas the proposed standard
requires written exposure control
plans to be maintained in any facility
covered by the standard, Alternative
#8 would require only facilities with
exposures above the TWA PEL or
STEL to maintain a plan;
—PPE. Whereas the proposed standard
requires PPE for employees under a
variety of conditions, such as
exposure to soluble beryllium or
visible contamination with beryllium,
Alternative #8 would require PPE
only for employees exposed above the
TWA PEL or STEL;
—Housekeeping. Whereas the proposed
standard’s housekeeping requirements
apply across a wide variety of
beryllium exposure conditions,
Alternative #8 would limit
housekeeping requirements to areas
with exposures above the TWA PEL
or STEL.
—Medical Surveillance. Whereas the
proposed standard’s medical
surveillance provisions require
employers to offer medical
surveillance to employees with signs
or symptoms of beryllium-related
health effects regardless of their
exposure level, Alternative #8 would
make surveillance available to such
employees only if they were exposed
above the TWA PEL or STEL.
More detailed discussions of Regulatory
Alternatives #7 and #8, including a
description of the considerations
pertinent to these alternatives, appear in
Section IX of this preamble and in
Chapter VIII of the PEA (OSHA, 2014).
Exposure Monitoring
OSHA has examined three regulatory
alternatives that would modify the
proposed standard’s provisions on
exposure monitoring, which require
periodic monitoring annually where
exposures are at or above the action
level and at or below the TWA PEL.
Under Regulatory Alternative #9,
employers would be required to perform
periodic exposure monitoring every 180
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days where exposures are at or above
the action level or above the STEL, and
at or below the TWA PEL. Under
Regulatory Alternative #10, employers
would be required to perform periodic
exposure monitoring every 180 days
where exposures are at or above the
action level or above the STEL,
including where exposures exceed the
TWA PEL. Under Regulatory Alternative
#11, employers would be required to
perform periodic exposure monitoring
every 180 days where exposures are at
or above the action level or above the
STEL, and every 90 days where
exposures exceed the TWA PEL. More
detailed discussions of Regulatory
Alternatives #9, #10, and #11 appear in
Section IX of this preamble and in
Chapter VIII of the PEA (OSHA, 2014).
In addition, the discussion of proposed
paragraph (d) in Section XVIII of this
preamble, Summary and Explanation of
the Proposed Standard, provides a more
detailed explanation of the proposed
requirements for exposure monitoring,
issues with exposure monitoring, and
the considerations pertinent to
Regulatory Alternatives #9, #10, and
#11.
Regulated Areas
The proposed standard would require
employers to establish and maintain two
types of areas: beryllium work areas,
wherever employees are, or can
reasonably be expected to be, exposed to
any level of airborne beryllium; and
regulated areas, wherever employees
are, or can reasonably be expected to be,
exposed to airborne beryllium at levels
above the TWA PEL or STEL. Employers
are required to demarcate beryllium
work areas, but are not required to
restrict access to beryllium work areas
or provide respiratory protection or
other forms of PPE within work areas
that are not also regulated areas.
Employers must demarcate regulated
areas, restrict access to them, post
warning signs and provide respiratory
protection and other PPE within
regulated areas, as well as medical
surveillance for employees who work in
regulated areas for more than 30 days in
a 12-month period. During the SBREFA
process conducted in 2007, the SBAR
Panel recommended that OSHA
consider dropping or limiting the
provision for regulated areas (OSHA,
2008b). In response to this
recommendation, OSHA analyzed
Regulatory Alternative #12, which
would not require employers to
establish regulated areas. More detailed
discussion of Regulatory Alternative #12
appears in Section IX of this preamble
and in Chapter VIII of the PEA (OSHA,
2014). In addition, the discussion of
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paragraph (e) in Section XVIII of this
preamble, Summary and Explanation,
provides a more detailed explanation of
the proposed requirements for regulated
areas, issues with regulated areas, and
considerations pertinent to Regulatory
Alternative #12.
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Personal Protective Clothing and
Equipment (PPE)
Regulatory Alternative #13 would
modify the proposed requirements for
PPE, which require PPE where exposure
exceeds the TWA PEL or STEL; where
employees’ clothing or skin may become
visibly contaminated with beryllium;
and where employees may have skin
contact with soluble beryllium
compounds. The requirement to use
PPE where work clothing or skin may
become ‘‘visibly contaminated’’ with
beryllium differs from prior standards
that do not require contamination to be
visible in order for PPE to be required.
In the case of beryllium, which OSHA
has preliminarily concluded can
sensitize through dermal exposure, the
exposure levels capable of causing
adverse health effects and the PELs in
effect are so low that beryllium surface
contamination is unlikely to be visible
(see this preamble at section V, Health
Effects). OSHA is therefore considering
Regulatory Alternative #13, which
would require appropriate PPE
wherever there is potential for skin
contact with beryllium or berylliumcontaminated surfaces. More detailed
discussion of Regulatory Alternative #13
is provided in Section IX of this
preamble and in Chapter VIII of the PEA
(OSHA, 2014). In addition, the
discussion of paragraph (h) in Section
XVIII of this preamble, Summary and
Explanation, provides a more detailed
explanation of the proposed
requirements for PPE, issues with PPE,
and the considerations pertinent to
Regulatory Alternative #13.
Medical Surveillance
The proposed requirements for
medical surveillance include: (1)
Medical examinations, including a test
for beryllium sensitization, for
employees who are exposed to
beryllium above the proposed PEL for
30 days or more per year, who are
exposed to beryllium in an emergency,
or who show signs or symptoms of CBD;
and (2) low-dose helical tomography
(low-dose computed tomography,
hereafter referred to as ‘‘CT scans’’), for
employees who were exposed above the
proposed PEL for more than 30 days in
a 12-month period for 5 years or more.
This type of CT scan is a method of
detecting tumors, and is commonly used
to diagnose lung cancer. The proposed
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standard would require periodic
medical exams to be provided for
employees in the medical surveillance
program annually, while tests for
beryllium sensitization and CT scans
would be provided to eligible
employees biennially.
OSHA has examined eight regulatory
alternatives (#14 through #21) that
would modify the proposed rule’s
requirements for employee eligibility,
the types of exam that must be offered,
and the frequency of periodic exams.
Medical surveillance was a subject of
special concern to SERs during the
SBREFA process, and the SBREFA
Panel offered many comments and
recommendations related to medical
surveillance for OSHA’s consideration.
Some of the Panel’s concerns have been
addressed in this proposal, which was
modified since the SBREFA Panel was
convened (see this preamble at Section
XVIII, Summary and Explanation of the
Proposed Standard, for more detailed
discussion). Several of the alternatives
presented here (#16, #18, and #20) also
respond to recommendations by the
SBREFA Panel to reduce burdens on
small businesses by dropping or
reducing the frequency of medical
surveillance requirements. OSHA also
seeks to ensure that the requirements of
the final standard offer workers
adequate medical surveillance while
limiting the costs to employers. Thus,
OSHA requests feedback on several
additional alternatives and on a variety
of issues raised later in this section of
the preamble.
Regulatory Alternatives #14, #15, and
#21 would expand eligibility for
medical surveillance to a broader group
of employees than would be eligible in
the proposed standard. Under
Regulatory Alternative #14, medical
surveillance would be available to
employees who are exposed to
beryllium above the proposed PEL,
including employees exposed for fewer
than 30 days per year. Regulatory
Alternative #15 would expand
eligibility for medical surveillance to
employees who are exposed to
beryllium above the proposed action
level, including employees exposed for
fewer than 30 days per year. Regulatory
Alternative #21 would extend eligibility
for medical surveillance as set forth in
proposed paragraph (k) to all employees
in shipyards, construction, and general
industry who meet the criteria of
proposed paragraph (k)(1) (or any of the
alternative criteria under consideration).
However, all other provisions of the
standard would be in effect only for
employers and employees that fall
within the scope of the proposed rule.
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Regulatory Alternatives #16 and #17
would modify the proposed standard’s
requirements to offer beryllium
sensitization testing to eligible
employees. Under Regulatory
Alternative #16, employers would not
be required to offer employees testing
for beryllium sensitization. Regulatory
Alternative #17 would increase the
frequency of periodic sensitization
testing, from the proposed standard’s
biennial requirement to annual testing.
Regulatory Alternatives #18 and #19
would similarly modify the proposed
standard’s requirements to offer CT
scans to eligible employees. Regulatory
Alternative #18 would drop the CT scan
requirement from the proposed rule,
whereas Regulatory Alternative #19
would increase the frequency of
periodic CT scans from biennial to
annual scans. Finally, under Regulatory
Alternative #20, all periodic
components of the medical surveillance
exams would be available biennially to
eligible employees. Instead of requiring
employers to offer eligible employees a
medical examination every year,
employers would be required to offer
eligible employees a medical
examination every other year. The
frequency of testing for beryllium
sensitization and CT scans would also
be biennial for eligible employees, as in
the proposed standard.
More detailed discussions of
Regulatory Alternatives #14, #15, #16,
#17, #18, #19, #20, and #21 appear in
Section IX of this preamble and in
Chapter VIII of the PEA (OSHA, 2014).
In addition, Section XVIII of this
preamble, Summary and Explanation,
paragraph (k) provides a more detailed
explanation of the proposed
requirements for medical surveillance,
issues with medical surveillance, and
the considerations pertinent to
Regulatory Alternatives #14 through
#21.
Medical Removal Protection (MRP)
The proposed requirements for
medical removal protection provide an
option for medical removal to an
employee who is working in a job with
exposure at or above the action level
and is diagnosed with CBD or confirmed
positive for beryllium sensitization. If
the employee chooses removal, the
employer must either remove the
employee to comparable work in a work
environment where exposure is below
the action level, or if comparable work
is not available, must place the
employee on paid leave for 6 months or
until such time as comparable work
becomes available. In either case, the
employer must maintain for 6 months
the employee’s base earnings, seniority,
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and other rights and benefits that
existed at the time of removal. During
the SBREFA process, the Panel
recommended that OSHA give careful
consideration to the impacts that an
MRP requirement could have on small
businesses (OSHA, 2008b). In response
to this recommendation, OSHA
analyzed Regulatory Alternative #22,
which would not require employers to
offer MRP. More detailed discussion of
Regulatory Alternative #22 appears in
Section IX of this preamble and in
Chapter VIII of the PEA (OSHA, 2014).
In addition, the discussion of paragraph
(l) in section XVIII of this preamble,
Summary and Explanation, provides a
more detailed explanation of the
proposed requirements for MRP, issues
with MRP, and considerations pertinent
to Regulatory Alternative #22.
Timing of the Standard
The proposed standard would become
effective 60 days following publication
of the final standard in the Federal
Register. The effective date is the date
on which the standard imposes
compliance obligations on employers.
However, the standard would not
become enforceable by OSHA until 90
days following the effective date for
exposure monitoring, work areas and
regulated areas, written exposure
control plan, respiratory protection,
other personal protective clothing and
equipment, hygiene areas and practices
(except change rooms), housekeeping,
medical surveillance, and medical
removal. The proposed requirement for
change rooms would not be enforceable
until one year after the effective date,
and the requirements for engineering
controls would not be enforceable until
two years after the effective date. In
summary, employers will have some
period of time after the standard
becomes effective to come into
compliance before OSHA will begin
enforcing it: 90 days for most
provisions, one year for change rooms,
and two years for engineering controls.
Beginning 90 days following the
effective date, during periods necessary
to install or implement feasible
engineering controls where exposure
exceed the TWA PEL or STEL,
employers must provide employees
with respiratory protection as described
in the proposed standard under section
(g), Respiratory Protection.
OSHA invites comment and
suggestions for phasing in requirements
for engineering controls, medical
surveillance, and other provisions of the
standard. A longer phase-in time would
have several advantages, such as
reducing initial costs of the standard or
allowing employers to coordinate their
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environmental and occupational safety
and health control strategies to
minimize potential costs. However, a
longer phase-in would also postpone
and reduce the benefits of the standard.
Suggestions for alternatives may apply
to specific industries (e.g., industries
where first-year or annualized cost
impacts are highest), specific sizeclasses of employers (e.g., employers
with fewer than 20 employees),
combinations of these factors, or all
firms covered by the rule.
OSHA requests comments on these
regulatory alternatives, including the
Agency’s choice of regulatory
alternatives (and whether there are other
regulatory alternatives the Agency
should consider) and the Agency’s
analysis of them. In addition, OSHA
requests comments and information on
a number of specific topics and issues
pertinent to the proposed standard.
These are summarized below.
provisions should contain a heading
setting forth the section and the
paragraph in the proposed standard that
the comment addresses. Comments
addressing more than one section or
paragraph will have correspondingly
more headings.
Submitting comments in an organized
manner and with clear reference to the
issue raised will enable all participants
to easily see what issues the commenter
addressed and how they were
addressed. Many commenters,
especially small businesses, are likely to
confine their comments to the issues
that affect them, and they will benefit
from being able to quickly identify
comments on these issues in others’
submissions. The Agency welcomes
comments concerning all aspects of this
proposal. However, OSHA is especially
interested in responses, supported by
evidence and reasons, to the following
questions:
Regulatory Issues
In this section, we solicit public
feedback on issues associated with the
proposed standard and request
information that would help the Agency
craft the final standard. In addition to
the issues specified here, OSHA also
raises issues for comment on technical
questions and discussions of economic
issues in the PEA (OSHA, 2014). OSHA
requests comment on all relevant issues,
including health effects, risk
assessment, significance of risk,
technological and economic feasibility,
and the provisions of the proposed
regulatory text. In addition, OSHA
requests comments on all of the issues
raised by the Small Business Advocacy
Review (SBAR) Panel, as summarized in
the SBAR report (OSHA, 2008b)
We present these issues and requests
for information in the first chapter of the
preamble to assist readers as they
review the preamble and consider any
comments they may want to submit.
The issues are presented here in
summary form. However, to fully
understand the questions in this section
and provide substantive input in
response to them, the sections of the
preamble relevant to these issues should
be reviewed. These include: Section V,
Health Effects; Section VI, the
Preliminary Risk Assessment; Section
VIII, Significance of Risk; Section IX,
Summary of the Preliminary Economic
Analysis and Initial Regulatory
Flexibility Analysis; and Section XVIII,
Summary and Explanation of the
Proposed Standard.
OSHA requests that comments be
organized, to the extent possible, around
the following issues and numbered
questions. Comment on particular
Health Effects
1. OSHA has described a variety of
studies addressing the major adverse
health effects that have been associated
with exposure to beryllium. Using
currently available epidemiologic and
experimental studies, OSHA has made a
preliminary determination that
beryllium presents risks of lung cancer;
sensitization; CBD at 0.1 mg/m3; and at
higher exposures acute beryllium
disease, and hepatic, renal,
cardiovascular and ocular diseases. Is
this determination correct? Are there
additional studies or other data OSHA
should consider in evaluating any of
these health outcomes?
2. Has OSHA adequately identified
and documented all critical health
impairments associated with
occupational exposure to beryllium? If
not, what other adverse health effects
should be added? Are there additional
studies or other data OSHA should
consider in evaluating any of these
health outcomes?
3. Are there any additional studies,
other data, or information that would
affect the information discussed or
significantly change the determination
of material health impairment?
Please submit any relevant
information, data, or additional studies
(or citations to studies), and explain
your reasons for recommending any
studies you suggest.
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Risk Assessment and Significance of
Risk
4. OSHA has developed an analysis of
health risks associated with
occupational beryllium exposure,
including an analysis of sensitization
and CBD based on a selection of recent
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studies in the epidemiological literature,
a data set on a population of beryllium
machinists provided by the National
Jewish Medical Research Center
(NJMRC), and an assessment of lung
cancer risk using an analysis provided
by NIOSH. Did OSHA rely on the best
available evidence in its risk
assessment? Are there additional studies
or other data OSHA should consider in
evaluating risk for these health
outcomes? Please provide the studies,
citations to studies, or data you suggest.
5. OSHA preliminarily concluded that
there is significant risk of material
health impairment (lung cancer or CBD)
from a working lifetime of occupational
exposure to beryllium at the current
TWA PEL of 2 mg/m3, which would be
substantially reduced by the proposed
TWA PEL of 0.2 mg/m3 and the
alternative TWA PEL of 0.1 mg/m3.
OSHA’s preliminary risk assessment
also concludes that there is still
significant risk of CBD and lung cancer
at the proposed PEL and the alternative
PELs, although substantially less than at
the current PEL. Are these preliminary
conclusions reasonable, based on the
best available evidence? If not, please
provide a detailed explanation of your
position, including data to support your
position and a detailed analysis of
OSHA’s risk assessment if appropriate.
6. Please provide comment on
OSHA’s analysis of risk for beryllium
sensitization, CBD and lung cancer. Are
there important gaps or uncertainties in
the analysis, such that the Agency’s
preliminary conclusions regarding
significance of risk at the current,
proposed, and alternative PELs may be
in error? If so, please provide a detailed
explanation and suggestions for how
OSHA’s analysis should be corrected or
improved.
7. OSHA has made a preliminary
determination that the available data are
not sufficient or suitable for risk
analysis of effects other than beryllium
sensitization, CBD and lung cancer. Do
you have, or are you aware of, studies
or data that would be suitable for a risk
assessment for these adverse health
effects? Please provide the studies,
citations to studies, or data you suggest.
(a) Scope
8. Has OSHA defined the scope of the
proposed standard appropriately? Does
it currently include employers who
should not be covered, or exclude
employers who should be covered by a
comprehensive beryllium standard? Are
you aware of employees in construction
or maritime, or in general industry who
deal with beryllium only as a trace
contaminant, who may be at significant
risk from occupational beryllium
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exposure? Please provide the basis for
your response and any applicable
supporting information.
(b) Definitions
9. Has OSHA defined the Beryllium
lymphocyte proliferation test
appropriately? If not, please provide the
definition that you believe is
appropriate. Please provide rationale
and citations supporting your
comments.
10. Has OSHA defined CBD
Diagnostic Center appropriately? In
particular, should a CBD diagnostic
center be required to analyze biological
samples on-site, or should diagnostic
centers be allowed to send samples offsite for analysis? Is the list of tests and
procedures a CBD Diagnostic Center is
required to be able to perform
appropriate? Should any of the tests or
procedures be removed from the
definition? Should other tests or
procedures be added to the definition?
Please provide rationale and
information supporting your comments.
(d) Exposure Monitoring
11. Do you currently monitor for
beryllium exposures in your workplace?
If so, how often? Please provide the
reasoning for the frequency of your
monitoring. If periodic monitoring is
performed at your workplace for
exposures other than beryllium, with
what frequency is it repeated?
12. Is it reasonable to allow
discontinuation of monitoring based on
one sample below the action level?
Should more than one result below the
action level be required to discontinue
monitoring?
(e) Work Areas and Regulated Areas
The proposed standard would require
employers to establish and maintain two
types of areas: beryllium work areas,
wherever employees are, or can
reasonably be expected to be, exposed to
any level of airborne beryllium; and
regulated areas, wherever employees
are, or can reasonably be expected to be,
exposed to airborne beryllium at levels
above the TWA PEL or STEL. Employers
are required to demarcate beryllium
work areas, but are not required to
restrict access to beryllium work areas
or provide respiratory protection or
other forms of PPE within work areas
with exposures at or below the TWA
PEL or STEL. Employers must also
demarcate regulated areas, including
posting warning signs; restrict access to
regulated areas; and provide respiratory
protection and other PPE within
regulated areas.
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13. Does your workplace currently
have regulated areas? If so, how are
regulated areas demarcated?
14. Please describe work settings
where establishing regulated areas could
be problematic or infeasible. If
establishing regulated areas is
problematic, what approaches might be
used to warn employees in such work
settings of high risk areas?
(f) Methods of Compliance
Paragraph (f)(2) of the proposed
standard would require employers to
implement engineering and work
practice controls to reduce employees’
exposures to or below the TWA PEL and
STEL. Where engineering and work
practice controls are insufficient to
reduce exposures to or below the TWA
PEL and STEL, employers would still be
required to implement them to reduce
exposure as much as possible, and to
supplement them with a respiratory
protection program. In addition, for
each operation where there is airborne
beryllium exposure, the employer must
ensure that at least one of the
engineering and work practice controls
listed in paragraph (f)(2) is in place,
unless all of the listed controls are
infeasible, or the employer can
demonstrate that exposures are below
the action level based on no fewer than
two samples taken seven days apart.
15. Do you usually use engineering or
work practices controls (local exhaust
ventilation, isolation, substitution) to
reduce beryllium exposures? If so,
which controls do you use?
16. Are the controls and processes
listed in paragraph (f)(2)(i)(A)
appropriate for controlling beryllium
exposures? Are there additional controls
or processes that should be added to
paragraph (f)(2)(i)(A)?
(g) Respiratory Protection
17. OSHA’s asbestos standard (CFR
1910.1001) requires employers to
provide each employee with a tightfitting, powered air-purifying respirator
(PAPR) instead of a negative pressure
respirator when the employee chooses
to use a PAPR and it provides adequate
protection to the employee. Should the
beryllium standard similarly require
employers to provide PAPRs (instead of
allowing a negative pressure respirator)
when requested by the employee? Are
there other circumstances where a PAPR
should be specified as the appropriate
respiratory protection? Please provide
the basis for your response and any
applicable supporting information.
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(h) Personal Protective Clothing and
Equipment
18. Do you currently require specific
PPE or respirators when employees are
working with beryllium? If so, what
type?
19. The proposal requires PPE
wherever work clothing or skin may
become visibly contaminated with
beryllium; where employees’ skin can
reasonably be expected to be exposed to
soluble beryllium compounds; or where
employee exposure exceeds or can
reasonably be expected to exceed the
TWA PEL or STEL. The requirement to
use PPE where work clothing or skin
may become ‘‘visibly contaminated’’
with beryllium differs from prior
standards which do not require
contamination to be visible in order for
PPE to be required. Is ‘‘visibly
contaminated’’ an appropriate trigger for
PPE? Is there reason to require PPE
where employees’ skin can be exposed
to insoluble beryllium compounds?
Please provide the basis for your
response and any applicable supporting
information.
(i) Hygiene Areas and Practices
20. The proposal requires employers
to provide showers in their facilities if
(A) Exposure exceeds or can reasonably
be expected to exceed the TWA PEL or
STEL; and (B) Beryllium can reasonably
be expected to contaminate employees’
hair or body parts other than hands,
face, and neck. Is this requirement
reasonable and adequately protective of
beryllium-exposed workers? Should
OSHA amend the provision to require
showers in facilities where exposures
exceed the PEL or STEL, without regard
to areas of bodily contamination?
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(j) Housekeeping
21. The proposed rule prohibits dry
sweeping or brushing for cleaning
surfaces in beryllium work areas unless
HEPA-filtered vacuuming or other
methods that minimize the likelihood
and level of exposure have been tried
and were not effective. Please comment
on this provision. What methods do you
use to clean work surfaces at your
facility? Are HEPA-filtered vacuuming
or other methods to minimize beryllium
exposure used to clean surfaces at your
facility? Have they been effective? Are
there any circumstances under which
dry sweeping or brushing are necessary?
Please explain your response.
22. The proposed rule requires that
materials designated for recycling that
are visibly contaminated with beryllium
particulate shall be cleaned to remove
visible particulate, or placed in sealed,
impermeable enclosures. However,
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small particles (<10 mg) may not be
visible to the naked eye, and there are
studies suggesting that small particles
may penetrate the skin, beyond which
beryllium sensitization can occur
(Tinkle et al., 2003). OSHA requests
feedback on this provision. Should
OSHA require that all material to be
recycled be decontaminated regardless
of perceived surface cleanliness? Should
OSHA require that all material disposed
or discarded be in enclosures regardless
of perceived surface cleanliness? Please
provide explanation or data to support
your comments.
(k) Medical Surveillance
The proposed requirements for
medical surveillance include: (1)
Medical examinations, including a test
for beryllium sensitization, for
employees who are exposed to
beryllium above the proposed PEL for
30 days or more per year, who are
exposed to beryllium in an emergency,
or who show signs or symptoms of CBD;
and (2) CT scans for employees who
were exposed above the proposed PEL
for more than 30 days in a 12-month
period for 5 years or more. The
proposed standard would require
periodic medical exams to be provided
for employees in the medical
surveillance program annually, while
tests for beryllium sensitization and CT
scans would be provided to eligible
employees biennially.
23. Is medical surveillance being
provided for beryllium-exposed
employees at your worksite? If so:
a. Do you provide medical
surveillance to employees under
another OSHA standard or as a matter
of company policy? What OSHA
standard(s) does the program address?
b. How many employees are included,
and how do you determine which
employees receive medical surveillance
(e.g., by exposure level, other factors)?
c. Who administers and implements
the medical surveillance (e.g., company
doctor, nurse practitioner, physician
assistant, or nurse; or outside doctor,
nurse practitioner, physician assistant,
or nurse)?
d. What examinations, tests, or
evaluations are included in the medical
surveillance program, and with what
frequency are they administered? Does
your program include a surveillance
program specifically for berylliumrelated health effects (e.g., the BeLPT or
other tests for beryllium sensitization)?
e. If your facility offers the BeLPT,
please provide feedback and data on
your experience with the BeLPT,
including the analytical or interpretive
procedure you use and its role in your
facility’s exposure control program. Has
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identification of sensitized workers led
to interventions to reduce exposures to
sensitized individuals, or in the facility
generally? If a worker is found to be
sensitized, do you track worker health
and possible progression of disease
beyond sensitization? If so, how is this
done?
f. What difficulties and benefits (e.g.,
health, reduction in absenteeism, or
financial) have you experienced with
your medical surveillance program? If
applicable, please discuss benefits and
difficulties you have experienced with
the use of the BeLPT, providing detailed
information or examples if possible.
g. What are the costs of your medical
surveillance program? How do your
costs compare with OSHA’s estimated
unit costs for the physical examination
and employee time involved in the
medical surveillance program? Are
OSHA’s baseline assumptions and cost
estimates for medical surveillance
consistent with your experiences
providing medical surveillance to your
employees?
24. Please review paragraph (k) of the
proposed rule, Medical Surveillance,
and comment on the frequency and
contents of medical surveillance in the
proposed rule. Is 30 days from initial
assignment a reasonable time at which
to provide a medical exam? Should
there be a requirement for beryllium
sensitization testing at time of
employment? Should there be a
requirement for beryllium sensitization
testing at an employee’s exit exam,
regardless of when the employee’s most
recent sensitization test was
administered? Are the tests required and
the testing frequencies specified
appropriate? Should sensitized
employees have the opportunity to be
examined at a CBD Diagnostic Center
more than once following a confirmed
positive BeLPT? Are there additional
tests or alternate testing schedules you
would suggest? Should the skin be
examined for signs and symptoms of
beryllium exposure or other medical
issues, as well as for breaks and
wounds? Please explain the basis for
your position and provide data or
studies if applicable.
25. Please provide comments on the
proposed requirements regarding
referral of a sensitized employee to a
CBD diagnostic center, which specify
referral to a diagnostic center ‘‘mutually
agreed upon’’ by the employer and
employee. Is this requirement for
mutual agreement necessary and
appropriate? How should a diagnostic
center be chosen if the employee and
employer cannot come to agreement?
Should OSHA consider alternate
language, such as referral for CBD
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evaluation at a diagnostic center in a
reasonable location?
26. In the proposed rule, OSHA
specifies that all medical examinations
and procedures required by the standard
must be performed by or under the
direction of a licensed physician. Are
physicians available in your geographic
area to provide medical surveillance to
workers who are covered by the
proposed rule? Are other licensed
health care professionals available to
provide medical surveillance? Do you
have access to other qualified personnel
such as qualified X-ray technicians, and
pulmonary specialists? Should the
proposal be amended to allow
examination by, or under the direction
of, a physician or other licensed health
care professional (PLHCP)? Please
explain your position. Please note what
you consider your geographic area in
responding to this question.
27. The proposed standard requires
the employer to obtain the Licensed
Physician’s Written Medical Opinion
from the PLHCP within 30 days of the
examination. Should OSHA revise the
medical surveillance provisions of the
proposed standard to allow employees
to choose what, if any, medical
information goes to the employer from
the PLHCP? For example, the employer
could instead be required to obtain a
certification from the PLCHP within 30
days of the examination stating (1) when
the examination took place, (2) that the
examination complied with the
standard, and (3) that the PLHCP
provided the employee a copy of the
Licensed Physician’s Written Medical
Opinion required by the standard. The
PLHCP would need the employee’s
written consent to send the employer
the Licensed Physician’s Written
Medical Opinion or any other medical
information about the employee. This
approach might lead to corresponding
changes in proposed paragraphs (f)(1)
(written exposure control program), (l)
(medical removal) and (n)
(recordkeeping) to reflect that employers
will not automatically be receiving any
medical information about employees as
a result of the medical surveillance
required by the proposed standard, but
would instead only receive medical
information the employee chooses to
share with the employer. Please
comment on the relative merits of the
proposed standard’s requirement that
employers obtain the PLHCP’s written
opinion or an alternative that would
provide employees with greater
discretion over the information that goes
to employers, and explain the basis for
your position and the potential impact
on the benefits of medical surveillance.
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28. Appendix A to the proposed
standard reviews procedures for
conducting and interpreting the results
of BeLPT testing for beryllium
sensitization. Is there now, or should
there be, a standard method for BeLPT
laboratory procedure? If yes, please
describe the existing or proposed
method. Is there now, or should there
be, a standard algorithm for interpreting
BeLPT results to determine
sensitization? Please describe the
existing or proposed laboratory method
or interpretation algorithm. Should
OSHA require that BeLPTs performed to
comply with the medical surveillance
provisions of this rule adhere to the
Department of Energy (DOE) analytical
and interpretive specifications issued in
2001? Should interpretation of
laboratory results be delegated to the
employee’s occupational physician or
PLHCP?
29. Should OSHA require the clinical
laboratories performing the BeLPT to be
accredited by the College of American
Pathologists or another accreditation
organization approved under the
Clinical Laboratory Improvement
Amendments (CLIA)? What other
standards, if any, should be required for
clinical laboratories providing the
BeLPT?
30. Are there now, or are there being
developed, alternative tests to the
BeLPT you would suggest? Please
explain the reasons for your suggestion.
How should alternative tests for
beryllium sensitization be evaluated and
validated? How should OSHA
determine whether a test for beryllium
sensitization is more reliable and
accurate than the BeLPT? Please see
Appendix A to the proposed standard
for a discussion of the accuracy of the
BeLPT.
31. The proposed rule requires
employers to provide OSHA with the
results of BeLPTs performed to comply
with the medical surveillance
provisions upon request, provided that
the employer obtains a release from the
tested employee. Will this requirement
be unduly burdensome for employers?
Are there alternative organizations that
would be appropriate to send test
results to?
(l) Medical Removal Protection
The proposed requirements for
medical removal protection provide an
option for medical removal to an
employee who is working in a job with
exposure at or above the action level
and is diagnosed with CBD or confirmed
positive for beryllium sensitization. If
the employee chooses removal, the
employer must remove the employee to
comparable work in a work
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environment where exposure is below
the action level, or if comparable work
is not available, must place the
employee on paid leave for 6 months or
until such time as comparable work
becomes available. In either case, the
employer must maintain for 6 months
the employee’s base earnings, seniority,
and other rights and benefits that
existed at the time of removal.
32. Do you provide MRP at your
facility? If so, please comment on the
program’s benefits, difficulties, and
costs, and the extent to which eligible
employees make use of MRP.
33. OSHA has included requirements
for medical removal protection (MRP) in
the proposed rule, which includes
provisions for medical removal for
employees with beryllium sensitization
or CBD, and an extension of removed
employees’ rights and benefits for six
months. Are beryllium sensitization and
CBD appropriate triggers for medical
removal? Are there other medical
conditions or findings that should
trigger medical removal? For what
amount of time should a removed
employee’s benefits be extended?
(p) Appendices
34. Some OSHA health standards
include appendices that address topics
such as the hazards associated with the
regulated substance, health screening
considerations, occupational disease
questionnaires, and PLHCP obligations.
In this proposed rule, OSHA has
included a non-mandatory appendix to
describe and discuss the BeLPT
(Appendix A), and a non-mandatory
appendix presenting a non-exhaustive
list of engineering controls employers
may use to comply with paragraph (f)
(Appendix B). What would be the
advantages and disadvantages of
including each appendix in the final
rule? What would be the advantages and
disadvantages of providing this
information in guidance materials?
35. What additional information, if
any, should be included in the
appendices? What additional
information, if any, should be provided
in guidance materials?
General
36. The current beryllium proposal
includes triggers that require employers
to initiate certain provisions, programs,
and activities to protect workers from
beryllium exposure. All employers
covered under an OSHA health standard
are required to initiate certain activities
such as initial monitoring to evaluate
the potential hazard to employees.
OSHA health standards typically
include ancillary provisions with
various triggers indicating when an
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employer covered under the standard
would need to comply with a provision.
The most common triggers are ones
based an exposure level such as the PEL
or action level. These exposure level
triggers are sometimes combined with a
minimum duration of exposure (e.g., ≥
30 days per year). Other triggers may
include reasonably anticipated
exposure, medical surveillance findings,
certain work activities, or simply the
presence of the regulated substance in
the workplace.
For the current Proposal, exposures to
beryllium above the TWA PEL or STEL
trigger the provisions for regulated
areas, additional or enhanced
engineering or work practice controls to
reduce airborne exposures to or below
the TWA PEL and STEL, personal
protective clothing and equipment,
medical surveillance, showers, and
respiratory protection if feasible
engineering and work practice controls
cannot reduce airborne exposures to or
below the TWA PEL and STEL.
Exposures at or above the action level in
turn trigger the provisions for periodic
exposure monitoring, and medical
removal eligibility (along with a
diagnosis of CBD or confirmed positive
for beryllium sensitization). Finally, an
employer covered under the scope of
the proposed standard must establish a
beryllium work area where employees
are, or can reasonably be expected to be,
exposed to airborne beryllium
regardless of the level of exposure. In
beryllium work areas, employers must
implement a written exposure control
plan, provide washing facilities and
change rooms (change rooms are only
necessary if employees are required to
remove their personal clothing), and
follow housekeeping provisions. The
employers must also implement at least
one of the engineering and work
practice controls listed in paragraph
(f)(2) of the proposed standard. An
employer is exempt from this
requirement if he or she can
demonstrate that such controls are not
feasible or that exposures are below the
action level.
Certain provisions are triggered by
one condition and other provisions are
triggered only if multiple conditions are
present. For example, medical removal
is only triggered if an employee has CBD
or is confirmed positive AND the
employee is exposed at or above the
action level.
OSHA is requesting comment on the
triggers in the proposed beryllium
standard. Are the triggers OSHA has
proposed appropriate? OSHA is also
requesting comment on these triggers
relative to the regulatory alternatives
affecting the scope and PELs as
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described in this preamble in section I,
Issues and Alternatives. For example,
are the triggers in the proposed standard
appropriate for Alternative #1a, which
would expand the scope of the proposed
standard to include all operations in
general industry where beryllium exists
only as a trace contaminant (less than
0.1% beryllium by weight)? Are the
triggers appropriate for the alternatives
that change the TWA PEL, STEL, and
action level? Please specify the trigger
and the alternative, if applicable, and
why you agree or disagree with the
trigger.
Relevant Federal Rules Which May
Duplicate, Overlap, or Conflict With the
Proposed Rule
37. In Section IX—Preliminary
Economic Analysis under the Initial
Regulatory Flexibility Analysis, OSHA
identifies, to the extent practicable, all
relevant Federal rules which may
duplicate, overlap, or conflict with the
proposed rule. One potential area of
overlap is with the U.S. Department of
Energy (DOE) beryllium program. In
1999, DOE established a chronic
beryllium disease prevention program
(CBDPP) to reduce the number of
workers (DOE employees and DOE
contractors) exposed to beryllium at
DOE facilities (10 CFR part 850,
published at 64 FR 68854–68914 (Dec.
8, 1999)). In establishing this program,
DOE has exercised its statutory
authority to prescribe and enforce
occupational safety and health
standards. Therefore pursuant to section
4(b)(1) of the OSH Act, 29 U.S.C.
653(b)(1), the DOE facilities are exempt
from OSHA jurisdiction.
Nevertheless, under 10 CFR 850.22,
DOE has included in its CBDPP
regulation a requirement for compliance
with the current OSHA permissible
exposure limit (PEL), and any lower PEL
that OSHA establishes in the future.
Thus, although DOE has preempted
OSHA’s standard from applying at DOE
facilities and OSHA cannot exercise any
authority at those facilities, DOE relies
on OSHA’s PEL in implementing its
own program. However, DOE’s decision
to tie its own standard to OSHA’s PEL
has little consequence to this
rulemaking because the requirements in
DOE’s beryllium program (controls,
medical surveillance, etc.) are triggered
by DOE’s action level of 0.2 mg/m3,
which is much lower than DOE’s
existing PEL and the same as OSHA’s
proposed PEL. DOE’s action level is not
tied to OSHA’s standard, so 10 CFR
850.22 would not require the CBDPP’s
action level or any non-PEL
requirements to be automatically
adjusted as a result of OSHA’s
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rulemaking. For this reason, DOE has
indicated to OSHA that OSHA’s
proposed rule would not have any
impact on DOE’s CBDPP, particularly
since 10 CFR 850.25(b), Exposure
reduction and minimization, requires
DOE contractors to reduce exposures to
below the DOE’s action level of 0.2 mg/
m3, if practicable.
DOE has expressed to OSHA that DOE
facilities are already in compliance with
10 CFR 850 and its action level of 0.2
mg/m3,2 so the only potential impact on
DOE’s CBDPP that could flow from
OSHA’s rulemaking would be if OSHA
ultimately adopted a PEL of 0.1 mg/m3,
as discussed in alternative #4, instead of
the proposed PEL of 0.2 mg/m3, and DOE
did not make any additional
adjustments to its standards. Even in
that hypothetical scenario, the impact
would still be limited because of the
odd result that DOE’s PEL would drop
below its own action level, while the
action level would continue to serve as
the trigger for most of DOE’s program
requirements.
DOE also has noted some potential
overlap with a separate DOE provision
in 10 CFR part 851, which requires its
contractors to comply with DOE’s
CBDPP (10 CFR 851.23(a)(1)) and also
with all OSHA standards under 29 CFR
part 1910 except ‘‘Ionizing Radiation’’
(§ 1910.1096) (10 CFR 851.23(a)(3)).
These requirements, which DOE
established in 2006 (71 FR 6858
(February 9, 2006)), make sense in light
of OSHA’s current regulation because
OSHA’s only beryllium protection is a
PEL, so compliance with 10 CFR
851.23(a)(1) and (3) merely make
OSHA’s current PEL the relevant level
for purposes of the CBDPP. However, its
function would be less clear if OSHA
adopts a beryllium standard as
proposed. OSHA’s proposed beryllium
standard would establish additional
substantive protections beyond the PEL.
Consequently, notwithstanding the
CBDPP’s preemptive effect on the OSHA
beryllium standard as a result of 29
U.S.C. 653(b)(1), 10 CFR 851.23(a)(3)
could be read to require DOE
contractors to comply with all
provisions in OSHA’s proposal (if
finalized), including the ancillary
provisions, creating a dual regulatory
scheme for beryllium protection at DOE
facilities.
DOE officials have indicated that this
is not their intent. Instead, their intent
is that DOE contractors comply solely
with the CBDPP provisions in 10 CFR
part 850 for protection from beryllium.
2 This would mean the prevailing beryllium
exposures at DOE facilities are at or below 0.2 mg/
m3.
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Based on its discussions with DOE
officials, OSHA anticipates that DOE
will clarify that its contractors do not
need to comply with any ancillary
provisions in a beryllium standard that
OSHA may promulgate.
OSHA can envision several potential
scenarios developing from its
rulemaking, ranging from OSHA
retaining the proposed PEL of 0.2 mg/m3
and action level of 0.1 mg/m3 in the final
rule to adopting the PEL of 0.1 mg/m3,
as discussed in alternative #4. Because
OSHA’s beryllium standard does not
apply directly to DOE facilities, and the
only impact of its rules on those
facilities is the result of DOE’s
regulatory choices, there is also a range
of actions that DOE could take to
minimize any potential impact of any
change to OSHA’s rules, including (1)
taking no action at all, (2) simply
clarifying the CBDPP, as described
above, to mean that OSHA’s beryllium
standard (other than its PEL) does not
apply to contractors, or (3) revising both
parts 850 and 851 to completely
disassociate DOE’s regulation of
beryllium at DOE facilities from OSHA’s
regulation of beryllium.
OSHA is aware that, in the preamble
to its 1999 CBDPP rule, DOE analyzed
the costs for implementing the CBDPP
for action levels of 0.1 mg/m3, 0.2 mg/m3,
and 0.5 mg/m3 (64 FR 68875, December
8, 1999). DOE estimated costs for
periodic exposure monitoring, notifying
workers of the results of such
monitoring, exposure reduction and
minimization, regulated areas, change
rooms and showers, respiratory
protection, protective clothing, and
disposal of protective clothing. All of
these provisions are triggered by DOE’s
action level (64 FR 68874, December 8,
1999). Although DOE’s rule is not
identical to OSHA’s proposed standard,
OSHA believes that DOE’s costs are
sufficiently representative to form the
basis of a preliminary estimate of the
costs that could flow from OSHA’s
standard, if finalized.
Based on the range of potential
scenarios and the prior DOE cost
estimates, OSHA estimates that the
annual cost impact on DOE facilities
could range from $0 to $4,065,768 (2010
dollars). The upper end of the cost range
would reflect the unlikely scenario in
which OSHA promulgates a final PEL of
0.1 mg/m3, 10 CFR 851.23(a)(3) is found
to compel DOE contractors to comply
with OSHA’s comprehensive beryllium
standard in addition to DOE’s CBDPP,
and DOE takes no action to clarify that
OSHA’s beryllium standard does not
apply to DOE contractors. The lower
end of the cost range assumes OSHA
promulgates its rule as proposed with a
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PEL of 0.2 mg/m3 and action level of 0.1
mg/m3, and DOE clarifies that it intends
its contractors to follow DOE’s CBDPP
and not OSHA’s beryllium standard, so
that the ancillary provisions of OSHA’s
beryllium standard do not apply to DOE
facilities. Additionally, OSHA assumes
that DOE contractors are in compliance
with DOE’s current rule and therefore
took the difference in cost between
implementation of an action level of 0.2
mg/m3 and an action level of 0.1 mg/m3
for the above estimates. Finally, OSHA
used the GDP price deflator to present
the cost estimate in 2010 dollars.
OSHA requests comment on the
potential overlap of DOE’s rule with
OSHA’s proposed rule.
II. Pertinent Legal Authority
The purpose of the Occupational
Safety and Health Act, 29 U.S.C. 651 et
seq. (‘‘the Act’’), is to ‘‘. . . assure so far
as possible every working man and
woman in the nation safe and healthful
working conditions and to preserve our
human resources.’’ 29 U.S.C. 651(b).
To achieve this goal Congress
authorized the Secretary of Labor (the
Secretary) to promulgate and enforce
occupational safety and health
standards. 29 U.S.C. 654(b) (requiring
employers to comply with OSHA
standards), 655(a) (authorizing summary
adoption of existing consensus and
federal standards within two years of
the Act’s enactment), and 655(b)
(authorizing promulgation, modification
or revocation of standards pursuant to
notice and comment).
The Act provides that in promulgating
health standards dealing with toxic
materials or harmful physical agents,
such as this proposed standard
regulating occupational exposure to
beryllium, the Secretary, shall set the
standard which most adequately
assures, to the extent feasible, on the
basis of the best available evidence that
no employee will suffer material
impairment of health or functional
capacity even if such employee has
regular exposure to the hazard dealt
with by such standard for the period of
his working life. See 29 U.S.C. 655(b)(5).
The Supreme Court has held that
before the Secretary can promulgate any
permanent health or safety standard, he
must make a threshold finding that
significant risk is present and that such
risk can be eliminated or lessened by a
change in practices. Industrial Union
Dept., AFL–CIO v. American Petroleum
Institute, 448 U.S. 607, 641–42 (1980)
(plurality opinion) (‘‘The Benzene
case’’). Thus, section 6(b)(5) of the Act
requires health standards to reduce
significant risk to the extent feasible. Id.
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The Court further observed that what
constitutes ‘‘significant risk’’ is ‘‘not a
mathematical straitjacket’’ and must be
‘‘based largely on policy
considerations.’’ The Benzene case, 448
U.S. at 655. The Court gave the example
that if,
. . . the odds are one in a billion that a
person will die from cancer . . . the risk
clearly could not be considered significant.
On the other hand, if the odds are one in one
thousand that regular inhalation of gasoline
vapors that are 2% benzene will be fatal, a
reasonable person might well consider the
risk significant. [Id.]
OSHA standards must be both
technologically and economically
feasible. United Steelworkers v.
Marshall, 647 F.2d 1189, 1264 (D.C. Cir.
1980) (‘‘The Lead I case’’). The Supreme
Court has defined feasibility as ‘‘capable
of being done.’’ Am. Textile Mfrs. Inst.
v. Donovan, 452 U.S. 490, 509–510
(1981) (‘‘The Cotton Dust case’’). The
courts have further clarified that a
standard is technologically feasible if
OSHA proves a reasonable possibility,
. . . within the limits of the best available
evidence . . . that the typical firm will be able
to develop and install engineering and work
practice controls that can meet the PEL in
most of its operations. [See The Lead I case,
647 F.2d at 1272]
With respect to economic feasibility,
the courts have held that a standard is
feasible if it does not threaten massive
dislocation to or imperil the existence of
the industry. Id. at 1265. A court must
examine the cost of compliance with an
OSHA standard,
. . . in relation to the financial health and
profitability of the industry and the likely
effect of such costs on unit consumer prices
. . . [T]he practical question is whether the
standard threatens the competitive stability
of an industry, . . . or whether any intraindustry or inter-industry discrimination in
the standard might wreck such stability or
lead to undue concentration. [Id. (citing
Indus. Union Dep’t, AFL–CIO v. Hodgson,
499 F.2d 467 (D.C. Cir. 1974))]
The courts have further observed that
granting companies reasonable time to
comply with new PELs may enhance
economic feasibility. The Lead I case at
1265. While a standard must be
economically feasible, the Supreme
Court has held that a cost-benefit
analysis of health standards is not
required by the Act because a feasibility
analysis is required. The Cotton Dust
case, 453 U.S. at 509.
Finally, sections 6(b)(7) and 8(c) of
the Act authorize OSHA to include
among a standard’s requirements
labeling, monitoring, medical testing,
and other information-gathering and
-transmittal provisions. 29 U.S.C.
655(b)(7), 657(c).
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III. Events Leading to the Proposed
Standards
The first occupational exposure limit
for beryllium was set in 1949 by the
Atomic Energy Commission (AEC),
which required that beryllium exposure
in the workplaces under its jurisdiction
be limited to 2 mg/m3 as an 8-hour timeweighted average (TWA), and 25 mg/m3
as a peak exposure never to be exceeded
(Department of Energy, 1999). These
exposure limits were adopted by all
AEC installations handling beryllium,
and were binding on all AEC contractors
involved in the handling of beryllium.
In 1956, the American Industrial
Hygiene Association (AIHA) published
a Hygienic Guide which supported the
AEC exposure limits. In 1959, the
American Conference of Governmental
Industrial Hygienists (ACGIH®) also
adopted a Threshold Limit Value
(TLV®) of 2 mg/m3 as an 8-hour TWA
(Borak, 2006).
In 1971, OSHA adopted, under
Section 6(a) of the Occupational Safety
and Health Act of 1970, and made
applicable to general industry, a
national consensus standard (ANSI
Z37.29–1970) for beryllium and
beryllium compounds. The standard set
a permissible exposure limit (PEL) for
beryllium and beryllium compounds at
2 mg/m3 as an 8-hour TWA; 5 mg/m3 as
an acceptable ceiling concentration; and
25 mg/m3 as an acceptable maximum
peak above the acceptable ceiling
concentration for a maximum duration
of 30 minutes in an 8-hour shift (OSHA,
1971).
Section 6(a) stipulated that in the first
two years after the effective date of the
Act, OSHA was to promulgate ‘‘startup’’ standards, on an expedited basis
and without public hearing or comment,
based on national consensus or
established Federal standards that
improved employee safety or health.
Pursuant to that authority, in 1971,
OSHA promulgated approximately 425
PELs for air contaminants, including
beryllium, derived principally from
Federal standards applicable to
government contractors under the
Walsh-Healey Public Contracts Act, 41
U.S.C. 35, and the Contract Work Hours
and Safety Standards Act (commonly
known as the Construction Safety Act),
40 U.S.C. 333. The Walsh-Healey Act
and Construction Safety Act standards,
in turn, had been adopted primarily
from ACGIH®’s TLV®s.
The National Institute for
Occupational Safety and Health
(NIOSH) issued a document entitled
Criteria for a Recommended Standard:
Occupational Exposure to Beryllium
(Criteria Document) in June 1972. OSHA
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reviewed the findings and
recommendations contained in the
Criteria Document along with the AEC
control requirements for beryllium
exposure. OSHA also considered
existing data from animal and
epidemiological studies, and studies of
industrial processes of beryllium
extraction, refinement, fabrication, and
machining. In 1975, OSHA asked
NIOSH to update the evaluation of the
existing data pertaining to the
carcinogenic potential of beryllium. In
response to OSHA’s request, the
Director of NIOSH stated that, based on
animal data and through all possible
routes of exposure including inhalation,
‘‘beryllium in all likelihood represents a
carcinogenic risk to man.’’
In October 1975, OSHA proposed a
new beryllium standard for all
industries based on information that
beryllium caused cancer in animal
experiments (40 FR 48814 (October 17,
1975)). Adoption of this proposal would
have lowered the 8-hour TWA exposure
limit from 2 mg/m3 to 1 mg/m3. In
addition, the proposal included
ancillary provisions for such topics as
exposure monitoring, hygiene facilities,
medical surveillance, and training
related to the health hazards from
beryllium exposure. The rulemaking
was never completed.
In 1977, NIOSH recommended an
exposure limit of 0.5 mg/m3 and
identified beryllium as a potential
occupational carcinogen. In December
1998, ACGIH published a Notice of
Intended Change for its beryllium
exposure limit. The notice proposed a
lower TLV of 0.2 mg/m3 over an 8-hour
TWA based on evidence of CBD and
sensitization in exposed workers.
In 1999, the Department of Energy
(DOE) issued a Chronic Beryllium
Disease Prevention Program (CBDPP)
Final Rule for employees exposed to
beryllium in its facilities (DOE, 1999).
The DOE rule set an action level of 0.2
mg/m3, and adopted OSHA’s PEL of 2
mg/m3 or any more stringent PEL OSHA
might adopt in the future. The DOE
action level triggers workplace
precautions and control measures such
as periodic monitoring, exposure
reduction or minimization, regulated
areas, hygiene facilities and practices,
respiratory protection, protective
clothing and equipment, and warning
signs (DOE, 1999).
Also in 1999, OSHA was petitioned
by the Paper, Allied-Industrial,
Chemical and Energy Workers
International Union (PACE) (OSHA,
2002) and by Dr. Lee Newman and Ms.
Margaret Mroz, from the National
Jewish Medical Research Center
(NJMRC) (OSHA, 2002), to promulgate
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an Emergency Temporary Standard
(ETS) for beryllium in the workplace. In
2001, OSHA was petitioned for an ETS
by Public Citizen Health Research
Group and again by PACE (OSHA,
2002). In order to promulgate an ETS,
the Secretary of Labor must prove (1)
that employees are exposed to grave
danger from exposure to a hazard, and
(2) that such an emergency standard is
necessary to protect employees from
such danger (29 U.S.C. 655(c)). The
burden of proof is on the Department
and because of the difficulty of meeting
this burden, the Department usually
proceeds when appropriate with 6(b)
rulemaking rather than a 6(c) ETS. Thus,
instead of granting the ETS requests,
OSHA instructed staff to further collect
and analyze research regarding the
harmful effects of beryllium.
On November 26, 2002, OSHA
published a Request for Information
(RFI) for ‘‘Occupational Exposure to
Beryllium’’ (OSHA, 2002). The RFI
contained questions on employee
exposure, health effects, risk
assessment, exposure assessment and
monitoring methods, control measures
and technological feasibility, training,
medical surveillance, and impact on
small business entities. In the RFI,
OSHA expressed concerns about health
effects such as CBD, lung cancer, and
beryllium sensitization. OSHA pointed
to studies indicating that even shortterm exposures below OSHA’s PEL of 2
mg/m3 could lead to CBD. The RFI also
cited studies describing the relationship
between beryllium sensitization and
CBD (67 FR at 70708). In addition,
OSHA stated that beryllium had been
identified as a carcinogen by
organizations such as NIOSH, the
International Agency for Research on
Cancer (IARC), and the Environmental
Protection Agency (EPA); and cancer
had been evidenced in animal studies
(67 FR at 70709).
On November 15, 2007, OSHA
convened a Small Business Advocacy
Review Panel for a draft proposed
standard for occupational exposure to
beryllium. OSHA convened this panel
under Section 609(b) of the Regulatory
Flexibility Act (RFA), as amended by
the Small Business Regulatory
Enforcement Fairness Act of 1996
(SBREFA) (5 U.S.C. 601 et seq.).
The Panel included representatives
from OSHA, the Solicitor’s Office of the
Department of Labor, the Office of
Advocacy within the Small Business
Administration, and the Office of
Information and Regulatory Affairs of
the Office of Management and Budget.
Small Entity Representatives (SERs)
made oral and written comments on the
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draft rule and submitted them to the
panel.
The SBREFA Panel issued a report
which included the SERs’ comments on
January 15, 2008. SERs expressed
concerns about the impact of the
ancillary requirements such as exposure
monitoring and medical surveillance.
Their comments addressed potential
costs associated with compliance with
the draft standard, and possible impacts
of the standard on market conditions,
among other issues. In addition, many
SERs sought clarification of some of the
ancillary requirements such as the
meaning of ‘‘routine’’ contact or
‘‘contaminated surfaces.’’
The SBREFA Panel issued a number
of recommendations, which OSHA
carefully considered. In section XVIII of
this preamble, Summary and
Explanation, OSHA has responded to
the Panel’s recommendations and
clarified the requirements about which
SERs expressed confusion. OSHA also
examined the regulatory alternatives
recommended by the SBREFA Panel.
The regulatory alternatives examined by
OSHA are listed in section I of this
preamble, Issues and Alternatives. The
alternatives are discussed in greater
detail in section XVIII of this preamble,
Summary and Explanation, and in the
PEA (OSHA, 2014). In addition, the
Agency intends to develop interpretive
guidance documents following the
publication of a final rule.
In 2010, OSHA hired a contractor to
oversee an independent scientific peer
review of a draft preliminary beryllium
health effects evaluation (OSHA, 2010a)
and a draft preliminary beryllium risk
assessment (OSHA, 2010b). The
contractor identified experts familiar
with beryllium health effects research
and ensured that these experts had no
conflict of interest or apparent bias in
performing the review. The contractor
selected five experts with expertise in
such areas as pulmonary and
occupational medicine, CBD, beryllium
sensitization, the BeLPT, beryllium
toxicity and carcinogenicity, and
medical surveillance. Other areas of
expertise included animal modeling,
occupational epidemiology,
biostatistics, risk and exposure
assessment, exposure-response
modeling, beryllium exposure
assessment, industrial hygiene, and
occupational/environmental health
engineering.
Regarding the health effects
evaluation, the peer reviewers
concluded that the health effect studies
were described accurately and in
sufficient detail, and OSHA’s
conclusions based on the studies were
reasonable. The reviewers agreed that
the OSHA document covered the
significant health endpoints related to
occupational beryllium exposure. Peer
reviewers considered the preliminary
conclusions regarding beryllium
sensitization and CBD to be reasonable
and well presented in the draft health
evaluation section. All reviewers agreed
that the scientific evidence supports
sensitization as a necessary condition in
the development of CBD. In response to
reviewers’ comments, OSHA made
revisions to more clearly describe
certain sections of the health effects
evaluation. In addition, OSHA
expanded its discussion regarding the
BeLPT.
Regarding the preliminary risk
assessment, the peer reviewers were
highly supportive of the Agency’s
approach and major conclusions. The
peer reviewers stated that the key
studies were appropriate and their
selection clearly explained in the
document. They regarded the
preliminary analysis of these studies to
be reasonable and scientifically sound.
The reviewers supported OSHA’s
conclusion that substantial risk of
sensitization and CBD were observed in
facilities where the highest exposure
generating processes had median fullshift exposures around 0.2 mg/m3 or
higher, and that the greatest reduction
in risk was achieved when exposures for
all processes were lowered to 0.1 mg/m3
or below.
In February 2012 the Agency received
for consideration a draft recommended
standard for beryllium (Materion and
USW, 2012). This draft proposal was the
product of a joint effort between two
stakeholders: Materion Corporation, a
leading producer of beryllium and
beryllium products in the United States,
and the United Steelworkers, an
international labor union representing
workers who manufacture beryllium
alloys and beryllium-containing
products in a number of industries. The
United Steelworkers and Materion
sought to craft an OSHA-like model
beryllium standard that would have
support from both labor and industry.
OSHA has considered this proposal
along with other information submitted
during the development of the Notice of
Proposed Rulemaking for beryllium.
IV. Chemical Properties and Industrial
Uses
Chemical and Physical Properties
Beryllium (Be; CAS Number 7440–
41–7) is a silver-grey to greyish-white,
strong, lightweight, and brittle metal. It
is a Group IIA element with an atomic
weight of 9.01, atomic number of 4,
melting point of 1,287 °C, boiling point
of 2,970°C, and a density of 1.85 at 20
°C (NTP 2014). It occurs naturally in
rocks, soil, coal, and volcanic dust
(ATSDR, 2002). Beryllium is insoluble
in water and soluble in acids and
alkalis. It has two common oxidation
states, Be(0) and Be(+2). There are
several beryllium compounds with
unique CAS numbers and chemical and
physical properties. Table IV–1
describes the most common beryllium
compounds.
TABLE IV—1, PROPERTIES OF BERYLLIUM AND BERYLLIUM COMPOUNDS
CAS No.
Beryllium metal
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Chemical name
7440–41–7
Beryllium chloride.
7787–47–5
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Synonyms
and trade
names
Molecular
weight
Beryllium; beryllium-9,
beryllium
element;
beryllium
metallic.
Beryllium dichloride.
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9.0122
79.92
Frm 00015
Melting point
(°C)
Density
(g/cm3)
Description
Solubility
1287 ..............
Grey, closepacked, hexagonal, brittle
metal.
1.85 (20
°C).
Soluble in most dilute acids
and alkali; decomposes in
hot water; insoluble in
mercury and cold water.
399.2 .............
Colorless to
slightly yellow;
orthorhombic,
deliquescent
crystal.
1.899 (25
°C).
Soluble in water, ethanol,
diethyl ether and pyridine;
slightly soluble in benzene, carbon disulfide and
chloroform; insoluble in
acetone, ammonia, and
toluene.
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TABLE IV—1, PROPERTIES OF BERYLLIUM AND BERYLLIUM COMPOUNDS—Continued
Chemical name
CAS No.
Synonyms
and trade
names
Molecular
weight
Melting point
(°C)
Description
Density
(g/cm3)
Solubility
Soluble in water, sulfuric
acid, mixture of ethanol
and diethyl ether; slightly
soluble in ethanol; insoluble in hydrofluoric acid.
Soluble in hot concentrated
acids and alkali; slightly
soluble in dilute alkali; insoluble in water.
Forms soluble tetrahydrate
in hot water; insoluble in
cold water.
Beryllium fluoride.
7787–49–7
(12323–05–
6)
Beryllium
difluoride.
47.01
555 ................
Colorless or
white, amorphous, hygroscopic solid.
1.986 ........
Beryllium hydroxide.
13327–32–7
(1304–49–
0)
Beryllium
dihydroxide.
43.3
White, amorphous, amphoteric powder.
1.92 ..........
Beryllium sulfate
13510–49–1
Sulfuric acid,
beryllium
salt (1:1).
105.07
Colorless crystal
2.443 ........
Beryllium sulfate
tetrhydrate.
7787–56–6
177.14
Colorless, tetragonal crystal.
1.713 ........
Beryllium Oxide
1304–56–9
Sulfuric acid;
beryllium
salt (1:1),
tetrahydrate.
Beryllia; beryllium monoxide
thermalox
TM.
138 (decomposes to
beryllium
oxide).
550–600 °C
(decomposes to
beryllium
oxide).
100 °C ...........
25.01
2508–2547 °C
3.01 (20
°C).
Beryllium carbonate.
1319–43–3
112.05
No data .........
No data ....
Soluble in acids and alkali;
insoluble in cold water; decomposes in hot water.
Beryllium nitrate
trihydrate.
7787–55–5
Carbonic acid,
beryllium
salt, mixture
with beryllium hydroxide.
Nitric acid, beryllium salt,
trihydrate.
Colorless to
white, hexagonal crystal
or amorphous,
amphoteric
powder.
White powder ....
187.97
60 ..................
1.56 ..........
Very soluble in water and
ethanol.
Beryllium phosphate.
13598–15–7
Phosphoric
acid, beryllium salt
(1:1).
104.99
No data .........
White to faintly
yellowish,
deliquescent
mass.
Not reported ......
Not reported.
Slightly soluble in water.
Soluble in water; slightly
soluble in concentrated
sulfuric acid; insoluble in
ethanol.
Soluble in concentrated
acids and alkali; insoluble
in water.
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ATSDR, 2002.
The physical and chemical properties
of beryllium were realized early in the
20th century, and it has since gained
commercial importance in a wide range
of industries. Beryllium is lightweight,
hard, spark resistant, non-magnetic, and
has a high melting point. It lends
strength, electrical and thermal
conductivity, and fatigue resistance to
alloys (NTP, 2014). Beryllium also has
a high affinity for oxygen in air and
water, which can cause a thin surface
film of beryllium oxide to form on the
bare metal, making it extremely resistant
to corrosion. These properties make
beryllium alloys highly suitable for
defense, nuclear, and aerospace
applications (IARC, 1993).
There are approximately 45
mineralized forms of beryllium. In the
United States, the predominant mineral
form mined commercially and refined
into pure beryllium and beryllium
alloys is bertrandite. Bertrandite, while
containing less than 1% beryllium
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compared to 4% in beryl, is easily and
efficiently processed into beryllium
hydroxide (IARC, 1993). Imported beryl
is also converted into beryllium
hydroxide as the United States has very
little beryl that can be economically
mined (USGS, 2013a).
Industrial Uses
Materion Corporation, formerly called
Brush Wellman, is the only producer of
primary beryllium in the United States.
Beryllium is used in a variety of
industries, including aerospace,
defense, telecommunications,
automotive, electronic, and medical
specialty industries. Pure beryllium
metal is used in a range of products
such as X-ray transmission windows,
nuclear reactor neutron reflectors,
nuclear weapons, precision instruments,
rocket propellants, mirrors, and
computers (NTP, 2014). Beryllium oxide
is used in components such as ceramics,
electrical insulators, microwave oven
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components, military vehicle armor,
laser structural components, and
automotive ignition systems (ATSDR,
2002). Beryllium oxide ceramics are
used to produce sensitive electronic
items such as lasers and satellite heat
sinks.
Beryllium alloys, typically beryllium/
copper or beryllium/aluminum, are
manufactured as high beryllium content
or low beryllium content alloys. High
content alloys contain greater than 30%
beryllium. Low content alloys are
typically less than 3% beryllium.
Beryllium alloys are used in automotive
electronics (e.g., electrical connectors
and relays and audio components),
computer components, home appliance
parts, dental appliances (e.g., crowns),
bicycle frames, golf clubs, and other
articles (NTP, 2014; Ballance et al.,
1978; Cunningham et al., 1998; Mroz, et
al., 2001). Electrical components and
conductors are stamped and formed
from beryllium alloys. Beryllium-copper
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alloys are used to make switches in
automobiles (Ballance et al., 1978, 2002;
Cunningham et al., 1998) and
connectors, relays, and switches in
computers, radar, satellite, and
telecommunications equipment (Mroz et
al., 2001). Beryllium-aluminum alloys
are used in the construction of aircraft,
high resolution medical and industrial
X-ray equipment, and mirrors to
measure weather patterns (Mroz et al.,
2001). High content and low content
beryllium alloys are precision machined
for military and aerospace applications.
Some welding consumables are also
manufactured using beryllium.
Beryllium is also found as a trace
metal in materials such as aluminum
ore, abrasive blasting grit, and coal fly
ash. Abrasive blasting grits such as coal
slag and copper slag contain varying
concentrations of beryllium, usually less
than 0.1% by weight. The burning of
bituminous and sub-bituminous coal for
power generation causes the naturally
occurring beryllium in coal to
accumulate in the coal fly ash
byproduct. Scrap and waste metal for
smelting and refining may also contain
beryllium. A detailed discussion of the
industries and job tasks using beryllium
is included in the Preliminary Economic
Analysis (OSHA, 2014).
Occupational exposure to beryllium
can occur from inhalation of dusts,
fume, and mist. Beryllium dusts are
created during operations where
beryllium is cut, machined, crushed,
ground, or otherwise mechanically
sheared. Mists can also form during
operations that use machining fluids.
Beryllium fume can form while welding
with or on beryllium components, and
from hot processes such as those found
in metal foundries.
Occupational exposure to beryllium
can also occur from skin, eye, and
mucous membrane contact with
beryllium particulate or solutions.
V. Health Effects
Beryllium-associated health effects,
including acute beryllium disease
(ABD), beryllium sensitization (also
referred to in this preamble as
‘‘sensitization’’), chronic beryllium
disease (CBD), and lung cancer, can lead
to a number of highly debilitating and
life-altering conditions including
pneumonitis, loss of lung capacity
(reduction in pulmonary function
leading to pulmonary dysfunction), loss
of physical capacity associated with
reduced lung capacity, systemic effects
related to pulmonary dysfunction, and
decreased life expectancy (NIOSH,
1972).
This Health Effects section presents
information on beryllium and its
compounds, the fate of beryllium in the
body, research that relates to its toxic
mechanisms of action, and the scientific
literature on the adverse health effects
associated with beryllium exposure,
including ABD, sensitization, CBD, and
lung cancer. OSHA considers CBD to be
a progressive illness with a continuous
spectrum of symptoms ranging from no
symptomatology at its earliest stage
following sensitization to mild
symptoms such as a slight almost
imperceptible shortness of breath, to
loss of pulmonary function, debilitating
lung disease, and, in many cases, death.
This section also discusses the nature of
these illnesses, the scientific evidence
that they are causally associated with
occupational exposure to beryllium, and
the probable mechanisms of action with
a more thorough review of the
supporting studies.
A. Beryllium and Beryllium Compounds
1. Particle Physical/Chemical Properties
Beryllium (Be; CAS No. 7440–41–7) is
a steel-grey, brittle metal with an atomic
number of 4 and an atomic weight of
9.01 (Group IIA of the periodic table).
Because of its high reactivity, beryllium
is not found as a free metal in nature;
however, there are approximately 45
mineralized forms of beryllium.
Beryllium compounds and alloys
include commercially valuable metals
and gemstones.
Beryllium has two oxidative states:
Be(0) and Be(2+) Agency for Toxic
Substance and Disease Registry
(ATSDR) 2002). It is likely that the
Be(2+) state is the most biologically
reactive and able to form a bond with
peptides leading to it becoming
antigenic (Snyder et al., 2003). This will
be discussed in more detail in the
Beryllium Sensitization section below.
Beryllium has a high charge-to-radius
ratio and in addition to forming various
types of ionic bonds, beryllium has a
strong tendency for covalent bond
formation (e.g., it can form
organometallic compounds such as
Be(CH3)2 and many other complexes)
(ATSDR, 2002; Greene et al., 1998).
However, it appears that few, if any,
toxicity studies exist for the
organometallic compounds. Additional
physical/chemical properties for
beryllium compounds that may be
important in their biological response
are summarized in Table 1 below. This
information was obtained from their
International Chemical Safety Cards
(ICSC) (beryllium metal (ICSC 0226),
beryllium oxide (ICSC 1325), beryllium
sulfate (ICSC 1351), beryllium nitrate
(ICSC 1352), beryllium carbonate (ICSC
1353), beryllium chloride (ICSC 1354),
beryllium fluoride (ICSC 1355)) and
from the hazardous substance data bank
(HSDB) for beryllium hydroxide
(CASRN: 13327–32–7), and beryllium
phosphate (CASRN: 13598–15–7).
Additional information on chemical and
physical properties as well as industrial
uses for beryllium can be found in this
preamble at Section IV, Chemical
Properties and Industrial Uses.
TABLE 1—PHYSICAL/CHEMICAL PROPERTIES OF BERYLLIUM AND COMPOUNDS
Compound name
Physical
appearance
Chemical formula
Beryllium Metal .......
Grey to White
Powder.
White Crystals or
Powder.
White Powder .......
Be ..........................
9.0
BeO .......................
25.0
Combustible; Finely dispersed particles—Explosive.
Not combustible or explosive ...............
Be2CO3(OH)/
Be2CO5H2.
BeSO4 ...................
BeN2O6/Be(NO3)2
181.07
Not combustible or explosive ...............
105.1
133.0
Be(OH)2 ................
43.0
Not combustible or explosive ...............
Enhances combustion of other substances.
Not reported .........................................
BeCl2 .....................
79.9
Not combustible or explosive ...............
Slightly soluble.
Very soluble (1.66
× 106 mg/L).
Slightly soluble 0.8
× 10¥4 mol/L
(3.44 mg/L).
Soluble.
BeF2 ......................
47.0
Not combustible or explosive ...............
Very soluble.
Beryllium Oxide ......
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Beryllium Carbonate
Beryllium Sulfate .....
Beryllium Nitrate .....
Beryllium Hydroxide
Beryllium Chloride ..
Beryllium Fluoride ...
VerDate Sep<11>2014
Colorless Crystals
White to Yellow
Solid.
White amorphous
powder or crystalline solid.
Colorless to Yellow
Crystals.
Colorless Lumps ...
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Molecular
mass
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Acute physical hazards
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Solubility in water
at 20 °C
None.
Very sparingly
soluble.
None.
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TABLE 1—PHYSICAL/CHEMICAL PROPERTIES OF BERYLLIUM AND COMPOUNDS—Continued
Compound name
Physical
appearance
Chemical formula
Beryllium Phosphate
White solid ............
Molecular
mass
Be3(PO4)2 ..............
271.0
Acute physical hazards
Not reported .........................................
Solubility in water
at 20 °C
Soluble.
Source: International Chemical Safety Cards (except beryllium phosphate and hydroxide—HSDB).
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Beryllium shows a high affinity for
oxygen in air and water, resulting in a
thin surface film of beryllium oxide on
the bare metal. If the surface film is
disturbed, it may become airborne or
dermal exposure may occur. The
solubility, particle surface area, and
particle size of some beryllium
compounds are examined in more detail
below. These properties have been
evaluated in many toxicological studies.
In particular, the properties related to
the calcination (firing temperatures) and
differences in crystal size and solubility
are important aspects in their
toxicological profile.
2. Factors Affecting Potency and Effect
of Beryllium Exposure
The effect and potency of beryllium
and its compounds, as for any toxicant,
immunogen, or immunotoxicant, may
be dependent upon the physical state in
which they are presented to a host. For
occupational airborne materials and
surface contaminants, it is especially
critical to understand those physical
parameters in order to determine the
extent of exposure to the respiratory
tract and skin since these are generally
the initial target organs for either route
of exposure.
For example, large particles may have
less of an effect in the lung than smaller
particles due to reduced potential to
stay airborne to be inhaled or be
deposited along the respiratory tract. In
addition, once inhalation occurs particle
size is critical in determining where the
particle will deposit along the
respiratory tract. Solubility also has an
important part in determining the
toxicity and bioavailability of airborne
materials as well. Respiratory tract
retention and skin penetration are
directly influenced by the solubility and
reactivity of airborne material.
These factors may be responsible, at
least in part, for the process by which
beryllium sensitization progresses to
CBD in exposed workers. Other factors
influencing beryllium-induced toxicity
include the surface area of beryllium
particles and their persistence in the
lung. With respect to dermal exposure,
the physical characteristics of the
particle are important as well since they
can influence skin absorption and
bioavailability. This section addresses
certain physical characteristics (i.e.,
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solubility, particle size, particle surface
area) that are important in influencing
the toxicity of beryllium materials in
occupational settings.
a. Solubility
Solubility may be an important
determinant of the toxicity of airborne
materials, influencing the deposition
and persistence of inhaled particles in
the respiratory tract, their
bioavailability, and the likelihood of
presentation to the immune system. A
number of chemical agents, including
metals that contact and penetrate the
skin, are able to induce an immune
response, such as sensitization
(Boeniger, 2003; Mandervelt et al.,
1997). Similar to inhaled agents, the
ability of materials to penetrate the skin
is also influenced by solubility since
dermal absorption may occur at a
greater rate for soluble materials than
insoluble materials (Kimber et al.,
2011).
This section reviews the relevant
information regarding solubility, its
importance in a biological matrix and its
relevance to sensitization and beryllium
lung disease. The weight of evidence
presented below suggests that both
soluble and non-soluble forms of
beryllium can induce a sensitization
response and result in progression of
lung disease.
Beryllium salts, including the
chloride (BeCl2), fluoride (BeF2), nitrate
(Be(NO3)2), phosphate (Be3(PO4)2), and
sulfate (tetrahydrate) (BeSO4 · 4H2O)
salts, are all water soluble. However,
soluble beryllium salts can be converted
to less soluble forms in the lung (Reeves
and Vorwald, 1967). Aqueous solutions
of the soluble beryllium salts are acidic
as a result of the formation of Be(OH2)4
2+, the tetrahydrate, which will react to
form insoluble hydroxides or hydrated
complexes within the general
physiological range of pH values
(between 5 and 8) (EPA, 1998). This
may be an important factor in the
development of CBD since lowersolubility forms of beryllium have been
shown to persist in the lung for longer
periods of time and persistence in the
lung may be needed in order for this
disease to occur (NAS, 2008).
Beryllium oxide (BeO), hydroxide
(Be(OH)2), carbonate (Be2CO3(OH)2), and
sulfate (anhydrous) (BeSO4) are either
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insoluble, slightly soluble, or
considered to be sparingly soluble
(almost insoluble or having an
extremely slow rate of dissolution). The
solubility of beryllium oxide, which is
prepared from beryllium hydroxide by
calcining (heating to a high temperature
without fusing in order to drive off
volatile chemicals) at temperatures
between 500 and 1,750 °C, has an
inverse relationship with calcination
temperature. Although the solubility of
the low-fired crystals can be as much as
10 times that of the high-fired crystals,
low-fired beryllium oxide is still only
sparingly soluble (Delic, 1992). In a
study that measured the dissolution
kinetics (rate to dissolve) of beryllium
compounds calcined at different
temperatures, Hoover et al., compared
beryllium metal to beryllium oxide
particles and found them to have similar
solubilities. This was attributed to a fine
layer of beryllium oxide that coats the
metal particles (Hoover et al., 1989). A
study conducted by Deubner et al.,
(2011) determined ore materials to be
more soluble than beryllium oxide at pH
7.2 but similar in solubility at pH 4.5.
Beryllium hydroxide was more soluble
than beryllium oxide at both pHs
(Deubner et al., 2011).
Investigators have also attempted to
determine how biological fluids can
dissolve beryllium materials. In two
studies, insoluble beryllium, taken up
by activated phagocytes, was shown to
be ionized by myeloperoxidases
(Leonard and Lauwerys, 1987;
Lansdown, 1995). The positive charge
resulting from ionization enabled the
beryllium to bind to receptors on the
surface of cells such as lymphocytes or
antigen-presenting cells which could
make it more biologically active (NAS,
2008). In a study utilizing
phagolysosomal-simulating fluid (PSF)
with a pH of 4.5, both beryllium metal
and beryllium oxide dissolved at a
greater rate than that previously
reported in water or SUF (simulant
fluid) (Stefaniak et al., 2006), and the
rate of dissolution of the multiconstituent (mixed) particles was greater
than that of the single-constituent
beryllium oxide powder. The authors
speculated that copper in the particles
rapidly dissolves, exposing the small
inclusions of beryllium oxide, which
have higher specific surface areas (SSA)
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and therefore dissolve at a higher rate.
A follow-up study by the same
investigational team (Duling et al., 2012)
confirmed dissolution of beryllium
oxide by PSF and determined the
release rate was biphasic (initial rapid
diffusion followed by a latter slower
surface reaction-driven release). During
the latter phase, dissolution half-times
were 1,400 to 2,000 days. The authors
speculated this indicated bertrandite
was persistent in the lung (Duling et al.,
2012).
In a recent study investigating the
dissolution and release of beryllium
ions for 17 beryllium-containing
materials (ore, hydroxide, metal, oxide,
alloys, and processing intermediates)
using artificial human airway epithelial
lining fluid, Stefaniak et al., (2011)
found release of beryllium ions within
7 days (beryl ore melter dust). The
authors calculated dissolution halftimes ranging from 30 days (reduction
furnace material) to 74,000 days
(hydroxide). Stefaniak et al., (2011)
speculated that despite the rapid
mechanical clearance, billions of
beryllium ions could be released in the
respiratory tract via dissolution in
airway lining fluid (ALF). Under this
scenario beryllium-containing particles
depositing in the respiratory tract
dissolving in ALF could provide
beryllium ions for absorption in the
lung and interact with immune cells in
the respiratory tract (Stefaniak et al.,
2011).
Huang et al., (2011) investigated the
effect of simulated lung fluid (SLF) on
dissolution and nanoparticle generation
and beryllium-containing materials.
Bertrandite-containing ore, berylcontaining ore, frit (a processing
intermediate), beryllium hydroxide (a
processing intermediate) and silica
(used as a control), were equilibrated in
SLF at two pH values (4.5 and 7.2) to
reflect inter- and intra-cellular
environments in the lung tissue.
Concentrations of beryllium, aluminum,
and silica ions increased linearly during
the first 20 days in SLF, rose slowly
thereafter, reaching equilibrium over
time. The study also found nanoparticle
formation (in the size range of 10–100
nm) for all materials (Huang et al.,
2011).
In an in vitro skin model, Sutton et
al., (2003) demonstrated the dissolution
of beryllium compounds (insoluble
beryllium hydroxide, soluble beryllium
phosphate) in a simulated sweat fluid.
This model showed beryllium can be
dissolved in biological fluids and be
available for cellular uptake in the skin.
Duling et al., (2012) confirmed
dissolution and release of ions from
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bertrandite ore in an artificial sweat
model (pH 5.3 and pH 6.5).
b. Particle Size
The toxicity of beryllium as
exemplified by beryllium oxide also is
dependent, in part, on the particle size,
with smaller particles (<10 mm) able to
penetrate beyond the larynx (Stefaniak
et al., 2008). Most inhalation studies
and occupational exposures involve
quite small (<1–2 mm) beryllium oxide
particles that can penetrate to the
pulmonary regions of the lung
(Stefaniak et al., 2008). In inhalation
studies with beryllium ores, particle
sizes are generally much larger, with
deposition occurring in several areas
throughout the respiratory tract for
particles <10 mm.
The temperature at which beryllium
oxide is calcined influences its particle
size, surface area, solubility, and
ultimately its toxicity (Delic, 1992).
Low-fired (500 °C) beryllium oxide is
predominantly made up of poorly
crystallized small particles, while
higher firing temperatures (1000—1750
°C) result in larger particle sizes (Delic,
1992).
In order to determine the extent to
which particle size plays a role in the
toxicity of beryllium in occupational
settings, several key studies are
reviewed and detailed below. The
findings on particle size have been
related, where possible, to work process
and biologically relevant toxicity
endpoints of either sensitization or CBD.
Numerous studies have been
conducted evaluating the particle size
generated during basic industrial and
machining operations. In a study by
Cohen et al., (1983), a multi-cyclone
sampler was utilized to measure the size
mass distribution of the beryllium
aerosol at a beryllium-copper alloy
casting operation. Briefly, Cohen et al.,
(1983) found variable particle size
generation based on the operations
being sampled with particle size ranging
from 3 to 16 mm. Hoover et al., (1990)
also found variable particle sizes being
generated based on operations. In
general, Hoover et al., (1990) found that
milling operations generated smaller
particle sizes than sawing operations.
Hoover et al., (1990) also found that
beryllium metal generated higher
concentrations than metal alloys.
Martyny et al., (2000) characterized
generation of particle size during
precision beryllium machining
processes. The study found that more
than 50 percent of the beryllium
machining particles collected in the
breathing zone of machinists were less
than 10 mm in aerodynamic diameter
with 30 percent of that fraction being
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particles of less than 0.6 mm. A study by
Thorat et al., (2003) found similar
results with ore mixing, crushing,
powder production and machining
ranging from 5.0 to 9.5 mm. Kent et al.,
(2001) measured airborne beryllium
using size-selective samplers in five
furnace areas at a beryllium processing
facility. A statistically significant linear
trend was reported between the above
alveolar-deposited particle mass
concentration and prevalence of CBD
and sensitization in the furnace
production areas. The study authors
suggested that the concentration of
alveolar-deposited particles (e.g., <3.5
mm) may be a better predictor of
sensitization and CBD than the total
mass concentration of airborne
beryllium.
A recent study by Virji et al. (2011)
evaluated particle size distribution,
chemistry and solubility in areas with
historically elevated risk of sensitization
and CBD at a beryllium metal powder,
beryllium oxide, and alloy production
facility. The investigators observed that
historically, exposure-response
relationships have been inconsistent
when using mass concentration to
identify process-related risk, possibly
due to incomplete particle
characterization. Two separate exposure
surveys were conducted in March 1999
and June–August 1999 using multi-stage
personal impactor samplers (to
determine particle size distribution) and
personal 37 mm closed face cassette
(CFC) samplers, both located in workers’
breathing zones. One hundred and
ninety eight time-weighted-average
(TWA) personal impactor samples were
analyzed for representative jobs and
processes. A total of 4,026 CFC samples
were collected over the 5-month
collection period and analyzed for mass
concentration, particle size, chemical
content and solubility and compared to
process areas with high risk of
sensitization and CBD. The investigators
found that total beryllium concentration
varied greatly between workers and
among process areas. Analysis of
chemical form and solubility also
revealed wide variability among process
areas, but high risk process areas had
exposures to both soluble and insoluble
forms of beryllium. Analysis of particle
size revealed most process areas had
particles ranging from 5–14 mm mass
median aerodynamic diameter (MMAD).
Rank order correlating jobs to particle
size showed high overall consistency
(Spearman r=0.84) but moderate
correlation (Pearson r=0.43). The
investigators concluded that
consideration of relevant aspects of
exposure such as particle size
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distribution, chemical form, and
solubility will likely improve exposure
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c. Particle Surface Area.
Particle surface area has been
postulated as an important metric for
beryllium exposure. Several studies
have demonstrated a relationship
between the inflammatory and
tumorigenic potential of ultrafine
particles and their increased surface
area (Driscoll, 1996; Miller, 1995;
Oberdorster et al., 1996). While the
exact mechanism explaining how
particle surface area influences its
biological activity is not known, a
greater particle surface area has been
shown to increase inflammation,
cytokine production, anti-oxidant
defenses and apoptosis (Elder et al.,
2005; Carter et al., 2006; Refsne et al.,
2006).
Finch et al., (1988) found that
beryllium oxide calcined at 500 °C had
3.3 times greater specific surface area
(SSA) than beryllium oxide calcined at
1000 °C, although there was no
difference in size or structure of the
particles as a function of calcining
temperature. The beryllium-metal
aerosol (airborne beryllium particles),
although similar to the beryllium oxide
aerosols in aerodynamic size, had an
SSA about 30 percent that of the
beryllium oxide calcined at 1000 °C. As
discussed above, a later study by Delic
(1992) found calcining temperatures had
an effect on SSA as well as particle size.
Several studies have investigated the
lung toxicity of beryllium oxide
calcined at different temperatures and
generally had found that those calcined
at lower temperatures have greater
toxicity and effect than materials
calcined at higher temperatures. This
may be because beryllium oxide fired at
the lower temperature has a loosely
formed crystalline structure with greater
specific surface area than the fused
crystal structure of beryllium oxide fired
at the higher temperature. For example,
beryllium oxide calcined at 500 °C has
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been found to have stronger pathogenic
effects than material calcined at 1,000
°C, as shown in several of the beagle
dog, rat, mouse and guinea pig studies
discussed in the section on CBD
pathogenesis that follows (Finch et al.,
1988; Polak et al., 1968; Haley et al.,
1989; Haley et al., 1992; Hall et al.,
1950). Finch et al. have also observed
higher toxicity of beryllium oxide
calcined at 500 °C, an observation they
attribute to the greater surface area of
beryllium particles calcined at the lower
temperature (Finch et al., 1988). These
authors found that the in vitro
cytotoxicity to Chinese hamster ovary
(CHO) cells and cultured lung epithelial
cells of 500 °C beryllium oxide was
greater than that of 1,000 °C beryllium
oxide, which in turn was greater than
that of beryllium metal. However, when
toxicity was expressed in terms of
particle surface area, the cytotoxicity of
all three forms was similar. Similar
results were observed in a study
comparing the cytotoxicity of beryllium
metal particles of various sizes to
cultured rat alveolar macrophages,
although specific surface area did not
entirely predict cytotoxicity (Finch et
al., 1991).
Stefaniak et al., (2003b) investigated
the particle structure and surface area of
particles (powder and process-sampled)
of beryllium metal, beryllium oxide, and
copper-beryllium alloy. Each of these
samples was separated by aerodynamic
size, and their chemical compositions
and structures were determined with xray diffraction and transmission
electron microscopy, respectively. In
summary, beryllium-metal powder
varied remarkably from beryllium oxide
powder and alloy particles. The metal
powder consisted of compact particles,
in which SSA decreases with increasing
surface diameter. In contrast, the alloys
and oxides consisted of small primary
particles in clusters, in which the SSA
remains fairly constant with particle
size. SSA for the metal powders varied
based on production and manufacturing
process with variations among samples
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as high as a factor of 37. Stefaniak et al.
(2003b) found lesser variation in SSA
for the alloys or oxides. This is
consistent with data from other studies
summarized above showing that process
may affect particle size and surface area.
Particle size and/or surface area may
explain differences in the rate of BeS
and CBD observed in some
epidemiological studies. However, these
properties have not been consistently
characterized in most studies.
B. Kinetics and Metabolism of Beryllium
Beryllium enters the body by
inhalation, ingestion, or absorption
through the skin. For occupational
exposure, the airways and the skin are
the primary routes of uptake.
1. Exposure via the Respiratory System
The respiratory tract, especially the
lung, is the primary target of inhalation
exposure in workers. Inhaled beryllium
particles are deposited along the
respiratory tract in a size dependent
manner. In general, particles larger than
10 mm tend to deposit in the upper
respiratory tract or nasal region and do
not appreciably penetrate lower in the
tracheobronchial or pulmonary regions
(Figure 1). Particles less than 10 mm
increasingly penetrate and deposit in
the tracheobronchial and pulmonary
regions with peak deposition in the
pulmonary region occurring below 5 mm
in particle diameter. The CBD pathology
of concern is found in the pulmonary
region. For particles below 1 mm,
regional deposition changes
dramatically. Ultrafine particles
(generally considered to be 100 nm or
lower) have a higher rate of deposition
along the entire respiratory system
(ICRP model, 1994). Those particles
depositing in the lung and along the
entire respiratory tract may encounter
immunologic cells or may move into the
vascular system where they are free to
leave the lung and can contribute to
systemic beryllium concentrations.
BILLING CODE 4510–26–C
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Beryllium is removed from the
respiratory tract by various clearance
mechanisms. Soluble beryllium is
removed from the respiratory tract via
absorption. Sparingly soluble or
insoluble beryllium may remain in the
lungs for many years after exposure, as
has been observed in workers (Schepers,
1962). Clearance mechanisms for
sparingly soluble or insoluble beryllium
particles include: In the nasal passage,
sneezing, mucociliary transport to the
throat, or dissolution; in the
tracheobronchial region, mucociliary
transport, coughing, phagocytosis, or
dissolution; in the pulmonary or
alveolar region, phagocytosis,
movement through the interstitium
(translocation), or dissolution
(Schlesinger, 1997).
Clearance mechanisms may occur
slowly in humans, which is consistent
with some animal studies. For example,
subjects in the Beryllium Case Registry
(BCR), which identifies and tracks cases
of acute and chronic beryllium diseases,
had elevated concentrations of
beryllium in lung tissue (e.g., 3.1 mg/g of
dried lung tissue and 8.5 mg/g in a
mediastinal node) more than 20 years
after termination of short-term
(generally between 2 and 5 years)
occupational exposure to beryllium
(Sprince et al., 1976).
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Clearance rates may depend on the
solubility, dose, and size of the
beryllium particles inhaled as well as
the sex and species of the animal tested.
As reviewed in a WHO Report (2001),
more soluble beryllium compounds
generally tend to be cleared from the
respiratory system and absorbed into the
bloodstream more rapidly than less
soluble compounds (Van Cleave and
Kaylor, 1955; Hart et al., 1980; Finch et
al., 1990). Animal inhalation or
intratracheal instillation studies
administering soluble beryllium salts
demonstrated significant absorption of
approximately 20 percent of the initial
lung burden, while sparingly soluble
compounds such as beryllium oxide
demonstrated that absorption was
slower and less significant (Delic, 1992).
Additional animal studies have
demonstrated that clearance of soluble
and sparingly soluble beryllium
compounds was biphasic: A more rapid
initial mucociliary transport phase of
particles from the tracheobronchial tree
to the gastrointestinal tract, followed by
a slower phase via translocation to
tracheobronchial lymph nodes, alveolar
macrophages uptake, and beryllium
particles dissolution (Camner et al.,
1977; Sanders et al., 1978; Delic, 1992;
WHO, 2001). Confirmatory studies in
rats have shown the half-time for the
rapid phase between 1–60 days, while
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the slow phase ranged from 0.6–2.3
years. It was also shown that this
process was influenced by the solubility
of the beryllium compounds: Weeks/
months for soluble compounds, months/
years for sparingly soluble compounds
(Reeves and Vorwald, 1967; Reeves et
al., 1967; Zorn et al., 1977; Rhoads and
Sanders, 1985). Studies in guinea-pigs
and rats indicate that 40–50 percent of
the inhaled soluble beryllium salts are
retained in the respiratory tract. Similar
data could not be found for the
sparingly or less soluble beryllium
compounds or metal administered by
this exposure route. (WHO, 2001;
ATSDR, 2002).
Evidence from animal studies
suggests that greater amounts of
beryllium deposited in the lung may
result in slower clearance times. A
comparative study of rats and mice
using a single dose of inhaled
aerosolized beryllium metal
demonstrated that an acute inhalation
exposure to beryllium metal can slow
particle clearance and induce lung
damage in rats (Haley et al., 1990) and
mice (Finch et al., 1998a). In another
study Finch et al. (1994) exposed male
F344/N rats to beryllium metal at
concentrations resulting in beryllium
lung burdens of 1.8, 10, and 100 mg.
These exposure levels resulted in an
estimated clearance half-life ranging
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from 250–380 days for the three
concentrations. For mice (Finch et al.,
1998a), lung clearance half-lives were
91–150 days (for 1.7- and 2.6-mg lung
burden groups) or 360–400 days (for 12and 34-mg lung burden groups). While
the lower exposure groups were quite
different for rats and mice, the highest
groups were similar in clearance halflives for both species.
Beryllium absorbed from the
respiratory system is mainly distributed
to the tracheobronchial lymph nodes via
the lymph system, bloodstream, and
skeleton, which is the ultimate site of
beryllium storage (Stokinger et al., 1953;
Clary et al., 1975; Sanders et al., 1975;
Finch et al., 1990). Trace amounts are
distributed throughout the body (Zorn et
al., 1977; WHO, 2001). Studies in rats
have demonstrated accumulation of
beryllium chloride in the skeletal
system following intraperitoneal
injection (Crowley et al., 1949; Scott et
al., 1950) and accumulation of
beryllium phosphate and beryllium
sulfate in both nonparenchymal and
parenchymal cells of the liver after
intravenous administration in rats
(Skilleter and Price, 1978). Studies have
also demonstrated intracellular
accumulation of beryllium oxide in
bone marrow throughout the skeletal
system after intravenous administration
to rabbits (Fodor, 1977; WHO, 2001).
Systemic distribution of the more
soluble compounds appears to be
greater than that of the insoluble
compounds (Stokinger et al., 1953).
Distribution has also been shown to be
dose dependent in research using
intravenous administration of beryllium
in rats; small doses were preferentially
taken up in the skeleton, while higher
doses were initially distributed
preferentially to the liver. Beryllium
was later mobilized from the liver and
transferred to the skeleton (IARC, 1993).
A half-life of 450 days has been
estimated for beryllium in the human
skeleton (ICRP, 1960). This indicates the
skeleton may serve as a repository for
beryllium that may later be reabsorbed
by the circulatory system, making
beryllium available to the
immunological system.
2. Dermal Exposure
Beryllium compounds have been
shown to cause skin irritation and
sensitization in humans and certain
animal models (Van Orstrand et al.,
1945; de Nardi et al., 1953; Nishimura
1966; Epstein 1990; Belman, 1969;
Tinkle et al., 2003; Delic, 1992). The
Agency for Toxic Substances and
Disease Registry (ATSDR) estimated that
less than 0.1 percent of beryllium
compounds are absorbed through the
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skin (ATSDR, 2002). However, even
minute contact and absorption across
the skin may directly elicit an
immunological sensitization response
(Deubner et al., 2001; Toledo et al.,
2011). Recent studies by Tinkle et al.
(2003) showed that penetration of
beryllium oxide particles was possible
ex vivo for human intact skin at particle
sizes of ≤ 1mm, as confirmed by
scanning electron microscopy. Using
confocal microscopy, Tinkle et al.
demonstrated that surrogate fluorescent
particles up to 1 mm in size could
penetrate the mouse epidermis and
dermis layers in a model designed to
mimic the flexing and stretching of
human skin in motion. Other poorly
soluble particles, such as titanium
dioxide, have been shown to penetrate
normal human skin (Tan et al., 1996)
suggesting the flexing and stretching
motion as a plausible mechanism for
dermal penetration of beryllium as well.
As earlier summarized, insoluble forms
of beryllium can be solubilized in
biological fluids (e.g., sweat) making
them available for absorption through
intact skin (Sutton et al., 2003; Stefaniak
et al., 2011; Duling et al., 2012).
Although its precise role remains to
be elucidated, there is evidence to
indicate that dermal exposure can
contribute to beryllium sensitization. As
early as the 1940s it was recognized that
dermatitis experienced by workers in
primary beryllium production facilities
was linked to exposures to the soluble
beryllium salts. Except in cases of
wound contamination, dermatitis was
rare in workers whose exposures were
restricted to exposure to poorly soluble
beryllium-containing particles (Van
Ordstrand et al., 1945). Further
investigation by McCord in 1951
indicated that direct skin contact with
soluble beryllium compounds, but not
beryllium hydroxide or beryllium metal,
caused dermal lesions (reddened,
elevated, or fluid-filled lesions on
exposed body surfaces) in susceptible
persons. Curtis, in 1951, demonstrated
skin sensitization to beryllium with
patch testing using soluble and
insoluble forms of beryllium in
¨
beryllium-naıve subjects. These subjects
later developed granulomatous skin
lesions with the classical delayed-type
contact dermatitis following repeat
challenge (Curtis, 1951). These lesions
appeared after a latent period of 1–2
weeks, suggesting a delayed allergic
reaction. The dermal reaction occurred
more rapidly and in response to smaller
amounts of beryllium in those
individuals previously sensitized (Van
Ordstrand et al., 1945). Contamination
of cuts and scrapes with beryllium can
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result in the beryllium becoming
embedded within the skin causing a
granuloma to develop in the skin
(Epstein, 1991). Introduction of soluble
or insoluble beryllium compounds into
or under the skin as a result of abrasions
or cuts at work has been shown to result
in chronic ulcerations with granuloma
formation (Van Orstrand et al., 1945;
Lederer and Savage, 1954). Beryllium
absorption through bruises and cuts has
been demonstrated as well (Rossman et
al., 1991). In a study by Invannikov et
al., (1982), beryllium chloride was
applied directly to the skin of live
animals with three types of wounds:
abrasions (superficial skin trauma), cuts
(skin and superficial muscle trauma),
and penetration wounds (deep muscle
trauma). The percentage of the applied
dose absorbed into the systemic
circulation during a 24-hour exposure
was significant, ranging from 7.8
percent to 11.4 percent for abrasions,
from 18.3 percent to 22.9 percent for
cuts, and from 34 percent to 38.8
percent for penetration wounds (WHO,
2001).
A study by Deubner et al., (2001)
concluded that exposure across
damaged skin can contribute as much
systemic loading of beryllium as
inhalation (Deubner et al., 2001).
Deubner et al., (2001) estimated dermal
loading (amount of particles penetrating
into the skin) in workers as compared to
inhalation exposure. Deubner’s
calculations assumed a dermal loading
rate for beryllium on skin of 0.43 mg/
cm2, based on the studies of loading on
skin after workers cleaned up
(Sanderson et al., 1999), multiplied by
a factor of 10 to approximate the
workplace concentrations and the very
low absorption rate of 0.001 percent
(taken from EPA estimates). It should be
noted that these calculations did not
take into account absorption of soluble
beryllium salts that might occur across
nasal mucus membranes, which may
result from contact between
contaminated skin and the nose (EPA,
1998).
A study conducted by Day et al.
(2007) evaluated the effectiveness of a
dermal protection program
implemented in a beryllium alloy
facility in 2002. The investigators
evaluated levels of beryllium in air, on
workplace surfaces, on cotton gloves
worn over nitrile gloves, and on the
necks and faces of workers over a six
day period. The investigators found a
good correlation between air samples
and work surface contamination at this
facility. The investigators also found
measurable levels of beryllium on the
skin of workers as a result of work
processes even from workplace areas
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promoted as ‘‘visually clean’’ by the
company housekeeping policy.
Importantly, the investigators found that
the beryllium contamination could be
transferred from body region to body
region (e.g., hand to face, neck to face).
The investigators demonstrated multiple
pathways of exposure which could lead
to sensitization, increasing risk for
developing CBD (Day, et al., 2007).
The same group of investigators
(Armstrong et al., 2014) extended their
work on investigating multiple exposure
pathways contributing to sensitization
and CBD. The investigators evaluated
four different beryllium manufacturing
and processing facilities to assess the
contribution of various exposure
pathways on worker exposure.
Airborne, work surface and cotton glove
beryllium concentrations were
evaluated. The investigators found
strong correlations between air-surface
concentrations, glove-surface
concentrations, and air-glove
concentrations at this facility. This work
confirms findings from Day et al. (2007)
demonstrating the importance of
airborne beryllium concentrations to
surface contamination and dermal
exposure even at exposures below the
current OSHA PEL (Armstrong et al.,
2014).
3. Oral and Gastrointestinal Exposure
According to the WHO Report (2001),
gastrointestinal absorption of beryllium
can occur by both the inhalation and
oral routes of exposure. Through
inhalation exposure, a fraction of the
inhaled material is transported to the
gastrointestinal tract by the mucociliary
escalator or by the swallowing of the
insoluble material deposited in the
upper respiratory tract (WHO, 2001).
Gastrointestinal absorption of beryllium
can occur by both the inhalation and
oral routes of exposure. In the case of
inhalation, a portion of the inhaled
material is transported to the
gastrointestinal tract by the mucociliary
escalator or by the swallowing of the
insoluble material deposited in the
upper respiratory tract (Schlesinger,
1997). Animal studies have shown oral
administration of beryllium compounds
to result in very limited absorption and
storage (as reviewed by U.S. EPA, 1998).
In animal ingestion studies using radiolabeled beryllium chloride in rats, mice,
dogs, and monkeys, the vast majority of
the ingested dose passed through the
gastrointestinal tract unabsorbed and
was excreted in the feces. In most
studies, <1 percent of the administered
radioactivity was absorbed into the
bloodstream and subsequently excreted
in the urine (Crowley et al., 1949;
Furchner et al., 1973; LeFevre and Joel,
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1986). Research using soluble beryllium
sulfate has shown that as the compound
passes into the intestine, which has a
higher pH than the stomach
(approximate pH of 6 to 8 for the
intestine, pH of 1 or 2 for the stomach),
the beryllium is precipitated as the
insoluble phosphate and thus is no
longer available for absorption (Reeves,
1965; WHO, 2001).
Urinary excretion of beryllium has
been shown to correlate with the
amount of occupational exposure
(Klemperer et al., 1951). Beryllium that
is absorbed into the bloodstream is
excreted primarily in the urine (Crowley
et al., 1949; Scott et al., 1950; Furchner
et al., 1973; Stiefel et al., 1980), whereas
excretion of unabsorbed beryllium is
primarily via the fecal route (Hart et al.,
1980; Finch et al., 1990). A far higher
percentage of the beryllium
administered parenterally in various
animal species was eliminated in the
urine than in the feces (Crowley et al.,
1949; Scott et al., 1950; Furchner et al.,
1973), confirming that beryllium found
in the feces following oral exposure is
primarily unabsorbed material. A study
using percutaneous incorporation of
soluble beryllium nitrate in rats
similarly demonstrated that more than
90 percent of the beryllium in the
bloodstream was eliminated via urine
(Zorn et al., 1977; WHO, 2001). More
than 99 percent of ingested beryllium
chloride was excreted in the feces
(Mullen et al., 1972). Elimination halftimes of 890–1,770 days (2.4–4.8 years)
were calculated for mice, rats, monkeys,
and dogs injected intravenously with
beryllium chloride (Furchner et al.,
1973). Mean daily excretion of
beryllium metal was 4.6 × 10¥5 percent
of the dose administered by
intratracheal instillation in baboons and
3.1 × 10¥5 percent in rats (Andre et al.,
1987).
4. Metabolism
Beryllium and its compounds are not
metabolized or biotransformed, but
soluble beryllium salts may be
converted to less soluble forms in the
lung (Reeves and Vorwald, 1967). As
stated earlier, solubility is an important
factor for persistence of beryllium in the
lung. Insoluble beryllium, engulfed by
activated phagocytes, can be ionized by
an acidic environment and by
myeloperoxidases (Leonard and
Lauwerys, 1987; Lansdown, 1995;
WHO, 2001), and this positive charge
could potentially make it more
biologically reactive because it may
allow the beryllium to bind to a peptide
or protein and be presented to the T cell
receptor or antigen-presenting cell
(Fontenot, 2000).
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5. Preliminary Conclusion for Particle
Characterization and Kinetics of
Beryllium
The forms and concentrations of
beryllium across the workplace vary
substantially based upon location,
process, production and work task.
Many factors influence the potency of
beryllium including concentration,
composition, structure, size and surface
area of the particle.
Studies have demonstrated that
beryllium sensitization can occur via
the skin or inhalation from soluble or
poorly soluble beryllium particles.
Beryllium must be presented to a cell in
a soluble form for activation of the
immune system (NAS, 2008), and this
will be discussed in more detail in the
section to follow. Poorly soluble
beryllium can be solubilized via
intracellular fluid, lung fluid and sweat
(Sutton et al., 2003; Stefaniak et al.,
2011). For beryllium to persist in the
lung it needs to be insoluble. However,
soluble beryllium has been shown to
precipitate in the lung to form insoluble
beryllium (Reeves and Vorwald, 1967).
Some animal and epidemiological
studies suggest that the form of
beryllium may affect the rate of
development of BeS and CBD.
Beryllium in an inhalable form (either
as soluble or insoluble particles or mist)
can deposit in the respiratory tract and
interact with immune cells located
along the entire respiratory tract
(Scheslinger, 1997). However, more
study is needed to precisely determine
the physiochemical characteristics of
beryllium that influence toxicity and
immunogenicity.
C. Acute Beryllium Diseases
Acute beryllium disease (ABD) is a
relatively rapid onset inflammatory
reaction resulting from breathing high
airborne concentrations of beryllium. It
was first reported in workers extracting
beryllium oxide (Van Ordstrand et al.,
1943). Since the Atomic Energy
Commission’s adoption of occupational
exposure limits for beryllium beginning
in 1949, cases of ABD have been rare.
According to the World Health
Organization (2001), ABD is generally
associated with exposure to beryllium
levels at or above 100 mg/m3 and may
be fatal in 10 percent of cases. However,
cases have been reported with beryllium
exposures below 100 mg/m3 (Cummings
et al., 2009). The disease involves an
inflammatory reaction that may include
the entire respiratory tract, involving the
nasal passages, pharynx, bronchial
airways and alveoli. Other tissues
including skin and conjunctivae may be
affected as well. The clinical features of
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ABD include a nonproductive cough,
chest pain, cyanosis, shortness of
breath, low-grade fever and a sharp drop
in functional parameters of the lungs.
Pathological features of ABD include
edematous distension, round cell
infiltration of the septa, proteinaceous
materials, and desquamated alveolar
cells in the lung. Monocytes,
lymphocytes and plasma cells within
the alveoli are also characteristic of the
acute disease process (Freiman and
Hardy, 1970).
Two types of acute beryllium disease
have been characterized in the
literature: a rapid and severe course of
acute fulminating pneumonitis
generally developing within 48 to 72
hours of a massive exposure, and a
second form that takes several days to
develop from exposure to lower
concentrations of beryllium (still above
the levels set by regulatory and
guidance agencies) (Hall, 1950; DeNardi
et al., 1953; Newman and Kreiss, 1992).
Evidence of a dose-response
relationship to the concentration of
beryllium is limited (Eisenbud et al.,
1948; Stokinger, 1950; Sterner and
Eisenbud, 1951). Recovery from either
type of ABD is generally complete after
a period of several weeks or months
(DeNardi et al., 1953). However, deaths
have been reported in more severe cases
(Freiman and Hardy, 1970). There have
been documented cases of progression
to CBD (ACCP, 1965; Hall, 1950)
suggesting the possibility of an immune
component to this disease (Cummings et
al., 2009) as well. According to the BCR,
in the United States, approximately 17
percent of ABD patients developed CBD
(BCR, 2010). The majority of ABD cases
occurred between 1932 and 1970
(Eisenbud, 1983; Middleton, 1998). ABD
is extremely rare in the workplace today
due to more stringent exposure controls
implemented following occupational
and environmental standards set in
1970–1972 (OSHA, 1971; ACGIH, 1971;
ANSI, 1970) and 1974 (EPA, 1974).
D. Chronic Beryllium Disease
This section provides an overview of
the immunology and pathogenesis of
BeS and CBD, with particular attention
to the role of skin sensitization, particle
size, beryllium compound solubility,
and genetic variability in individuals’
susceptibility to beryllium sensitization
and CBD.
Chronic beryllium disease (CBD),
formerly known as ‘‘berylliosis’’ or
‘‘chronic berylliosis,’’ is a
granulomatous disorder primarily
affecting the lungs. CBD was first
described in the literature by Hardy and
Tabershaw (1946) as a chronic
granulomatous pneumonitis. It was
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proposed as early as 1951 that CBD
could be a chronic disease resulting
from an immune sensitization to
beryllium (Sterner and Eisenbud, 1951;
Curtis, 1959; Nishimura, 1966).
However, for a time, there remained
some controversy as to whether CBD
was a delayed-onset hypersensitivity
disease or a toxicant-induced disease
(NAS, 2008). Wide acceptance of CBD as
a hypersensitivity lung disease did not
occur until bronchoscopy studies and
bronchoalveolar lavage (BAL) studies
were performed demonstrating that BAL
cells from CBD patients responded to
beryllium challenge (Epstein et al.,
1982; Rossman et al., 1988; Saltini et al.,
1989).
CBD shares many clinical and
histopathological features with
pulmonary sarcoidosis, a granulomatous
lung disease of unknown etiology. This
includes such debilitating effects as
airway obstruction, diminishment of
physical capacity associated with
reduced lung function, possible
depression associated with decreased
physical capacity, and decreased life
expectancy. Without appropriate
information, CBD may be difficult to
distinguish from sarcoidosis. It is
estimated that up to 6 percent of all
patients diagnosed with sarcoidosis may
actually have CBD (Fireman et al., 2003;
Rossman and Kreiber, 2003). Among
patients diagnosed with sarcoidosis in
which beryllium exposure can be
confirmed, as many as 40 percent may
actually have CBD (Muller-Quernheim
et al., 2006; Cherry et al., 2015).
Clinical signs and symptoms of CBD
may include, but are not limited to, a
simple cough, shortness of breath or
dypsnea, fever, weight loss or anorexia,
skin lesions, clubbing of fingers,
cyanosis, night sweats, cor pulmonale,
tachycardia, edema, chest pain and
arthralgia. Changes or loss of pulmonary
function also occur with CBD such as
decrease in vital capacity, reduced
diffusing capacity, and restrictive
breathing patterns. The signs and
symptoms of CBD constitute a
continuum of symptoms that are
progressive in nature with no clear
demarcation between any stages in the
disease (Rossman, 1996; NAS, 2008).
Besides these listed symptoms from
CBD patients, there have been reported
cases of CBD that remained
asymptomatic (Muller-Querheim, 2005;
NAS, 2008).
Unlike ABD, CBD can result from
inhalation exposure to beryllium at
levels below the current OSHA PEL, can
take months to years after initial
beryllium exposure before signs and
symptoms of CBD occur (Newman 1996,
2005 and 2007; Henneberger, 2001;
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Seidler et al., 2012; Schuler et al., 2012),
and may continue to progress following
removal from beryllium exposure
(Newman, 2005; Sawyer et al., 2005;
Seidler et al., 2012). Patients with CBD
can progress to a chronic obstructive
lung disorder resulting in loss of quality
of life and the potential for decreased
life expectancy (Rossman, et al., 1996;
Newman et al., 2005). The NAS report
(2008) noted the general lack of
published studies on progression of
CBD from an early asymptomatic stage
to functionally significant lung disease
(NAS, 2008). The report emphasized
that risk factors and time course for
clinical disease have not been fully
delineated. However, for people now
under surveillance, clinical progression
from immunological sensitization and
early pathological lesions (i.e.,
granulomatous inflammation) prior to
onset of symptoms to symptomatic
disease appears to be slow, although
more follow-up is needed (NAS, 2008).
A study by Newman (1996) emphasized
the need for prospective studies to
determine the natural history and time
course from BeS and asymptomatic CBD
to full-blown disease (Newman, 1996).
Drawing from his own clinical
experience, Newman was able to
identify the sequence of events for those
with symptomatic disease as follows:
Initial determination of beryllium
sensitization; gradual emergence of
chronic inflammation of the lung;
pathologic alterations with measurable
physiologic changes (e.g., pulmonary
function and gas exchange); progression
to a more severe lung disease (with
extrapulmonary effects such as clubbing
and cor pulmonale in some cases); and
finally death in some cases (reported
between 5.8 to 38 percent) (NAS, 2008;
Newman, 1996).
In contrast to some occupationally
related lung diseases, the early detection
of chronic beryllium disease may be
useful since treatment of this condition
can lead not only to regression of the
signs and symptoms, but also may
prevent further progression of the
disease in certain individuals
(Marchand-Adam, 2008; NAS, 2008).
The management of CBD is based on the
hypothesis that suppression of the
hypersensitivity reaction (i.e.,
granulomatous process) will prevent the
development of fibrosis. However, once
fibrosis has developed, therapy cannot
reverse the damage.
To date, there have been no controlled
studies to determine the optimal
treatment for CBD (Rossman, 1996; NAS
2008; Sood, 2009). Management of CBD
is generally modeled after sarcoidosis
treatment. Oral corticosteroid treatment
can be initiated in patients with
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evidence of disease (either by
bronchoscopy or other diagnostic
measures before progression of disease
or after clinical signs of pulmonary
deterioration occur). This includes
treatment with other anti-inflammatory
agents (NAS, 2008; Maier et al., 2012;
Salvator et al., 2013) as well. It should
be noted, however, that treatment with
corticosteroids has side-effects of their
own that need to be measured against
the possibility of progression of disease
(Gibson et al., 1996; Zaki et al., 1987).
Alternative treatments such as
azathiopurine and infliximab, while
successful at treating symptoms of CBD,
have been demonstrated to have sideeffects as well (Pallavicino et al., 2013;
Freeman, 2012).
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1. Development of Beryllium
Sensitization
Sensitization to beryllium is an
essential step for worker development of
CBD. Sensitization to beryllium can
result from inhalation exposure to
beryllium (Newman et al., 2005; NAS,
2008), as well as from skin exposure to
beryllium (Curtis, 1951; Newman et al.,
1996; Tinkle et al., 2003). Sensitization
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is currently detected using a laboratory
blood test described in Appendix A.
Although there may be no clinical
symptoms associated with BeS, a
sensitized worker’s immune system has
been activated to react to beryllium
exposures such that subsequent
exposure to beryllium can progress to
serious lung disease (Kreiss et al., 1996;
Kreiss et al., 1997; Kelleher et al., 2001;
and Rossman, 2001). Since the
pathogenesis of CBD involves a
beryllium-specific, cell-mediated
immune response, CBD cannot occur in
the absence of sensitization (NAS,
2008). Various factors, including genetic
susceptibility, have been shown to
influence risk of developing
sensitization and CBD (NAS 2008) and
will be discussed later in this section.
While various mechanisms or
pathways may exist for beryllium
sensitization, the most plausible
mechanisms supported by the best
available and most current science are
discussed below. Sensitization occurs
via the formation of a beryllium-protein
complex (an antigen) that causes an
immunological response. In some
instances, onset of sensitization has
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47589
been observed in individuals exposed to
beryllium for only a few months
(Kelleher et al., 2001; Henneberger et
al., 2001). This suggests the possibility
that relatively brief, short-term
beryllium exposures may be sufficient
to trigger the immune hypersensitivity
reaction. Several studies (Newman et
al., 2001; Henneberger et al., 2001;
Rossman, 2001; Schuler et al., 2005;
Donovan et al., 2007, Schuler et al.,
2012) have detected a higher prevalence
of sensitization among workers with less
than one year of employment compared
to some cross-sectional studies which,
due to lack of information regarding
initial exposure, cannot determine time
of sensitization (Kreiss et al., 1996;
Kreiss et al., 1997). While only very
limited evidence has described humoral
changes in certain patients with CBD
(Cianciara et al., 1980), clear evidence
exists for an immune cell-mediated
response, specifically the T-cell (NAS,
2008). Figure 2 delineates the major
steps required for progression from
beryllium contact to sensitization to
CBD.
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Beryllium presentation to the immune
system is believed to occur either by
direct presentation or by antigen
processing. It has been postulated that
beryllium must be presented to the
immune system in an ionic form for
cell-mediated immune activation to
occur (Kreiss et al., 2007). Some soluble
forms of beryllium are readily
presented, since the soluble beryllium
form disassociates into its ionic
components. However, for insoluble
forms, dissolution may need to occur. A
study by Harmsen et al. (1986)
suggested that a sufficient rate of
dissolution of small amounts of poorly
soluble beryllium compounds might
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occur in the lungs to allow persistent
low-level beryllium presentation to the
immune system. Stefaniak et al. (2005
and 2012) reported that insoluble
beryllium particles phagocytized by
macrophages were dissolved in
phagolysomal fluid (Stefaniak et al.,
2005; Stefaniak et al., 2012) and that the
dissolution rate stimulated by
phagolysomal fluid was different for
various forms of beryllium (Stefaniak et
al., 2006; Duling et al., 2012). Several
studies have demonstrated that
macrophage uptake of beryllium can
induce aberrant apoptotic processes
leading to the continued release of
beryllium ions which will continually
stimulate T-cell activation (Sawyer et
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al., 2000; Sawyer et al., 2004; Kittle et
al., 2002). Antigen processing can be
mediated by antigen-presenting cells
(APC). These may include macrophages,
dendritic cells, or other antigenpresenting cells, although this has not
been well defined in most studies (NAS,
2008).
Because of their strong positive
charge, beryllium ions have the ability
to haptenate and alter the structure of
peptides occupying the antigen-binding
cleft of major histocompatibility
complex (MHC) class II on antigenpresenting cells (APC). The MHC class
II antigen-binding molecule for
beryllium is the human leukocyte
antigen (HLA) with specific alleles (e.g.,
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bond with the Be-O-Be molecule when
the pH of the substrate is neutral (Keizer
et al., 2005). The direct binding of BeO
may eliminate the biological
requirement for antigen processing or
dissolution of beryllium oxide to
activate an immune response.
Next in sequence is the berylliumMHC–APC complex binding to a T-cell
¨
receptor (TCR) on a naıve T-cell which
stimulates the proliferation and
accumulation of beryllium-specific
CD4+ (cluster of differentiation 4+) Tcells (Saltini et al., 1989 and 1990;
Martin et al., 2011) as depicted in Figure
3. Fontenot et al. (1999) demonstrated
that diversely different variants of TCR
were expressed by CD4+ T-cells in
peripheral blood cells of CBD patients.
However, the CD4+ T-cells from the lung
were more homologous in expression of
TCR variants in CBD patients,
suggesting clonal expansion of a subset
of T-cells in the lung (Fontenot et al.,
1999). This may also indicate a
pathogenic potential for subsets of Tcell clones expressing this homologous
TCR (NAS, 2008). Fontenot et al. (2006)
reported beryllium self-presentation by
HLA–DP expressing BAL CD4+ T-cells.
Self-presentation by BAL T-cells in the
lung granuloma may result in
activation-induced cell death, which
may then lead to oligoclonality of the Tcell population characteristic of CBD
(NAS, 2008).
As CD4+ T-cells proliferate, clonal
expansion of various subsets of the
CD4+ beryllium specific T-cells occurs
(Figure 3). In the peripheral blood, the
beryllium-specific CD4+ T cells require
co-stimulation with a co-stimulant CD28
(cluster of differentiation 28). During the
proliferation and differentiation process
CD4+ T-cells secrete pro-inflammatory
cytokines that may influence this
process (Sawyer et al., 2004; Kimber et
al., 2011).
cytokines necessary for additional
recruitment of inflammatory and
immunological cells; however, they
were less proliferative and less
susceptible to cell death compared to
the CD28 dependent cells (Fontenot et
al., 2005; Mack et al., 2008). These
beryllium-specific CD4+ independent
cells are considered to be mature
memory effector cells (Ndejembi et al.,
2006; Bian et al., 2005). Repeat exposure
to beryllium in the lung resulting in a
mature population of T cell
development independent of costimulation by CD28 and development
of a population of T effector memory
cells (Tem cells) may be one of the
mechanisms that lead to the more severe
reactions observed specifically in the
lung (Fontenot et al., 2005).
CD4+ T cells created in the
sensitization process recognize the
beryllium antigen, and respond by
proliferating and secreting cytokines
and inflammatory mediators, including
IL–2, IFN-g, and TNF-a (Tinkle et al.,
1997a and b; Fontenot et al., 2002) and
MIP–1a and GRO–1 (Hong-Geller,
2006). This also results in the
accumulation of various types of
inflammatory cells including
mononuclear cells (mostly CD4+ T cells)
in the bronchoalveolar lavage fluid
(BAL fluid) (Saltini et al., 1989, 1990).
The development of granulomatous
inflammation in the lung of CBD
patients has been associated with the
accumulation of beryllium responsive
CD4+ Tem cells in BAL fluid (NAS,
2008). The subsequent release of proinflammatory cytokines, chemokines
and reactive oxygen species by these
cells may lead to migration of additional
inflammatory/immune cells and the
development of a microenvironment
that contributes to the development of
CBD (Sawyer et al., 2005; Tinkle et al.,
1996; Hong-Geller et al., 2006; NAS,
2008).
The cascade of events described above
results in the formation of a
noncaseating granulomatous lesion.
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2. Development of CBD
The continued persistence of residual
beryllium in the lung leads to a T-cell
maturation process. A large portion of
beryllium-specific CD4+ T cells were
shown to cease expression of CD28
mRNA and protein, indicating these
cells no longer required co-stimulation
with the CD28 ligand (Fontenot et al.,
2003). This change in phenotype
correlated with lung inflammation
(Fontenot et al., 2003). The CD4+
independent cells continued to secrete
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HLA–DP, HLA–DR, HLA–DQ)
associated with the progression to CBD
(NAS, 2008; Yucesoy and Johnson,
2011). Several studies have also
demonstrated that the electrostatic
charge of HLA may be a factor in
binding beryllium (Snyder et al., 2003;
Bill et al., 2005; Dai et al., 2010). The
strong positive ionic charge of the
beryllium ion would have a strong
attraction for the negatively charged
patches of certain HLA alleles (Snyder
et al., 2008; Dai et al., 2010).
Alternatively, beryllium oxide has been
demonstrated to bind to the MHC class
II receptor in a neutral pH. The six
carboxylates in the amino acid sequence
of the binding pocket provide a stable
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Release of cytokines by the
accumulating T cells leads to the
formation of granulomatous lesions that
are characterized by an outer ring of
histiocytes surrounding non-necrotic
tissue with embedded multi-nucleated
giant cells (Saltini et al., 1989, 1990).
Over time, the granulomas spread and
can lead to lung fibrosis and abnormal
pulmonary function, with symptoms
including a persistent dry cough and
shortness of breath (Saber and Dweik,
2000). Fatigue, night sweats, chest and
joint pain, clubbing of fingers (due to
impaired oxygen exchange), loss of
appetite or unexplained weight loss,
and cor pulmonale have been
experienced in certain patients as the
disease progresses (Conradi et al., 1971;
ACCP, 1965; Kriebel et al., 1988a and b).
While CBD primarily affects the lungs,
it can also involve other organs such as
the liver, skin, spleen, and kidneys
(ATSDR, 2002).
As previously mentioned, the uptake
of beryllium may lead to an aberrant
apoptotic process with rerelease of
beryllium ions and continual
stimulation of beryllium-responsive
CD4∂ cells in the lung (Sawyer et al.,
2000; Kittle et al., 2002; Sawyer et al.,
2004). Several research studies suggest
apoptosis may be one mechanism that
enhances inflammatory cell recruitment,
cytokine production and inflammation,
thus creating a scenario for progressive
granulomatous inflammation (Palmer et
al., 2008; Rana, 2008). Macrophages and
neutrophils can phagocytize beryllium
particles in an attempt to remove the
beryllium from the lung (Ding, et al.,
2009). Multiple studies (Sawyer et al.,
2004; Kittle et al., 2002) using BAL cells
(mostly macrophages and neutrophils)
from patients with CBD found that in
vitro stimulation with beryllium sulfate
induced the production of TNF-a (one
of many cytokines produced in response
to beryllium), and that production of
TNF-a might induce apoptosis in CBD
and sarcoidosis patients (Bost et al.,
1994; Dai et al., 1999). The stimulation
of CBD-derived macrophages by
beryllium sulphate resulted in cells
becoming apoptotic, as measured by
propidium iodide. These results were
confirmed in a mouse macrophage cellline (p388D1) (Sawyer et al., 2000).
However, other factors may influence
the development of CBD and are
outlined in the following section.
3. Genetic and Other Susceptibility
Factors
Evidence from a variety of sources
indicates genetic susceptibility may
play an important role in the
development of CBD in certain
individuals, especially at levels low
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enough not to invoke a response in
other individuals. Early occupational
studies proposed that CBD was an
immune reaction based on the high
susceptibility of some individuals to
become sensitized and progress to CBD
and the lack of CBD in others who were
exposed to levels several orders of
magnitude higher (Sterner and
Eisenbud, 1951). Additional in vitro
human research has identified genes
coding for specific protein molecules on
the surface of their immune cells that
place carriers at greater risk of becoming
sensitized to beryllium and developing
CBD (McCanlies et al., 2004). Recent
studies have confirmed genetic
susceptibility to CBD involves either
HLA variants, T-cell receptor clonality,
tumor necrosis factor (TNF-a)
polymorphisms and/or transforming
growth factor-beta (TGF-b)
polymorphisms (Fontenot et al., 2000;
Amicosante et al., 2005; Tinkle et al.,
1996; Gaede et al., 2005; Van Dyke et
al., 2011; Silveira et al., 2012).
Single Nucleotide Polymorphisms
(SNPs) have been studied with regard to
genetic variations associated with
increased risk of developing CBD. SNPs
are the most abundant type of human
genetic variation. Polymorphisms in
MHC class II and pro-inflammatory
genes have been shown to contribute to
variations in immune responses
contributing to the susceptibility and
resistance in many diseases including
auto-immunity, and beryllium
sensitization and CBD (McClesky et al.,
2009). Specific SNPs have been
evaluated as a factor in Glu69 variant
from the HLA–DPB1 locus (Richeldi et
al., 1993; Cai et al., 2000; Saltini et al.,
2001; Silviera et al., 2012; Dai et al.,
2013), HLA–DRPheb47 (Amicosante et
al., 2005).
HLA–DPB1 with a glutamic acid at
amino position 69 (Glu 69) has been
shown to confer increased risk of
beryllium sensitization and CBD
(Richeldi et al., 1993; Saltini et al.,
2001; Amicosante et al., 2005; Van Dyke
et al., 2011; Silveira et al., 2012).
Fontenot et al. (2000) demonstrated that
beryllium presentation by certain alleles
of the class II human leukocyte antigenDP (HLA–DP) to CD4+ T cells is the
mechanism underlying the development
of CBD. Richeldi et al. (1993) reported
a strong association between the MHC
class II allele HLA–DP 1 and the
development of CBD in berylliumexposed workers from a Tucson, AZ
facility. This marker was found in 32 of
the 33 workers who developed CBD, but
in only 14 of 44 similarly exposed
workers without CBD. The more
common allele of the HLA–DP 1 variant
is negatively charged at this site and
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could directly interact with the
positively charged beryllium ion. The
high percentage (∼30 percent) of
beryllium-exposed workers without
CBD who had this allele indicates that
other factors also contribute to the
development of CBD (EPA, 1998).
Additional studies by Amicosante et al.
(2005) using blood lymphocytes derived
from beryllium-exposed workers found
a high frequency of this gene in those
sensitized to beryllium. In a study of 82
CBD patients (beryllium-exposed
workers), Stubbs et al. (1996) also found
a relationship between the HLA–DP 1
allele and BeS. The glutamate-69 allele
was present in 86 percent of sensitized
subjects, but in only 48 percent of
beryllium-exposed, non-sensitized
subjects. Some variants of the HLA–
DPB1 allele convey higher risk of BeS
and CBD than others. For example,
HLA–DPB1*0201 yielded an
approximately 3-fold increase in disease
outcome relative to controls; HLA–
DPB1*1901 yielded an approximately 5fold increase, and HLA–DPB1*1701 an
approximately 10-fold increase (Weston
et al., 2005; Snyder et al., 2008). By
assigning odds ratios for specific alleles
on the basis of previous studies
discussed above, the researchers found
a strong correlation (88 percent)
between the reported risk of CBD and
the predicted surface electrostatic
potential and charge of the isotypes of
the genes. They were able to conclude
that the alleles associated with the most
negatively charged proteins carry the
greatest risk of developing beryllium
sensitization and CBD. This confirms
the importance of beryllium charge as a
key factor in haptogenic potential.
In contrast, the HLA–DRB1 allele,
which lacks Glu 69, has also been
shown to increase the risk of developing
sensitization and CBD (Amicosante et
al., 2005; Maier et al., 2003). Bill et al.
(2005) found that HLA–DR has a
glutamic acid at position 71 of the b
chain, functionally equivalent to the Glu
69 of HLA–DP (Bill et al., 2005).
Associations with BeS and CBD have
also been reported with the HLA–DQ
markers (Amicosante et al., 2005; Maier
et al., 2003). Stubbs et al. also found a
biased distribution of the MHC class II
HLA–DR gene between sensitized and
non-sensitized subjects. Neither of these
markers was completely specific for
CBD, as each study found beryllium
sensitization or CBD among individuals
without the genetic risk factor. While
there remains uncertainty as to which of
the MHC class II genes interact directly
with the beryllium ion, antibody
inhibition data suggest that the HLA–DR
gene product may be involved in the
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presentation of beryllium to T
lymphocytes (Amicosante et al., 2002).
In addition, antibody blocking
experiments revealed that anti-HLA–DP
strongly reduced proliferation responses
and cytokine secretion by BAL CD4 T
cells (Chou et al., 2005). In the study by
Chou (2005), anti-HLA–DR ligand
antibodies mainly affected berylliuminduced proliferation responses with
little impact on cytokines other than IL–
2, thus implying that nonproliferating
BAL CD4 T cells may still contribute to
inflammation leading to the progression
of CBD (Chou et al., 2005).
TNF alpha (TNF-a) polymorphisms
and TGF beta (TGF-b) polymorphisms
have also been shown to confer a
genetic susceptibility for developing
CBD in certain individuals. TNF-a is a
pro-inflammatory cytokine associated
with a more severe pulmonary disease
in CBD (NAS, 2008). Beryllium
exposure has been shown to upregulate
transcription factors AP–1 and NF-kB
(Sawyer et al., 2007) inducing an
inflammatory response by stimulating
production of pro-inflammatory
cytokines such as TNF-a by
inflammatory cells. Polymorphisms in
the 308 position of the TNF-a gene have
been demonstrated to increase
production of the cytokine and increase
severity of disease (Maier et al., 2001;
Saltini et al., 2001; Dotti et al., 2004).
While a study by McCanlies et al. (2007)
found no relationship between TNF-a
polymorphism and BeS or CBD, the
inconsistency may be due to
misclassification, exposure differences
or statistical power (NAS, 2008).
Other genetic variations have been
shown to be associated with increased
risk of beryllium sensitization and CBD
(NAS, 2008). These include TGF-b
(Gaede et al., 2005), angiotensin-1
converting enzyme (ACE) (Newman et
al., 1992; Maier et al., 1999) and an
enzyme involved in glutathione
synthesis (glutamate cysteine ligase)
(Bekris et al., 2006). McCanlies et al.
(2010) evaluated the association
between polymorphisms in a select
group of interleukin genes (IL–1A; IL–
1B, IL–1RN, IL–2, IL–9, IL–9R) due to
their role in immune and inflammatory
processes. The study evaluated SNPs in
three groups of workers from large
beryllium manufacturing facilities in
OH and AZ. The investigators found a
significant association between variants
IL–1A–1142, IL–1A–3769 and IL–1A–
4697 and CBD but not with beryllium
sensitization. However, these still
require confirmation in larger studies
(NAS, 2008).
In addition to the genetic factors
which may contribute to the
susceptibility and severity of disease,
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other factors such as smoking and
gender may play a role in the
development of CBD (NAS, 2008). A
recent longitudinal cohort study by
Mroz et al. (2009) of 229 individuals
identified with beryllium sensitization
or CBD through workplace medical
surveillance found that the prevalence
of CBD among ever smokers was
significantly lower than among never
smokers (38.1 percent versus 49.4
percent, p=0.025). BeS subjects that
never smoked were found to be more
likely to develop CBD over the course of
the study compared to current smokers
(12.6 percent versus 6.4 percent,
p=0.10). The authors suggested smoking
may confer a protective effect against
development of lung granulomas as has
been demonstrated with
hypersensitivity pneumonitis (Mroz et
al., 2009).
4. Beryllium Sensitization and CBD in
the Workforce
Sensitization to beryllium is currently
detected in the workforce with the
beryllium lymphocyte proliferation test
(BeLPT), a laboratory blood test
developed in the 1980s, also referred to
as the LTT (Lymphocyte Transformation
Test) or BeLT (Beryllium Lymphocyte
Transformation Test). In this test,
lymphocytes obtained from either
bronchoalveolar lavage fluid (the BAL
BeLPT) or from peripheral blood (the
blood BeLPT) are cultured in vitro and
exposed to beryllium sulfate to
stimulate lymphocyte proliferation. The
observation of beryllium-specific
proliferation indicates beryllium
sensitization. Hereafter, ‘‘BeLPT’’
generally refers to the blood BeLPT,
which is typically used in screening for
beryllium sensitization. This test is
described in more detail in subsection
D.5.b.
CBD can be detected at an
asymptomatic stage by a number of
techniques including bronchoalveolar
lavage and biopsy (Cordeiro et al., 2007;
Maier, 2001). Bronchoalveolar lavage is
a method of ‘‘washing’’ the lungs with
fluid inserted via a flexible fiberoptic
instrument known as a bronchoscope,
removing the fluid and analyzing the
content for the inclusion of immune
cells reactive to beryllium exposure, as
described earlier in this section.
Fiberoptic bronchoscopy can be used to
detect granulomatous lung
inflammation prior to the onset of CBD
symptoms as well, and has been used in
combination with the BeLPT to
diagnose pre-symptomatic CBD in a
number of recent screening studies of
beryllium-exposed workers, which are
discussed in the following section
detailing diagnostic procedures. Of
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workers who were found to be
sensitized and underwent clinical
evaluation, 31–49 percent of them were
diagnosed with CBD (Kreiss et al., 1993;
Newman et al., 1996, 2005, 2007; Mroz,
2009), however some estimate that with
increased surveillance the percent could
be much higher (Newman, 2005; Mroz,
2009). It has been estimated from
ongoing surveillance studies of
sensitized individuals with an average
follow-up time of 4.5 years that 31
percent of beryllium-sensitized
employees were estimated to progress to
CBD (Newman et al., 2005). A study of
nuclear weapons facility employees
enrolled in an ongoing medical
surveillance program found that only 20
percent of sensitized workers employed
less than 5 years eventually were
diagnosed with CBD, while 40 percent
of sensitized workers employed 10 years
or more developed CBD (Stange et al.,
2001). One limitation for all these
studies is lack of long-term follow-up. It
may be necessary to continue to monitor
these workers in order to determine
whether all BeS workers will develop
CBD (Newman et al., 2005).
CBD has a clinical spectrum ranging
from evidence of beryllium sensitization
and granulomas in the lung with little
symptomatology to loss of lung function
and end stage disease which may result
in the need for lung transplantation and
decreased life expectancy.
Unfortunately, there are very few
published clinical studies describing the
full range and progression of CBD from
the beginning to the end stages and very
few of the risk factors for progression of
disease have been delineated (NAS,
2008). Clinical management of CBD is
modeled after sarcoidosis where oral
corticosteroid treatment is initiated in
patients who have evidence of
progressive lung disease, although
progressive lung disease has not been
well defined (NAS, 2008). In advanced
cases of CBD, corticosteroids are the
standard treatment (NAS, 2008). No
comprehensive studies have been
published measuring the overall effect
of removal of workers from beryllium
exposure on sensitization and CBD
(NAS, 2008) although this has been
suggested as part of an overall treatment
regime for CBD (Mapel et al., 2002; Sood
et al., 2004; Maier et al., 2006; Sood,
2009; Maier et al., 2012). Sood et al.
reported that cessation of exposure can
sometimes have beneficial effects on
lung function (Sood et al., 2004).
However, this was based on anecdotal
evidence from six patients with CBD, so
more research is needed to better
determine the relationship between
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progression
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5. Human Epidemiological Studies
This section describes the human
epidemiological data supporting the
mechanistic overview of berylliuminduced disease in workers. It has been
divided into reviews of epidemiological
studies performed prior to development
and implementation of the BeLPT in the
late 1980s and after wide use of the
BeLPT for screening purposes. Use of
the BeLPT has allowed investigators to
screen for beryllium sensitization and
CBD prior to the onset of clinical
symptoms, providing a more sensitive
and thorough analysis of the worker
population. The discussion of the
studies has been further divided by
manufacturing processes that may have
similar exposure profiles. Table A.1 in
the Appendix summarizes the
prevalence of beryllium sensitization
and CBD, range of exposure
measurements, and other salient
information from the key
epidemiological studies.
It has been well-established that
beryllium exposure, either via
inhalation or skin, may lead to
beryllium sensitization, or, with
inhalation exposure, may lead to the
onset and progression of CBD. The
available published epidemiological
literature discussed below provides
strong evidence of beryllium
sensitization and CBD in workers
exposed to airborne beryllium well
below the current OSHA PEL of 2 mg/
m3. Several studies demonstrate the
prevalence of sensitization and CBD is
related to the level of airborne exposure,
including a cross-sectional survey of
employees at a beryllium ceramics plant
in Tucson, AZ (Henneberger et al.,
2001), case-control studies of workers at
the Rocky Flats nuclear weapons facility
(Viet et al., 2000), and workers from a
beryllium machining plant in Cullman,
AL (Kelleher et al., 2001). The
prevalence of beryllium sensitization
also may be related to dermal exposure.
An increased risk of CBD has been
reported in workers with skin lesions,
potentially increasing the uptake of
beryllium (Curtis, 1951; Johnson et al.,
2001; Schuler et al., 2005). Three
studies describe comprehensive
preventive programs, which included
expanded respiratory protection, dermal
protection, and improved control of
beryllium dust migration, that
substantially reduced the rate of
beryllium sensitization among new
hires (Cummings et al., 2007; Thomas et
al., 2009; Bailey et al., 2010; Schuler et
al., 2012).
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Some of the epidemiological studies
presented in this review suffer from
challenges common to many published
epidemiological studies: Limitations in
study design (particularly crosssectional); small sample size; lack of
personal and/or short-term exposure
data, particularly those published before
the late 1990s; and incomplete
information regarding specific chemical
form and/or particle characterization.
Challenges that are specific to beryllium
epidemiological studies include:
uncertainty regarding the contribution
of dermal exposure; use of various
BeLPT protocols; a variety of case
definitions for determining CBD; and
use of various exposure sampling/
assessment methods (e.g., daily
weighted average (DWA), lapel
sampling). Even with these limitations,
the epidemiological evidence presented
in this section clearly demonstrates that
beryllium sensitization and CBD are
continuing to occur from present-day
exposures below OSHA’s PEL. The
available literature also indicates that
the rate of BeS can be substantially
lowered by reducing inhalation
exposure and minimizing dermal
contact.
a. Studies Conducted Prior to the BeLPT
First reports of CBD came from
studies performed by Hardy and
Tabershaw (1946). Cases were observed
in industrial plants that were refining
and manufacturing beryllium metal and
beryllium alloys and in plants
manufacturing fluorescent light bulbs
(NAS, 2008). From the late 1940s
through the 1960s, clusters of nonoccupational CBD cases were identified
around beryllium refineries in Ohio and
Pennsylvania, and outbreaks in family
members of beryllium factory workers
were assumed to be from exposure to
contaminated clothes (Hardy, 1980). It
had been established that the risk of
disease among beryllium workers was
variable and generally rose with the
levels of airborne concentrations
(Machle et al., 1948). And while there
was a relationship between air
concentrations of beryllium and risk of
developing disease both in and
surrounding these plants, the disease
rates outside the plants were higher
than expected and not very different
from the rate of CBD within the plants
(Eisenbud et al., 1949; Lieben and
Metzner, 1959). There remained
considerable uncertainty regarding
diagnosis due to lack of well-defined
cohorts, modern diagnostic methods, or
inadequate follow-up. In fact, many
patients with CBD may have been
misdiagnosed with sarcoidosis (NAS,
2008).
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The difficulties in distinguishing lung
disease caused by beryllium from other
lung diseases led to the establishment of
the BCR in 1952 to identify and track
cases of ABD and CBD. A uniform
diagnostic criterion was introduced in
1959 as a way to delineate CBD from
sarcoidosis. Patient entry into the BCR
required either: documented past
exposure to beryllium or the presence of
beryllium in lung tissue as well as
clinical evidence of beryllium disease
(Hardy et al., 1967); or any three of the
six criteria listed below (Hasan and
Kazemi, 1974). Patients identified using
the above criteria were registered and
added to the BCR from 1952 through
1983 (Eisenbud and Lisson, 1983).
The BCR listed the following criteria
for diagnosing CBD (Eisenbud and
Lisson, 1983):
(1) Establishment of significant
beryllium exposure based on sound
epidemiologic history;
(2) Objective evidence of lower
respiratory tract disease and clinical
course consistent with beryllium
disease;
(3) Chest X-ray films with radiologic
evidence of interstitial fibronodular
disease;
(4) Evidence of restrictive or
obstructive defect with diminished
carbon monoxide diffusing capacity
(DLCO) by physiologic studies of lung
function;
(5) Pathologic changes consistent with
beryllium disease on examination of
lung tissue; and
(6) Presence of beryllium in lung
tissue or thoracic lymph nodes.
Prevalence of CBD in workers during
the time period between the 1940s and
1950s was estimated to be between 1–
10% (Eisenbud and Lisson, 1983). In a
1969 study, Stoeckle et al. presented 60
case histories with a selective literature
review utilizing the above criteria
except that urinary beryllium was
substituted for lung beryllium to
demonstrate beryllium exposure.
Stoeckle et al. (1969) were able to
demonstrate corticosteroids as a
successful treatment option in one case
of confirmed CBD. This study also
presented a 28 percent mortality rate
from complications of CBD at the time
of publication. However, even with the
improved methodology for determining
CBD based on the BCR criteria, these
studies suffered from lack of welldefined cohorts, modern diagnostic
techniques or adequate follow-up.
b. Criteria for Beryllium Sensitization
and CBD Case Definition Following the
Development of the BeLPT
The criteria for diagnosis of CBD have
evolved over time as more advanced
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diagnostic technology, such as the
(blood) BeLPT and BAL BeLPT, has
become available. More recent
diagnostic criteria have both higher
specificity than earlier methods and
higher sensitivity, identifying
subclinical effects. Recent studies
typically use the following criteria
(Newman et al., 1989; Pappas and
Newman, 1993; Maier et al., 1999):
(1) History of beryllium exposure;
(2) Histopathological evidence of
noncaseating granulomas or
mononuclear cell infiltrates in the
absence of infection; and
(3) Positive blood or BAL BeLPT
(Newman et al., 1989).
The availability of transbronchial lung
biopsy facilitates the evaluation of the
second criterion, by making
histopathological confirmation possible
in almost all cases.
A significant component for the
identification of CBD is the
demonstration of a confirmed abnormal
BeLPT result in a blood or BAL sample
(Newman, 1996). Since the development
of the BeLPT in the 1980s, it has been
used to screen beryllium-exposed
workers for sensitization in a number of
studies to be discussed below. The
BeLPT is a non-invasive in vitro blood
test which measures the beryllium
antigen-specific T-cell mediated
immune response and is the most
commonly available diagnostic tool for
identifying beryllium sensitization. The
BeLPT measures the degree to which
beryllium stimulates lymphocyte
proliferation under a specific set of
conditions, and is interpreted based
upon the number of stimulation indices
that exceed the normal value. The ‘cutoff’ is based on the mean value of the
peak stimulation index among controls
plus 2 or 3 standard deviations. This
methodology was modeled into a
statistical method known as the ‘‘least
absolute values’’ or ‘‘statisticalbiological positive’’ method and relies
on natural log modeling of the median
stimulation index values (DOE, 2001;
Frome, 2003). In most applications, two
or more stimulation indices that exceed
the cut-off constitute an abnormal test.
Early versions of the BeLPT test had
high variability, but the use of tritiated
thymidine to identify proliferating cells
has led to a more reliable test (Mroz et
al., 1991; Rossman et al., 2001). In
recent years, the peripheral blood test
has been found to be as sensitive as the
BAL assay, although larger abnormal
responses have been observed with the
BAL assay (Kreiss et al., 1993; Pappas
and Newman, 1993). False negative
results have also been observed with the
BAL BeLPT in cigarette smokers who
have marked excess of alveolar
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macrophages in lavage fluid (Kreiss et
al., 1993). The BeLPT has also been a
useful tool in animal studies to identify
those species with a beryllium-specific
immune response (Haley et al., 1994).
Screenings for beryllium sensitization
have been conducted using the BeLPT
in several occupational surveys and
surveillance programs, including
nuclear weapons facilities operated by
the Department of Energy (Viet et al.,
2000; Strange et al., 2001; DOE/HSS
Report, 2006), a beryllium ceramics
plant in Arizona (Kreiss et al., 1996;
Henneberger et al., 2001; Cummings et
al., 2007), a beryllium production plant
in Ohio (Kreiss et al., 1997; Kent et al.,
2001), a beryllium machining facility in
Alabama (Kelleher et al., 2001; Madl et
al., 2007), a beryllium alloy plant
(Schuler et al., 2005, Thomas et al.,
2009), and another beryllium processing
plant (Rosenman et al., 2005) in
Pennsylvania. In most of these studies,
individuals with an abnormal BeLPT
result were retested and were identified
as sensitized (i.e., confirmed positive) if
the abnormal result was repeated.
There has been criticism regarding the
reliability and specificity of the BeLPT
as a screening tool (Borak et al., 2006).
Stange et al. (2004) studied the
reliability and laboratory variability of
the BeLPT by splitting blood samples
and sending samples to two laboratories
simultaneously for BeLPT analysis.
Stange et al. found the range of
agreement on abnormal (positive
BeLPT) results was 26.2—61.8 percent
depending upon the labs tested (Stange
et al., 2004). Borak et al. (2006)
contended that the positive predictive
value (PPV) (PPV is the portion of
patients with positive test result
correctly diagnosed) is not high enough
to meet the criteria of a good screening
tool. Middleton et al. (2008) used the
data from the Stange et al. (2004) study
to estimate the PPV and determined that
the PPV of the BeLPT could be
improved from 0.383 to 0.968 when an
abnormal BeLPT result is confirmed
with a second abnormal result
(Middleton et al., 2008). However, an
apparent false positive can occur in
people not occupationally exposed to
beryllium (NAS, 2008). An analysis of
survey data from the general workforce
and new employees at a beryllium
manufacturer was performed to assess
the reliability of the BeLPT (Donovan et
al. 2007). Donovan et al. analyzed more
than 10,000 test results from nearly
2400 participants over a 12-year period.
Donovan et al. found that approximately
2 percent of new employees had at least
one positive BeLPT at the time of hire
and 1 percent of new hires with no
known occupational exposure were
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confirmed positive at the time of hire
with two BeLPTs. Since there are
currently no alternatives to the BeLPT
in a screening program many programs
rely on a second test to confirm a
positive result (NAS, 2008).
The epidemiological studies
presented in this section utilized the
BeLPT as either a surveillance tool or a
screening tool for determining
sensitization status and/or sensitization/
CBD prevalence in workers for inclusion
in the published studies. Most
epidemiological studies have reported
rates of sensitization and disease based
on a single screening of a working
population (‘cross-sectional’ or
’population prevalence’ rates). Studies
of workers in a beryllium machining
plant and a nuclear weapons facility
have included follow-up of the
population originally screened,
resulting in the detection of additional
cases of sensitization over several years
(Newman et al., 2001, Stange et al.,
2001). OSHA regards the BeLPT as a
reliable medical surveillance tool. The
BeLPT is discussed in more detail in
Non-Mandatory Appendix A to the
proposed standard, Immunological
Testing for the Determination of
Beryllium Sensitization.
c. Beryllium Mining and Extraction
Mining and extraction of beryllium
usually involves the two major
beryllium minerals, beryl (an
aluminosilicate containing up to 4
percent beryllium) and bertrandite (a
beryllium silicate hydrate containing
generally less than 1 percent beryllium)
(WHO, 2001). The United States is the
world leader in beryllium extraction
and also leads the world in production
and use of beryllium and its alloys
(WHO, 2001). Most exposures from
mining and extraction come in the form
of beryllium ore, beryllium salts,
beryllium hydroxide (NAS 2008) or
beryllium oxide (Stefaniak et al., 2008).
Deubner et al. published a study of 75
workers employed at a beryllium
mining and extraction facility in Delta,
UT (Deubner et al., 2001b). Of the 75
workers surveyed for sensitization with
the BeLPT, three were identified as
sensitized by an abnormal BeLPT result.
One of those found to be sensitized was
diagnosed with CBD. Exposures at the
facility included primarily beryllium
ore and salts. General area (GA),
breathing zone (BZ), and personal lapel
(LP) exposure samples were collected
from 1970 to 1999. Jobs involving
beryllium hydrolysis and wet-grinding
activities had the highest air
concentrations, with an annual median
GA concentration ranging from 0.1 to
0.4 mg/m3. Median BZ concentrations
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were higher than either LP or GA. The
average duration of exposure for
beryllium sensitized workers was 21.3
years (27.7 years for the worker with
CBD), compared to an average duration
for all workers of 14.9 years. However,
these exposures were less than either
the Elmore, OH, or Tucson, AZ,
facilities described below, which also
had higher reported rates of BeS and
CBD. A study by Stefaniak et al. (2008)
demonstrated that beryllium was
present at the mill in three forms:
mineral, poorly crystalline oxide, and
hydroxide.
There was no sensitization or CBD
among those who worked only at the
mine where exposure to beryllium
resulted solely from working with
bertrandite ore. The authors concluded
that the results of this study indicated
that beryllium ore and salts may pose
less of a hazard than beryllium metal
and beryllium hydroxide. These results
are consistent with the previously
discussed animal studies examining
solubility and particle size.
d. Beryllium Metal Processing and Alloy
Production
Kreiss et al. (1997) conducted a study
of workers at a beryllium production
facility in Elmore, OH. The plant, which
opened in 1953 and initially specialized
in production of beryllium-copper alloy,
later expanded its operations to include
beryllium metal, beryllium oxide, and
beryllium-aluminum alloy production;
beryllium and beryllium alloy
machining; and beryllium ceramics
production, which was moved to a
different factory in the early 1980s.
Production operations included a wide
variety of jobs and processes, such as
work in arc furnaces and furnace
rebuilding, alloy melting and casting,
beryllium powder processing, and work
in the pebble plant. Non-production
work included jobs in the analytical
laboratory, engineering research and
development, maintenance, laundry,
production-area management, and
office-area administration. While the
publication refers to the use of
respiratory protection in some areas,
such as the pebble plant, the extent of
its use across all jobs or time periods
was not reported. Use of dermal PPE
was not reported.
The authors characterized exposures
at the plant using industrial hygiene
(IH) samples collected between 1980
and 1993. The exposure samples and
the plant’s formulas for estimating
workers’ DWA exposures were used,
together with study participants’ work
histories, to estimate their cumulative
and average beryllium exposure levels.
Exposure concentrations reflected the
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high exposures found historically in
beryllium production and processing.
Short-term BZ measurements had a
median of 1.4, with 18.5 percent of
samples exceeding OSHA’s STEL of 5.0
mg/m3. Particularly high beryllium
concentrations were reported in the
areas of beryllium powder production,
laundry, alloy arc furnace
(approximately 40 percent of DWA
estimates over 2.0 mg/m3) and furnace
rebuild (28.6 percent of short-term BZ
samples over the OSHA STEL of 5 mg/
m3). LP samples (n = 179), which were
available from 1990 to 1992, had a
median value of 1 mg/m3.
Of 655 workers employed at the time
of the study, 627 underwent BeLPT
screening. Blood samples were divided
and split between two labs for analysis,
with repeat testing for results that were
abnormal or indeterminate. Thirty-one
workers had an abnormal blood test
upon initial testing and at least one of
two subsequent tests was classified as
sensitized. These workers, together with
19 workers who had an initial abnormal
result and one subsequent
indeterminate result, were offered
clinical evaluation for CBD including
the BAL-BeLPT and transbronchial lung
biopsy. Nine with an initial abnormal
test followed by two subsequent normal
tests were not clinically evaluated,
although four were found to be
sensitized upon retesting in 1995. Of 47
workers who proceeded with evaluation
for CBD (3 of the 50 initial workers with
abnormal results declined to
participate), 24 workers were diagnosed
with CBD based on evidence of
granulomas on lung biopsy (20 workers)
or on other findings consistent with
CBD (4 workers) (Kreiss et al., 1997).
After including five workers who had
been diagnosed prior to the study, a
total of 29 (4.6 percent) current workers
were found to have CBD. In addition,
the plant medical department identified
24 former workers diagnosed with CBD
before the study.
Kreiss et al. reported that the highest
prevalence of sensitization and CBD
occurred among workers employed in
beryllium metal production, even
though the highest airborne total mass
concentrations of beryllium were
generally among employees operating
the beryllium alloy furnaces in a
different area of the plant (Kreiss et al.,
1997). Preliminary follow-up
investigations of particle size-specific
sampling at five furnace sites within the
plant determined that the highest
respirable (e.g., particles <10 mm in
diameter as defined by the authors) and
alveolar-deposited (e.g., particles <1 mm
in diameter as defined by the authors)
beryllium mass and particle number
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concentrations, as collected by a general
area impactor device, were measured at
the beryllium metal production furnaces
rather than the beryllium alloy furnaces
(Kent et al., 2001; McCawley et al.,
2001). A statistically significant linear
trend was reported between the above
alveolar-deposited particle mass
concentration and prevalence of CBD
and sensitization in the furnace
production areas. The authors
concluded that alveolar-deposited
particles may be a more relevant
exposure metric for predicting the
incidence of CBD or sensitization than
the total mass concentration of airborne
beryllium.
Bailey et al. (2010) evaluated the
effectiveness of a workplace preventive
program in lowering BeS at the
beryllium metal, oxide, and alloy
production plant studied by Kreiss et al.
(1997). The preventive program
included use of administrative and PPE
controls (e.g., improved training, skin
protection and other PPE, half-mask or
air-purified respirators, medical
surveillance, improved housekeeping
standards, clean uniforms) as well as
engineering controls (e.g., migration
controls, physical separation of
administrative offices from production
facilities) implemented over the course
of five years.
In a cross-sectional/longitudinal
hybrid study, Bailey et al. compared
rates of sensitization in pre-program
workers to those hired after the
preventive program began. Pre-program
workers were surveyed cross-sectionally
in 1993–1994, and again in 1999 using
the BeLPT to determine sensitization
and CBD prevalence rates. The 1999
cross-sectional survey was conducted to
determine if improvements in
engineering and administrative controls
were successful, however, results
indicated no improvement in reducing
rates of sensitization or CBD.
An enhanced preventive program
including particle migration control,
respiratory and dermal protection, and
process enclosure was implemented in
2000, with continuing improvements
made to the program in 2001, 2002–
2004, and 2005. Workers hired during
this period were longitudinally
surveyed for sensitization using the
BeLPT. Both the pre-program and
program survey of worker sensitization
status utilized split-sample testing to
verify positive test results using the
BeLPT. Of the total 660 workers
employed at the production plant, 258
workers participated from the preprogram group while 290 participated
from the program group (206 partial
program, 84 full program). Prevalence
comparisons of the pre-program and
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program groups (partial and full) were
performed by calculating prevalence
ratios. A 95 percent confidence interval
(95 percent CI) was derived using a
cohort study method that accounted for
the variance in survey techniques
(cross-sectional versus longitudinal)
(Bailey et al., 2010). The sensitization
prevalence of the pre-program group
was 3.8 times higher (95 percent CI, 1.5–
9.3) than the program group, 4.0 times
higher (95 percent CI, 1.4–11.6) than the
partial program subgroup, and 3.3 times
higher (95 percent CI, 0.8–13.7) than the
full program subgroup indicating that a
comprehensive preventive program can
reduce, but not eliminate, occurrence of
sensitization among non-sensitized
workers (Bailey et al., 2010).
Rosenman et al. (2005) studied a
group of several hundred workers who
had been employed at a beryllium
production and processing facility that
operated in eastern Pennsylvania
between 1957 and 1978. Of 715 former
workers located, 577 were screened for
BeS with the BLPT and 544 underwent
chest radiography to identify cases of
BeS and CBD. Workers were reported to
have exposure to beryllium dust and
fume in a variety of chemical forms
including beryl ore, beryllium metal,
beryllium fluoride, beryllium
hydroxide, and beryllium oxide.
Rosenman et al. used the plant’s DWA
formulas to assess workers’ full-shift
exposure levels, based on IH data
collected between 1957–1962 and 1971–
1976, to calculate exposure metrics
including cumulative, average, and peak
for each worker in the study. The DWA
was calculated based on air monitoring
that consisted of GA and short-term
task-based BZ samples. Workers’
exposures to specific chemical and
physical forms of beryllium were
assessed, including insoluble beryllium
(metal and oxide), soluble beryllium
(fluoride and hydroxide), mixed soluble
and insoluble beryllium, beryllium dust
(metal, hydroxide, or oxide), fume
(fluoride), and mixed dust and fume.
Use of respiratory or dermal protection
by workers was not reported. Exposures
in the plant were high overall.
Representative task-based IH samples
ranged from 0.9 m g/m3 to 84 m g/m3 in
the 1960s, falling to a range of 0.5–16.7
m g/m3 in the 1970s. A large number of
workers’ mean DWA estimates (25
percent) were above the OSHA PEL of
2.0 m g/m3, while most workers had
mean DWA exposures between 0.2 and
2.0 m g/m3 (74 percent) or below 0.02
m g/m3 (1 percent) (Rosenman et al.,
Table 11; revised erratum April, 2006).
Blood samples for the BeLPT were
collected from the former workers
between 1996 and 2001 and were
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evaluated at a single laboratory.
Individuals with an abnormal test result
were offered repeat testing, and were
classified as sensitized if the second test
was also abnormal. Sixty workers with
two positive BeLPTs and 50 additional
workers with chest radiography
suggestive of disease were offered
clinical evaluation, including
bronchoscopy with bronchial biopsy
and BAL-BeLPT. Seven workers met
both criteria. Only 56 (51 percent) of
these workers proceeded with clinical
evaluation, including 57 percent of
those referred on the basis of confirmed
abnormal BeLPT and 47 percent of those
with abnormal radiographs.
Of those workers who underwent
bronchoscopy, 32 (5.5 percent) with
evidence of granulomas were classified
as ‘‘definite’’ CBD cases. Twelve (2.1
percent) additional workers with
positive BAL-BeLPT or confirmed
positive BeLPT and radiographic
evidence of upper lobe fibrosis were
classified as ‘‘probable’’ CBD cases.
Forty workers (6.9 percent) without
upper lobe fibrosis who had confirmed
abnormal BeLPT, but who were not
biopsied or who underwent biopsy with
no evidence of granuloma, were
classified as sensitized without disease.
It is not clear how many of the 40
workers underwent biopsy. Another 12
(2.1 percent) workers with upper lobe
fibrosis and negative or unconfirmed
positive BeLPT were classified as
‘‘possible’’ CBD cases. Nine additional
workers who were diagnosed with CBD
before the screening were included in
some parts of the authors’ analysis.
The authors reported a total
prevalence of 14.5 percent for CBD
(definite and probable) and
sensitization. This rate, considerably
higher than the overall prevalence of
sensitization and disease in several
other worker cohorts as described
earlier in this section, reflects in part the
very high exposures experienced by
many workers during the plant’s
operation in the 1950s, 1960s and
1970s. A total of 115 workers had mean
DWAs above the OSHA PEL of 2 m g/m3.
Of those, 7 (6.0 percent) had definite or
probable CBD and another 13 (11
percent) were classified as sensitized
without disease. The true prevalence of
CBD in the group may be higher than
reported, due to the low rate of clinical
evaluation among sensitized workers.
Although most of the workers in this
study had high exposures, sensitization
and CBD also were observed within the
small subgroup of participants believed
to have relatively low beryllium
exposures. Thirty-three cases of CBD
and 24 additional cases of sensitization
occurred among 339 workers with mean
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DWA exposures below OSHA’s PEL of
2.0 m g/m3 (Rosenman et al., Table 11,
erratum 2006). Ten cases of
sensitization and five cases of CBD were
found among office and clerical
workers, who were believed to have low
exposures (levels not reported).
Follow-up time for sensitization
screening of workers in this study who
became sensitized during their
employment had a minimum of 20 years
to develop CBD prior to screening. In
this sense the cohort is especially well
suited to compare the exposure patterns
of workers with CBD and those
sensitized without disease, in contrast
to several other studies of workers with
only recent beryllium exposures.
Rosenman et al. characterized and
compared the exposures of workers with
definite and probable CBD, sensitization
only, and no disease or sensitization
using chi-squared tests for discrete
outcomes and analysis of variance
(ANOVA) for continuous variables
(cumulative, mean, and peak exposure
levels). Exposure-response relationships
were further examined with logistic
regression analysis, adjusting for
potential confounders including
smoking, age, and beryllium exposure
from outside of the plant. The authors
found that cumulative, peak, and
duration of exposure were significantly
higher for workers with CBD than for
sensitized workers without disease (p
<0.05), suggesting that the risk of
progressing from sensitization to CBD is
related to the level or extent of exposure
a worker experiences. The risk of
developing CBD following sensitization
appeared strongly related to exposure to
insoluble forms of beryllium, which are
cleared slowly from the lung and
increase beryllium lung burden more
rapidly than quickly mobilized soluble
forms. Individuals with CBD had higher
exposures to insoluble beryllium than
those classified as sensitized without
disease, while exposure to soluble
beryllium was higher among sensitized
individuals than those with CBD.
Cumulative, mean, peak, and duration
of exposure were found to be
comparable for workers with CBD and
workers without sensitization or CBD
(‘‘normal’’ workers). Cumulative, peak,
and duration of exposure were
significantly lower for sensitized
workers without disease than for normal
workers. Rosenman et al. suggested that
genetic predisposition to sensitization
and CBD may have obscured an
exposure-response relationship in this
study, and plan to control for genetic
risk factors in future studies. Exposure
misclassification from the 1950s and
1960s may have been another limitation
in this study, introducing bias that
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could have influenced the lack of
exposure response. It is also unknown if
the 25 percent who died from CBDrelated conditions may have had higher
exposures.
A follow-up was conducted of the
cross-sectional study of a population of
workers first evaluated by Kreiss et al.
(1997) and Rosenman et al. (2005) at a
beryllium production and processing
facility in eastern Pennsylvania by
Schuler et al. (2012), and in a
companion study by Virji et al. (2012).
Schuler et al. evaluated the worker
population employed in 1999 with six
years or less work tenure in a crosssectional study. The investigators
evaluated the worker population by
administering a work history
questionnaire with a follow-up
examination for sensitization and CBD.
A job-exposure matrix (JEM) was
combined with work histories to create
individual estimates of average,
cumulative, and highest-job-related
exposure for total, respirable, and submicron beryllium mass concentration.
Of the 291 eligible workers, 90.7 percent
(264) participated in the study.
Sensitization prevalence was 9.8
percent (26/264) with CBD prevalence
of 2.3 percent (6/264). The investigators
found a general pattern of increasing
sensitization prevalence as the exposure
quartile increased indicating an
exposure-response relationship. The
investigators found positive associations
with both total and respirable mass
concentration with sensitization
(average and highest job) and CBD
(cumulative). Increased sensitization
prevalence was observed with metal
oxide production alloy melting and
casting, and maintenance. CBD was
associated with melting and casting.
The investigators summarized that both
total and respirable mass concentration
were relevant predictors of risk (Schuler
et al., 2012).
In the companion study by Virji et al.
(2012), the investigators reconstructed
historical exposure from 1994 to 1999
utilizing the personal sampling data
collected in 1999 as baseline exposure
estimates (BEE). The study evaluated
techniques for reconstructing historical
data to evaluate exposure-response
relationships for epidemiological
studies. The investigators constructed
JEMs using the BEE and estimates of
annual changes in exposure for 25
different process areas. The
investigators concluded these
reconstructed JEMs could be used to
evaluate a range of exposure parameters
from total, respirable and submicron
mass concentration including
cumulative, average, and highest
exposure. These two studies
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demonstrate that high-quality exposure
estimates can be developed both for
total mass and respirable mass
concentrations.
e. Beryllium Machining Operations
Newman et al. (2001) and Kelleher et
al. (2001) studied a group of 235
workers at a beryllium metal machining
plant. Since the plant opened in 1969,
its primary operations have been
machining and polishing beryllium
metal and high-beryllium content
composite materials, with occasional
machining of beryllium oxide/metal
matrix (‘E-metal’), and beryllium alloys.
Other functions include machining of
metals other than beryllium; receipt and
inspection of materials; acid etching;
final inspection, quality control, and
shipping of finished materials; tool
making; and engineering, maintenance,
administrative and supervisory
functions (Newman et al., 2001; Madl et
al., 2007). Machining operations,
including milling, grinding, lapping,
deburring, lathing, and electrical
discharge machining (EDM), were
performed in an open-floor plan
production area. Most non-machining
jobs were located in a separate, adjacent
area; however, non-production
employees had access to the machining
area.
Engineering and administrative
measures, rather than PPE, were
primarily used to control beryllium
exposures at the plant (Madl et al.,
2007). Based on interviews with longstanding employees of the plant,
Kelleher et al. reported that work
practices were relatively stable until
1994, when a worker was diagnosed
with CBD and a new exposure control
program was initiated. Between 1995
and 1999 new engineering and work
practice controls were implemented,
including removal of pressurized air
hoses and discouragement of dry
sweeping (1995), enclosure of deburring
processes (1996), mandatory uniforms
(1997), and installation or updating of
local exhaust ventilation (LEV) in EDM,
lapping, deburring, and grinding
processes (1998) (Madl et al., 2007).
Throughout the plant’s history,
respiratory protection was used mainly
for ‘‘unusually large, anticipated
exposures’’ to beryllium (Kelleher et al.,
2001), and was not routinely used
otherwise (Newman et al., 2001).
All workers at the plant participated
in a beryllium disease surveillance
program initiated in 1994, and were
screened for beryllium sensitization
with the BeLPT beginning in 1995. A
BeLPT result was considered abnormal
if two or more of six stimulation indices
exceeded the normal range (see section
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on BeLPT testing above), and was
considered borderline if one of the
indices exceeded the normal range. A
repeat BeLPT was conducted for
workers with abnormal or borderline
initial results. Workers were identified
as beryllium sensitized and referred for
a clinical evaluation, including
bronchoalveolar lavage (BAL) and
transbronchial lung biopsy, if the repeat
test was abnormal. CBD was diagnosed
upon evidence of sensititization with
granulomas or mononuclear cell
infiltrates in the lung tissue (Newman et
al., 2001). Following the initial plantwide screening, plant employees were
offered BeLPT testing at two-year
intervals. Workers hired after the initial
screening were offered a BeLPT within
3 months of their hire date, and at 2year intervals thereafter (Madl et al.,
2007).
Kelleher et al. performed a nested
case-control study of the 235 workers
evaluated in Newman et al. (2001) to
evaluate the relationship between
beryllium exposure levels and risk of
sensitization and CBD (Kelleher et al.,
2001). The authors evaluated exposures
at the plant using IH samples they had
collected between 1996 and 1999, using
personal cascade impactors designed to
measure the mass of beryllium particles
less than 6 m m, particles less than 1 mm
in diameter, and total mass. The great
majority of workers’ exposures were
below the OSHA PEL of 2 m g/m3.
However, a few higher levels were
observed in machining jobs including
deburring, lathing, lapping, and
grinding. Based on a statistical
comparison between their samples and
historical data provided by the plant,
the authors concluded that worker
beryllium exposures across all time
periods could be approximated using
the 1996–1999 data. They estimated
workers’ cumulative and ‘lifetime
weighted’ (LTW) beryllium exposure
based on the exposure samples they
collected for each job in 1996–1999 and
company records of each worker’s job
history.
Twenty workers with beryllium
sensitization or CBD (cases) were
compared to 206 workers (controls) for
the case-control analysis from the study
evaluating workers originally conducted
by Newman et al. Thirteen workers
were diagnosed with CBD based on lung
biopsy evidence of granulomas and/or
mononuclear cell infiltrates (11) or
positive BAL results with evidence of
lymphocytosis (2). Seven were
evaluated for CBD and found to be
sensitized only, thus twenty composing
the case group. Nine of the remaining
215 workers first identified in original
study (Newman et al., 2001) were
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excluded due to incomplete job history
information, leaving 206 workers in the
control group.
Kelleher et al.’s analysis included
comparisons of the case and control
groups’ median exposure levels;
calculation of odds ratios for workers in
high, medium, and low exposure
groups; and logistic regression testing of
the association of sensitization or CBD
with exposure level and other variables.
Median cumulative exposures for total
mass, particles <6 m m, and particles <1
mm were approximately three times
higher among the cases than controls,
although the relationships observed
were not statistically significant (p
values ∼ 0.2). No clear difference
between cases and controls was
observed for the median LTW
exposures. Odds ratios with
sensitization and CBD as outcomes were
elevated in high (upper third) and
intermediate exposure groups relative to
low (lowest third) exposure groups for
both cumulative and LTW exposure,
though the results were not statistically
significant (p > 0.1). In the logistic
regression analysis, only machinist
work history was a significant predictor
of case status in the final model.
Quantitative exposure measures were
not significant predictors of
sensitization or disease risk.
Citing an 11.5 percent prevalence of
beryllium sensitization or CBD among
machinists as compared with 2.9
percent prevalence among workers with
no machinist work history, the authors
concluded that the risk of sensitization
and CBD is increased among workers
who machine beryllium. Although
differences between cases and controls
in median cumulative exposure did not
achieve conventional thresholds for
statistical significance, the authors
noted that cumulative exposures were
consistently higher among cases than
controls for all categories of exposure
estimates and for all particle sizes,
suggesting an effect of cumulative
exposure on risk. The levels at which
workers developed CBD and
sensitization were predominantly below
OSHA’s current PEL of 2 m g/m3, and no
cases of sensitization or CBD were
observed among workers with LTW
exposure <0.02 mg/m3. Twelve (60
percent) of the 20 sensitized workers
had LTW exposures > 0.20 m g/m3.
In 2007, Madl et al. published an
additional study of 27 workers at the
machining plant who were found to be
sensitized or diagnosed with CBD
between the start of medical
surveillance in 1995 and 2005. As
previously described, workers were
offered a BeLPT in the initial 1995
screening (or within 3 months of their
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hire date if hired after 1995) and at 2year intervals after their first screening.
Workers with two positive BeLPTs were
identified as sensitized and offered
clinical evaluation for CBD, including
bronchoscopy with BAL and
transbronchial lung biopsy. The criteria
for CBD in this study were somewhat
stricter than those used in the Newman
et al. study, requiring evidence of
granulomas on lung biopsy or detection
of X-ray or pulmonary function changes
associated with CBD, in combination
with two positive BeLPTs or one
positive BAL-BeLPT.
Based on the history of the plant’s
control efforts and their analysis of
historical IH data, Madl et al. identified
three ‘‘exposure control eras’’: A
relatively uncontrolled period from
1980–1995; a transitional period from
1996 to 1999; and a relatively wellcontrolled ‘‘modern’’ period from 2000–
2005. They found that the engineering
and work practice controls instituted in
the mid-1990s reduced workers’
exposures substantially, with nearly a
15-fold difference in reported exposure
levels between the pre-control and the
modern period (Madl et al., 2007). Madl
et al. estimated workers’ exposures
using LP samples collected between
1980 and 2005, including those
collected by Kelleher et al., and work
histories provided by the plant. As
described more fully in the study, they
used a variety of approaches to describe
individual workers’ exposures,
including approaches designed to
characterize the highest exposures
workers were likely to have
experienced. Their exposure-response
analysis was based primarily on an
exposure metric they derived by
identifying the year and job of each
worker’s pre-diagnosis work history
with the highest reported exposures.
They used the upper 95th percentile of
the LP samples collected in that job and
year (in some cases supplemented with
data from other years) to characterize
the worker’s upper-level exposures.
Based on their estimates of workers’
upper level exposures, Madl et al.
concluded that workers with
sensitization or CBD were likely to have
been exposed to airborne beryllium
levels greater than 0.2 mg/m3 as an 8hour TWA at some point in their history
of employment in the plant. They also
concluded that most sensitization and
CBD cases were likely to have been
exposed to levels greater than 0.4 mg/m3
at some point in their work at the plant.
Madl et al. did not reconstruct
exposures for workers at the plant who
did not have sensitization or CBD and
therefore could not determine whether
non-cases had upper-bound exposures
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lower than these levels. They found that
upper-bound exposure estimates were
generally higher for workers with CBD
than for those who were sensitized but
not diagnosed with CBD at the
conclusion of the study (Madl et al.,
2007). Because CBD is an
immunological disease and beryllium
sensitization has been shown to occur
within a year of exposure for some
workers, Madl et al. argued that their
estimates of workers’ short-term upperbound exposures may better capture the
exposure levels that led to sensitization
and disease than estimates of long-term
cumulative or average exposures such as
the LTW exposure measure constructed
by Kelleher et al. (Madl et al., 2007).
f. Beryllium Oxide Ceramics
Kreiss et al. (1993) conducted a
screening of current and former workers
at a plant that manufactured beryllium
ceramics from beryllium oxide between
1958 and 1975, and then transitioned to
metalizing circuitry onto beryllium
ceramics produced elsewhere. Of the
plant’s 1,316 current and 350 retired
workers, 505 participated who had not
previously been diagnosed with CBD or
sarcoidosis, including 377 current and
128 former workers. Although beryllium
exposure was not estimated
quantitatively in this survey, the authors
conducted a questionnaire to assess
study participants’ exposures
qualitatively. Results showed that 55
percent of participants reported working
in jobs with exposure to beryllium dust.
Close to 25 percent of participants did
not know if they had exposure to
beryllium, and just over 20 percent
believed they had not been exposed.
BeLPT tests were administered to all
505 participants in the 1989–1990
screening period and evaluated at a
single lab. Seven workers had confirmed
abnormal BeLPT results and were
identified as sensitized; these workers
were also diagnosed with CBD based on
findings of granulomas upon clinical
evaluation. Radiograph screening led to
clinical evaluation and diagnosis of two
additional CBD cases, who were among
three participants with initially
abnormal BeLPT results that could not
be confirmed on repeat testing. In
addition, nine workers had been
previously diagnosed with CBD, and
another five were diagnosed shortly
after the screening period, in 1991–
1992.
Eight (3.7 percent of the screening
population) of the nine CBD cases
identified in the screening population
were hired before the plant stopped
producing beryllium ceramics in 1975,
and were among the 216 participants
who had reported having been near or
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exposed to beryllium dust. Particularly
high CBD rates of 11.1–15.8 percent
were found among screening
participants who had worked in process
development/engineering, dry pressing,
and ventilation maintenance jobs
believed to have high or uncontrolled
dust exposure. One case (0.6 percent) of
CBD was diagnosed among the 171
study participants who had been hired
after the plant stopped producing
beryllium ceramics. Although this
worker was hired eight years after the
end of ceramics production, he had
worked in an area later found to be
contaminated with beryllium dust. The
authors concluded that the study results
suggested an exposure-response
relationship between beryllium
exposure and CBD, and recommended
beryllium exposure control to reduce
workers’ risk of CBD.
Kreiss et al. later published a study of
workers at a second ceramics plant
located in Tucson, AZ (Kreiss et al.,
1996), which since 1980 had produced
beryllium ceramics from beryllium
oxide powder manufactured elsewhere.
IH measurements collected between
1981 and 1992, primarily GA or shortterm BZ samples and a few (<100) LP
samples, were available from the plant.
Airborne beryllium exposures were
generally low. The majority of area
samples were below the analytical
detection limit of 0.1 mg/m3, while LP
and short-term BZ samples had medians
of 0.3 mg/m3. However, 3.6 percent of
short-term BZ samples and 0.7 percent
of GA samples exceeded 5.0 mg/mg3,
while LP samples ranged from 0.1 to 1.8
mg/m3. Machining jobs had the highest
beryllium exposure levels among job
tasks, with short-term BZ samples
significantly higher for machining jobs
than for non-machining jobs (median
0.6 mg/m3 vs. 0.3 mg/mg3, p = 0.0001).
The authors used DWA formulas
provided by the plant to estimate
workers’ full-shift exposure levels, and
to calculate cumulative and average
beryllium exposures for each worker in
the study. The median cumulative
exposure was 591.7 mg-days/m3 and the
median average exposure was 0.35 mg/
m3.
One hundred thirty-six of the 139
workers employed at the plant at the
time of the Kreiss et al. (1996) study
underwent BeLPT screening and chest
radiographs in 1992. Blood samples
were split between two laboratories. If
one or both test results were abnormal,
an additional sample was collected and
split between the labs. Seven workers
with an abnormal result on two draws
were initially identified as sensitized.
Those with confirmed abnormal BeLPTs
or abnormal chest X-rays were offered
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clinical evaluation for CBD, including
transbronchial lung biopsy and BAL
BeLPT. CBD was diagnosed based on
observation of granulomas on lung
biopsy, in five of the six sensitized
workers who accepted evaluation. An
eighth case of sensitization and sixth
case of CBD were diagnosed in one
worker hired in October 1991 whose
initial BeLPT was normal, but who was
confirmed as sensitized and found to
have lung granulomas less than two
years later, after sustaining a berylliumcontaminated skin wound. The plant
medical department reported 11
additional cases of CBD among former
workers (Kreiss et al., 1996). The overall
prevalence of sensitization in the plant
was 5.9 percent, with a 4.4 percent
prevalence of CBD.
Kreiss et al. reported that six (75
percent) of the eight sensitized workers
were exposed as machinists during or
before the period October 1985–March
1988, when measurements were first
available for machining jobs. The
authors reported that 14.3 percent of
machinists were sensitized, compared to
1.2 percent of workers who had never
been machinists (p <0.01). Workers’
estimated cumulative and average
beryllium exposures did not differ
significantly for machinists and nonmachinists, or for cases and non-cases.
As in the previous study of the same
ceramics plant published by Kreiss et al.
in 1993, one case of CBD was diagnosed
in a worker who had never been
employed in a production job. This
worker was employed in administration,
a job with a median DWA of 0.1 mg/m3
(range 0.1–0.3).
In 1998, Henneberger et al. conducted
a follow-up cross-sectional survey of
151 employees employed at the
beryllium ceramics plant studied by
Kreiss et al. (1996) (Henneberger et al.,
2001). Employees were eligible who
either had not participated in the Kreiss
et al. survey (‘‘short-term workers’’—74
of those studied by Henneberger et al.),
or who had participated and were not
found to have sensitization or disease
(‘‘long-term workers’’—77 of those
studied by Henneberger et al.).
The authors estimated workers’
cumulative, average, and peak beryllium
exposures based on the plant’s formulas
for estimating job-specific DWA
exposures, participants’ work histories,
and area and short-term task-specific BZ
samples collected from the start of full
production at the plant in 1981 to 1998.
The long-term workers, who were hired
before the 1992 study was conducted,
had generally higher estimated
exposures (median of average
exposures—0.39 mg/m3; mean—14.9 mg/
m3) than the short-term workers, who
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were hired after 1992 (median 0.28 mg/
m3, mean 6.1 mg/m3).
Fifteen cases of sensitization were
found, including eight among short-term
and seven among long-term workers.
Eight of the 15 workers were found to
have CBD. Of the workers diagnosed
with CBD, seven (88 percent) were longterm workers. One non-sensitized longterm worker and one sensitized longterm worker declined clinical
examination.
Henneberger et al. reported a higher
prevalence of sensitization among longterm workers with ‘‘high’’ (greater than
median) peak exposures compared to
long-term workers with ‘‘low’’
exposures; however, this relationship
was not statistically significant. No
association was observed for average or
cumulative exposures. The authors
reported higher prevalence of
sensitization (but not statistically
significant) among short-term workers
with ‘‘high’’ (greater than median)
average, cumulative, and peak
exposures compared to short-term
workers with ‘‘low’’ exposures of each
type.
The cumulative incidence of
sensitization and CBD was investigated
in a cohort of 136 workers at the
beryllium ceramics plant previously
studied by the Kreiss and Henneberger
groups (Schuler et al., 2008). The study
cohort consisted of those who
participated in the plant-wide BeLPT
screening in 1992. Both current and
former workers from this group were
invited to participate in follow-up
BeLPT screenings in 1998, 2000, and
2002–03. A total of 106 of the 128 nonsensitized individuals in 1992
participated in the 11-year follow-up.
Sensitization was defined as a
confirmed abnormal BeLPT based on
the split blood sample-dual laboratory
protocol described earlier. CBD was
diagnosed in sensitized individuals
based on pathological findings from
transbronchial biopsy and BAL fluid
analysis. The 11-year crude cumulative
incidence of sensitization and CBD was
13 percent (14 of 106) and 8 percent (9
of 106) respectively. The cumulative
prevalence was about triple the point
prevalences determined in the initial
1992 cross-sectional survey. The
corrected cumulative prevalences for
those that ever worked in machining
were nearly twice that for nonmachinists. The data illustrate the value
of longitudinal medical screening over
time to obtain a more accurate estimate
of the occurrence of sensitization and
CBD among an exposed working
population.
Following the 1998 survey, the
company continued efforts to reduce
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exposures and risk of sensitization and
CBD by implementing additional
engineering, administrative, and PPE
measures (Cummings et al., 2007).
Respirator use was required in
production areas beginning in 1999, and
latex gloves were required beginning in
2000. The lapping area was enclosed in
2000, and enclosures were installed for
all mechanical presses in 2001. Between
2000 and 2003, water-resistant or waterproof garments, shoe covers, and taped
gloves were incorporated to keep
beryllium-containing fluids from wet
machining processes off the skin. The
new engineering measures did not
appear to substantially reduce airborne
beryllium levels in the plant. LP
samples collected between 2000 and
2003 had a median of 0.18 mg/m3,
similar to the 1994–1999 samples.
However, respiratory protection
requirements to control workers’
airborne beryllium exposures were
instituted prior to the 2000 sample
collections.
To test the efficacy of the new
measures instituted after 1998, in
January 2000 the company began
screening new workers for sensitization
at the time of hire and at 3, 6, 12, 24,
and 48 months of employment. These
more stringent measures appear to have
substantially reduced the risk of
sensitization among new employees. Of
126 workers hired between 2000 and
2004, 93 completed BeLPT testing at
hire and at least one additional test at
3 months of employment. One case of
sensitization was identified at 24
months of employment (1 percent). This
worker had experienced a rash after an
incident of dermal exposure to lapping
fluid through a gap between his glove
and uniform sleeve, indicating that he
may have become sensitized via the
skin. He was tested again at 48 months
of employment, with an abnormal
result.
A second worker in the 2000–2004
group had two abnormal BeLPT tests at
the time of hire, and a third had one
abnormal test at hire and a second
abnormal test at 3 months. Both had
normal BeLPTs at 6 months, and were
not tested thereafter. A fourth worker
had one abnormal BeLPT result at the
time of hire, a normal result at 3
months, an abnormal result at 6 months,
and a normal result at 12 months. Four
additional workers had one abnormal
result during surveillance, which could
not be confirmed upon repeat testing.
Cummings et al. calculated two
sensitization rates based on these
screening results: (1) a rate using only
the sensitized worker identified at 24
months, and (2) a rate including all four
workers who had repeated abnormal
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results. They reported a sensitization
incidence rate (IR) of 0.7 per 1,000
person-months to 2.7 per 1,000 personmonths for the workers hired between
2000 and 2004, using the sum of
sensitization-free months of
employment among all 93 workers as
the denominator.
The authors also estimated an
incidence rate (IR) of 5.6 per 1,000
person-months for workers hired
between 1993 and the 1998 survey. This
estimated IR was based on one BeLPT
screening, rather than BeLPTs
conducted throughout the workers’
employment. The denominator in this
case was the total months of
employment until the 1998 screening.
Because sensitized workers may have
been sensitized prior to the screening,
the denominator may overestimate
sensitization-free time in the legacy
group, and the actual sensitization IR for
legacy workers may be somewhat higher
than 5.6 per 1,000 person-months.
Based on comparison of the IRs, the
authors concluded that the addition of
respirator use, dermal protection, and
housekeeping improvements appeared
to have reduced the risk of sensitization
among workers at the plant, even
though airborne beryllium levels in
some areas of the plant had not changed
significantly since the 1998 survey.
g. Copper-Beryllium Alloy Processing
and Distribution
Schuler et al. (2005) studied a group
of 152 workers at a facility processing
copper-beryllium alloys and small
quantities of nickel-beryllium alloys,
and converting semi-finished alloy strip
and wire into finished strip, wire and
rod. Production activities included
annealing, drawing, straightening, point
and chamfer, rod and wire packing, die
grinding, pickling, slitting, and
degreasing. Periodically in the plant’s
history, they also did salt baths,
cadmium plating, welding and
deburring. Since the late 1980s, rod and
wire production processes were
physically segregated from strip metal
production. Production support jobs
included mechanical maintenance,
quality assurance, shipping and
receiving, inspection, and wastewater
treatment. Administration was divided
into staff primarily working within the
plant and personnel who mostly worked
in office areas (Schuler, et al., 2005).
Workers’ respirator use was limited,
mostly to occasional tasks where high
exposures were anticipated.
Following the 1999 diagnosis of a
worker with CBD, the company
surveyed the workforce, offering all
current employees BeLPT testing in
2000 and offering sensitized workers
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clinical evaluation for CBD, including
BAL and transbronchial biopsy. Of the
facility’s 185 employees, 152
participated in the BeLPT screening.
Samples were split between two
laboratories, with additional draws and
testing for confirmation if conflicting
tests resulted in the initial draw. Ten
participants (7 percent) had at least two
abnormal BeLPT results. The results of
nine workers who had abnormal BeLPT
results from only one laboratory were
not included because the authors
believed it was experiencing technical
problems with the test (Schuler et al.,
2005). CBD was diagnosed in six
workers (4 percent) on evidence of
pathogenic abnormalities (e.g.,
granulomas) or evidence of clinical
abnormalities consistent with CBD
based on pulmonary function testing,
pulmonary exercise testing, and/or chest
radiography. One worker diagnosed
with CBD had been exposed to
beryllium during previous work at
another copper-beryllium processing
facility.
Schuler et al. evaluated airborne
beryllium levels at the plant using IH
samples collected between 1969 and
2000, including 4,524 GA samples, 650
LP samples and 815 short-duration (3–
5 min) high volume (SD–HV) BZ taskspecific samples. Occupational
exposures to airborne beryllium were
generally low. Ninety-nine percent of all
LP measurements were below the
current OSHA PEL of 2.0 mg/m3 (8-hr
TWA); 93 percent were below the DOE
action level of 0.2 mg/m3; and the
median value was 0.02 mg/m3. The SD–
HV BZ samples had a median value of
0.44 mg/m3, with 90 percent below the
OSHA Short-Term Exposure Limit
(STEL) of 5.0 mg/m3. The highest levels
of beryllium were found in rod and wire
production, particularly in wire
annealing and pickling, the only
production job with a median personal
sample measurement greater than 0.1
mg/m3 (median 0.12 mg/m3; range 0.01–
7.8 mg/m3) (Schuler et al., Table 4).
These concentrations were significantly
higher than the exposure levels in the
strip metal area (median 0.02, range
0.01–0.72 mg/m3), in production support
jobs (median 0.02, range <0.01–0.33 mg/
m3), plant administration (median 0.02,
range <0.01–0.11 mg/m3), and office
administration jobs (median 0.01, range
<0.01–0.06 mg/m3).
The authors reported that eight of the
ten sensitized employees, including all
six CBD cases, had worked in both
major production areas during their
tenure with the plant. The 7 percent
prevalence (6 of 81 workers) of CBD
among employees who had ever worked
in rod and wire was statistically
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significantly elevated compared with
employees who had never worked in
rod and wire (p <0.05), while the 6
percent prevalence (6 of 94 workers)
among those who had worked in strip
metal was not significantly elevated
compared to non-strip metal workers (p
> 0.1). Based on these results, together
with the higher exposure levels reported
for the rod and wire production area,
Schuler et al. concluded that work in
rod and wire was a key risk factor for
CBD in this population. Schuler et al.
also found a high prevalence (13
percent) of sensitization among workers
who had been exposed to beryllium for
less than a year at the time of the
screening, a rate similar to that found by
Henneberger et al. among beryllium
ceramics workers exposed for one year
or less (16 percent, Henneberger et al.,
2001). All four workers who were
sensitized without disease had been
exposed 5 years or less; conversely, all
six of the workers with CBD had first
been exposed to beryllium at least five
years prior to the screening (Schuler et
al., Table 2).
As has been seen in other studies,
beryllium sensitization and CBD were
found among workers who were
typically exposed to low time-weighted
average airborne concentrations of
beryllium. While jobs in the rod and
wire area had the highest exposure
levels in the plant, the median personal
sample value was only 0.12 mg/m3.
However, workers may have
occasionally been exposed to higher
beryllium levels for short periods during
specific tasks. A small fraction of
personal samples recorded in rod and
wire were above the OSHA PEL of 2.0
mg/m3, and half of workers with
sensitization or CBD reported that they
had experienced a ‘‘high-exposure
incident’’ at some point in their work
history (Schuler et al., 2005). The only
group of workers with no cases of
sensitization or CBD, a group of 26
office administration workers, was the
group with the lowest recorded
exposures (median personal sample 0.01
mg/m3, range <0.01–0.06 mg/m3).
After the BeLPT screening was
conducted in 2000, the company began
implementing new measures to further
reduce workers’ exposure to beryllium
(Thomas et al., 2009). Requirements
designed to minimize dermal contact
with beryllium, including long-sleeve
facility uniforms and polymer gloves,
were instituted in production areas in
2000. In 2001 the company installed
LEV in die grinding and polishing. LP
samples collected between June 2000
and December 2001 show reduced
exposures plant-wide. Of 2,211
exposure samples collected, 98 percent
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were below 0.2 mg/m3, and 59 percent
below the limit of detection (LOD),
which was either 0.02 mg/m3 or 0.2 mg/
m3 depending on the method of sample
analysis (Thomas et al., 2009). Median
values below 0.03 mg/m3 were reported
for all processes except the wire
annealing and pickling process.
Samples for this process remained
somewhat elevated, with a median of
0.1 mg/m3. In January 2002, the plant
enclosed the wire annealing and
pickling process in a restricted access
zone (RAZ), requiring respiratory PPE in
the RAZ and implementing stringent
measures to minimize the potential for
skin contact and beryllium transfer out
of the zone. While exposure samples
collected by the facility were sparse
following the enclosure, they suggest
exposure levels comparable to the 2000–
01 samples in areas other than the RAZ.
Within the RAZ, required use of
powered air-purifying respirators
indicates that respiratory exposure was
negligible.
To test the efficacy of the new
measures in preventing sensitization
and CBD, in June 2000 the facility began
an intensive BeLPT screening program
for all new workers. The company
screened workers at the time of hire; at
intervals of 3, 6, 12, 24, and 48 months;
and at 3-year intervals thereafter.
Among 82 workers hired after 1999,
three (3.7 percent) cases of sensitization
were found. Two (5.4 percent) of 37
workers hired prior to enclosure of the
wire annealing and pickling process
were found to be sensitized within 3
and 6 months of beginning work at the
plant. One (2.2 percent) of 45 workers
hired after the enclosure was confirmed
as sensitized.
Thomas et al. calculated a
sensitization IR of 1.9 per 1,000 personmonths for the workers hired after the
exposure control program was initiated
in 2000 (‘‘program workers’’), using the
sum of sensitization-free months of
employment among all 82 workers as
the denominator (Thomas et al., 2009).
They calculated an estimated IR of 3.8
per 1,000 person-months for 43 workers
hired between 1993 and 2000 who had
participated in the 2000 BeLPT
screening (‘‘legacy workers’’). This
estimated IR was based on one BeLPT
screening, rather than BeLPTs
conducted throughout the legacy
workers’ employment. The denominator
in this case is the total months of
employment until the 2000 screening.
Because sensitized workers may have
been sensitized prior to the screening,
the denominator may overestimate
sensitization-free time in the legacy
group, and the actual sensitization IR for
legacy workers may be somewhat higher
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than 3.8 per 1,000 person-months.
Based on comparison of the IRs and the
prevalence rates discussed previously,
the authors concluded that the
combination of dermal protection,
respiratory protection, housekeeping
improvements and engineering controls
implemented beginning in 2000
appeared to have reduced the risk of
sensitization among workers at the
plant. However, they noted that the
small size of the study population and
the short follow-up time for the program
workers suggested that further research
is needed to confirm the program’s
efficacy (Thomas et al., 2009).
Stanton et al. (2006) conducted a
study of workers in three different
copper-beryllium alloy distribution
centers in the United States. The
distribution centers, including one bulk
products center established in 1963 and
strip metal centers established in 1968
and 1972, sell products received from
beryllium production and finishing
facilities and small quantities of copperberyllium, aluminum-beryllium, and
nickel-beryllium alloy materials. Work
at distribution centers does not require
large-scale heat treatment or
manipulation of material typical of
beryllium processing and machining
plants, but involves final processing
steps that can generate airborne
beryllium. Slitting, the main production
activity at the two strip product
distribution centers, generates low
levels of airborne beryllium particles,
while operations such as tensioning and
welding used more frequently at the
bulk products center can generate
somewhat higher levels. Nonproduction jobs at all three centers
included shipping and receiving,
palletizing and wrapping, productionarea administrative work, and officearea administrative work.
The authors estimated workers’
beryllium exposures using IH data from
company records and job history
information collected through
interviews conducted by a company
occupational health nurse. Stanton et al.
evaluated airborne beryllium levels in
various jobs based on 393 full-shift LP
samples collected from 1996 to 2004.
Airborne beryllium levels at the plant
were generally very low, with 54
percent of all samples at or below the
LOD, which ranged from 0.02 to 0.1 mg/
m3. The authors reported a median of
0.03 mg/m3 and an arithmetic mean of
0.05 mg/m3 for the 393 full-shift LP
samples, where samples below the LOD
were assigned a value of half the
applicable LOD. Median and geometric
mean values for specific jobs ranged
from 0.01–0.07 and 0.02–0.07 mg/m3,
respectively. All measurements were
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below the OSHA PEL of 2.0 mg/m3 and
97 percent were below the DOE action
level of 0.2 mg/m3. The paper does not
report use of respiratory or skin
protection. Exposure conditions may
have changed somewhat over the
history of the plant due to changes in
exposure control measures, including
improvements to product and container
cleaning practices instituted during the
1990s.
Eighty-eight of the 100 workers (88
percent) employed at the three centers
at the time of the study participated in
screening for beryllium sensitization.
Blood samples were collected between
November 2000 and March 2001 by the
company’s medical staff. Samples
collected from employees of the strip
metal centers were split and evaluated
at two laboratories, while samples from
the bulk product center workers were
evaluated at a single laboratory.
Participants were considered to be
‘‘sensitized’’ to beryllium if two or more
BeLPT results, from two laboratories or
from repeat testing at the same
laboratory, were found to be abnormal.
One individual was found to be
sensitized and was offered clinical
evaluation, including BAL and
fiberoptic bronchoscopy. He was found
to have lung granulomas and was
diagnosed with CBD.
The worker diagnosed with CBD had
been employed at a strip metal
distribution center from 1978 to 2000 as
a shipper and receiver, loading and
unloading trucks delivering materials
from a beryllium production facility and
to the distribution center’s customers.
Although the LP samples collected for
his job between 1996 and 2000 were
generally low (n = 35, median 0.01,
range < 0.02–0.13 mg/m3), it is not clear
whether these samples adequately
characterize his exposure conditions
over the course of his work history. He
reported that early in his work history,
containers of beryllium oxide powder
were transported on the trucks he
entered. While he did not recall seeing
any breaks or leaks in the beryllium
oxide containers, some containers were
known to have been punctured by
forklifts on trailers used by the company
during the period of his employment,
and could have contaminated trucks he
entered. With 22 years of employment at
the facility, this worker had begun
beryllium-related work earlier and
performed it longer than about 90
percent of the study population (Stanton
et al., 2006).
h. Nuclear Weapons Production
Facilities & Cleanup of Former Facilities
Primary exposure from nuclear
weapons production facilities comes
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from beryllium metal and beryllium
alloys. A study conducted by Kreiss et
al. (1989) documented sensitization and
CBD among beryllium-exposed workers
in the nuclear industry. A company
medical department identified 58
workers with beryllium exposure among
a work force of 500, of whom 51 (88
percent) participated in the study.
Twenty-four workers were involved in
research and development (R&D), while
the remaining 27 were production
workers. The R&D workers had a longer
tenure with a mean time from first
exposure of 21.2 years, compared to a
mean time since first exposure of 5
years among the production workers.
The number of workers with abnormal
BeLPT readings was 6, with 4 being
diagnosed with CBD. This resulted in an
estimated 11.8 percent prevalence of
sensitization.
Kreiss et al. (1993) expanded the work
of Kreiss et al. (1989) by performing a
cross-sectional study of 895 (current and
former) beryllium workers in the same
nuclear weapons plant. Participants
were placed in qualitative exposure
groups (‘‘no exposure,’’ ‘‘minimal
exposure,’’ ‘‘intermittent exposure,’’ and
‘‘consistent exposure’’) based on
questionnaire responses. The number of
workers with abnormal BeLPT totaled
18 with 12 being diagnosed with CBD.
Three additional workers with
sensitization developed CBD over the
next 2 years. Sensitization occurred in
all of the qualitatively defined exposure
groups. Individuals who had worked as
machinists were statistically
overrepresented among berylliumsensitized cases, compared with noncases. Cases were more likely than noncases to report having had a measured
overexposure to beryllium (p = 0.009),
a factor which proved to be a significant
predictor of sensitization in logistic
regression analyses, as was exposure to
beryllium prior to 1970. Beryllium
sensitized cases were also significantly
more likely to report having had cuts
that were delayed in healing (p = 0.02).
The authors concluded that individual
variability and susceptibility along with
exposure circumstances are important
factors in developing beryllium
sensitization and CBD.
In 1991, the Beryllium Health
Surveillance Program (BHSP) was
established at the Rocky Flats Nuclear
Weapons Facility to offer BLPT
screening to current and former
employees who may have been exposed
to beryllium (Stange et al., 1996).
Participants received an initial BeLPT
and follow-ups at one and three years.
Based on histologic evidence of
pulmonary granulomas and a positive
BAL-BeLPT, Stange et al. published a
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study of 4,397 BHSP participants tested
from June 1991 to March 1995,
including current employees (42.8
percent) and former employees (57.2
percent). Twenty-nine cases of CBD and
76 cases of sensitization were identified.
The sensitization rate for the population
was 2.43 percent. Available exposure
data included fixed airhead (FAH)
exposure samples collected between
1970 and 1988 (mean concentration
0.016 mg/m3) and personal samples
collected between 1984 and 1987 (mean
concentration 1.04 mg/m3). Cases of CBD
and sensitization were noted in
individuals in all jobs classifications,
including those believed to involve
minimal exposure to beryllium. The
authors recommended ongoing
surveillance for workers in all jobs with
potential for beryllium exposure.
Stange et al. (2001) extended the
previous study, evaluating 5,173
participants in the Rocky Flats BHSP
who were tested between June 1991 and
December 1997. Three-year serial testing
was offered to employees who had not
been tested for three years or more and
did not show beryllium sensitization
during the previous study. This resulted
in 2,891 employees being tested. Of the
5,173 workers participating in the study,
172 were found to have abnormal
BeLPT. Ninety-eight (3.33 percent) of
the workers were found to be sensitized
(confirmed abnormal BeLPT results) in
the initial screening, conducted in 1991.
Of these workers 74 were diagnosed
with CBD (history of beryllium
exposure, evidence of non-caseating
granulomas or mononuclear cell
infiltrates on lung biopsy, and a positive
BeLPT or BAL-BeLPT). A follow-up
survey of 2,891 workers three years later
identified an additional 56 sensitized
workers and an additional seven cases
of CBD. Sensitization and CBD rates
were analyzed with respect to gender,
building work locations, and length of
employment. Historical employee data
included hire date, termination date,
leave of absences, and job title changes.
Exposure to beryllium was determined
by job categories and building or work
area codes. Personal beryllium air
monitoring results were used, when
available, from employees with the
same job title or similar job. However,
no quantitative information was
presented in the study. The authors
conclude that for some individuals,
exposure to beryllium at levels less that
the OSHA PEL could cause sensitization
and CBD.
Viet et al. (2001) conducted a casecontrol study of the Rocky Flats worker
population studied by Stange et al.
(1996 and 2001) to examine the
relationship between estimated
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beryllium exposure level and risk of
sensitization or CBD. The worker
population included 74 berylliumsensitized workers and 50 workers
diagnosed with CBD. Beryllium
exposure levels were estimated based on
FAH airhead samples from one
building, the beryllium machine shop.
These were collected away from the BZ
of the machine operator and likely
underestimated exposure. To estimate
levels in other locations, these air
sample concentrations were used to
construct a job exposure matrix that
included the determination of the
Building 444 exposure estimates for a
30-year period; each subject’s work
history by job location, task, and time
period; and assignment of exposure
estimates to each combination of job
location, task, and time period as
compared to Building 444 machinists.
The authors adjusted the levels
observed in the machine shop by factors
based on interviews with former
workers. Workers’ estimated mean
exposure concentrations ranged from
0.083 mg/m3 to 0.622 mg/m3. Estimated
maximum air concentrations ranged
from 0.54 mg/m3 to 36.8 mg/m3. Cases
were matched to controls of the same
age, race, gender, and smoking status
(Viet et al., 2001).
Estimated mean and cumulative
exposure levels and duration of
employment were found to be
significantly higher for CBD cases than
for controls. Estimated mean exposure
levels were significantly higher for
sensitization cases than for controls. No
significant difference was observed for
estimated cumulative exposure or
duration of exposure. Similar results
were found using logistic regression
analysis, which identified statistically
significant relationships between CBD
and both cumulative and mean
estimated exposure, but did not find
significant relationships between
estimated exposure levels and
sensitization without CBD. Comparing
CBD with sensitization cases, Viet et al.
found that workers with CBD had
significantly higher estimated
cumulative and mean beryllium
exposure levels than workers who were
sensitized, but did not have CBD.
Johnson et al. (2001) conducted a
review of personal sampling records and
medical surveillance reports at an
atomic weapons establishment in
Cardiff, United Kingdom. The study
evaluated airborne samples collected
over the 36-year period of operation for
the plant. Data included 367,757 area
samples and 217,681 personal lapel
samples from 194 workers over the time
period from 1981–1997. Data was
available prior to this time period but
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was not analyzed since this data was not
available electronically. The authors
estimated that over the 17 years of
measurement data analyzed, airborne
beryllium concentrations did exceed 2.0
mg/m3, however, due to the limitations
with regard to collection times it is
difficult to assess the full reliability of
this estimate. The authors noted that in
the entire plant’s history, only one case
of CBD had been diagnosed. It was also
noted that BeLPT has not been routinely
conducted among any of the workers at
this facility.
Armojandi et al. (2010) conducted a
cross-sectional study of workers at a
nuclear weapons research and
development (R&D) facility to determine
the risk of developing CBD in sensitized
workers at facilities with exposures
much lower than production plants. Of
the 1875 current or former workers at
the R&D facility, 59 were determined to
be sensitized based on at least two
positive BeLPTs (i.e., samples drawn on
two separate occasions or on split
samples tested in two separate DOEapproved laboratories) for a
sensitization rate of 3.1 percent.
Workers found to have positive BeLPTs
were further evaluated in an
Occupational Medicine Clinic between
1999 through 2005. Armojandi et al.
(2010) evaluated 50 of the sensitized
workers who also had medical and
occupational histories, physical
examination, chest imaging with highresolution computed tomography
(HRCT) (N = 49), and pulmonary
function testing (nine of the 59 workers
refused physical examinations so were
not included in this study). Forty of the
50 workers chosen for this study
underwent bronchoscopy for
bronchoalveolar lavage and
transbronchial biopsies in additional to
the other testing. Five of the 49 workers
had CBD at the time of evaluation
(based on histology or high-resolution
computed tomography); three others
had evidence of probable CBD; however,
none of these cases were classified as
severe at the time of evaluation. The rate
of CBD at the time of study among
sensitized individuals was 12.5 percent
(5/40) for those using pathologic review
of lung tissue, and 10.2 percent (5/49)
for those using HRCT as a criteria for
diagnosis. The rate of CBD among the
entire population (5/1875) was 0.3
percent.
The mean duration of employment at
the facility was 18 years, and the mean
latency period (from first possible
exposure) to time of evaluation and
diagnosis was 32 years. There was no
available exposure monitoring in the
breathing zone of workers at the facility
but the beryllium levels were believed
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to be relatively low (possibly less than
0.1 mg/m3 for most jobs). There was not
an apparent exposure-response
relationship for sensitization or CBD.
The sensitization prevalence was
similar and the CBD prevalence higher
among workers with the lower-exposure
jobs. The authors concluded that these
sensitized workers, who were subjected
to an extended duration of low potential
beryllium exposures over a long latency
period, had a low prevalence of CBD
(Armojandi et al., 2010).
i. Aluminum Smelting
Bauxite ore, the primary source of
aluminum, contains naturally occurring
beryllium. Worker exposure to
beryllium can occur at aluminum
smelting facilities where aluminum
extraction occurs via electrolytic
reduction of aluminum oxide into
aluminum metal. Characterization of
beryllium exposures and sensitization
prevalence rates were examined by
Taiwo et al. (2010) in a study of nine
aluminum smelting facilities from four
different companies in the U.S., Canada,
Italy and Norway.
Of the 3,185 workers determined to be
potentially exposed to beryllium, 1,932
agreed to participate in a medical
surveillance program between 2000 and
2006 (60 percent participation rate). The
medical surveillance program included
serum BeLPT analysis, confirmation of
an abnormal BeLPT with a second
BeLPT, and follow-up of all confirmed
positive responses by a pulmonary
physician to evaluate for progression to
CBD.
Eight-hour TWAs were assessed
utilizing 1,345 personal samples
collected from the 9 smelters. The
personal beryllium samples obtained
showed a range of 0.01–13.00 mg/m3
time-weighted average with an
arithmetic mean of 0.25 mg/m3 and
geometric mean of 0.06 mg/m3. Exposure
levels to beryllium observed in
aluminum smelters are similar to those
seen in other industries that utilize
beryllium. Of the 1,932 workers
surveyed by BeLPT, nine workers were
diagnosed with sensitization
(prevalence rate of 0.47 percent, 95%
confidence interval = 0.21–0.88 percent)
with 2 of these workers diagnosed with
probable CBD after additional medical
evaluations.
The authors concluded that compared
with beryllium-exposed workers in
other industries, the rate of sensitization
among aluminum smelter workers
appears lower. The authors speculated
that this lower observed rate could be
related to a more soluble form of
beryllium found in the aluminum
smelting work environment as well as
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the consistent use of respiratory
protection. However, the authors also
speculated that the 60 percent
participation rate may have
underestimated the sensitization rate in
this worker population.
A study by Nilsen et al. (2010) also
found a low rate of sensitization among
aluminum workers in Norway. Threehundred sixty-two workers and thirtyone control individuals were tested for
beryllium sensitization based on the
BeLPT. The results found that one
(0.28%) of the smelter workers had been
sensitized. No borderline results were
reported. The exposure estimated in this
plant was 0.1 mg/m3 to 0.31 mg/m3
(Nilsen et al., 2010).
6. Animal Models of CBD
This section reviews the relevant
animal studies supporting the
mechanisms outlined above.
Researchers have attempted to identify
animal models with which to further
investigate the mechanisms underlying
the development of CBD. A suitable
animal model should exhibit major
characteristics of CBD, including the
demonstration of a beryllium-specific
immune response, the formation of
immune granulomas following
inhalation exposure to beryllium, and
mimicking the progressive nature of the
human disease. While exposure to
beryllium has been shown to cause
chronic granulomatous inflammation of
the lung in animal studies using a
variety of species, most of the
granulomatous lesions were formed by
foreign-body reactions, which result
from persistent irritation and consist
predominantly of macrophages and
monocytes, and small numbers of
lymphocytes. Foreign-body granulomas
are distinct from the immune
granulomas of CBD, which are caused
by antigenic stimulation of the immune
system and contain large numbers of
lymphocytes. Animal studies have been
useful in providing biological
plausibility for the role of
immunological alterations and lung
inflammation and in clarifying certain
specific mechanistic aspects of
beryllium disease. However, the lack of
a dependable animal model that mimics
all facets of the human response
combined with study limitations in
terms of single dose experiments, few
animals, or abbreviated observation
periods have limited the utility of the
data. Currently, no single model has
completely mimicked the disease
process as it progresses in humans. The
following is a discussion of the most
relevant animal studies regarding the
mechanisms of sensitization and CBD
development in humans. Table A.2 in
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the Appendix summarizes species,
route, chemical form of beryllium, dose
levels, and pathological findings of the
key studies.
Harmsen et al. performed a study to
assess whether the beagle dog could
provide an adequate model for the study
of beryllium-induced lung diseases
(Harmsen et al., 1986). One group of
dogs served as a control group (air
inhalation only) and four other groups
received high (approximately 50 mg/kg)
and low (approximately 20 mg/kg) doses
of beryllium oxide calcined at 500 °C or
1,000° C, administered as aerosols in a
single exposure. As discussed above,
calcining temperature controls the
solubility and SSA of beryllium
particles. Those particles calcined at
higher temperatures (e.g., 1,000° C) are
less soluble and have lower SSA than
particles calcined at lower temperatures
(e.g., 500 °C). Solubility and SSA are
factors in determining the toxic
potential of beryllium compounds or
materials.
Cells were collected from the dogs by
BAL at 30, 60, 90, 180, and 210 days
after exposure, and the percentages of
neutrophils and lymphocytes were
determined. In addition, the mitogenic
responses of blood lymphocytes and
lavage cells collected at 210 days were
determined with either
phytohemagglutinin or beryllium sulfate
as mitogen. The percentage of
neutrophils in the lavage fluid was
significantly elevated only at 30 days
with exposure to either dose of 500 °C
beryllium oxide. The percentage of
lymphocytes in the fluid was
significantly elevated in samples across
all times with exposure to the high dose
of this beryllium oxide form. Beryllium
oxide calcined at 1,000° C elevated
lavage lymphocytes only in high dose at
30 days. No significant effect of 1,000°
C beryllium oxide exposure on
mitogenic response of any lymphocytes
was seen. In contrast, peripheral blood
lymphocytes from the 500 °C beryllium
oxide exposed groups were significantly
stimulated by beryllium sulfate
compared with the phytohemagglutinin
exposed cells. The investigators in this
study were able to replicate some of the
same findings as those observed in
human studies—specifically, that
beryllium in soluble and insoluble
forms can be mitogenic to immune cells,
an important finding for progression of
sensitization and proliferation of
immune cells to developing full-blown
CBD.
In another beagle study Haley et al.
also found that the beagle dog appears
to model some aspects of human CBD
(Haley et al., 1989). The authors
monitored lung pathologic effects,
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particle clearance, and immune
sensitization of peripheral blood
leukocytes following a single exposure
to beryllium oxide aerosol generated
from beryllium oxide calcined at 500 °C
or 1,000° C. The aerosol was
administered to the dogs perinasally to
attain initial lung burdens of 6 or 18 mg
beryllium/kg body weight.
Granulomatous lesions and lung
lymphocyte responses consistent with
those observed in humans with CBD
were observed, including perivascular
and peribronchiolar infiltrates of
lymphocytes and macrophages,
progressing to microgranulomas with
areas of granulomatous pneumonia and
interstitial fibrosis. Beryllium specificity
of the immune response was
demonstrated by positive results in the
BeLPT, although there was considerable
inter-animal variation. The lesions
declined in severity after 64 days postexposure. Thus, while this model was
able to mimic the formation of Bespecific immune granulomas, it was not
able to mimic the progressive nature of
disease.
This study also provided an
opportunity to compare the effects of
beryllium oxide calcination temperature
on granulomatous disease in the beagle
respiratory system. Haley et al. found an
increase in the percentage and numbers
of lymphocytes in BAL fluid at 3
months post-exposure in dogs exposed
to either dose of beryllium oxide
calcined at 500 °C, but not in dogs
exposed to the material calcined at the
higher temperature. Although there was
considerable inter-animal variation,
lesions were generally more severe in
the dogs exposed to material calcined at
500 °C. Positive BeLPT results were
observed with BAL lymphocytes only in
the group with a high initial lung
burden of the material calcined at 500
°C, but positive results with peripheral
blood lymphocytes were observed at
both doses with material calcined at
both temperatures.
The histologic and immunologic
responses of canine lungs to aerosolized
beryllium oxide were investigated in
another Haley et al. (1989) study.
Beagle-dogs were exposed in a single
exposure to high dose (50 mg/kg of body
weight) or low dose (l7 mg/kg) levels of
beryllium oxide calcined at either 500°
or 1000° C. One group of dogs was
examined up to 365 days after exposure
for lung histology and biochemical
assay to determine the fate of inhaled
beryllium oxide. A second group
underwent BAL for lung lymphocyte
analysis for up to 22 months after
exposure. Histopathologic examination
revealed peribronchiolar and
perivascular lymphocytic histiocytic
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inflammation, peaking at 64 days after
beryllium oxide exposure. Lymphocytes
were initially well differentiated, but
progressed to lymphoblastic cells and
aggregated in lymphofollicular nodules
or microgranulomas over time. Alveolar
macrophages were large, and filled with
intracytoplasmic material. Cortical and
paracortical lymphoid hyperplasia of
the tracheobronchial nodes was found.
Lung lymphocyte concentrations were
increased at 3 months and returned to
normal in both dose groups given 500 °C
treated beryllium chloride. No
significant elevations in lymphocyte
concentrations were found in dogs given
1,000° C treated beryllium oxide. Lung
retention was higher in the 500 °C
treated beryllium oxide group. The
lesions found in dog lungs closely
resembled those found in humans with
CBD: severe granulomas, lymphoblast
transformation, increased pulmonary
lymphocyte concentrations and
variation in beryllium sensitivity. It was
concluded that the canine model for
berylliosis may provide insight into this
disease.
In a follow-up experiment, control
dogs and those exposed to beryllium
oxide calcined at 500 °C were allowed
to rest for 2.5 years, and then re-exposed
to filtered air (controls) or beryllium
oxide calcined at 500 °C for an initial
lung burden (ILB) target of 50 mg
beryllium oxide/kg body weight (Haley
et al., 1992). Immune responses of blood
and BAL lymphocytes, and lung lesions
in dogs sacrificed 210 days postexposure, were compared with results
following the initial exposure. The
severity of lung lesions was comparable
under both conditions, suggesting that a
2.5-year interval was sufficient to
prevent cumulative pathologic effects.
Conradi et al. (1971) found no exposurerelated histological alterations in the
lungs of six beagle dogs exposed to a
range of 3,300–4,380 mg Be/m3 as
beryllium oxide calcined at 1,400° C for
30 min, once per month for 3 months.
Because the dogs were sacrificed 2 years
post-exposure, the long time period
between exposure and response may
have allowed for the reversal of any
beryllium-induced changes (EPA, 1998).
A 1994 study by Haley et al. showed
that intra-bronchiolar instillation of
beryllium induced immune granulomas
and sensitization in monkeys. Haley et
al. (1994) exposed male cynomolgus
monkeys to either beryllium metal or
beryllium oxide calcined at 500 °C by
intrabronchiolar instillation as a saline
suspension. Lymphocyte counts in BAL
fluid were observed, and were found to
be significantly increased in monkeys
exposed to beryllium metal on postexposure days 14 to 90, and on post-
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exposure day 60 in monkeys exposed to
beryllium oxide. The lungs of monkeys
exposed to beryllium metal had lesions
characterized by interstitial fibrosis,
Type II cell hyperplasia, and
lymphocyte infiltration. Some monkeys
also exhibited immune granulomas.
Similar lesions were observed in
monkeys exposed to beryllium oxide,
but the incidence and severity were
much less. BAL lymphocytes from
monkeys exposed to beryllium metal,
but not from monkeys exposed to
beryllium oxide, proliferated in
response to beryllium sulfate in the
BeLPT (EPA, 1998).
In an experiment similar to the one
conducted with dogs, Conradi et al.
(1971) found no effect in monkeys
(Macaca irus) exposed via whole-body
inhalation for three 30-minute monthly
exposures to a range of 3,300–4,380 mg
Be/m3 as beryllium oxide calcined at
1,400° C. The lack of effect may have
been related to the long period (2 years)
between exposure and sacrifice, or to
low toxicity of beryllium oxide calcined
at such a high temperature.
As discussed earlier in this Health
Effects section, at the cellular level,
beryllium dissolution must occur for
either a dendritic cell or a macrophage
to present beryllium as an antigen to
induce the cell-mediated CBD immune
reactions (Stefaniak et al., 2006). Several
studies have shown that low-fired
beryllium oxide, which is
predominantly made up of poorly
crystallized small particles, is more
immunologically reactive than
beryllium oxide calcined at higher firing
temperatures that result in less
reactivity due to increasing crystal size.
As discussed previously, Haley et al.
(1989a) found more severe lung lesions
and a stronger immune response in
beagle dogs receiving a single inhalation
exposure to beryllium oxide calcined at
500 °C than in dogs receiving an
equivalent initial lung burden of
beryllium oxide calcined at 1,000° C.
Haley et al. found that beryllium oxide
calcined at 1,000° C elicited little local
pulmonary immune response, whereas
the much more soluble beryllium oxide
calcined at 500 °C produced a
beryllium-specific, cell-mediated
immune response in dogs (Haley et al.,
1991).
In a later study, beryllium metal
appeared to induce a greater toxic
response than beryllium oxide following
intrabronchiolar instillation in
cynomolgus monkeys, as evidenced by
more severe lung lesions, a larger effect
on BAL lymphocyte counts, and a
positive response in the BeLPT with
BAL lymphocytes only after exposure to
beryllium metal (Haley et al., 1994).
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Because an oxide layer may form on
beryllium-metal surfaces after exposure
to air (Mueller and Adolphson, 1979;
Harmsen et al., 1986) dissolution of
small amounts of poorly soluble
beryllium compounds in the lungs
might be sufficient to allow persistent
low-level beryllium presentation to the
immune system (NAS, 2008).
Genetic studies in humans led to the
creation of an animal model containing
different human HLA–DP alleles
inserted into FVB/N mice for
mechanistic studies of CBD. Three
strains of genetically engineered mice
(transgenic mice) were created that
conferred different risks for developing
CBD based on human studies (Weston et
al., 2005; Snyder et al., 2008): (1) the
HLDPB1*401 transgenic strain, where
the transgene codes for lysine residue at
the 69th position of the B-chain
conferred low risk of CBD; (2) the HLA–
DPB1*201 mice, where the transgene
codes for glutamic acid residue at the
69th position of the B-chain and glycine
residues at positions 84 and 85
conferred medium risk of CBD; and (3)
the HLA–DPB1*1701 mice, where the
transgene codes for glutamic acid at the
69th position of the B-chain and
aspartic acid and glutamic acid residues
at positions 84 and 85, respectively,
conferred high risk of CBD (TarantinoHutchinson et al., 2009).
In order to validate the transgenic
model, Tarantino-Hutchison et al.
challenged the transgenic mice along
with seven different inbred mouse
strains to determine the susceptibility
and sensitivity to beryllium exposure.
Mice were dermally exposed with either
saline or beryllium, then challenged
with either saline or beryllium (as
beryllium sulfate) using the MEST
protocol (mouse ear-swelling test). The
authors determined that the high risk
HLA–DPB1*1701 transgenic strain
responded 4 times greater (as measured
via ear swelling) than control mice and
at least 2 times greater than other strains
of mice. The findings correspond to
epidemiological study results reporting
an enhanced CBD odds ratio for the
HLA–DPB1*1701 in humans (Weston et
al., 2005; Snyder et al., 2008).
Transgenic mice with the genes
corresponding to the low and medium
odds ratio study did not respond
significantly over the control group. The
authors concluded that while HLA–
DPB1*1701 is important to beryllium
sensitization and progression to CBD,
other genetic and environmental factors
contribute to the disease process as
well.
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7. Preliminary Beryllium Sensitization
and CBD Conclusions
It is well-established that skin and
inhalation exposure to beryllium may
lead to sensitization and that inhalation
exposure, or skin exposure coupled
with inhalation exposure, may lead to
the onset and progression of CBD. This
is supported by extensive human
studies. While all facets of the biological
mechanism for this complex disease
have yet to be fully elucidated, many of
the key events in the disease sequence
have been identified and described in
the previous sections. Sensitization is a
necessary first step to the onset of CBD
(NAS, 2008). Sensitization is the process
by which the immune system recognizes
beryllium as a foreign substance and
responds in a manner that may lead to
development of CBD. It has been
documented that a substantial
proportion of sensitized workers
exposed to airborne beryllium progress
to CBD (Rosenman et al., 2005; NAS,
2008; Mroz et al., 2009). Animal studies,
particularly in dogs and monkeys, have
provided supporting evidence for T-cell
lymphocyte proliferation in the
development of granulomatous lung
lesions after exposure to beryllium
(Harmsen et al., 1986; Haley et al., 1989,
1992, 1994). The animal studies have
also provided important insights into
the roles of chemical form, genetic
susceptibility, and residual lung burden
in the development of beryllium lung
disease (Harmsen et al., 1986; Haley et
al., 1992; Tarantino-Hutchison et al.,
2009). OSHA has made a preliminary
determination to consider sensitization
and CBD to be adverse events along the
pathological continuum in the disease
process, with sensitization being the
necessary first step in the progression to
CBD.
The epidemiological evidence
presented in this section demonstrates
that sensitization and CBD are
continuing to occur from present-day
exposures below OSHA’s PEL
(Rosenman, 2005 with erratum
published 2006). The available literature
discussed above shows that disease
prevalence can be reduced by reducing
inhalation exposure (Thomas et al.,
2009). However, the available
epidemiological studies also indicate
that it may be necessary to minimize
skin exposure to further reduce the
incidence of sensitization (Bailey et al.,
2010). The preliminary risk assessment
further discusses the effectiveness of
interventions to reduce beryllium
exposures and the risk of sensitization
and CBD (see section VI, Preliminary
Risk Assessment).
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Studies have demonstrated there
remains a prevalence of sensitization
and CBD in facilities with exposure
levels below the current OSHA PEL
(Rosenman et al., 2005; Thomas et al.,
2009), that risk of sensitization and CBD
appears to vary across industries and
processes (Deubner et al., 2001; Kreiss et
al., 1997; Newman et al., 2001;
Henneberger et al., 2001; Schuler et al.,
2005; Stange et al., 2001; Taiwo et al.,
2010), and that efforts to reduce
exposure have succeeded in reducing
the frequency of beryllium sensitization
and CBD (Bailey et al., 2010) (See Table
A–1 in the Appendix).
Of workers who were found to be
sensitized and underwent clinical
evaluation, 20–49 percent were
diagnosed with CBD (Kreiss et al., 1993;
Newman, 1996, 2005 and 2007; Stange
et al., 2001). Overall prevalence of CBD
in cross-sectional screenings ranges
from 0.6 to 8 percent (Kreiss et al.,
2007). A study by Newman (2005)
estimated from ongoing surveillance of
sensitized individuals, with an average
follow-up time of 6 years, that 31
percent of beryllium-exposed employees
progressed to CBD (Newman, 2005).
However, Newman (2005) went on to
suggest that if follow-up times were
increased the rate of progression from
sensitization to CBD could be much
higher. A study of nuclear weapons
facility employees enrolled in an
ongoing medical surveillance program
found that only about 20 percent of
sensitized individuals employed less
than five years eventually were
diagnosed with CBD, while 40 percent
of sensitized employees employed ten
years or more developed CBD (Stange et
al., 2001) indicating length of exposure
may play a role in further development
of the disease. In addition, Mroz et al.
(2009) conducted a longitudinal study
of individuals clinically evaluated at
National Jewish Health (between 1982
and 2002) who were identified as
having sensitization and CBD through
workforce medical surveillance. The
authors identified 171 cases of CBD and
229 cases of sensitization; all
individuals were identified through
workplace screening using the BeLPT
(Mroz et al., 2009). Over the 20-year
study period, 8.8 percent (i.e., 22 cases
out 251 sensitized) of individuals with
sensitization went on to develop CBD.
The findings from this study indicated
that on the average span of time from
initial beryllium exposure to CBD
diagnosis was 24 years (Mroz et al.,
2009).
E. Beryllium Lung Cancer Section
Beryllium exposure has been
associated with a variety of adverse
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health effects including lung cancer.
The potential for beryllium and its
compounds to cause cancer has been
previously assessed by various other
agencies (EPA, ATSDR, NAS, NIEHS,
and NIOSH) with each agency
identifying beryllium as a potential
carcinogen. In addition, the
International Agency for Research on
Cancer (IARC) did an extensive
evaluation in 1993 and reevaluation in
April 2009 (IARC, 2012). In brief, IARC
determined beryllium and its
compounds to be carcinogenic to
humans (Group 1 category), while EPA
considers beryllium to be a probable
human carcinogen (EPA, 1998), and the
National Toxicology Program (NTP) has
determined beryllium and its
compounds to be known carcinogens
(NTP, 2014). OSHA has conducted an
independent evaluation of the
carcinogenic potential of beryllium and
these compounds as well. The following
is a summary of the studies used to
support the Agency findings that
beryllium and its compounds are
human carcinogens.
1. Genotoxicity Studies
Genotoxicity can be an important
indicator for screening the potential of
a material to induce cancer and an
important mechanism leading to tumor
formation and carcinogenesis. In a
review conducted by the National
Academy of Science, beryllium and its
compounds have tested positively in
nearly 50 percent of the genotoxicity
studies conducted without exogenous
metabolic activity. However, they were
found to be non-genotoxic in most
bacterial assays (NAS, 2008).
Gene mutations have been observed
in mammalian cells cultured with
beryllium chloride in a limited number
of studies (EPA, 1998; ATSDR, 2002;
Gordon and Bowser, 2003). Culturing
mammalian cells with beryllium
chloride, beryllium sulfate, or beryllium
nitrate has resulted in clastogenic
alterations. However, most studies have
found that beryllium chloride,
beryllium nitrate, beryllium sulfate, and
beryllium oxide did not induce gene
mutations in bacterial assays with or
without metabolic activation. In the case
of beryllium sulfate, all mutagenicity
studies (Ames (Simmon, 1979; Dunkel
et al., 1984; Arlauskas et al., 1985;
Ashby et al., 1990); E. coli pol A
(Rosenkranz and Poirer, 1979); E. coli
WP2 uvr A (Dunkel et al., 1984) and
Saccharomyces cerevisiae (Simmon,
1979)) were negative with the exception
of results reported for Bacillus subtilis
rec assay (Kada et al., 1980; Kanematsu
et al., 1980; EPA, 1998). Beryllium
sulfate did not induce unscheduled
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DNA synthesis in primary rat
hepatocytes and was not mutagenic
when injected intraperitoneally in adult
mice in a host-mediated assay using
Salmonella typhimurium (Williams et
al., 1982).
Beryllium nitrate was negative in the
Ames assay (Tso and Fung, 1981;
Kuroda et al., 1991) but positive in a
Bacillus subtilis rec assay (Kuroda et al.,
1991). Beryllium chloride was negative
in a variety of studies (Ames (Ogawa et
al., 1987; Kuroda et al., 1991); E. coli
WP2 uvr A (Rossman and Molina,
1984); and Bacillus subtilis rec assay
(Nishioka, 1975)). In addition, beryllium
chloride failed to induce SOS DNA
repair in E. coli (Rossman et al., 1984).
However, positive results were reported
for Bacillus subtilis rec assay using
spores (Kuroda et al., 1991), E. coli
KMBL 3835; lacI gene (Zakour and
Glickman, 1984), and hprt locus in
Chinese hamster lung V79 cells (Miyaki
et al., 1979). Beryllium oxide was
negative in the Ames assay and Bacillus
subtilis rec assays (Kuroda et al., 1991;
EPA, 1998).
Gene mutations have been observed
in mammalian cells (V79 and CHO)
cultured with beryllium chloride
(Miyaki et al., 1979; Hsie et al., 1979a,
b), and culturing of mammalian cells
with beryllium chloride (Vegni-Talluri
and Guiggiani, 1967), and beryllium
sulfate (Brooks et al., 1989; Larramendy
et al., 1981) has resulted in clastogenic
alterations—producing breakage or
disrupting chromosomes (EPA, 1998).
Beryllium chloride evaluated in a
mouse model indicated increased DNA
strand breaks and the formation of
micronuclei in bone marrow (Attia et
al., 2013).
Data on the in vivo genotoxicity of
beryllium are limited to a single study
that found beryllium sulfate (1.4 and 2.3
g/kg, 50 percent and 80 percent of
median lethal dose) administered by
gavage did not induce micronuclei in
the bone marrow of CBA mice.
However, a marked depression of
erythropoiesis (red blood cell
production) was suggestive of bone
marrow toxicity which was evident 24
hours after dosing. No mutations were
seen in p53 or c-raf-1 and only weak
mutations were detected in K-ras in
lung carcinomas from F344/N rats given
a single nose-only exposure to beryllium
metal (Nickell-Brady et al., 1994). The
authors concluded that the mechanisms
for the development of lung carcinomas
from inhaled beryllium in the rat do not
involve gene dysfunctions commonly
associated with human non-small-cell
lung cancer (EPA, 1998).
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2. Human Epidemiological Studies
This section reviews in greater detail
the studies used to support the
mechanistic findings for berylliuminduced cancer. Table A.3 in the
Appendix summarizes the important
features and characteristics of each
study.
a. Beryllium Case Registry (BCR).
Two studies evaluated participants in
the BCR (Infante et al., 1980; Steenland
and Ward, 1991). Infante et al. (1980)
evaluated the mortality patterns of
white male participants in the BCR
diagnosed with non-neoplastic
respiratory symptoms of beryllium
disease. Of the 421 cases evaluated, 7 of
the participants had died of lung cancer.
Six of the deaths occurred more than 15
years after initial beryllium exposure.
The duration of exposure for 5 of the 7
participants with lung cancer was less
than 1 year, with the time since initial
exposure ranging from 12 to 29 years.
One of the participants was exposed for
4 years with a 26-year interval since the
initial exposure. Exposure duration for
one participant diagnosed with
pulmonary fibrosis could not be
determined; however, it had been 32
years since the initial exposure. Based
on BCR records, the participants were
classified as being in the acute
respiratory group (i.e., those diagnosed
with acute respiratory illness at the time
of entry in the registry) or the chronic
respiratory group (i.e., those diagnosed
with pulmonary fibrosis or some other
chronic lung condition at the time of
entry into the BCR). The 7 participants
with lung cancer were in the BCR
because of diagnoses of acute
respiratory illness. For only one of those
individuals was initial beryllium
exposure less than 15 years prior. Only
1 of the 6 (with greater than 15 years
since initial exposure to beryllium) had
been diagnosed with chronic respiratory
disease. The study did not report
exposure concentrations or smoking
habits. The authors concluded that the
results of this cohort agreed with
previous animal studies and with
epidemiological studies demonstrating
an increased risk of lung cancer in
workers exposed to beryllium.
Steenland and Ward (1991) extended
the work of Infante et al. (1980) to
include females and to include 13
additional years of follow-up. At the
time of entry in the BCR, 93 percent of
the women in the study, but only 50
percent of the men, had been diagnosed
with CBD. In addition, 61 percent of the
women had worked in the fluorescent
tube industry and 50 percent of the men
had worked in the basic manufacturing
industry. A total of 22 males and 6
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females died of lung cancer. Of the 28
total deaths from lung cancer, 17 had
been exposed to beryllium for less than
4 years and 11 had been exposed for
greater than 4 years. The study did not
report exposure concentrations. Survey
data collected in 1965 provided
information on smoking habits for 223
cohort members (32 percent), on the
basis of which the authors suggested
that the rate of smoking among workers
in the cohort may have been lower than
U.S. rates. The authors concluded that
there was evidence of increased risk of
lung cancer in workers exposed to
beryllium and diagnosed with beryllium
disease.
b. Beryllium Manufacturing and/or
Processing Plants (Extraction,
Fabrication, and Processing)
Several epidemiological cohort
studies have reported excess lung
cancer mortality among workers
employed in U.S. beryllium production
and processing plants during the 1930s
to 1960s. The largest and most
comprehensive study investigated the
mortality experience of 9,225 workers
employed in seven different beryllium
processing plants over a 30-year period
(Ward et al., 1992). The workers at the
two oldest facilities (i.e., Lorain, OH,
and Reading, PA) were found to have
significant excess lung cancer mortality
relative to the U.S. population. Of the
seven plants in the study, these two
plants were believed to have the highest
exposure levels to beryllium. A different
analysis of the lung cancer mortality in
this cohort using various local reference
populations and alternate adjustments
for smoking generally found smaller,
non-significant rates of excess mortality
among the beryllium employees (Levy et
al., 2002). Both cohort studies are
limited by a lack of job history and air
monitoring data that would allow
investigation of mortality trends with
beryllium exposure. The majority of
employees at the Lorain, OH, and
Reading, PA, facilities were employed
for a relatively short period of less than
one year.
Bayliss et al. (1971) performed a
nested cohort study of more than 7,000
former workers from the beryllium
processing industry employed from
1942–1967. Information for the workers
was collected from the personnel files of
participating companies. Of the more
than 7,000 employees, a cause of death
was known for 753 male workers. The
number of observed lung cancer deaths
was 36 compared to 34.06 expected for
a standardized mortality ratio (SMR) of
1.06. When evaluated by the number of
years of employment, 24 of the 36 men
were employed for less than 1 year in
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the industry (SMR = 1.24), 8 were
employed for 1 to 5 years (SMR 1.40),
and 4 were employed for more than 5
years (SMR = 0.54). Half of the workers
who died from lung cancer began
employment in the beryllium
production industry prior to 1947.
When grouped by job classification,
over two thirds of the workers with lung
cancer were in production-related jobs
while the rest were classified as office
workers. The authors concluded that
while the lung cancer mortality rates
were the highest of all other mortality
rates, the SMR for lung cancer was still
within range of the expected based on
death rates in the United States. The
limitations of this study included the
lack of information regarding exposure
concentrations, smoking habits, and the
age and race of the participants.
Mancuso (1970, 1979, 1980) and
Mancuso and El-Attar (1969) performed
a series of occupational cohort studies
on a group of over 3,685 workers
(primarily white males) employed in the
beryllium manufacturing industry
during 1937–1948.3 The beryllium
production facilities were located in
Ohio and Pennsylvania and the records
for the employees, including periods of
employment, were obtained from the
Social Security Administration. These
studies did not include analyses of
mortality by job title or exposure
category. In addition, there were no
exposure concentrations estimated or
adjustments for smoking. The estimated
duration of employment ranged from
less than 1 year to greater than 5 years.
In the most recent study (Mancuso,
1980), employees from the viscose rayon
industry served as a comparison
population. There was a significant
excess of lung cancer deaths based on
the total number of 80 observed lung
cancer mortalities at the end of 1976
compared to an expected number of
57.06 based on the comparison
population resulting in an SMR of 1.40
(p < 0.01) (Mancuso, 1980). There was
a statistically significant excess in lung
cancer deaths for the shortest duration
of employment (< 12 months, p < 0.05)
and the longest duration of employment
(≤ 49 months, p < 0.01). Based on the
results of this study, the author
concluded that the ability of beryllium
to induce cancer in workers does not
require continuous exposure and that it
is reasonable to assume that the amount
of exposure required to produce lung
cancer can occur within a few months
3 The third study (Mancuso et al., 1979) restricted
the cohort to workers employed between 1942 and
1948.
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of exposure regardless of the length of
employment.
Wagoner et al. (1980) expanded the
work of Mancuso (1970; 1979; 1980)
using a cohort of 3,055 white males
from the beryllium extraction,
processing, and fabrication facility
located in Reading, Pennsylvania. The
men included in the study worked at
the facility sometime between 1942 and
1968, and were followed through 1976.
The study accounted for length of
employment. Other factors accounted
for included age, smoking history, and
regional lung cancer mortality. Fortyseven members of the cohort died of
lung cancer compared to an expected
34.29 based on U.S. white male lung
cancer mortality rates (p < .05). The
results of this cohort showed an excess
risk of lung cancer in beryllium-exposed
workers at each duration of employment
(< 5 years and ≥ 5 years), with a
statistically significant excess noted at <
5 years durations of employment and a
≥ 25-year interval since the beginning of
employment (p < 0.05). The study was
criticized by several epidemiologists
(MacMahon, 1978, 1979; Roth, 1983), by
a CDC Review Committee appointed to
evaluate the study, and by one of the
study’s coauthors (Bayliss, 1980) for
inadequate discussion of possible
alternative explanations of excess lung
cancer in the cohort. The specific issues
identified include the use of 1965–1967
U.S. white male lung cancer mortality
rates to generate expected numbers of
lung cancers in the period 1968–1975
and inadequate adjustment for smoking.
Ward et al. (1992) performed a
retrospective mortality cohort study of
9,225 male workers employed at seven
beryllium processing facilities,
including the Ohio and Pennsylvania
facilities studied by Mancuso and ElAttar (1969), Mancuso (1970; 1979;
1980), and Wagoner et al. (1980). The
men were employed for no less than 2
days between January 1940 and
December 1988. At the end of the study
61.1 percent of the cohort was known to
be living and 35.1 percent was known
to be deceased. The duration of
employment ranged from 1 year or less
to greater than 10 years with the largest
percentage of the cohort (49.7 percent)
employed for less than one year,
followed by 1 to 5 years of employment
(23.4 percent), greater than 10 years
(19.1 percent), and 5 to 10 years (7.9
percent). Of the 3,240 deaths, 280
observed deaths were caused by lung
cancer compared to 221.5 expected
deaths, yielding a statistically
significant SMR of 1.26 (p < 0.01).
Information on the smoking habits of
15.9 percent of the cohort members,
obtained from a 1968 Public Health
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Service survey conducted at four of the
plants, was used to calculate a smokingadjusted SMR of 1.12, which was not
statistically significant. The number of
deaths from lung cancer was also
examined by decade of hire. The
authors reported a relationship between
earlier decades of hire and increased
lung cancer risk.
The EPA Integrated Risk Information
System (IRIS), IARC, and California EPA
Office of Environmental Health Hazard
Assessment (OEHHA) have all based
their cancer assessment on the Ward et
al. 1992 study, with supporting data
concerning exposure concentrations
from Eisenbud and Lisson (1983) and
NIOSH (1972), who estimated that the
lower-bound estimate of the median
exposure concentration exceeded 100
mg/m3 and found that concentrations in
excess of 1,000 mg/m3 were common.
The IRIS cancer risk assessment
recalculated expected lung cancers
based on U.S. white male lung cancer
rates (including the period 1968–1975)
and used an alternative adjustment for
smoking. In addition, one individual
with lung cancer, who had not worked
at the plant, was removed from the
cohort. After these adjustments were
made, an elevated rate of lung cancer
was still observed in the overall cohort
(46 cases vs. 41.9 expected cases).
However, based on duration of
employment or interval since beginning
of employment, neither the total cohort
nor any of the subgroups had a
statistically significant excess in lung
cancer (EPA, 1987). Based on their
evaluation of this and other
epidemiological studies, the EPA
characterized the human
carcinogenicity data then available as
‘‘limited’’ but ‘‘suggestive of a causal
relationship between beryllium
exposure and an increased risk of lung
cancer’’ (IRIS database). This report
includes quantitative estimates of risk
that were derived using the information
presented in Wagoner et al. (1980), the
expected lung cancers recalculated by
the EPA, and bounds on presumed
exposure levels.
Levy et al. (2002) questioned the
results of Ward et al. (1992) and
performed a reanalysis of the Ward et al.
data. The Levy et al. reanalysis differed
from the Ward et al. analysis in the
following significant ways. First, Levy et
al. (2002) examined two alternative
adjustments for smoking, which were
based on (1) a different analysis of the
American Cancer Society (ACS) data
used by Ward et al. (1992) for their
smoking adjustment, or (2) results from
a smoking/lung cancer study of veterans
(Levy and Marimont, 1998). Second,
Levy et al. (2002) also examined the
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impact of computing different reference
rates derived from information about the
lung cancer rates in the cities in which
most of the workers at two of the plants
lived. Finally, Levy et al. (2002)
considered a meta-analytical approach
to combining the results across
beryllium facilities. For all of the
alternatives Levy et al. (2002)
considered, except the meta-analysis,
the facility-specific and combined SMRs
derived were lower than those reported
by Ward et al. (1992). Only the SMR for
the Lorain, OH, facility remained
statistically significantly elevated in
some reanalyses. The SMR obtained
when combining over the plants was not
statistically significant in eight of the
nine approaches they examined, leading
Levy et al. (2002) to conclude that there
was little evidence of statistically
significant elevated SMRs in those
plants.
One occupational nested case-control
study evaluated lung cancer mortality in
a cohort of 3,569 male workers
employed at a beryllium alloy
production plant in Reading, PA, from
1940 to 1969 and followed through 1992
(Sanderson et al., 2001). There were a
total of 142 known lung cancer cases
and 710 controls. For each lung cancer
death, 5 age- and race-matched controls
were selected by incidence density
sampling. Confounding effects of
smoking were evaluated. Job history and
historical air measurements at the plant
were used to estimate job-specific
beryllium exposures from the 1930s to
1990s. Calendar-time-specific beryllium
exposure estimates were made for every
job and used to estimate workers’
cumulative, average, and maximum
exposure. Because of the long period of
time required for the onset of lung
cancer, an ‘‘exposure lag’’ was
employed to discount recent exposures
less likely to contribute to the disease.
The cumulative, average, and
maximum beryllium exposure
concentration estimates for the 142
known lung cancer cases were 46.06 ±
9.3mg/m3-days, 22.8 ± 3.4 mg/m3, and
32.4 ± 13.8 mg/m3, respectively. The
lung cancer mortality rate was 1.22 (95
percent CI = 1.03 ¥ 1.43). Exposure
estimates were lagged by 10 and 20
years in order to account for exposures
that did not contribute to lung cancer
because they occurred after the
induction of cancer. In the 10- and 20year lagged exposures the geometric
mean tenures and cumulative exposures
of the lung cancer mortality cases were
higher than the controls. In addition, the
geometric mean and maximum
exposures of the workers were
significantly higher than controls when
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the exposure estimates were lagged 10
and 20 years (p < 0.01).
Results of a conditional logistic
regression analysis indicated that there
was an increased risk of lung cancer in
workers with higher exposures when
dose estimates were lagged by 10 and 20
years. There was also a lack of evidence
that confounding factors such as
smoking affected the results of the
regression analysis. The authors noted
that there was considerable uncertainty
in the estimation of exposure in the
1940’s and 1950’s and the shape of the
dose-response curve for lung cancer.
Another analysis of the study data using
a different statistical method did not
find a significantly greater relative risk
of lung cancer with increasing beryllium
exposures (Levy et al., 2007). The
average beryllium air levels for the lung
cancer cases were estimated to be an
order of magnitude above the current 8hour OSHA TWA PEL (2 mg/m3) and
roughly two orders of magnitude higher
than the typical air levels in workplaces
where beryllium sensitization and
pathological evidence of CBD have been
observed. IARC evaluated this
reanalysis in 2012 and found the study
introduced a downward bias into risk
estimates (IARC, 2012).
Schubauer-Berigan et al. reanalyzed
data from the nested case-control study
of 142 lung cancer cases in the Reading,
PA, beryllium processing plant
(Schubauer-Berigan et al., 2008). This
dataset was reanalyzed using
conditional (stratified by case age)
logistic regression. Independent
adjustments were made for potential
confounders of birth year and hire age.
Average and cumulative exposures were
analyzed using the values reported in
the original study. The objective of the
reanalysis was to correct for the known
differences in smoking rates by birth
year. In addition, the authors evaluated
the effects of age at hire to determine
differences observed by Sanderson et al.
in 2001. The effect of birth cohort
adjustment on lung cancer rates in
beryllium-exposed workers was
evaluated by adjusting in a
multivariable model for indicator
variables for the birth cohort quartiles.
Unadjusted analyses showed little
evidence of lung cancer risk associated
with beryllium occupational exposure
using cumulative exposure until a 20year lag was used. Adjusting for either
birth cohort or hire age attenuated the
risk for lung cancer associated with
cumulative exposure. Using a 10- or 20year lag in workers born after 1900 also
showed little evidence of lung cancer
risk, while those born prior to 1900 did
show a slight elevation in risk. Unlagged
and lagged analysis for average exposure
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showed an increase in lung cancer risk
associated with occupational exposure
to beryllium. The finding was consistent
for either workers adjusted or
unadjusted for birth cohort or hire age.
Using a 10-year lag for average exposure
showed a significant effect by birth
cohort.
The authors stated that the reanalysis
indicated that differences in the hire
ages among cases and controls, first
noted by Deubner et al. (2001) and Levy
et al. (2007), were primarily due to the
fact that birth years were earlier among
controls than among cases, resulting
from much lower baseline risk of lung
cancer for men born prior to 1900
(Schubauer-Berigan et al., 2008). The
authors went on to state that the
reanalysis of the previous NIOSH casecontrol study suggested the relationship
observed previously between
cumulative beryllium exposure and
lung cancer was greatly attenuated by
birth cohort adjustment.
Hollins et al. (2009) re-examined the
weight of evidence of beryllium as a
lung carcinogen in a recent publication
(Hollins et al., 2009). Citing more than
50 relevant papers, the authors noted
the methodological shortcomings
examined above, including lack of wellcharacterized historical occupational
exposures and inadequacy of the
availability of smoking history for
workers. They concluded that the
increase in potential risk of lung cancer
was observed among those exposed to
very high levels of beryllium and that
beryllium’s carcinogenic potential in
humans at these very high exposure
levels were not relevant to today’s
industrial settings. IARC performed a
similar re-evaluation in 2009 (IARC,
2012) and found that the weight of
evidence for beryllium lung
carcinogenicity, including the animal
studies described below, still warranted
a Group I classification, and that
beryllium should be considered
carcinogenic to humans.
Schubauer-Berigan et al. (2010)
extended their analysis from a previous
study estimating associations between
mortality risk and beryllium exposure to
include workers at 7 beryllium
processing plants. The study
(Schubauer-Berigan et al., 2010)
followed the mortality incidences of
9,199 workers from 1940 through 2005
at the 7 beryllium plants. JEMs were
developed for three plants in the cohort:
The Reading plant, the Hazleton plant,
and the Elmore plant. The last is
described in Couch et al. 2010.
Including these JEMs substantially
improved the evidence base for
evaluating the carcinogenicity of
beryllium and, and this change
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represents more than an update of the
beryllium cohort. Standardized
mortality ratios (SMRs) were estimated
based on US population comparisons
for lung, nervous system and urinary
tract cancers, chronic obstructive
pulmonary disease (COPD), chronic
kidney disease, and categories
containing chronic beryllium disease
(CBD) and cor pulmonale. Associations
with maximum and cumulative
exposure were calculated for a subset of
the workers.
Overall mortality in the cohort
compared with the US population was
elevated for lung cancer (SMR 1.17;
95% CI 1.08 to 1.28), COPD (SMR 1.23;
95% CI 1.13 to 1.32), and the categories
containing CBD (SMR 7.80; 95% CI 6.26
to 9.60) and cor pulmonale (SMR 1.17;
95% CI 1.08 to 1.26). Mortality rates for
most diseases of interest increased with
time-since-hire. For the category
including CBD, rates were substantially
elevated compared to the US population
across all exposure groups. Workers
whose maximum beryllium exposure
was ≥ 10 mg/m3 had higher rates of lung
cancer, urinary tract cancer, COPD and
the category containing cor pulmonale
than workers with lower exposure.
These studies showed strong
associations for cumulative exposure
(when short-term workers were
excluded), maximum exposure or both.
Significant positive trends with
cumulative exposure were observed for
nervous system cancers (p = 0.0006)
and, when short-term workers were
excluded, lung cancer (p = 0.01),
urinary tract cancer (p = 0.003) and
COPD (p < 0.0001).
The authors concluded the findings
from this reanalysis reaffirmed that lung
cancer and CBD are related to beryllium
exposure. The authors went on to
suggest that beryllium exposures may be
associated with nervous system and
urinary tract cancers and that cigarette
smoking and other lung carcinogens
were unlikely to explain the increased
incidences in these cancers. The study
corrected an error that was discovered
in the indirect smoking adjustment
initially conducted by Ward et al.,
concluding that cigarette smoking rates
did not differ between the cohort and
the general U.S. population. No
association was found between cigarette
smoking and either cumulative or
maximum beryllium exposure, making
it very unlikely that smoking was a
substantial confounder in this study
(Schubauer-Berigan et al., 2010).
3. Animal Cancer Studies
This section reviews the animal
literature used to support the findings
for beryllium-induced lung cancer. Lung
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tumors have been induced via
inhalation and intratracheal
administration of beryllium to rats and
monkeys, and osteosarcomas have been
induced via intravenous and
intramedullary (inside the bone)
injection of beryllium in rabbits and
possibly in mice. The chronic oral
studies did not report increased
incidences of tumors in rodents, but
these were conducted at doses below
the maximum tolerated dose (MTD)
(EPA, 1998).
Early animal studies revealed that
some beryllium compounds are
carcinogenic when inhaled (ATSDR,
2002). Animal experiments have shown
consistent increases in lung cancers in
rats, mice and rabbits chronically
exposed to beryllium and beryllium
compounds by inhalation or
intratracheal instillation. In addition to
lung cancer, osteosarcomas have been
produced in mice and rabbits exposed
to various beryllium salts by
intravenous injection or implantation
into the bone (NTP, 1999).
In an inhalation study assessing the
potential tumorigenicity of beryllium,
Schepers et al. (1957) exposed 115
albino Sherman and Wistar rats (male
and female) via inhalation to 0.0357 mg
beryllium/m3 (1 g beryllium/ft3) 4 as an
aqueous aerosol of beryllium sulfate for
44 hours/week for 6 months, and
observed the rats for 18 months after
exposure. Three to four control rats
were killed every two months for
comparison purposes. Seventy-six lung
neoplasms, 5 including adenomas,
squamous-cell carcinomas, acinous
adenocarcinomas, papillary
adenocarcinomas, and alveolar-cell
adenocarcinomas, were observed in 52
rats exposed to beryllium sulfate
aerosol. Adenocarcinomata were the
most numerous. Pulmonary metastases
tended to localize in areas with foam
cell clustering and granulomatosis. No
neoplasia was observed in any of the
control rats. The incidence of lung
tumors in exposed rats is presented in
the following Table 2:
TABLE 2—NEOPLASM ANALYSIS
Neoplasm
Number
Adenoma ................
Metastases
18
4 Schepers et al. (1957) reported concentrations in
g Be/ft3; however, g/ft3 is no longer a common unit.
Therefore, the concentration was converted to mg/
m3.
5 While a total of 89 tumors were observed or
palpated at the time of autopsy in the BeSO4exposed animals, only 76 tumors are listed as
histologically neoplastic. Only the new growths
identified in single midcoronal sections of both
lungs were recorded.
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TABLE 2—NEOPLASM ANALYSIS—
Continued
Neoplasm
Squamous carcinoma .................
Acinous adenocarcinoma .................
Papillary adenocarcinoma .................
Alveolar-cell adenocarcinoma ............
Mucigenous tumor ..
Endothelioma ..........
Retesarcoma ..........
Total ....................
Number
Metastases
5
1
24
2
11
1
7
7
1
3
1
3
76
8
Schepers (1962) reviewed 38 existing
beryllium studies that evaluated seven
beryllium compounds and seven
mammalian species. Beryllium sulfate,
beryllium fluoride, beryllium
phosphate, beryllium alloy
(BeZnMnSiO4), and beryllium oxide
were proven to be carcinogenic and
have remarkable pleomorphic
neoplasiogenic proclivities. Ten
varieties of tumors were observed, with
adenocarcinoma being the most
common variety.
In another study, Vorwald and Reeves
(1959) exposed Sherman albino rats via
the inhalation route to aerosols of 0.006
mg beryllium/m3 as beryllium oxide
and 0.0547 mg beryllium/m3 as
beryllium sulfate for 6 hours/day, 5
days/week for an unspecified duration.
Lung tumors (single or multifocal) were
observed in the animals sacrificed
following 9 months of daily inhalation
exposure. The histologic pattern of the
cancer was primarily adenomatous;
however, epidermoid and squamous cell
cancers were also observed. Infiltrative,
vascular, and lymphogenous extensions
often developed with secondary
metastatic growth in the
tracheobronchial lymph nodes, the
mediastinal connective tissue, the
parietal pleura, and the diaphragm.
In the first of two articles, Reeves et
al. (1967a) investigated the carcinogenic
process in lungs resulting from chronic
(up to 72 weeks) beryllium sulfate
inhalation. One hundred fifty male and
female Sprague Dawley C.D. strain rats
were exposed to beryllium sulfate
aerosol at a mean atmospheric
concentration of 34.25 mg beryllium/m3
(with an average particle diameter of
0.12 mm). Prior to initial exposure and
again during the 67–68 and 75–76
weeks of life, the animals received
prophylactic treatments of tetracyclineHCl to combat recurrent pulmonary
infections.
The animals entered the exposure
chamber at 6 weeks of age and were
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exposed 7 hours per day/5 days per
week for up to 2,400 hours of total
exposure time. An equal number of
unexposed controls were held in a
separate chamber. Three male and three
female rats were sacrificed monthly
during the 72-week exposure period.
Mortality due to respiratory or other
infections did not appear until 55 weeks
of age, and 87 percent of all animals
survived until their scheduled
sacrifices.
Average lung weight towards the end
of exposure was 4.25 times normal with
progressively increasing differences
between control and exposed animals.
The increase in lung weight was
accompanied by notable changes in
tissue texture with two distinct
pathological processes—inflammatory
and proliferative. The inflammatory
response was characterized by marked
accumulation of histiocytic elements
forming clusters of macrophages in the
alveolar spaces. The proliferative
response progressed from early
epithelial hyperplasia of the alveolar
surfaces, through metaplasia (after 20–
22 weeks of exposure), anaplasia
(cellular dedifferentiation) (after 32–40
weeks of exposure), and finally to lung
tumors.
Although the initial proliferative
response occurred early in the exposure
period, tumor development required
considerable time. Tumors were first
identified after nine months of
beryllium sulfate exposure, with rapidly
increasing rates of incidence until
tumors were observed in 100 percent of
exposed animals by 13 months. The 9to-13-month interval is consistent with
earlier studies. The tumors showed a
high degree of local invasiveness. No
tumors were observed in control rats.
All 56 tumors studied appeared to be
alveolar adenocarcinomas and 3 ‘‘fast-
growing’’ tumors that reached a very
large size comparatively early. About
one-third of the tumors showed small
foci where the histologic pattern
differed. Most of the early tumor foci
appeared to be alveolar rather than
bronchiolar, which is consistent with
the expected pathogenesis, since
permanent deposition of beryllium was
more likely on the alveolar epithelium
rather than on the bronchiolar
epithelium. Female rats appeared to
have an increased susceptibility to
beryllium exposure. Not only did they
have a higher mortality (control males
[n = 8], exposed males [n = 9] versus
control females [n = 4], exposed females
[n = 17]) and body weight loss than male
rats, but the three ‘‘fast-growing’’ tumors
only occurred in females.
In the second article, Reeves et al.
(1967b) described the rate of
accumulation and clearance of
beryllium sulfate aerosol from the same
experiment (Reeves et al., 1967a). At the
time of the monthly sacrifice, beryllium
assays were performed on the lungs,
tracheobronchial lymph nodes, and
blood of the exposed rats. The
pulmonary beryllium levels of rats
showed a rate of accumulation which
decreased during continuing exposure
and reached a plateau (defined as
equilibrium between deposition and
clearance) of about 13.5 mg beryllium for
males and 9 mg beryllium for females in
whole lungs after approximately 36
weeks. Females were notably less
efficient than males in utilizing the
lymphatic route as a method of
clearance, resulting in slower removal of
pulmonary beryllium deposits, lower
accumulation of the inhaled material in
the tracheobronchial lymph nodes, and
higher morbidity and mortality.
There was no apparent correlation
between the extent and severity of
pulmonary pathology and total lung
load. However, when the beryllium
content of the excised tumors was
compared with that of surrounding
nonmalignant pulmonary tissues, the
former showed a notable decrease (0.50
± 0.35 mg beryllium/gram versus 1.50 ±
0.55 mg beryllium/gram). This was
believed to be largely a result of the
dilution factor operating in the rapidly
growing tumor tissue. However, other
factors, such as lack of continued local
deposition due to impaired respiratory
function and enhanced clearance due to
high vascularity of the tumor, may also
have played a role. The portion of
inhaled beryllium retained in the lungs
for a longer duration, which is in the
range of one-half of the original
pulmonary load, may have significance
for pulmonary carcinogenesis. This
pulmonary beryllium burden becomes
localized in the cell nuclei and may be
an important factor in eliciting the
carcinogenic response associated with
beryllium inhalation.
Groth et al. (1980) conducted a series
of experiments to assess the
carcinogenic effects of beryllium,
beryllium hydroxide, and various
beryllium alloys. For the beryllium
metal/alloys experiment, 12 groups of 3month-old female Wistar rats (35 rats/
group) were used. All rats in each group
received a single intratracheal injection
of either 2.5 or 0.5 mg of one of the
beryllium metals or beryllium alloys as
described in Table 3 below. These
materials were suspended in 0.4 cc of
isotonic saline followed by 0.2 cc of
saline. Forty control rats were injected
with 0.6 cc of saline. The geometric
mean particle sizes varied from 1 to 2
mm. Rats were sacrificed and autopsied
at various intervals ranging from 1 to 18
months post-injection.
TABLE 3—SUMMARY OF BERYLLIUM DOSE FROM GROTH ET AL. (1980)
Percent Be
Percent other compounds
Be metal ..........................................
100 .....................
99 .......................
0.26% Chromium ...........................
BeAl alloy ........................................
62 .......................
38% Aluminum ...............................
BeCu alloy .......................................
4 .........................
96% Copper ...................................
BeCuCo alloy ..................................
2.4 ......................
BeNi alloy ........................................
2.2 ......................
Total No. rats
autopsied
None ...............................................
Passivated Be metal .......................
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Form of Be
0.4% Cobalt ...................................
96% Copper ...................................
97.8% Nickel ..................................
Lung tumors were observed only in
rats exposed to beryllium metal,
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passivated beryllium metal, and
beryllium-aluminum alloy. Passivation
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16
21
26
20
24
21
28
24
33
30
28
27
Compound
dose
(mg)
2.5
0.5
2.5
0.5
2.5
0.5
2.5
0.5
2.5
0.5
2.5
0.5
Be dose
(mg)
2.5
0.5
2.5
0.5
1.55
0.3
0.1
0.02
0.06
0.012
0.056
0.011
refers to the process of removing iron
contamination from the surface of
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beryllium metal. As discussed, metal
alloys may have a different toxicity than
beryllium alone. Rats exposed to 100
percent beryllium exhibited relatively
high mortality rates, especially in the
groups where lung tumors were
observed. Nodules varying from 1 to 10
mm in diameter were also observed in
the lungs of rats exposed to beryllium
metal, passivated beryllium metal, and
beryllium-aluminum alloy. These
nodules were suspected of being
malignant.
To test this hypothesis,
transplantation experiments involving
the suspicious nodules were conducted
in nine rats. Seven of the nine suspected
tumors grew upon transplantation. All
transplanted tumor types metastasized
to the lungs of their hosts. Lung tumors
were observed in rats injected with both
the high and low doses of beryllium
metal, passivated beryllium metal, and
beryllium-aluminum alloy. No lung
tumors were observed in rats injected
with the other compounds. From a total
of 32 lung tumors detected, most were
adenocarcinomas and adenomas;
however, two epidermoid carcinomas
and at least one poorly differentiated
carcinoma were observed. Bronchiolar
alveolar cell tumors were frequently
observed in rats injected with beryllium
metal, passivated beryllium metal, and
beryllium-aluminum alloy. All stages of
cuboidal, columnar, and squamous cell
metaplasia were observed on the
alveolar walls in the lungs of rats
injected with beryllium metal,
passivated beryllium metal, and
beryllium-aluminum alloy. These
lesions were generally reduced in size
and number or absent from the lungs of
animals injected with the other alloys
(BeCu, BeCuCo, BeNi).
The extent of alveolar metaplasia
could be correlated with the incidence
of lung cancer. The incidences of lung
tumors in the rats that received 2.5 mg
of beryllium metal, and 2.5 and 0.5 mg
of passivated beryllium metal, were
significantly different (p ≤ 0.008) from
controls. When autopsies were
performed at the 16-to-19-month
interval, the incidence (2/6) of lung
tumors in rats exposed to 2.5 mg of
beryllium-aluminum alloy was
statistically significant (p = 0.004) when
compared to the lung tumor incidence
(0/84) in rats exposed to BeCu, BeNi,
and BeCuCo alloys, which contained
much lower concentrations of Be (Groth
et al., 1980).
Finch et al. (1998b) investigated the
carcinogenic effects of inhaled
beryllium on heterozygous TSG-p53
knockout mice (p53∂/¥) and wild-type
(p53+/+) mice. Knockout mice can be
valuable tools in determining the role of
specific genes on the toxicity of a
material of interest, in this case,
beryllium. Equal numbers of
approximately 10-week-old male and
female mice were used for this study.
Two exposure groups were used to
provide dose-response information on
lung carcinogenicity. The maximum
initial lung burden (ILB) target of 60 mg
beryllium was based on previous acute
inhalation exposure studies in mice.
The lower exposure target level of 15 mg
was selected to provide a lung burden
significantly less than the high-level
group, but high enough to yield
carcinogenic responses. Mice were
exposed in groups to beryllium metal or
to filtered air (controls) via nose-only
inhalation. The specific exposure
parameters are presented in Table 4
below. Mice were sacrificed 7 days post
exposure for ILB analysis, and either at
6 months post exposure (n = 4–5 mice
per group per gender) or when 10
percent or less of the original
population remained (19 months post
exposure for p53∂/¥ knockout and 22.5
months post exposure for p53+/+ wildtype mice). The sacrifice time was
extended in the study because a
significant number of lung tumors were
not observed at 6 months post exposure.
TABLE 4—SUMMARY OF ANIMAL DATA FROM FINCH ET AL., 1998 b
Mouse strain
Knockout (p53∂/¥)
Wild-type (p53 ⁄ )
++
Knockout (p53∂/¥)
Mean
exposure concentration
(μg Be/L)
34
36
34
36
NA (air)
Target be lung
burden
(μg)
15
60
15
60
Control
Number of mice
30
30
6*
36†
30
Mean daily
exposure duration
(minutes)
112 (single)
139‡
112 (single)
139‡
60–180 (single)
Mean ILB
(μg)
NA
NA
12 ± 4
54 ± 6
NA
Number of mice
with 1 or more
lung tumors/total
number
examined
0/29
4/28
NA
0/28
0/30
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ILB = initial lung burden; NA = not applicable
Median aerodynamic diameter of Be aerosol = 1.4 μm (sg = 1.8)
* Wild-type mice in the low exposure group were not evaluated for carcinogenic effects; however ILB was analyzed in six wild-type mice.
† Thirty wild-type mice were analyzed for carcinogenic effects; six wild-type mice were analyzed for ILB.
‡ Mice were exposed for 2.3 hours/day for three consecutive days.
Lung burdens of beryllium measured
in wild-type mice at 7 days post
exposure were approximately 70–90
percent of target levels. No exposurerelated effects on body weight were
observed in mice; however, lung
weights and lung-to-body-weight ratios
were somewhat elevated in 60 mg target
ILB p53∂/¥ knockout mice compared to
controls (0.05 < p < 0.10). In general,
p53+/+ wild-type mice survived longer
than p53∂/¥ knockout mice and
beryllium exposure tended to decrease
survival time in both groups. The
incidence of beryllium-induced lung
tumors was marginally higher in the 60
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mg target ILB p53∂/¥ knockout mice
compared to 60 mg target ILB p53+/+
wild-type mice (p = 0.056). The
incidence of lung tumors in the 60 mg
target ILB p53∂/¥ knockout mice was
also significantly higher than controls (p
= 0.048). No tumors developed in the
control mice, 15 mg target ILB p53∂/¥
knockout mice, or 60 mg target ILB
p53+/+ wild-type mice throughout the
length of the study. Most lung tumors in
beryllium-exposed mice were squamous
cell carcinomas, three of four of which
were poorly circumscribed and all were
associated with at least some degree of
granulomatous pneumonia. The study
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results suggest that having an
inactivated p53 allele is associated with
lung tumor progression in p53∂/¥
knockout mice. This is based on the
significant difference seen in the
incidence of beryllium-induced lung
neoplasms for the p53∂/¥knockout
mice compared with the p53+⁄+ wildtype mice. The authors conclude that
since there was a relatively late onset of
tumors in the beryllium-exposed
p53∂/¥ knockout mice, a 6-month
bioassay in this mouse strain might not
be an appropriate model for lung
carcinogenesis (Finch et al., 1998b).
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Nickell-Brady et al. (1994)
investigated the development of lung
tumors in 12-week-old F344/N rats after
a single nose-only inhalation exposure
to beryllium aerosol, and evaluated
whether beryllium lung tumor
induction involves alterations in the Kras, p53, and c-raf¥1 genes. Four
groups of rats (30 males and 30 females
per group) were exposed to different
mass concentrations of beryllium
(Group 1: 500 mg/m3 for 8 min; Group
2: 410 mg/m3 for 30 min; Group 3: 830
mg/m3 for 48 min; Group 4: 980 mg/m3
for 39 min). The beryllium mass median
aerodynamic diameter was 1.4 mm (sg =
1.9). The mean beryllium lung burdens
for each exposure group were 40, 110,
360, and 430 mg, respectively.
To examine genetic alterations, DNA
isolation and sequencing techniques
(PCR amplification and direct DNA
sequence analysis) were performed on
wild-type rat lung tissue (i.e., control
samples) along with two mouse lung
tumor cell lines containing known K-ras
mutations, 12 carcinomas induced by
beryllium (i.e., experimental samples),
and 12 other formalin-fixed specimens.
Tumors appeared in beryllium-exposed
rats by 14 months, and 64 percent of
exposed rats developed lung tumors
during their lifetime. Lungs frequently
contained multiple tumor sites, with
some of the tumors greater than 1 cm.
A total of 24 tumors were observed.
Most of the tumors (n = 22) were
adenocarcinomas exhibiting a papillary
pattern characterized by cuboidal or
columnar cells, although a few had a
tubular or solid pattern. Fewer than 10
percent of the tumors were
adenosquamous (n = 1) or squamous
cell (n = 1) carcinomas.
No transforming mutations of the Kras gene (codons 12, 13, or 61) were
detected by direct sequence analysis in
any of the lung tumors induced by
beryllium. However, using a more
sensitive sequencing technique (PCR
enrichment restriction fragment length
polymorphism (RFLP) analysis) resulted
in the detection of K-ras codon 12 GGT
to GTT transversions in 2 of 12
beryllium-induced adenocarcinomas.
No p53 and c-raf-1 alterations were
observed in any of the tumors induced
by beryllium exposure (i.e., no
differences observed between berylliumexposed and control rat tissues). The
authors note that the results suggest that
activation of the K-ras proto-oncogene is
both a rare and late event, possibly
caused by genomic instability during
the progression of beryllium-induced rat
pulmonary adenocarcinomas. It is
unlikely that the K-ras gene plays a role
in the carcinogenicity of beryllium. The
results also indicate that p53 mutation
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is unlikely to play a role in tumor
development in rats exposed to
beryllium.
Belinsky et al. (1997) reviewed the
findings by Nickell-Brady et al. (1994)
to further examine the role of the K-ras
and p53 genes in lung tumors induced
in the F344 rat by non-mutagenic (nongenotoxic) exposures to beryllium. Their
findings are discussed along with the
results of other genomic studies that
look at carcinogenic agents that are
either similarly non-mutagenic or, in
other cases, mutagenic. The authors
conclude that the identification of nonras transforming genes in rat lung
tumors induced by non-mutagenic
exposures, such as beryllium, as well as
mutagenic exposures will help define
some of the mechanisms underlying
cancer induction by different types of
DNA damage.
The inactivation of the p16INK4a (p16)
gene is a contributing factor in
disrupting control of the normal cell
cycle and may be an important
mechanism of action in berylliuminduced lung tumors. Swafford et al.
(1997) investigated the aberrant
methylation and subsequent
inactivation of the p16 gene in primary
lung tumors induced in F344/N rats
exposed to known carcinogens via
inhalation. The research involved a total
of 18 primary lung tumors that
developed after exposing rats to five
agents, one of which was beryllium. In
this study, only one of the 18 lung
tumors was induced by beryllium
exposure; the majority of the other
tumors were induced by radiation (xrays or plutonium-239 oxide). The
authors hypothesized that if p16
inactivation plays a central role in
development of non-small-cell lung
cancer, then the frequency of gene
inactivation in primary tumors should
parallel that observed in the
corresponding cell lines. To test the
hypothesis, a rat model for lung cancer
was used to determine the frequency
and mechanism for inactivation of p16
in matched primary lung tumors and
derived cell lines. The methylationspecific PCR (MSP) method was used to
detect methylation of p16 alleles. The
results showed that the presence of
aberrant p16 methylation in cell lines
was strongly correlated with absent or
low expression of the gene. The findings
also demonstrated that aberrant p16
CpG island methylation, an important
mechanism in gene silencing leading to
the loss of p16 expression, originates in
primary tumors.
Building on the rat model for lung
cancer and associated findings from
Swafford et al. (1997), Belinsky et al.
(2002) conducted experiments in 12-
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week-old F344/N rats (male and female)
to determine whether berylliuminduced lung tumors involve
inactivation of the p16 gene and
estrogen receptor a (ER) gene. Rats
received a single nose-only inhalation
exposure to beryllium aerosol at four
different exposure levels. The mean
lung burdens measured in each
exposure group were 40, 110, 360, and
430 mg. The methylation status of the
p16 and ER genes was determined by
MSP. A total of 20 tumors detected in
beryllium-exposed rats were available
for analysis of gene-specific promoter
methylation. Three tumors were
classified as squamous cell carcinomas
and the others were determined to be
adenocarcinomas. Methylated p16 was
present in 80 percent (16/20), and
methylated ER was present in one-half
(10/20), of the lung tumors induced by
exposure to beryllium. Additionally,
both genes were methylated in 40
percent of the tumors. The authors
noted that four tumors from berylliumexposed rats appeared to be partially
methylated at the p16 locus. Bisulfite
sequencing of exon 1 of the ER gene was
conducted on normal lung DNA and
DNA from three methylated, berylliuminduced tumors to determine the
density of methylation within amplified
regions of exon 1 (referred to as CpG
sites). Two of the three methylated,
beryllium-induced lung tumors showed
extensive methylation, with more than
80 percent of all CpG sites methylated.
The overall findings of this study
suggest that inactivation of the p16 and
ER genes by promoter hypermethylation
are likely to contribute to the
development of lung tumors in
beryllium-exposed rats. The results
showed a correlation between changes
in p16 methylation and loss of gene
transcription. The authors hypothesize
that the mechanism of action for
beryllium-induced p16 gene
inactivation in lung tumors may be
inflammatory mediators that result in
oxidative stress. The oxidative stress
damages DNA directly through free
radicals or indirectly through the
formation of 8-hydroxyguanosine DNA
adducts, resulting primarily in a singlestrand DNA break.
Wagner et al. (1969) studied the
development of pulmonary tumors after
intermittent daily chronic inhalation
exposure to beryllium ores in three
groups of male squirrel monkeys. One
group was exposed to bertrandite ore, a
second to beryl ore, and the third served
as unexposed controls. Each of these
three exposure groups contained 12
monkeys. Monkeys from each group
were sacrificed after 6, 12, or 23 months
of exposure. The 12-month sacrificed
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monkeys (n = 4 for bertrandite and
control groups; n = 2 for beryl group)
were replaced by a separate replacement
group to maintain a total animal
population approximating the original
numbers and to provide a source of
confirming data for biologic responses
that might arise following the ore
exposures. Animals were exposed to
bertrandite and beryl ore concentrations
of 15 mg/m3, corresponding to 210 mg
beryllium/m3 and 620 mg beryllium/m3
in each exposure chamber, respectively.
The parent ores were reduced to
particles with geometric mean diameters
of 0.27 mm (± 2.4) for bertrandite and
0.64 mm (± 2.5) for beryl. Animals were
exposed for approximately 6 hours/day,
5 days/week. The histological changes
in the lungs of monkeys exposed to
bertrandite and beryl ore exhibited a
similar pattern. The changes generally
consisted of aggregates of dust-laden
macrophages, lymphocytes, and plasma
cells near respiratory bronchioles and
small blood vessels. There were,
however, no consistent or significant
pulmonary lesions or tumors observed
in monkeys exposed to either of the
beryllium ores. This is in contrast to the
findings in rats exposed to beryl ore and
to a lesser extent bertrandite, where
atypical cell proliferation and tumors
were frequently observed in the lungs.
The authors hypothesized that the rats’
greater susceptibility may be attributed
to the spontaneous lung disease
characteristic of rats, which might have
interfered with lung clearance.
As previously described, Conradi et
al. (1971) investigated changes in the
lungs of monkeys and dogs two years
after intermittent inhalation exposure to
beryllium oxide calcined at 1,400 °C.
Five adult male and female monkeys
(Macaca irus) weighing between 3 and
5.75 kg were used in the study. The
study included two control monkeys.
Beryllium concentrations in the
atmosphere of whole-body exposed
monkeys varied between 3.30 and 4.38
mg/m3. Thirty-minute exposures
occurred once a month for three
months, with beryllium oxide
concentrations increasing at each
exposure interval. Lung tissue was
investigated using electron microscopy
and morphometric methods. Beryllium
content in portions of the lungs of five
monkeys was measured two years
following exposure by emission
spectrography. The reported
concentrations in monkeys (82.5, 143.0,
and 112.7 mg beryllium per 100 gm of
wet tissue in the upper lobe, lower lobe,
and combined lobes, respectively) were
higher than those in dogs. No neoplastic
or granulomatous lesions were observed
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in the lungs of any exposed animals and
there was no evidence of chronic
proliferative lung changes after two
years.
4. In vitro Studies
The exact mechanism by which
beryllium induces pulmonary
neoplasms in animals remains unknown
(NAS 2008). Keshava et al. (2001)
performed studies to determine the
carcinogenic potential of beryllium
sulfate in cultured mammalian cells.
Joseph et al. (2001) investigated
differential gene expression to
understand the possible mechanisms of
beryllium-induced cell transformation
and tumorigenesis. Both investigations
used cell transformation assays to study
the cellular/molecular mechanisms of
beryllium carcinogenesis and assess
carcinogenicity. Cell lines were derived
from tumors developed in nude mice
injected subcutaneously with nontransformed BALB/c-3T3 cells that were
morphologically transformed in vitro
with 50–200 mg beryllium sulfate/ml for
72 hours. The non-transformed cells
were used as controls.
Keshava et al. (2001) found that
beryllium sulfate is capable of inducing
morphological cell transformation in
mammalian cells and that transformed
cells are potentially tumorigenic. A
dose-dependent increase (9–41 fold) in
transformation frequency was noted.
Using differential polymerase chain
reaction (PCR), gene amplification was
investigated in six proto-oncogenes (Kras, c-myc, c-fos, c-jun, c-sis, erb-B2)
and one tumor suppressor gene (p53).
Gene amplification was found in c-jun
and K-ras. None of the other genes
tested showed amplification.
Additionally, Western blot analysis
showed no change in gene expression or
protein level in any of the genes
examined. Genomic instability in both
the non-transformed and transformed
cell lines was evaluated using random
amplified polymorphic DNA
fingerprinting (RAPD analysis). Using
different primers, 5 of the 10
transformed cell lines showed genomic
instability when compared to the nontransformed BALB/c-3T3 cells. The
results indicate that beryllium sulfateinduced cell transformation might, in
part, involve gene amplification of K-ras
and c-jun and that some transformed
cells possess neoplastic potential
resulting from genomic instability.
Using the Atlas mouse 1.2 cDNA
expression microarrays, Joseph et al.
(2001) studied the expression profiles of
1,176 genes belonging to several
different functional categories.
Compared to the control cells,
expression of 18 genes belonging to two
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functional groups (nine cancer-related
genes and nine DNA synthesis, repair,
and recombination genes) was found to
be consistently and reproducibly
different (at least 2-fold) in the tumor
cells. Differential gene expression
profile was confirmed using reverse
transcription-PCR with primers specific
to the differentially expressed genes.
Two of the differentially expressed
genes (c-fos and c-jun) were used as
model genes to demonstrate that the
beryllium-induced transcriptional
activation of these genes was dependent
on pathways of protein kinase C and
mitogen-activated protein kinase and
independent of reactive oxygen species
in the control cells. These results
indicate that beryllium-induced cell
transformation and tumorigenesis are
associated with up-regulated expression
of the cancer-related genes (such as cfos, c-jun, c-myc, and R-ras) and downregulated expression of genes involved
in DNA synthesis, repair, and
recombination (such as MCM4, MCM5,
PMS2, Rad23, and DNA ligase I).
5. Preliminary Lung Cancer Conclusions
OSHA has preliminarily determined
that the weight of evidence indicates
that beryllium compounds should be
regarded as potential occupational lung
carcinogens. Other scientific
organizations, including the
International Agency for Research on
Cancer (IARC), the National Toxicology
Program (NTP), the U.S. Environmental
Protection Agency (EPA), the National
Institute for Occupational Safety and
Health (NIOSH), and the American
Conference of Governmental Industrial
Hygienists (ACGIH) have reached
similar conclusions with respect to the
carcinogenicity of beryllium.
While some evidence exists for directacting genotoxicity as a possible
mechanism for beryllium
carcinogenesis, the weight of evidence
suggests a possible indirect mechanism
may be responsible for most
tumorigenic activity of beryllium in
animal models and possibly humans
(EPA, 1998). Inflammation has been
postulated to be a key contributor to
many different forms of cancer (Jackson
et al., 2006; Pikarsky et al., 2004; Greten
et al., 2004; Leek, 2002). In fact, chronic
inflammation may be a primary factor in
the development of up to one-third of
all cancers (Ames et al., 1990; NCI,
2010).
In addition to a T-cell mediated
response beryllium has been
demonstrated to produce an
inflammatory response in animal
models similar to other particles (Reeves
et al., 1967; Swafford et al., 1997;
Wagner et al., 1969) possibly
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contributing to its carcinogenic
potential. Animal studies, as
summarized above, have demonstrated a
consistent scenario of beryllium
exposure resulting in chronic
pulmonary inflammation. Studies
conducted in rats have demonstrated
that chronic inhalation of materials
similar in solubility to beryllium result
in increased pulmonary inflammation,
fibrosis, epithelial hyperplasia, and, in
some cases, pulmonary adenomas and
carcinomas (Heinrich et al., 1995;
Nikula et al., 1995; NTP, 1993; Lee et
al., 1985; Warheit et al., 1996). This
response is generally referred to as an
‘‘overload’’ response or threshold effect.
Substantial data indicate that tumor
formation in the rat after exposure to
some sparingly soluble particles at
doses causing marked, chronic
inflammation is due to a secondary
mechanism unrelated to the
genotoxicity (or lack thereof) of the
particle itself.
It has been hypothesized that the
recruitment of neutrophils during the
inflammatory response and subsequent
release of oxidants from these cells have
been demonstrated to play an important
role in the pathogenesis of rat lung
tumors (Borm et al., 2004; Carter and
Driscoll, 2001; Carter et al., 2006;
Johnston et al., 2000; Knaapen et al.,
2004; Mossman, 2000). Inflammatory
mediators, as characterized in many of
the studies summarized above, have
been shown to play a significant role in
the recruitment of cells responsible for
the release of reactive oxygen and
hydrogen species. These species have
been determined to be highly mutagenic
themselves as well as mitogenic,
inducing a proliferative response
(Feriola and Nettesheim, 1994; Jetten et
al., 1990; Moss et al., 1994; Coussens
and Werb, 2002). The resultant effect is
an environment rich for neoplastic
transformations and the progression of
fibrosis and tumor formation. This
finding does not imply no risk at levels
below an inflammatory response; rather,
the overall weight of evidence is
suggestive of a mechanism of an indirect
carcinogen at levels where inflammation
is seen. While tumorigenesis secondary
to inflammation is one reasonable mode
of action, other plausible modes of
action independent of inflammation
(e.g., epigenetic, mitogenic, reactive
oxygen mediated, indirect genotoxicity,
etc.) may also contribute to the lung
cancer associated with beryllium
exposure.
Epidemiological studies indicate
excess risk of lung cancer mortality from
occupational beryllium exposure levels
at or below the current OSHA PEL
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(Schubauer-Berigan et al., 2010; Table
4).
F. Other Health Effects
Past studies on other health effects
have been thoroughly reviewed by
several scientific organizations (NTP,
1999; EPA, 1998; ATSDR, 2002; WHO,
2001; HSDB, 2010). These studies
include summaries of animal studies, in
vitro studies, and human
epidemiological studies associated with
cardiovascular, hematological, hepatic,
renal, endocrine, reproductive, ocular
and mucosal, and developmental
effects. High-dose exposures to
beryllium have been shown to have an
adverse effect upon a variety of organs
and tissues in the body, particularly the
liver. The adverse systemic effects from
human exposures mostly occurred prior
to the introduction of occupational and
environmental standards set in 1970–
1972 (OSHA, 1971; ACGIH, 1971; ANSI,
1970) and 1974 (EPA, 1974) and
therefore are less relevant today than in
the past. The available data is fairly
limited. The hepatic, cardiovascular,
renal, and ocular and mucosal effects
are briefly summarized below. Health
effects in other organ systems listed
above were only observed in animal
studies at very high exposure levels and
are, therefore, not discussed here.
1. Hepatic Effects
Beryllium has been shown to
accumulate in the liver and a correlation
has been demonstrated between
beryllium content and hepatic damage.
Different compounds have been shown
to distribute differently within the
hepatic tissues. For example, beryllium
phosphate had accumulated almost
exclusively within sinusoidal (Kupffer)
cells of the liver, while the beryllium
derived from beryllium sulfate was
found mainly in parenchymal cells.
Conversely, beryllium sulphosalicylic
acid complexes were rapidly excreted
(Skillteter and Paine, 1979).
According to a few autopsies,
beryllium-laden liver had central
necrosis, mild focal necrosis as well as
congestion, and occasionally beryllium
granuloma.
Residents near a beryllium plant may
have been exposed by inhaling trace
amounts of beryllium powder, and
different beryllium compounds may
have induced different toxicant
reactions (Yian and Yin, 1982).
2. Cardiovascular Effects
There is very limited evidence of
cardiovascular effects of beryllium and
its compounds in humans. Severe cases
of chronic beryllium disease can result
in cor pulmonale, which is hypertrophy
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of the right heart ventricle. In a case
history study of 17 individuals exposed
to beryllium in a plant that
manufactured fluorescent lamps,
autopsies revealed right atrial and
ventricular hypertrophy (Hardy and
Tabershaw, 1946). It is not likely that
these cardiac effects were due to direct
toxicity to the heart, but rather were a
response to impaired lung function.
However, an increase in deaths due to
heart disease or ischemic heart disease
was found in workers at a beryllium
manufacturing facility (Ward et al.,
1992).
Animal studies performed in monkeys
indicate heart enlargement after acute
inhalation exposure to 13 mg beryllium/
m3 as beryllium hydrogen phosphate,
0.184 mg beryllium/m3 as beryllium
fluoride, or 0.198 mg beryllium/m3 as
beryllium sulfate (Schepers 1964).
Decreased arterial oxygen tension was
observed in dogs exposed to 30 mg
beryllium/m3 as beryllium oxide for 15
days (HSDB, 2010), 3.6 mg beryllium/
m3 as beryllium oxide for 40 days (Hall
et al., 1950), or 0.04 mg beryllium/m3 as
beryllium sulfate for 100 days
(Stokinger et al., 1950). These are
expected to be indirect effects on the
heart due to pulmonary fibrosis and
toxicity which can increase arterial
pressure and restrict blood flow.
3. Renal Effects
Renal calculi (stones) were unusually
prevalent in severe cases that resulted
from high levels of beryllium exposure.
Renal stones containing beryllium
occurred in about 10 percent of patients
affected by high exposures (Barnett, et
al., 1961). Kidney stones were observed
in 10 percent of the CBD cases collected
by the BCR up to 1959 (Hall et al.,
1959). In addition, an excess of calcium
in the blood and urine has been seen
frequently in patients with chronic
beryllium disease (ATSDR, 2002).
4. Ocular and Mucosal Effects
Both the soluble, sparingly soluble,
and insoluble beryllium compounds
have been shown to cause ocular
irritation in humans (Van Orstrand et
al., 1945; De Nardi et al., 1953;
Nishimura, 1966; Epstein, 1990; NIOSH,
1994). In addition, beryllium
compounds (soluble, sparingly soluble,
or insoluble) have been demonstrated to
induce acute conjunctivitis with corneal
maculae and diffuse erythema (HSDB,
2010).
The mucosa (mucosal membrane) is
the moist lining of certain tissues/organs
including the eyes, nose, mouth, lungs,
and the urinary and digestive tracts.
Soluble beryllium salts have been
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shown to be directly irritating to
mucous membranes (HSDB, 2010).
G. Summary of Preliminary Conclusions
Regarding Health Effects
Through careful analysis of the
current best available scientific
information outlined in this Health
Effects Section V, OSHA has
preliminarily determined that beryllium
and beryllium-containing compounds
are able to cause sensitization, chronic
beryllium disease (CBD) and lung
cancer below the current OSHA PEL of
2 mg/m3. The Agency has preliminarily
determined through the studies outlined
in section V.A.2 of this health effects
section that skin and inhalation
exposure to beryllium can lead to
sensitization; and inhalation exposure,
or skin exposure coupled with
inhalation, can cause onset and
progression of CBD. In addition, the
Agency has preliminarily determined
through studies outlined in section V.E.
of this health effects section that
inhalation exposure to beryllium and
beryllium containing materials causes
lung cancer.
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1. Beryllium Causes Sensitization Below
the Current PEL and Sensitization is a
Precursor to CBD
Through the biological and
immunological processes outlined in
section V.B. of the Health Effects, the
Agency believes that the scientific
evidence supports the following
mechanism for the development of
sensitization and CBD.
• Inhaled beryllium and berylliumcontaining materials able to be retained
and solubilized in the lungs initiate
sensitization and facilitate CBD
development (Section V.B.5).
• Beryllium compounds that dissolve
in biological fluids, such as sweat, can
penetrate intact skin and initiate
sensitization (section V.A.2; V.B).
Phagosomal fluid and lung fluid have
been demonstrated to dissolve
beryllium compounds in the lung
(section V.A.2a).
• Sensitization occurs through a
CD4+ T-cell mediated process with both
soluble and insoluble beryllium and
beryllium-containing compounds
through direct antigen presentation or
through further antigen processing
(section V.D.1) in the skin or lung. Tcell mediated responses, such as
sensitization, are generally regarded as
long-lasting (e.g., not transient or readily
reversible) immune conditions.
• Beryllium sensitization and CBD
are adverse events along a pathological
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continuum in the disease process with
sensitization being the necessary first
step in the progression to CBD (section
V.D).
Æ Animal studies have provided
supporting evidence for T-cell
proliferation in the development of
granulomatous lung lesions after
beryllium exposure (section V.D.2;
V.D.6).
Æ Since the pathogenesis of CBD
involves a beryllium-specific, cellmediated immune response, CBD
cannot occur in the absence of
beryllium sensitization (V.D.1). While
no clinical symptoms are associated
with sensitization, a sensitized worker
is at risk of developing CBD upon
subsequent inhalation exposure to
beryllium.
Æ Epidemiological evidence that
covers a wide variety of different
beryllium compounds and industrial
processes demonstrates that
sensitization and CBD are continuing to
occur at present-day exposures below
OSHA’s PEL (section V.D.4; V.D.5).
• OSHA considers CBD to be a
progressive illness with a continuous
spectrum of symptoms ranging from its
earliest asymptomatic stage following
sensitization through to full-blown CBD
and death (section V.D.7).
• Genetic variabilities may enhance
risk for developing sensitization and
CBD in some groups (section V.D.3).
In addition, epidemiological studies
outlined in section V.D.5 have
demonstrated that efforts to reduce
exposures have succeeded in reducing
the frequency of sensitization and CBD.
2. Evidence Indicates Beryllium is a
Human Carcinogen
OSHA has conducted an evaluation of
the current available scientific
information of the carcinogenic
potential of beryllium and berylliumcontaining compounds (section V.E).
Based on weight of evidence and
plausible mechanistic information
obtained from in vitro and in vivo
animal studies as well as clinical and
epidemiological investigations, the
Agency has preliminarily determined
that beryllium and beryllium-containing
materials should be regarded as human
carcinogens. This information is in
accordance with findings from IARC,
NTP, EPA, NIOSH, and ACGIH (section
V.E).
• Lung cancer is an irreversible and
frequently fatal disease with an
extremely poor 5-year survival rate
(NCI, 2009).
• Epidemiological cohort studies
have reported statistically significant
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47617
excess lung cancer mortality among
workers employed in U.S. beryllium
production and processing plants
during the 1930s to 1970s (Section
V.E.2).
• Significant positive associations
were found between lung cancer
mortality and both average and
cumulative beryllium exposures when
appropriately adjusted for birth cohort
and short-term work status (Section
V.E.2).
• Studies in which large amounts of
different beryllium compounds were
inhaled or instilled in the respiratory
tracts of experimental animals resulted
in an increased incidence of lung
tumors (Section V.E.3).
• Authoritative scientific
organizations, such as the IARC, NTP,
and EPA, have classified beryllium as a
known or probable human carcinogen.
While OSHA has preliminarily
determined there is sufficient evidence
of beryllium carcinogenicity, the exact
tumorigenic mechanism for beryllium is
unclear and a number of mechanisms
are plausibly involved, including
chronic inflammation, genotoxicity,
mitogenicity oxidative stress, and
epigenetic changes (section V.E.3).
• Studies of beryllium exposed
animals have consistently demonstrated
chronic pulmonary inflammation after
exposure (section V.E.3).
Æ Substantial data indicate that tumor
formation in certain animal models after
inhalation exposure to sparingly soluble
particles at doses causing marked,
chronic inflammation is due to a
secondary mechanism unrelated to the
genotoxicty of the particle (section
V.E.5).
• A review conducted by the NAS
(2008) found that beryllium and
beryllium-containing compounds tested
positive for genotoxicity in nearly 50
percent of studies without exogenous
metabolic activity, suggesting a possible
direct-acting mechanism may exist
(section V.E.1) as well as the potential
for epigenetic changes (section V.E.4).
Other health effects have been
summarized in sections F of the Health
Effects Section and include hepatic,
cardiovascular, renal, ocular, and
mucosal effects. The adverse systemic
effects from human exposures mostly
occurred prior to the introduction of
occupational and environmental
standards set in 1970–1972 (OSHA,
1971; ACGIH, 1971; ANSI, 1970) and
1974 (EPA, 1974) and therefore are less
relevant today than in the past.
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APPENDIX
TABLE A.1—SUMMARY OF BERYLLIUM SENSITIZATION AND CHRONIC BERYLLIUM DISEASE EPIDEMIOLOGICAL STUDIES
(%) Prevalence
Reference
Study type
Sensitization
Range of exposure
measurements
CBD
Exposure-response
relationship
Study limitations
Additional
comments
Studies Conducted Prior to BeLPT
Hardy and
Tabershaw, 1946.
Hardy, 1980 ............
Machle et al., 1948
Case-series ...........
N/A ........
N/A ........
N/A ........................
N/A .........
Selection bias .......
Small sample size.
Case-series ...........
Case-series ...........
N/A ........
N/A ........
N/A ........
N/A ........
N/A ........................
Semi-quantitative ..
N/A .........
Yes ........
Selection bias .......
Selection bias .......
Eisenbud et al.,
1949.
Case-series ...........
N/A ........
N/A ........
...............................
Lieben and Metzner,
1959.
...............................
N/A ........
...............
Average concentra- ................
tion: 350–750 ft
from plant—
0.05–0.15 μg/m3;.
<350 ft from
plant—2.1 μg/m3.
N/A ........................ ................
Small sample size.
Small sample size;
unreliable exposure data.
Non-occupational;
ambient air sampling.
Hardy et al., 1967 ...
Case Registry Review.
N/A ........
N/A ........
N/A ........................
N/A .........
Hasan and Kazemi,
1974.
Eisenbud and
Lisson, 1983.
Stoeckle et al., 1969
...............................
N/A ........
...............
...............................
................
Incomplete exposure concentration data.
...............................
...............................
N/A ........
1–10 ......
...............................
................
...............................
Case-series (60
cases).
N/A ........
...............
...............................
No ..........
Selection bias .......
No quantitative exposure data.
Family member
contact with contaminated
clothes.
Provided information regarding
progression and
identifying sarcoidosis from
CBD.
Studies Conducted Following the Development of the BeLPT
Beryllium Mining and Extraction
Deubner et al.,
2001b.
Cross-sectional (75
workers).
4.0 (3
cases).
1.3 (1
case).
Mining, milling—
range 0.05–0.8
μg/m3;
Annual maximum
0.04–165.7 μg/
m 3.
No ..........
Small sample size
Personal sampling.
Short-term Breathing Zone sampling.
Daily weighted average:
High exposures
compared to
other studies.
Engineering and
administrative
controls primarily
used to control
exposures.
Beryllium Metal Processing and Alloy Production
Kreiss et al., 1997 ..
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Rosenman et al.,
2005.
Cross-sectional
study of 627
workers.
Cross-sectional
study of 577
workers.
6.9 (43
cases).
4.6 (29
cases).
Median—1.4 μg/m3
No ..........
14.5 (83
cases).
5.5 (32
cases).
Mean average
range—7.1–8.7
μg/m3;.
Mean peak
range—53–87
μg/m3;
Mean cumulative
range—100–209
μg/m3.
No ..........
Inconsistent BeLPT
results between
labs.
...............................
No ..........
...............................
Beryllium Machining Operations
Newman et al.,
2001.
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9.4 (22
cases).
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cases).
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TABLE A.1—SUMMARY OF BERYLLIUM SENSITIZATION AND CHRONIC BERYLLIUM DISEASE EPIDEMIOLOGICAL STUDIES—
Continued
(%) Prevalence
Reference
Study type
Kelleher et al., 2001
Case-control study
of 20 cases and
206 controls.
Madl et al., 2007 .....
Longitudinal study
of 27 cases.
Exposure-response
relationship
Study limitations
Additional
comments
0.08–0.6 μg/m3—
lifetime weighted
exposures.
Yes ........
...............................
Identified 20 workers with Sensitization or
CBD.
Machining ..............
1980–1995 median
¥0.33 μg/m3;
1996–1999 median—0.16 μg/
m3; 2000–2005
median—0.09
μg/m3;.
Non-machining
1980–1995 median—0.12 μg/
m3; 1996–1999
median—0.08
μg/m3; 2000–
2005 median—
0.06 μg/m3.
Yes ........
...............................
Personal sampling:
Required evidence
of granulomas
for CBD diagnosis.
Range of exposure
measurements
Sensitization
CBD
11.5 (machinists).
2.9 (nonmachinists).
...............
11.5 (machinists).
2.9 (nonmachinists).
...............
Beryllium Oxide Ceramics
Kreiss et al., 1993b
3.6 (18
cases).
1.8 (9
cases).
...............................
No
Kreiss et al., 1996 ..
Cross-sectional
survey of 505
workers.
Cross-sectional
survey of 136
workers.
5.9 (8
cases).
4.4 (6
cases).
No ..........
Small study population.
Breathing Zone
Sampling.
Henneberger et al.,
2001.
Cross-sectional
survey of 151
workers.
9.9 (15
cases).
5.3 (8
cases).
Yes ........
Small study population.
Breathing zone
sampling.
Cummings et al.,
2007.
Longitudinal study
of 93 workers.
0.7–5.6
(4
cases).
0.1—7.9
(3
cases).
Machining median—0.6 μg/m3;.
Other Areas median—<0.3 μg/
m 3;
6.4% samples >2
μg/m3; 2.4%
samples >5 μg/
m3;.
0.3% samples >25
μg/m3.
Production .............
1994–1999 median—0.1μg/m3;
2000–2003 median—0.04μg/m3;
Administrative
1994–1999 median <0.2 μg/m3;
2000–2003 median—0.02 μg/
m3
Yes ........
Small sample size
Personal sampling
was effective in
reducing rates of
new cases of
sensitization.
Small study population.
Personal sampling.
Copper-Beryllium Alloy Processing and Distribution
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cases).
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cases).
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Rod and Wire Production median—0.12 μg/
m3;
Strip Metal Production median—
0.02 μg/m3;
Production Support
median—0.02
μg/m3;
Administration median—0.02 μg/
m 3.
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Federal Register / Vol. 80, No. 152 / Friday, August 7, 2015 / Proposed Rules
TABLE A.1—SUMMARY OF BERYLLIUM SENSITIZATION AND CHRONIC BERYLLIUM DISEASE EPIDEMIOLOGICAL STUDIES—
Continued
(%) Prevalence
Reference
Study type
Sensitization
Range of exposure
measurements
CBD
Exposure-response
relationship
Thomas et al., 2009
Cross-sectional
study of 82 workers.
3.8 (3
cases).
1.9 (1
case).
Used exposure
profile from
Schuler study.
................
Stanton et al., 2006
Cross-sectional
study of 88 workers.
1.1 (1
case).
1.1 (1
case).
................
Bailey et al., 2010 ...
Cross-sectional
11.0 .......
study of 660 total
workers (258
partial program,
290 full program).
Bulk Products Production median
0.04 μg/m3; Strip
Metal Production
median—0.03
μg/m3; Production support.
median—0.01 μg/
m3; Administration median 0.01
μg/m3.
...............................
14.5 total
................
Study limitations
Authors noted
workers may
have been sensitized prior to
available screening, underestimating sensitization rate in
legacy workers.
Study did not report use of PPE
or respirators.
Additional
comments
Instituted PPE to
reduce dermal
exposures.
Personal sampling.
Study reported
prevalence rates
for pre enhanced
control-program,
partial enhanced
control program,
and full enhanced control
program.
Nuclear Weapons Production Facilities and Cleanup of Former Facilities
Kreiss et al., 1989 ..
Cross-sectional
survey of 51
workers.
Cross-sectional
survey of 895
workers.
11.8 (6
cases).
7.8 (4
cases).
...............................
No ..........
Small study population
1.9 (18
cases).
1.7 (15
cases).
...............................
No ..........
Stange et al., 1996
Longitudinal Study
of 4,397 BHSP
participants.
2.4 (76
cases).
0.7 (29
cases).
No ..........
Personal sampling.
Stange et al., 2001
Longitudinal study
of 5,173 workers.
4.5 (154
cases).
1.6 (81
cases).
No ..........
...............................
Personal sampling.
Viet et al., 2000 ......
Case-control ..........
74 workers
sensitized.
50 workers
CBD.
Annual mean concentration.
1970–1988 0.016
μg/m3; 1984–
1987 1.04 μg/m3.
No quantitative information presented in study.
Mean exposure
range: 0.083–
0.622 μg/m3.
Maximum exposures: 0.54–36.8
μg/m.3
Study population
includes some
workers with no
reported Be exposure.
...............................
Yes ........
Likely underestiFixed airhead sammated exposures.
pling away from
breathing zone:
Matched controls
for age, sex,
smoking.
Kreiss et al., 1993a
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Federal Register / Vol. 80, No. 152 / Friday, August 7, 2015 / Proposed Rules
47621
TABLE A.2—SUMMARY OF MECHANISTIC ANIMAL STUDIES FOR SENSITIZATION AND CBD
Reference
Species
Dose or
exposure
concentration
Study length
Type of beryllium
Study results
Other information
Intratracheal (intrabroncheal) or Nasal Instillation
Barna et al., 1981 ..
Guinea
pig.
3 month
10 mg5μm
particle
size.
beryllium oxide ......
Barna et al., 1984 ..
Guinea
pig.
3 month
5 mg ......
beryllium oxide ......
Benson et al., 2000
Mouse ....
..................................................
0, 12.5,
25,
100μg;
0, 2, 8
μg.
beryllium copper
alloy; beryllium
metal.
Haley et al., 1994 ...
Cynomolgus
monkey.
14, 60, 90 days
Huang et al., 1992
Mouse ....
..................................................
Votto et al., 1987 ....
Rat .........
3 month
0, 1, 50,
Beryllium metal,
150 μg.
beryllium oxide.
0, 2.5,
12.5,
37.5 μg.
5 μg ....... Beryllium sulfate
1–5 μg ...
immunization;
beryllium metal
challenge.
2.4 mg ...
8 mg/ml
Beryllium sulfate
immunization;
beryllium sulfate
challenge.
Granulomas, interstitial infiltrate
with fibrosis with
thickening of alveolar septae.
Granulomatous lesions in strain 2
but not strain 13
indicating a genetic component.
Acute pulmonary
toxicity associated with beryllium/copper alloy
but not beryllium
metal.
Beryllium oxide
particles were
less toxic than
the beryllium
metal.
Granulomas produced in A/J
strain but not
BALB/c or
C57BL/6.
Granulomas, however, no correlation between Tcell subsets in
lung and BAL
fluid.
Inhalation—Single Exposure
Haley et al., 1989a
Beagle
dog.
Chronic—one dose
0, 6 μg/
kg, 18
μg/kg.
500 °C; 1000 °C
beryllium oxide.
Haley et al., 1989b
Beagle
dog.
Chronic—one dose/2 year
recovery
0, 17 μg/
kg, 50
μg/kg.
500 °C; 1000 °C
beryllium oxide.
Robinson et al.,
1968.
Dog ........
Chronic
0. 115mg/
m3.
Sendelbach et al.,
1989.
Sendelbach and
Witschi, 1987.
Rat .........
2 week
Rat .........
2 week
0, 4.05
μg/L.
0, 3.3, 7
μg/L.
Beryllium oxide, beryllium fluoride,
beryllium chloride.
Beryllium as berylInterstial pneumolium sulfate.
nitis.
Beryllium as berylEnzyme changes in
lium sulfate.
BAL fluid.
Positive BeLPT results—developed
granulomas; lowcalcined beryllium oxide more
toxic than highcalcined.
Granulomas, sensitization, lowfired more toxic
than high fired.
Foreign body reaction in lung.
Granulomas resolved with time,
no full-blown
CBD.
Granulomas resolved over time.
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Inhalation—Repeat Exposure
Conradi et al., 1971
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0. 3300
1400 °C beryllium
μg/m3,
oxide.
4380
μg/m3
once/
month
for 3
months.
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May have been
due to short exposure time followed by long recovery.
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TABLE A.2—SUMMARY OF MECHANISTIC ANIMAL STUDIES FOR SENSITIZATION AND CBD—Continued
Reference
Species
Macaca
irus
Monkey.
Haley et al., 1992 ...
Harmsen et al.,
1985.
Dose or
exposure
concentration
Study length
Chronic—2 year
Beagle
dog.
Beagle
dog.
5 dogs
per
group.
Chronic—repeat dose (2.5
year intervals)
Chronic
Type of beryllium
0. 3300
1400 °C beryllium
μg/m3,
oxide.
4380
μg/m3
once/
month
for 3
months.
17, 50
500 °C; 1000 °C
μg/kg.
beryllium oxide.
0, 20 μg/
500°C; 1000 °C bekg, 50
ryllium oxide.
μg/kg.
Study results
No changes detected.
Other information
May have been
due to short exposure time followed by long recovery.
Granulomatous
pneumonitis.
Dermal or Intradermal
Kang et al., 1977 ....
Rabbit ....
..................................................
10mg .....
Beryllium sulfate ....
Tinkle et al., 2003 ..
Mouse ....
3 month
25 μL .....
70 μg .....
Beryllium sulfate ....
Beryllium oxide ......
Skin sensitization
and skin
granulomas.
Microgranulomas
with some resolution over time
of study.
Beryllium sulfate ....
Sensitization, evidence of CBD.
Intramuscular
Eskenasy, 1979 ......
Rabbit ....
35 days (injections at 7 day
intervals)
10mg.ml
Intraperitoneal Injection
Marx and Burrell,
1973.
Guinea
pig.
24 weeks (biweekly injections)
2.6 mg +
10 μg
dermal
injections.
Beryllium sulfate ....
Sensitization.
TABLE A–3—SUMMARY OF BERYLLIUM LUNG CANCER EPIDEMIOLOGICAL STUDIES
Reference
Study type
Exposure range
Study number
Mortality ratio
Confounding factors
Study limitations
Exposure concentration data
or smoking habits not reported.
..............................
Additional comments
Beryllium Case Registry
Cohort ..................
N/D ......................
421 cases from
the BCR.
SMR 2.12 ............
7 lung cancer
deaths.
Not reported ........
Steenland and
Ward, 1991.
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Infante et al., 1980
Cohort ..................
N/D ......................
689 cases from
the BCR.
SMR 2.00 (95%
CI 1.33–2.89).
28 lung cancer
deaths.
..............................
Included women:
93% women diagnosed with
CBD; 50% men
diagnosed with
CBD;
SMR 157 for
those with CBD
and SMR 232
for those with
ABD.
Beryllium Manufacturing and/or Processing Plants (Extraction, Fabrication, and Processing)
Ward et al., 1992 ..
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Mortality Cohort.
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9,225 males .........
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SMR 1.26 ............
(95% CI 1.12–
1.42).
280 lung cancer
deaths.
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Lack of job history
and air monitoring data.
07AUP2
Employment period 1940–1969.
Federal Register / Vol. 80, No. 152 / Friday, August 7, 2015 / Proposed Rules
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TABLE A–3—SUMMARY OF BERYLLIUM LUNG CANCER EPIDEMIOLOGICAL STUDIES—Continued
Study limitations
Additional comments
Adjusted for
smoking.
Lack of job history
and air monitoring data.
..............................
..............................
SMR 1.42 ............
(95% CI 1.1–1.8)
80 lung cancer
deaths.
Only partial smoking history.
Same OH and PA
plant analysis.
SMR 1.40 ............
No smoking adjustment.
Partial smoking
history; No job
analysis by title
or exposure category.
No adjustment by
job title or exposure.
Majority of workers studied employed for less
than one year
Employed prior to
1947 for almost
half lung cancer
deaths.
Employment period from 1937–
1948.
N/D ......................
3,685 white males
SMR 1.49 ............
Adjusted for age
and local.
Cohort ..................
N/D ......................
3,055 white males
PA plant.
SMR 1.25 ............
(95% CI 0.9–1.7)
47 lung cancer
deaths.
..............................
Sanderson et al.,
2001.
Nested case-control.
3,569 males PA
plant.
May not have adjusted properly
for birth-year or
age at hire.
Nested case-control.
SMR 1.22 ............
(95% CI 1.03–
1.43).
142 lung cancer
deaths.
SMR 1.04 ............
(95% CI 0.92–
1.17).
Smoking was
found not to be
a confounding
factor.
Levy et al., 2007 ...
— Average exposure 22.8μg/m3.
— Maximum exposure 32.4μg/
m 3.
Used log transformed exposure data.
Different methodology for smoking adjustment.
..............................
Schubauer-Berigan
et al., 2008.
Nested case-control.
Used exposure
data from
Sanderson et
al., 2001, Chen
2001, and
Couch et al.,
2010.
Reanalysis of
Sanderson et
al., 2001.
Used Odds ratio:
1.91 (95% CI
1.06–3.44)
unadjusted;.
1.29 (95% CI
0.61–2.71)
birth-year adjusted;.
1.24 (95% CI
0.58–2.65) agehire adjusted.
Adjusted for
smoking, birth
cohort, age.
..............................
Schubauer-Berigan
et al., 2010a.
Cohort ..................
N/D ......................
9199 workers
from 7 processing plants.
SMR 1.17 (95%CI
1.08–1.28).
545 deaths ..........
Adjusted for
smoking.
..............................
Schubauer-Berigan
et al., 2010b.
Cohort ..................
Used exposure
data from
Sanderson et
al., 2001.
5436 workers OH
and PA plants.
Evaluated using
hazard ratios
and excess absolute risk.
293 deaths ..........
Adjusted for age,
birth cohort, asbestos exposure, short-term
work status.
..............................
Study type
Exposure range
Study number
Mortality ratio
Levy et al., 2002 ...
Cohort ..................
N/D ......................
9225 males ..........
Bayliss et al., 1971
Nested cohort ......
..............................
8,000 workers ......
Statistically nonsignificant elevation in lung
cancer deaths.
SMR 1.06 ............
36 lung cancer
deaths.
Mancuso, 1970 .....
Cohort ..................
Cohort ..................
411–43,300 μg/m3
annual exposure (reported
from Zielinsky,
1961).
N/D ......................
1,222 workers at
OH plant; 2,044
workers at PA
plant.
Mancuso, 1980 .....
Mancuso and El
Attar, 1969.
Cohort ..................
Wagner et al.,
1980.
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Reference
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Reanalysis of
Sanderson et
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Confounding factors
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No job exposure
data or smoking
adjustment.
Inadequately adjusted for smoking; Used national lung-cancer risk for cancer not PA.
07AUP2
Employment period from 1942–
1948; Used
workers at
rayon plant for
comparison.
Employment history from 1937–
1944.
Reanalysis using
PA lung-cancer
rate revealed
19% underestimation of beryllium lung cancer deaths.
Found association
with 20 year latency.
Found no association between
beryllium exposure and increased risk of
lung cancer.
— Controlled for
birth-year and
age at hire;
— Found similar
results to
Sanderson et
al., 2001;
— Found association with 10
year latency
— ‘‘0’’ = used
minuscule value
at start to eliminate the use of
0 in a logarithmic analysis
Male workers employed at least
2 days between
1940 and 1970.
— Exposure response was
found between
0–10μg/m3
mean DWA;
— Increased with
statistical significance at 4μg/
m3;
— 1 in 1000 risk
at 0.033μg/m3
mean DWA.
47624
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TABLE A–3—SUMMARY OF BERYLLIUM LUNG CANCER EPIDEMIOLOGICAL STUDIES—Continued
Reference
Study type
Exposure range
Study number
Mortality ratio
Confounding factors
Study limitations
Additional comments
Found lung cancer excess risk
was associated
with higher levels of exposure
not relevant in
today’s industrial settings.
— Greater lung
cancer risk in
the BCR cohort
— Correlation between highest
lung cancer
rates and highest amounts of
ABD or other
non-malignant
lung diseases
— Increased risk
with longer latency
— Greater excess
lung cancers
among those
hired prior to
1950.
Re-evaluation of Published Studies
Hollins et al., 2009
Review .................
Re-examination of
weight-of-evidence from
more than 50
publications.
..............................
..............................
..............................
..............................
IARC, 2012 ...........
Multiple ................
Insufficient exposure concentration.
Data .....................
..............................
Sufficient evidence for carcinogenicity of
beryllium.
IARC concluded
beryllium lung
cancer risk was
not associated
with smoking.
..............................
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N/D = information not determined for most studies
DWA—daily weighted average
VI. Preliminary Beryllium Risk
Assessment
The Occupational Safety and Health
(OSH) Act and court cases arising under
it have led OSHA to rely on risk
assessment to support the risk
determinations required to set a
permissible exposure limit (PEL) for a
toxic substance in standards under the
OSH Act. Section 6(b)(5) of the OSH Act
states that ‘‘The Secretary [of Labor], in
promulgating standards dealing with
toxic materials or harmful physical
agents under this subsection, shall set
the standard which most adequately
assures, to the extent feasible, on the
basis of the best available evidence, that
no employee will suffer material
impairment of health or functional
capacity even if such employee has
regular exposure to the hazard dealt
with by such standard for the period of
his working life’’ (29 U.S.C. 655(b)(5)).
In Industrial Union Department, AFL–
CIO v. American Petroleum Institute,
448 U.S. 607 (1980) (Benzene), the
United States Supreme Court ruled that
the OSH Act requires that, prior to the
issuance of a new standard, a
determination must be made that there
is a significant risk of material
impairment of health at the existing PEL
and that issuance of a new standard will
significantly reduce or eliminate that
risk. The Court stated that ‘‘before [the
Secretary] can promulgate any
permanent health or safety standard, the
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Secretary is required to make a
threshold finding that a place of
employment is unsafe—in the sense that
significant risks are present and can be
eliminated or lessened by a change in
practices’’ (Id. at 642). The Court also
stated ‘‘that the Act does limit the
Secretary’s power to requiring the
elimination of significant risks’’ (488
U.S. at 644 n.49), and that ‘‘OSHA is not
required to support its finding that a
significant risk exists with anything
approaching scientific certainty’’ (Id. at
656).
OSHA’s approach for the risk
assessment incorporates both a review
of the recent literature on populations of
workers exposed to beryllium below the
current Permissible Exposure Limit
(PEL) of 2 mg/m3 and a statistical
exposure-response analysis. OSHA
evaluated risk at several alternate PELs
under consideration by the Agency: 2
mg/m3, 1 mg/m3, 0.5 mg/m3, 0.2 mg/m3,
and 0.1 mg/m3. A number of recently
published epidemiological studies
evaluate the risk of sensitization and
CBD for workers exposed at and below
the current PEL and the effectiveness of
exposure control programs in reducing
risk. OSHA also conducted a statistical
analysis of the exposure-response
relationship for sensitization and CBD at
the current PEL and alternate PELs the
Agency is considering. For this analysis,
OSHA used data provided by National
Jewish Medical and Research Center
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Sfmt 4702
(NJMRC) on a population of workers
employed at a beryllium machining
plant in Cullman, AL. The review of the
epidemiological studies and OSHA’s
own analysis show substantial risk of
sensitization and CBD among workers
exposed at and below the current PEL
of 2 mg/m3. They also show substantial
reduction in risk where employers have
implemented a combination of controls,
including stringent control of airborne
beryllium levels and additional
measures such as respirators, dermal
personal protective equipment (PPE),
and strict housekeeping to protect
workers against dermal and respiratory
beryllium exposure. To evaluate lung
cancer risk, OSHA relied primarily on a
quantitative risk assessment published
in 2011 by NIOSH. This risk assessment
was based on an update of the Reading
cohort analyzed by Sanderson et al., as
well as workers from two smaller plants
(Schubauer-Berigan et al., 2011) where
workers were exposed to lower levels of
beryllium and worked for longer periods
than at the Reading plant. The authors
found that lung cancer risk was strongly
and significantly related to mean,
cumulative, and maximum measures of
workers’ exposure; they predicted
substantial risk of lung cancer at the
current PEL, and substantial reductions
in risk at the alternate PELs OSHA
considered for the proposed rule
(Schubauer-Berigan et al., 2011).
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Federal Register / Vol. 80, No. 152 / Friday, August 7, 2015 / Proposed Rules
A. Review of Epidemiological Literature
on Sensitization and Chronic Beryllium
Disease From Occupational Exposure
As discussed in the Health Effects
section, studies of beryllium-exposed
workers conducted using the beryllium
lymphocyte proliferation test (BeLPT)
have found high rates of beryllium
sensitization and CBD among workers in
many industries, including at some
facilities where exposures were
primarily below OSHA’s PEL of 2 mg/m3
(Kreiss et al., 1993; Henneberger et al.,
2001; Schuler et al., 2005; Schuler et al.,
2012). In the mid-1990s, some facilities
using beryllium began to aggressively
monitor and reduce workplace
exposures. Four plants where several
rounds of BeLPT screening were
conducted before and after
implementation of new exposure
control methods provide the best
currently available evidence on the
effectiveness of various exposure
control measures in reducing the risk of
sensitization and CBD. The experiences
of these plants—a copper-beryllium
processing facility in Reading, PA, a
beryllia ceramics facility in Tucson, AZ;
a beryllium processing facility in
Elmore, OH; and a machining facility in
Cullman, AL—show that efforts to
prevent sensitization and CBD by using
engineering controls to reduce workers’
beryllium exposures to median levels at
or around 0.2 mg/m3 and did not
emphasize PPE and stringent
housekeeping methods, had only
limited impact on risk. However,
exposure control programs implemented
more recently, which drastically
reduced respiratory exposure to
beryllium via a combination of
engineering controls and respiratory
protection, controlled dermal contact
with beryllium using PPE, and
employed stringent housekeeping
methods to keep work areas clean and
prevent transfer of beryllium between
work areas, sharply curtailed new cases
of sensitization among newly-hired
workers. There is additional, but more
limited, information available on the
occurrence of sensitization and CBD
among aluminum smelter workers with
low-level beryllium exposures (Taiwo et
al., 2008; Taiwo et al., 2010; Nilsen et
al., 2010). A discussion of the
experiences at these plants follows.
The Health Effects section also
discussed the role of particle
characteristics and beryllium compound
solubility in the development of
sensitization and CBD among berylliumexposed workers. Respirable particles
small enough to reach the deep lung are
responsible for CBD. However, larger
inhalable particles that deposit in the
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upper respiratory tract may lead to
sensitization. The weight of evidence
indicates that both soluble and
insoluble forms of beryllium are able to
induce sensitization and CBD. Insoluble
forms of beryllium that persist in the
lung for longer periods may pose greater
risk of CBD while soluble forms may
more easily trigger immune
sensitization. Although these factors
potentially influence the toxicity of
beryllium, the available data are too
limited to reliably account for solubility
and particle size in the Agency
estimates of risk. The qualitative impact
on conclusions and uncertainties with
regard to risk are discussed in a later
section.
1. Reading, PA, Plant
Schuler et al. conducted a study of
workers at a copper-beryllium
processing facility in Reading, PA,
screening 152 workers with the BeLPT
(Schuler et al., 2005). Exposures at this
plant were believed to be low
throughout its history due to the low
percentage of beryllium in the metal
alloys used, and the relatively low
exposures found in general area samples
collected starting in 1969 (sample
median ≤ 0.1 mg/m3, 97% < 0.5 mg/m3).
The reported prevalences of
sensitization (6.5 percent) and CBD (3.9
percent) showed substantial risk at this
facility, even though airborne exposures
were primarily below OSHA’s current
PEL of 2 mg/m3.
Personal lapel samples were collected
in production and production support
jobs between 1995 and May 2000. These
samples showed primarily very low
airborne beryllium levels, with a
median of 0.073 mg/m3.6 The wire
annealing and pickling process had the
highest personal lapel sample values,
with a median of 0.149 mg/m3. Despite
these low exposure levels, cases of
sensitization continued to occur among
workers whose first exposures to
beryllium occurred in the 1990s. Five
(11.5 percent) workers of 43 hired after
1992 who had no prior beryllium
exposure became sensitized, including
four in production work and one in
production support (Thomas et al.,
2009; evaluation for CBD not reported).
Two (13 percent) of these sensitized
workers were among 15 workers in this
group who had been hired less than a
year before the screening.
After the BeLPT screening was
conducted in 2000, the company began
implementing new measures to further
6 In their publication, Schuler et al. presented
median values for plant-wide and work-categoryspecific exposure levels; they did not present
arithmetic or geometric mean values for personal
samples.
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47625
reduce workers’ exposure to beryllium.
Requirements designed to minimize
dermal contact with beryllium,
including long-sleeve facility uniforms
and polymer gloves, were instituted in
production areas in 2000. In 2001 the
company installed local exhaust
ventilation (LEV) in die grinding and
polishing. Personal lapel samples
collected between June 2000 and
December 2001 show reduced exposures
plant-wide. Of 2,211 exposure samples
collected during this ‘‘pre-enclosure
program’’ period, 98 percent were below
0.2 mg/m3 (Thomas et al., 2009, p. 124).
Median, arithmetic mean, and geometric
mean values ≤ 0.03 mg/m3 were reported
in this period for all processes except
the wire annealing and pickling process.
Samples for this process remained
elevated, with a median of 0.1 mg/m3
(arithmetic mean of 0.127 mg/m3,
geometric mean of 0.083 mg/m3). In
January 2002, the plant enclosed the
wire annealing and pickling process in
a restricted access zone (RAZ), required
respiratory PPE in the RAZ, and
implemented stringent measures to
minimize the potential for skin contact
and beryllium transfer out of the zone.
While exposure samples collected by
the facility were sparse following the
enclosure, they suggest exposure levels
comparable to the 2000–01 samples in
areas other than the RAZ. Within the
RAZ, required use of powered airpurifying respirators (PAPRs) indicates
that respiratory exposure was negligible.
A 2009 publication on the facility
reported that outside the RAZ, ‘‘the vast
majority of employees do not wear any
form of respiratory protection due to
very low airborne beryllium
concentrations’’ (Thomas et al., 2009, p.
122).
To test the efficacy of the new
measures in preventing sensitization
and CBD, in June 2000 the facility began
an intensive BeLPT screening program
for all new workers. The company
screened workers at the time of hire; at
intervals of 3, 6, 12, 24, and 48 months;
and at 3-year intervals thereafter.
Among 82 workers hired after 1999,
three cases of sensitization were found
(3.7 percent). Two (5.4 percent) of 37
workers hired prior to enclosure of the
wire annealing and pickling process
were found to be sensitized within 3
and 6 months of beginning work at the
plant. One (2.2 percent) of 45 workers
hired after the enclosure was confirmed
as sensitized. Among these early results,
it appears that the greatest reduction in
sensitization risk was achieved after
median exposures in all areas of the
plant were reduced to below 0.1 mg/m3
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and PPE to prevent dermal contact was
instituted.
2. Tucson, AZ, Plant
Kreiss et al. conducted a study of
workers at a beryllia ceramics plant,
screening 136 workers with the BeLPT
in 1992 (Kreiss et al., 1996). Full-shift
area samples collected between 1983
and 1992 showed primarily low
airborne beryllium levels at this facility.
Of 774 area samples, 76 percent were at
or below 0.1 mg/m3 and less than 1
percent exceeded 2 mg/m3. A small set
(75) of personal lapel samples collected
at the plant beginning in 1991 had a
median of 0.2 mg/m3 and ranged from
0.1 to 1.8 mg/m3 (arithmetic and
geometric mean values not reported)
(Kreiss et al., 1996, p. 19). However,
area samples and short-term breathing
zone samples also showed occasional
instances of very high beryllium
exposure levels, with extreme values of
several hundred mg/m3 and 3.6 percent
of short-term breathing zone samples in
excess of 5 mg/m3.
Kreiss et al. reported that eight (5.9
percent) of 136 workers tested were
sensitized, six (4.4 percent) of whom
were diagnosed with CBD. Seven of the
eight sensitized employees had worked
in machining, where general area
samples collected between October 1985
and March 1988 had a median of 0.3 mg/
m3, in contrast to a median value of less
than 0.1 mg/m3 in other areas of the
plant (Kreiss et al., 1996, p. 20; mean
values not reported). Short-term
breathing zone measurements associated
with machining had a median of 0.6 mg/
m3, double the median of 0.3 mg/m3 for
breathing zone measurements associated
with other processes (id., p. 20; mean
values not reported). One sensitized
worker was one of 13 administrative
workers screened, and was among those
diagnosed with CBD. Exposures of
administrative workers were not wellcharacterized, but were believed to be
among the lowest in the plant. Of three
personal lapel samples reported for
administrative staff during the 1990s, all
were below the then detection limit of
0.2 mg/m3 (Cummings et al., 2007,
p.138).
Following the 1992 screening, the
facility reduced exposures in machining
areas by enclosing machines and
installing HEPA filter exhaust systems.
Personal samples collected between
1994 and 1999 had a median of 0.2 mg/
m3 in production jobs and 0.1 mg/m3 in
production support (geometric means
0.21 mg/m3 and 0.11 mg/m3, respectively;
arithmetic means not reported.
Cummings et al., 2007, p. 138). In 1998,
a second screening found that 9 percent
of tested workers hired after the 1992
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screening were sensitized, of whom one
was diagnosed with CBD. All of the
sensitized workers had been employed
at the plant for less than two years
(Henneberger et al., 2001).
Following the 1998 screening, the
company continued efforts to reduce
exposures and risk of sensitization and
CBD by implementing additional
engineering and administrative controls
and PPE. Respirator use was required in
production areas beginning in 1999, and
latex gloves were required beginning in
2000. The lapping area was enclosed in
2000, and enclosures were installed for
all mechanical presses in 2001. Between
2000 and 2003, water-resistant or waterproof garments, shoe covers, and taped
gloves were incorporated to keep
beryllium-containing fluids from wet
machining processes off the skin. The
new engineering measures did not
appear to substantially reduce airborne
beryllium levels in the plant. Personal
lapel samples collected in production
processes between 2000 and 2003 had a
median and geometric mean of 0.18 mg/
m3, similar to the 1994–1999 samples
(Cummings et al., 2007, p. 138).
However, respiratory protection
requirements were instituted in 2000 to
control workers’ airborne beryllium
exposures.
To test the efficacy of the new
measures instituted after 1998, in
January 2000 the company began
screening new workers for sensitization
at the time of hire and at 3, 6, 12, 24,
and 48 months of employment
(Cummings et al., 2007). These more
stringent measures appear to have
substantially reduced the risk of
sensitization among new employees. Of
97 workers hired between 2000 and
2004, one case of sensitization was
identified (1 percent). This worker had
experienced a rash after an incident of
dermal exposure to lapping fluid
through a gap between the glove and
uniform sleeve, indicating that
sensitization may have occurred via
skin exposure.
3. Elmore, OH, Plant
Kreiss et al., Schuler et al., and Bailey
et al. conducted studies of workers at a
beryllium metal, alloy, and oxide
production plant. Workers participated
in BeLPT surveys in 1992 (Kreiss et al.,
1997) and in 1997 and 1999 (Schuler et
al., 2012). Exposure levels at the plant
between 1984 and 1993 were
characterized by a mixture of general
area, short-term breathing zone, and
personal lapel samples. Kreiss et al.
reported that the median area samples
for various work areas ranged from 0.1
to 0.7 mg/m3, with the highest values in
the alloy arc furnace and alloy melting-
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casting areas (other measures of central
tendency not reported). Personal lapel
samples were available from 1990–1992,
and showed high exposures overall
(median value of 1.0 mg/m3) with very
high exposures for some processes. The
authors reported median sample values
of 3.8 mg/m3 for beryllium oxide
production, 1.75 mg/m3 for alloy melting
and casting, and 1.75 mg/m3 for the arc
furnace.
Kreiss et al. reported that 43 (6.9
percent) of 627 workers tested in 1992
were sensitized, six of whom were
diagnosed with CBD (4.4 percent).
Workers with less than one year tenure
at the plant were not tested in this
survey (Bailey et al., 2010, p. 511). The
work processes that appeared to carry
the highest risk for sensitization and
CBD (e.g., ceramics) were not those with
the highest reported exposure levels
(e.g., arc furnace and melting-casting).
The authors noted several possible
reasons for this, including factors such
as solubility, particle size/number, and
particle surface area that could not be
accounted for in their analysis (Kreiss et
al., 1997).
In 1996–1999, the company took steps
to reduce workers’ beryllium exposures:
some high-exposure processes were
enclosed, special restricted-access zones
were set up, HEPA filters were installed
in air handlers, and some ventilation
systems were updated. In 1997 workers
in the pebble plant restricted access
zone were required to wear half-face airpurifying respirators, and beginning in
1999 all new employees were required
to wear loose-fitting powered airpurifying respirators (PAPR) in
manufacturing buildings (Bailey et al.,
2010, p. 506). Skin protection became
part of the protection program for new
employees in 2000, and glove use was
required in production areas and for
handling work boots beginning in 2001.
Also beginning in 2001, either half-mask
respirators or PAPRs were required in
the production facility (type determined
by airborne beryllium levels), and
respiratory protection was required for
roof work and during removal of work
boots (Bailey et al., 2010, p. 506).
Respirator use was reported to be used
on about half or less of industrial
hygiene sample records for most
processes in 1990–1992 (Kreiss et al.,
1996).
Beginning in 2000, workers were
offered periodic BeLPT testing to
evaluate the effectiveness of a new
exposure control program implemented
by the company. Bailey et al. (2010)
reported on the results of this
surveillance for 290 workers hired
between February 21, 2000 and
December 18, 2006. They compared the
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occurrence of beryllium sensitization
and disease among 258 employees who
began work at the Elmore plant between
January 15, 1993 and August 9, 1999
(the ‘pre-program group’) and among
290 employees who were hired between
February 21, 2000 and December 18,
2006 and were tested at least once after
hire (the ‘program group’). They found
that, as of 1999, 23 (8.9 percent) of the
pre-program group were sensitized to
beryllium. Six (2.1 percent) of the
program group had confirmed abnormal
results on their final round of BeLPTs,
which occurred in different years for
different employees. In addition,
another five employees had confirmed
abnormal BeLPT results at some point
during the testing period, followed by at
least one instance of a normal test
result. One of these employees had a
confirmed abnormal baseline BeLPT at
hire, and had two subsequent normal
BeLPT results at 6 and 12 months after
hire. Four others had confirmed
abnormal BeLPT results at 3 or 6
months after hire, later followed by a
normal test. Including these four in the
count of sensitized workers, there were
a total of ten (3.5 percent) workers
sensitized after hire in the program
group. It is not clear whether the
occurrence of a normal result following
an abnormal result reflects an error in
one of the test results, a change in the
presence or level of memory T-cells
circulating in the worker’s blood, or
other possibilities. Because most of the
workers in the study had been
employed at the facility for less than
two years, Bailey et al. did not report
the incidence of CBD among the
sensitized workers (Bailey et al., 2010,
p. 511).
In addition, Bailey et al. divided the
program group into the ‘partial program
subgroup’ (206 employees hired
between February 21, 2000 and
December 31, 2003) and the ‘full
program subgroup’ (84 employees hired
between January 1, 2004 and December
18, 2006) to account for the greater
effectiveness of the exposure control
program after the first three years of
implementation (Bailey et al., pp 506–
507). Four (1.9 percent) of the partial
program group were found to be
sensitized on their final BeLPT
(excluding one with a confirmed
abnormal BeLPT from their baseline test
at hire). Two (2.4 percent) of the full
program group were found to be
sensitized on their final BeLPT (Bailey
et al., 2010, p. 509). An additional three
employees in the partial program group
and one in the full program group were
confirmed sensitized at 3 or 6 months
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after hire, then later had a single normal
BeLPT (Bailey et al., 2010, p. 509).
Schuler et al. (2012) published a
study examining beryllium sensitization
and CBD among short-term workers at
the Elmore, OH plant, using exposure
estimates created by Virji et al. (2012).
The study population included 264
workers employed in 1999 with up to
six years tenure at the plant (91 percent
of the 291 eligible workers). By
including only short-term workers, Virji
et al. were able to construct
participants’ exposures with more
precision than was possible in studies
involving workers exposed for longer
durations and in time periods with less
exposure sampling. Each participant
completed a work history questionnaire
and was tested for beryllium
sensitization. The overall prevalence of
sensitization was 9.8 percent (26/264).
Sensitized workers were offered further
evaluation for CBD. Twenty-two
sensitized workers consented to clinical
testing for CBD via transbronchial
biopsy. Six of those sensitized were
diagnosed with CBD (2.3 percent, 6/
264).
Exposure estimates were constructed
using two exposure surveys conducted
in 1999: a survey of total mass
exposures (4022 full-shift personal
samples) and a survey of size-separated
impactor samples (198 samples). The
1999 exposure surveys and work
histories were used to estimate longterm lifetime weighted (LTW) average,
cumulative, and highest-job-worked
exposure for total, respirable, and
submicron beryllium mass
concentrations. Schuler et al. (2012)
found no cases of sensitization among
workers with total mass LTW average
exposures below 0.09 mg/m3, among
workers with total mass cumulative
exposures below 0.08 mg/m3-yr, or
among workers with total mass highest
job worked exposures below 0.12 mg/m3.
Twenty-four percent, 16 percent, and 25
percent of the study population were
exposed below those levels,
respectively. Both total and respirable
beryllium mass concentration estimates
were positively associated with
sensitization (average and highest job),
and CBD (cumulative) in logistic
regression models.
4. Cullman, AL, Plant
Newman et al. conducted a series of
BeLPT screenings of workers at a
precision machining facility between
1995 and 1999 (Newman et al., 2001). A
small set of personal lapel samples
collected in the early 1980s and in 1995
suggests that exposures in the plant
varied widely during this time period.
In some processes, such as engineering,
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lapping, and electrical discharge
machining (EDM), exposures were
apparently low (≤ 0.1 mg/m3). Madl et al.
reported that personal lapel samples
from all machining processes combined
had a median of 0.33 mg/m3, with a
much higher arithmetic mean of 1.63
mg/m3 (Madl et al., 2007, Table IV, p.
457). The majority of these samples
were collected in the high-exposure
processes of grinding (median of 1.05
mg/m3, mean of 8.48 mg/m3), milling
(median of 0.3 mg/m3, mean of 0.82 mg/
m3), and lathing (median of 0.35 mg/m3,
mean of 0.88 mg/m3) (Madl et al., 2007,
Table IV, p. 457). As discussed in
greater detail in the background
document,7 the data set of machining
exposure measurements included a few
extremely high values (41–73 mg/m3)
that a NIOSH researcher identified as
probable errors, and that appear to be
included in Madl et al.’s arithmetic
mean calculations. Because high singledata point exposure errors influence the
arithmetic mean far more than the
median value of a data range, OSHA
believes the median values reported by
Madl et al. are more reliable than the
arithmetic means they reported.
After a sentinel case of CBD was
diagnosed at the plant in 1995, the
company began BeLPT screenings to
identify workers at increased risk of
CBD and implemented engineering and
administrative controls and PPE
designed to reduce workers’ beryllium
exposures in machining operations.
Newman et al. reported 22 (9.4 percent)
sensitized workers among 235 tested, 13
of whom were diagnosed with CBD
within the study period. Between 1995
and 1997, the company built enclosures
and installed or updated local exhaust
ventilation (LEV) for several machining
departments, removed pressurized air
hoses, and required the use of company
uniforms. Madl et al. reported that
historically, engineering and work
process controls, rather than personal
protective equipment, were used to
limit workers’ exposure to beryllium;
respirators were used only in cases of
high exposure, such as during
sandblasting (Madl et al., 2007, p. 450).
In contrast to the Reading and Tucson
plants, gloves were not required at this
plant.
Personal lapel samples collected
extensively between 1996 and 1999 in
machining jobs have an overall median
of 0.16 mg/m3, showing that the new
controls achieved a marked reduction in
machinists’ exposures during this
7 When used throughout this section,
‘‘background document’’ refers to a more
comprehensive, companion risk-assessment
document that can be found at www.regulations.gov
in OSHA Docket No. ___.
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period. Nearly half of the samples were
collected in milling (median = 0.18 mg/
m3). Exposures in other machining
processes were also reduced, including
grinding (median of 0.18 mg/m3) and
lathing (median of 0.13 mg/m3).
However, cases of sensitization and CBD
continued to occur.
At the time that Newman et al.
reviewed the results of BeLPT
screenings conducted in 1995–1999, a
subset of 60 workers had been employed
at the plant for less than a year. Four
(6.7 percent) of these workers were
found to be sensitized, of whom two
were diagnosed with CBD and one with
probable CBD (Newman et al., 2001).
All four had been hired in 1996. Two
(one CBD case, one sensitized only) had
worked only in milling, and had worked
for approximately 3–4 months (0.3–0.4
yrs) at the time of diagnosis. One of
those diagnosed with CBD worked only
in EDM, where lapel samples collected
between 1996 and 1999 had a median of
0.03 mg/m3. This worker was diagnosed
with CBD in the same year that he began
work at the plant. The last CBD case
worked as a shipper, where exposures
in 1996–1999 were similarly low, with
a median of 0.09 mg/m3.
Beginning in 2000, exposures in all
jobs at the machining facility were
reduced to extremely low levels.
Personal lapel samples collected in
machining processes between 2000 and
2005 had a median of 0.09 mg/m3, where
more than a third of samples came from
the milling process (n = 765, median of
0.09 mg/m3). A later publication on this
plant by Madl et al. reported that only
one worker hired after 1999 became
sensitized. This worker had been
employed for 2.7 years in chemical
finishing, where exposures were
roughly similar to other machining
processes (n = 153, median of 0.12 mg/
m3). Madl et al. did not report whether
this worker was evaluated for CBD.
5. Aluminum Smelting Plants
Taiwo et al. (2008) studied a
population of 734 employees at four
aluminum smelters located in Canada
(2), Italy (1), and the United States (1).
In 2000, a beryllium exposure limit of
0.2 mg/m3 8-hour TWA (action level 0.1
mg/m3) and a short-term exposure limit
(STEL) of 1.0 mg/m3 (15-minute sample)
were instituted at these plants.
Sampling to determine compliance with
the exposure limit began at all smelters
in 2000. Table VI–1 below, adapted
from Taiwo et al. (2008), shows
summary information on samples
collected from the start of sampling
through 2005.
TABLE VI–1—EXPOSURE SAMPLING DATA BY PLANT—2000–2005
Number of
samples
Smelter
Canadian smelter 1 .........................................................................................
Canadian smelter 2 .........................................................................................
Italian smelter ..................................................................................................
U.S. smelter .....................................................................................................
Arithmetic
mean
(μg/m3)
Median
(μg/m3)
246
329
44
346
0.03
0.11
0.12
0.03
Geometric
mean
(μg/m3)
0.09
0.29
0.14
0.26
0.03
0.08
0.10
0.04
Adapted from Taiwo et al., 2008, Table 1.
All employees potentially exposed to
beryllium levels at or above the action
level for at least 12 days per year, or
exposed at or above the STEL 12 or
more times per year, were offered
medical surveillance including the
BeLPT (Taiwo et al., 2008, p. 158).
Table VI–2 below, adapted from Taiwo
et al. (2008), shows test results for each
facility between 2001 and 2005.
TABLE VI–2—BeLPT RESULTS BY PLANT—2001–2005
Employees
tested
Smelter
Canadian smelter 1 .........................................................................................
Canadian smelter 2 .........................................................................................
Italian smelter ..................................................................................................
U.S. smelter .....................................................................................................
Abnormal
BeLPT
(unconfirmed)
Normal
109
291
64
270
107
290
63
268
1
1
0
2
Confirmed
Sensitized
1
0
1
0
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Adapted from Taiwo et al., 2008, Table 2.
The two workers with confirmed
beryllium sensitization were offered
further evaluation for CBD. Both were
diagnosed with CBD, based on bronchoalveolar lavage (BAL) results in one case
and pulmony function tests, respiratory
symptoms, and radiographic evidence
in the other.
In 2010, Taiwo et al. published a
study of beryllium-exposed workers
from smelters at four companies,
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including some of the workers from the
2008 publication. 3,185 workers were
determined to be ‘‘significantly
exposed’’ to beryllium and invited to
participate in BeLPT screening. Each
company used different criteria to
determine ‘‘significant’’ exposure,
which appeared to vary considerably (p.
570). About 60 percent of invited
workers participated in the program
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between 2000 and 2006, of whom nine
were determined to be sensitized (see
Table VI–3 below). The authors state
that all nine workers were referred to a
respiratory physician for further
evaluation for CBD. Two were
diagnosed with CBD, as described above
(Taiwo et al., 2008). The authors do not
report the details of other sensitized
workers’ evaluation for CBD.
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TABLE VI–3—MEDICAL SURVEILLANCE FOR BeS IN ALUMINUM SMELTERS
Number of
smelters
Company
A
B
C
D
At-risk
employees
Employees
tested
BeS
.......................................................................................................................
.......................................................................................................................
......................................................................................................................
......................................................................................................................
4
3
1
1
1278
423
1100
384
734
328
508
362
4
0
4
1
Total ..........................................................................................................
9
3185
1932
9
Adapted from Taiwo et al., 2011, Table 1.
In general, there appeared to be a low
level of sensitization and CBD among
employees at the aluminum smelters
studied by Taiwo et al. This is striking
in light of the fact that many of the
employees tested had worked at the
smelters long before the institution of
exposure limits for beryllium at some
smelters in 2000. However, the authors
note that respiratory protection had long
been used at these plants to protect
workers from other hazards. The results
are roughly consistent with the observed
prevalence of sensitization following the
institution of respiratory protection at
the Tucson beryllium ceramics plant
discussed previously. A study by Nilsen
et al. (2010) also found a low rate of
sensitization among aluminum workers
in Norway. Three-hundred sixty-two
workers and thirty-one control
individuals received BeLPT testing for
beryllium sensitization. The authors
found one sensitized worker (0.28
percent). No borderline results were
reported. The authors reported that
current exposures in this plant ranged
from 0.1 mg/m3 to 0.31 mg/m3 (Nilsen et
al., 2010) and that respiratory protection
was in use, as is the case in the smelters
studied by Taiwo et al. (2008, 2010).
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B. Preliminary Conclusions
The published literature on beryllium
sensitization and CBD shows that risk of
both can be substantial in workplaces in
compliance with OSHA’s current PEL
(Kreiss et al., 1993; Schuler et al., 2005).
The experiences of several facilities in
developing effective industrial hygiene
programs have shown that minimizing
both airborne and dermal exposure,
using a combination of engineering and
administrative controls, respiratory
protection, and dermal PPE, has
substantially lowered workers’ risk of
beryllium sensitization. In contrast, riskreduction programs that relied primarily
on engineering controls to reduce
workers’ exposures to median levels in
the range of 0.1–0.2 mg/m3, such as
those implemented in Tucson following
the 1992 survey and in Cullman during
1996–1999, had only limited impact on
reducing workers’ risk of sensitization.
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The prevalence of sensitization among
workers hired after such controls were
installed at the Cullman plant remained
high (Newman et al. (6.7 percent) and
Henneberger et al. (9 percent)). A
similar prevalence of sensitization was
found in the screening conducted in
2000 at the Reading plant, where the
available sampling data show median
exposure levels of less than 0.2 mg/m3
(6.5 percent). The risk of sensitization
was found to be particularly high among
newly-hired workers (≤1 year of
beryllium exposure) in the Reading
2000 screening (13 percent) and the
Tucson 1998 screening (16 percent).
Cases of CBD have also continued to
develop among workers in facilities and
jobs where exposures were below 0.2
mg/m3. One case of CBD was found in
the Tucson 1998 screening among nine
sensitized workers hired less than two
years previously (Henneberger et al.,
2001). At the Cullman plant, at least two
cases of CBD were found among four
sensitized workers screened in 1995–
1999 and hired less than a year
previously (Newman et al., 2001). These
results suggest a substantial risk of
progression from sensitization to CBD
among workers exposed at levels well
below the current PEL, especially
considering the extremely short time of
exposure and follow-up for these
workers. Six of 10 sensitized workers
identified at Reading in the 2000
screening were diagnosed with CBD.
The four sensitized workers who did not
have CBD at their last clinical
evaluation had been hired between one
and five years previously; therefore, the
time may have been too short for CBD
to develop.
In contrast, more recent exposure
control programs that have used a
combination of engineering controls,
PPE, and stringent housekeeping
measures to reduce workers’ airborne
and dermal exposures have
substantially lowered risk of
sensitization among newly-hired
workers. Of 97 workers hired between
2000 and 2004 in Tucson, where
respiratory and skin protection was
instituted for all workers in production
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areas, only one (1 percent) worker
became sensitized, and in that case the
worker’s dermal protection had failed
during wet-machining work (Thomas et
al., 2009). In the aluminum smelters
discussed by Taiwo et al., where
available exposure samples indicated
median beryllium levels of about 0.1 mg/
m3 or below (measured as an 8-hour
TWA) and workers used respiratory and
dermal protection, confirmed cases of
sensitization were rare (zero or one case
per location). Sensitization was also rare
among workers at a Norwegian
aluminum smelter (Nilsen et al., 2010),
where estimated exposures in the plant
ranged from 0.1 mg/m3 to 0.3 mg/m3 and
respiratory protection was regularly
used. In Reading, where in 2000–2001
airborne exposures in all jobs were
reduced to a median of 0.1 mg/m3 or
below (measured as an 8-hour TWA)
and dermal protection was required for
production-area workers, two (5.4
percent) of 37 newly hired workers
became sensitized (Thomas et al., 2009).
After the process with the highest
exposures (median of 0.1 mg/m3) was
enclosed in 2002 and workers in that
process were required to use respiratory
protection, the remaining jobs had very
low exposures (medians ∼ 0.03 mg/m3).
Among 45 workers hired after the
enclosure, one was found to be
sensitized (2.2 percent). In Elmore,
where all workers were required to wear
respirators and skin PPE in production
areas beginning in 2000–2001, the
estimated prevalence of sensitization
among workers hired after these
measures were put in place was around
2–3 percent (Bailey et al., 2010). In
addition, Schuler et al. (2012) found no
cases of sensitization among short-term
Elmore workers employed in 1999 who
had total mass LTW average exposures
below 0.09 mg/m3, among workers with
total mass cumulative exposures below
0.08 mg/m3-yr, or among workers with
total mass highest job worked exposures
below 0.12 mg/m3.
Madl et al. reported one case of
sensitization among workers at the
Cullman plant hired after 2000. The
median personal exposures were about
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0.1 mg/m3 or below for all jobs during
this period. Several changes in the
facility’s exposure control methods were
instituted in the late 1990s that were
likely to have reduced dermal as well as
respiratory exposure to beryllium. For
example, the plant installed change/
locker rooms for workers entering the
production facility, instituted
requirements for work uniforms and
dedicated work shoes for production
workers, implemented annual beryllium
hazard awareness training that
encouraged glove use, and purchased
high efficiency particulate air (HEPA)
filter vacuum cleaners for workplace
cleanup and decontamination.
The results of the Reading, Tucson,
and Elmore studies show that reducing
airborne exposures to below 0.1 mg/m3
and protecting workers from dermal
exposure, in combination, have
achieved a substantial reduction in
sensitization risk among newly-hired
workers. Because respirator use, dermal
protection, and engineering changes
were often implemented concurrently at
these plants, it is difficult to attribute
the reduced risk to any single control
measure. The reduction is particularly
evident when comparing newly-hired
workers in the most recent Reading
screenings (2.2–5.4 percent), and the
rate of sensitization found among
workers hired within the year before the
2000 screening (13 percent). There is a
similarly striking difference between the
rate of prevalence found among newlyhired workers in the most recent Tucson
study (1 percent) and the rate found
among workers hired within the year
before the 1998 screening at that plant
(16 percent). These results are echoed in
the Cullman facility, which combined
engineering controls to reduce airborne
exposures to below 0.1 mg/m3 with
measures such as housekeeping
improvements and worker training to
reduce dermal exposure.
The studies on recent programs to
reduce workers’ risk of sensitization and
CBD were conducted on populations
with very short exposure and follow-up
time. Therefore, they could not address
the question of how frequently workers
who become sensitized in environments
with extremely low airborne exposures
(median <0.1 mg/m3) develop CBD.
Clinical evaluation for CBD was not
reported for sensitized workers
identified in the most recent Tucson,
Reading, and Elmore studies. In
Cullman, however, two of the workers
with CBD had been employed for less
than a year and worked in jobs with
very low exposures (median 8-hour
personal sample values of 0.03–0.09 mg/
m3). The body of scientific literature on
occupational beryllium disease also
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includes case reports of workers with
CBD who are known or believed to have
experienced minimal beryllium
exposure, such as a worker employed
only in shipping at a copper-beryllium
distribution center (Stanton et al., 2006),
and workers employed only in
administration at a beryllium ceramics
facility (Kreiss et al., 1996).
Arjomandi et al. published a study of
50 sensitized workers from a nuclear
weapons research and development
facility (Arjomandi et al., 2010).
Occupational and medical histories
including physical examination and
chest imaging were available for the
great majority (49) of these individuals.
Forty underwent testing for CBD via
bronchoscopy and transbronchial
biopsies. In contrast to the studies of
low-exposure populations discussed
previously, this group had much longer
follow-up time (mean time since first
exposure = 32 years) and length of
employment at the facility (mean of 18
years). Quantitative exposure estimates
for the workers were not presented;
however, the authors characterized their
probable exposures as ‘‘low’’ (13
workers), ‘‘moderate’’ (28 workers), or
‘‘high’’ (nine workers) based on the jobs
they performed at the facility.
Five of the 50 sensitized workers (10
percent) were diagnosed with CBD
based on histology or high-resolution
computed tomography. An additional
three (who had not undergone full
clinical evaluation for CBD) were
identified as probable CBD cases,
bringing the total prevalence of CBD and
probable CBD in this group to 16
percent. As discussed in the
epidemiology section of the Health
Effects chapter, the prevalence of CBD
among worker populations regularly
exposed at higher levels (e.g., median >
0.1 mg/m3) is typically much greater,
approaching 80–100% in several
studies. The lower prevalence of CBD in
this group of sensitized workers, who
were believed to have primarily low
exposure levels, suggests that
controlling respiratory exposure to
beryllium may reduce risk of CBD
among sensitized workers as well as
reducing risk of CBD via prevention of
sensitization. However, it also
demonstrates that some workers in lowexposure environments can become
sensitized and go on to develop CBD.
The next section discusses an additional
source of information on low-level
beryllium exposure and CBD: studies of
community-acquired CBD in residential
areas surrounding beryllium production
facilities.
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C. Review of Community-Acquired CBD
Literature
The literature on community-acquired
chronic beryllium disease (CA–CBD)
documents cases of CBD among
individuals exposed to airborne
beryllium at concentrations below the
proposed PEL. OSHA notes that these
case studies do not provide information
on how frequently individuals exposed
to very low airborne levels develop CBD
and that reconstructed exposure
estimates for CA–CBD cases are less
reliable than exposure estimates for
working populations reviewed in the
previous sections. In addition, the
cumulative exposure that an
occupationally exposed person would
accrue at any given exposure
concentration is far less than would
typically accrue from long-term
environmental exposure. The literature
on CA–CBD thus has important
limitations and is not used as a basis for
quantitative risk assessment for CBD
from low-level beryllium exposure.
Nevertheless, these case reports and the
broader CA–CBD literature indicate that
individuals exposed to airborne
beryllium below the proposed PEL can
develop CBD.
Cases of CA–CBD were first reported
among residents of Lorain, OH, and
Reading, PA, who lived in the vicinity
of beryllium plants. More recently,
BeLPT screening has been used to
identify additional cases of CA–CBD in
Reading.
1. Lorain, OH
In 1948, the State of Ohio Department
of Public Health conducted an X-ray
program surveying more than 6,000
people who lived within 1.5 miles of a
Lorain beryllium plant (Eisenbud, 1949;
Eisenbud, 1982; Eisenbud, 1998). This
survey, together with a later review of
all reported cases of CBD in the area,
found 13 cases of CBD. All of the
residents who developed CBD lived
within 0.75 miles of the plant, and none
had occupational exposure or lived with
beryllium-exposed workers. Among the
population of 500 people living within
0.25 miles of the plant, seven residents
(1.4 percent) were diagnosed with CBD.
Five cases were diagnosed among
residents living between 0.25 and 0.5
miles from the plant, one case was
diagnosed among residents living
between 0.5 and 0.75 miles from the
plant, and no cases were found among
those living farther than 0.75 miles from
the plant (total populations not
reported) (Eisenbud, 1998).
Beginning in January 1948, air
sampling was conducted using a mobile
sampling station to measure
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atmospheric beryllium downwind from
the plant. An approximate
concentration of 0.2 mg/m3 was
measured at 0.25 miles from the plant’s
exhaust stack, and concentrations
decreased with greater distance from the
plant, to 0.003 mg/m3 at a distance of 5
miles (Eisenbud, 1982). A 10-week
sampling program was conducted using
three fixed monitoring stations within
700 feet of the plant and one station
7,000 feet from the plant. Interpolating
the measurements collected at these
locations, Eisenbud and colleagues
estimated an average airborne beryllium
concentration of between 0.004 and 0.02
mg/m3 at a distance of 0.75 miles from
the plant. Accounting for the possibility
that previous exposures may have been
higher due to production level
fluctuations and greater use of rooftop
emissions, they concluded that the
lowest airborne beryllium level
associated with CA–CBD in this
community was somewhere between
0.01 mg/m3 and 0.1 mg/m3 (Eisenbud,
1982).
2. Reading, PA
Thirty-two cases of CA–CBD were
reported in a series of papers published
in 1959–1969 concerning a beryllium
refinery in Reading (Lieben and
Metzner, 1959; Metzner and Lieben,
1961; Dattoli et al., 1964; Lieben and
Williams, 1969). The plant, which
opened in 1935, manufactured
beryllium oxide, alloys and metal, and
beryllium tools and metal products
(Maier et al., 2008; Sanderson et al.,
2001b). In a follow-up study, Maier et
al. presented eight additional cases of
CA–CBD who had lived within 1.5
miles of the plant (Maier et al., 2008).
Individuals with a history of
occupational beryllium exposure and
those who had resided with
occupationally exposed workers were
not classified as having CA–CBD.
The Pennsylvania Department of
Health conducted extensive
environmental sampling in the area of
the plant beginning in 1958. Based on
samples collected in 1958, Maier et al.
stated that most cases identified in their
study would typically have been
exposed to airborne beryllium at levels
between 0.0155 and 0.028 mg/m3 on
average, with the potential for some
excursions over 0.35 mg/m3 (Maier et al
2008, p. 1015). To characterize
exposures to cases identified in the
earlier publications, Lieben and
Williams cited a sampling program
conducted by the Department of Health
between January and July 1962, using
nine sampling stations located between
0.2 and 4.8 miles from the plant. They
reported that 72 percent of 24-hour
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samples collected were below 0.01 mg/
m3. Of samples that exceeded 0.01 mg/
m3, most were collected at close
proximity to the plant (e.g., 0.2 miles
from the plant).
In the early series of publications,
cases of CA–CBD were reported among
people living both close to the plant
(Maier et al., 2008; Dutra, 1948) and up
to several miles away. Of new cases
identified in the 1968 update, all lived
between 3 and 7.5 miles from the plant.
Lieben and Williams suggested that
some cases of CA–CBD found among
more distant residents might have
resulted from working or visiting a
graveyard closer to the plant (Lieben
and Williams, 1969). For example, a
milkman who developed CA–CBD had a
route in the neighborhood of the plant.
Another resident with CA–CBD had
worked as a cleaning woman in the area
of the plant, and a third worked within
a half-mile of the plant.
At the time of the final follow-up
study (1968), 11 residents diagnosed
with CA–CBD were alive and 21 were
deceased. Among those who had died,
berylliosis was listed as the cause of
death for three, including a 10-year-old
girl and two women in their sixties.
Fibrosis, granuloma or granulomatosis,
and chronic or fibrous pneumonitis
were listed as the cause of death for
eight more of those deceased. Histologic
evidence of CBD was reported for nine
of 12 deceased individuals who had
been evaluated for it. In addition to
showing radiologic abnormalities
associated with CBD, all living cases
were dyspneic.
Following the 1969 publication by
Liebman and Williams, no additional
CA–CBD cases were reported in the
Reading area until 1999, when a new
case was diagnosed. The individual was
a 72-year-old woman who had had
abnormal chest x-rays for the previous
six years (Maier et al., 2008). After the
diagnosis of this case, Maier et al.
reviewed medical records and/or
performed medical evaluations,
including BeLPT results for 16
community residents who were referred
by family members or an attorney.
Among those referred, eight cases of
definite or probable CBD were identified
between 1999 and 2002. All eight were
women who lived between 0.1 and 1.05
miles from the plant, beginning between
1943–1953 and ending between 1956–
2001. Five of the women were
considered definite cases of CA–CBD,
based on an abnormal blood or lavage
cell BeLPT and granulomatous
inflammation on lung biopsy. Three
probable cases of CA–CBD were
identified. One had an abnormal BeLPT
and radiography consistent with CBD,
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47631
but granulomatous disease was not
pathologically proven. Two met
Beryllium Case Registry epidemiologic
criteria for CBD based on radiography,
pathology and a clinical course
consistent with CBD, but both died
before they could be tested for beryllium
sensitization. One of the probable cases,
who could not be definitively diagnosed
with CBD because she died before she
could be tested, was the mother of both
a definite case and the probable case
who had an abnormal BeLPT but did
not show granulomatous disease.
The individuals with CA–CBD
identified in this study suffered
significant health impacts from the
disease, including obstructive,
restrictive, and gas exchange pulmonary
defects in the majority of cases. All but
two had abnormal pulmonary
physiology. Those two were evaluated
at early stages of disease following their
mother’s diagnosis. Six of the eight
women required treatment with
prednisone, a step typically reserved for
severe cases due to the adverse side
effects of steroid treatment. Despite
treatment, three had died of respiratory
impairment from CBD as of 2002 (Maier
et al., 2008). The authors concluded that
‘‘low levels of exposures with
significant disease latency can result in
significant morbidity and mortality’’
(id., p. 1017).
OSHA notes that compared with the
occupational studies discussed in the
previous section, there is comparatively
sparse information on exposure levels of
Lorain and Reading residents. There
remains the possibility that some
individuals with CA–CBD may have had
higher exposures than were known and
reported in these studies, or have had
unreported exposure to beryllium dust
via contact with beryllium-exposed
workers. Nevertheless, the studies
conducted in Lorain and Reading
demonstrate that long-term exposure to
the apparent low levels of airborne
beryllium, with sufficient disease
latency, can lead to serious or fatal CBD.
Genetic susceptibility may play a role in
cases of CBD among individuals with
very low or infrequent exposures to
beryllium. The role of genetic
susceptibility in the CBD disease
process is discussed in detail in section
V.D.3.
D. Exposure-Response Literature on
Beryllium Sensitization and CBD
To further examine the relationship
between exposure level and risk of both
sensitization and disease, we next
review exposure-response studies in the
CBD literature. Many publications have
reported that exposure levels correlate
with risk, including a small number of
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exposure-response analyses. Most of
these studies examined the association
between job-specific beryllium air
measurements and prevalence of
sensitization and CBD. This section
focuses on studies at three facilities that
included a more rigorous historical
reconstruction of individual worker
exposures in their exposure-response
analyses.
1. Rocky Flats, CO, Facility
In 2000, Viet et al. published a casecontrol study of participants in the
Rocky Flats Beryllium Health
Surveillance Program (BHSP), which
was established in 1991 to screen
workers at the Department of Energy’s
Rocky Flats, CO, nuclear weapons
facility for beryllium sensitization and
evaluate sensitized workers for CBD
(Viet et al., 2000). The program, which
at the time of publication had tested
over 5,000 current and former Rocky
Flats employees, had identified a total
of 127 sensitized individuals as of 1994
when Viet et al. initiated their study.
Workers were considered sensitized if
two BeLPT results were positive, either
from two blood draws or from a single
blood draw analyzed by two different
laboratories. All sensitized individuals
were offered clinical evaluation, and 51
were diagnosed with CBD based on
positive lung LPT and evidence of
noncaseating granulomas upon lung
biopsy. The number of sensitized
individuals who declined clinical
evaluation was not reported. Two cases,
one with CBD and one who was
sensitized but not diagnosed with CBD,
were excluded from the case-control
analysis due to reported or potential
prior beryllium exposure at a ceramics
plant. Another sensitized individual
who had not been diagnosed with CBD
was excluded because she could not be
matched by the study’s criteria to a nonsensitized control within the BHSP
database. Viet et al. matched a total of
50 CBD cases to 50 controls who were
negative on the BeLPT and had the same
age (± 3 years), gender, race and
smoking status, and were otherwise
randomly selected from the database.
Using the same matching criteria, 74
sensitized workers who were not
diagnosed with CBD were age-, gender, race-, and smoking status-matched to
74 control individuals who tested
negative by the BeLPT from the BHSP
database.
Viet et al. developed exposure
estimates for the cases and controls
based on daily beryllium air samples
collected in one of 36 buildings where
beryllium was used at Rocky Flats, the
Building 444 Beryllium Machine Shop.
Over half of the approximately 500,000
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industrial hygiene samples collected at
Rocky Flats were taken from this
building. Air monitoring in other
buildings was reported to be limited and
inconsistent and, thus, not utilized in
the exposure assessment. The sampling
data used to develop worker exposure
estimates were exclusively Building 444
fixed airhead (FAH) area samples
collected at permanent fixtures placed
around beryllium work areas and
machinery.
Exposure estimates for jobs in
Building 444 were constructed for the
years 1960–1988 from this database.
Viet et al. worked with Rocky Flats
industrial hygienists and staff to assign
a ‘‘building area factor’’ (BAF) to each
of the other buildings, indicating the
likely level of exposure in a building
relative to exposures in Building 444.
Industrial hygienists and staff similarly
assigned a job factor (JF) to all jobs,
representing the likely level of
beryllium exposure relative to the levels
experienced by beryllium machinists. A
JF of 1 indicated the lowest exposures,
and a JF of 10 indicated the highest
exposures. For example, administrative
work and vehicle operation were
assigned a JF of 1, while machining,
mill operation, and metallurgical
operation were each assigned a JF of 10.
Estimated FAH values for each
combination of job, building and year in
the study subjects’ work histories were
generated by multiplying together the
job and building factors and the mean
annual FAH exposure level. Using data
collected by questionnaire from each
BHSP participant, Viet et al.
reconstructed work histories for each
case and control, including job title and
building location in each year of their
employment at Rocky Flats. These work
histories and the estimated FAH values
were used to generate a cumulative
exposure estimate (CEE) for each case
and control in the study. A long-term
mean exposure estimate (MEE) was
generated by dividing each CEE by the
individual’s number of years employed
at Rocky Flats.
Viet et al.’s statistical analysis of the
resulting data set included conditional
logistic regression analysis, modeling
the relationship between risk of each
health outcome and log-transformed
CEE and MEE. They found highly
statistically significant relationships
between log-CEE and risk of CBD (coef
= 0.837, p = 0.0006) and between logMEE (coef = 0.855, p = 0.0012) and risk
of CBD, indicating that risk of CBD
increases with exposure level. These
coefficients correspond to odds ratios of
6.9 and 7.2 per 10-fold increase in
exposure, respectively. Risk of
sensitization without CBD did not show
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a statistically significant relationship
with log-CEE (coef = 0.111, p = 0.32),
but showed a nearly-significant
relationship with log-MEE (coef = 0.230,
p = 0.097).
2. Cullman, AL, Facility
The Cullman, AL, precision
machining facility discussed previously
was the subject of a case-control study
published by Kelleher et al. in 2001.
After the diagnosis of an index case of
CBD at the plant in 1995, NJMRC
researchers worked with the plant to
conduct a medical surveillance program
using the BeLPT to screen workers
biennially for beryllium sensitization
and CBD. Of 235 employees screened
between 1995 and 1999, 22 (9.4 percent)
were found to be sensitized, including
13 diagnosed with CBD (Newman et al.,
2001). Concurrently, research was
underway by Martyny et al. to
characterize the particle size
distribution of beryllium exposures
generated by processes at this plant
(Martyny et al., 2000). The exposure
research showed that the machining
operations during this time period
generated respirable particles (10 mm or
less) at the worker breathing zone that
made up greater than 50 percent of the
beryllium mass. Kelleher et al. used the
dataset of 100 personal lapel samples
collected by Martyny et al. and other
NJMRC researchers in 1996, 1997, and
1999 to characterize exposures for each
job in the plant. Following a statistical
analysis comparing the samples
collected by NJMRC with earlier
samples collected at the plant, Kelleher
et al. concluded that the 1996–1999 data
could be used to represent job-specific
exposures from earlier periods.
Detailed work history information
gathered from plant data and worker
interviews was used in combination
with job exposure estimates to
characterize cumulative and LTW
average beryllium exposures for workers
in the surveillance program. In addition
to cumulative and LTW exposure
estimates based the total mass of
beryllium reported in their exposure
samples, Kelleher et al. calculated
cumulative and LTW estimates based
specifically on exposure to particles < 6
mm and particles < 1 mm in diameter.
To analyze the relationship between
exposure level and risk of sensitization
and CBD, Kelleher et al. performed a
case-control analysis using measures of
both total beryllium exposure and
particle size-fractionated exposure. The
analysis included sensitization cases
identified in the 1995–1999 surveillance
and 206 controls from the group of 215
non-sensitized workers. For nine
workers, the researchers could not
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reconstruct complete job histories.
Logistic regression models using
categorical exposure variables showed
positive associations between risk of
sensitization and the six exposure
measures tested: Total CEE, total MEE,
and variations of CEE and MEE
constructed based on particles < 6 mm
and < 1 mm in diameter. None of the
associations were statistically
significant (p < 0.05); however, the
authors noted that the dataset was
relatively small, with limited power to
detect a statistically significant
exposure-response relationship.
Although the Viet et al. and Kelleher
et al. exposure-response analyses
provide valuable insight into exposureresponse for beryllium sensitization and
CBD, both studies have limitations that
affect their suitability as a basis for
quantitative risk assessment. Their
limitations primarily involve the
exposure data used to estimate workers’
exposures. Viet et al.’s exposure
reconstruction was based on area
samples from a single building within a
large, multi-building facility. Where
possible, OSHA prefers to base risk
estimates on exposure data collected in
the breathing zone of workers rather
than area samples, because data
collected in the breathing zone more
accurately represent workers’ exposures.
Kelleher’s analysis, on the other hand,
was based on personal lapel samples.
However, the samples Kelleher et al.
used were collected between 1996 and
1999, after the facility had initiated new
exposure control measures in response
to the diagnosis of a case of CBD in
1995. OSHA believes that industrial
hygiene samples collected at the
Cullman plant prior to 1996 better
characterize exposures prior to the new
exposure controls. In addition, since the
publication of the Kelleher study, the
population has continued to be screened
for sensitization and CBD. Data
collected on workers hired in 2000 and
later, after most exposure controls had
been completed, can be used to
characterize risk at lower levels of
exposure than have been examined in
many previous studies.
To better characterize the relationship
between exposure level and risk of
sensitization and CBD, OSHA
developed an independent exposureresponse analysis based on a dataset
maintained by NJMRC on workers at the
Cullman, AL, machining plant. The
dataset includes exposure samples
collected between 1980 and 2005, and
has updated work history and screening
information for several hundred workers
through 2003. OSHA’s analysis of the
NJMRC data set is presented in the next
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47633
elevated for average (OR 1.37) and
highest job (OR 1.32). Among the
submicron exposure estimates, only
3. Elmore, OH, Facility
highest job (OR 1.24) had a 95 percent
After OSHA completed its analysis of CI that just included unity for
the NJMRC data set, Schuler et al. (2012) sensitization. For CBD, elevated odds
published a study examining beryllium
ratios were observed only for the
sensitization and CBD among 264 short- cumulative exposure estimates and were
term workers employed at the
similar for total mass and respirable
previously described Elmore, OH plant
exposure (total mass OR 1.66, respirable
in 1999. The analysis used a high(OR 1.68). Cumulative submicron
quality exposure reconstruction by Virji exposure showed an elevated,
et al. (2012) and presented a regression
borderline significant odds ratio (OR
analysis of the relationship between
1.58). The odds ratios for average
beryllium exposure levels and beryllium exposure and highest-exposed job were
sensitization and CBD in the short-term
not statistically significantly elevated.
worker population. By including only
Schuler et al. concluded that both total
short-term workers, Virji et al. were able and respirable mass concentrations of
to construct participants’ exposures
beryllium exposure were relevant
with more precision than was possible
predictors of risk for beryllium
in studies involving workers exposed
sensitization and CBD.
for longer durations and in time periods
E. OSHA’s Exposure-Response Analysis
with less exposure sampling. In
OSHA evaluated exposure and health
addition, the focus on short-term
outcome data on a population of
workers allowed more precise
workers employed at the Cullman
knowledge of when sensitization and
CBD occurred than had been the case for machining facility. NJMRC researchers,
with consent and information provided
previously published cross-sectional
by the facility, compiled a dataset
studies of long-term workers. Each
containing employee work histories,
participant completed a work history
medical diagnoses, and air sampling
questionnaire and was tested for
results and provided it to OSHA for
beryllium sensitization, and sensitized
workers were offered further evaluation analysis. OSHA’s contractors from
Eastern Research Group (ERG) gathered
for CBD. The overall prevalence of
additional information from (1) two
sensitization was 9.8 percent (26/264).
surveys of the Cullman plant conducted
Twenty-two sensitized workers
consented to clinical testing for CBD via by OSHA’s contractor (ERG, 2003 and
ERG, 2004a), (2) published articles of
transbronchial biopsy. Six of those
investigations conducted at the plant by
sensitized were diagnosed with CBD
researchers from NJMRC (Kelleher et al.,
(2.3 percent, 6/264).
Schuler et al. (2012) used logistic
2001; Madl et al., 2007; Martyny et al.,
regression to explore the relationship
2000; and Newman et al., 2001), (3) a
between estimated beryllium exposure
case file from a 1980 OSHA complaint
and sensitization and CBD, using
inspection at the plant, (4) comments
estimates of total, respirable, and
submitted to the OSHA docket office in
submicron mass concentrations.
1976 and 1977 by representatives of the
Exposure estimates were constructed
metal machining plant regarding their
using two exposure surveys conducted
beryllium control program, and (5)
in 1999: a survey of total mass
personal communications with the
exposures (4,022 full-shift personal
plant’s current industrial hygienist
samples) and a survey of size-separated
(ERG, 2009b) and an industrial hygiene
impactor samples (198 samples). The
researcher at NJMRC (ERG, 2009a).
1999 exposure surveys and work
1. Plant Operations
histories were used to estimate longThe Cullman plant is a leading
term lifetime weighted (LTW) average,
fabricator of precision-machined and
cumulative, and highest-job-worked
processed materials including beryllium
exposure for total, respirable, and
and its alloys, titanium, aluminum,
submicron beryllium mass
quartz, and glass (ERG, 2009b). The
concentrations.
plant has approximately 210 machines,
For beryllium sensitization, logistic
primarily mills and lathes, and
models showed elevated odds ratios for
processes large quantities of beryllium
average (OR 1.48) and highest job (OR
on an annual basis. The plant provides
1.37) exposure for total mass exposure;
complete fabrication services including
the OR for cumulative exposure was
ultra-precision machining; ancillary
smaller (OR 1.23) and borderline
processing (brazing, ion milling, photo
statistically significant (95 percent CI
etching, precision cleaning, heat
barely included unity). Relationships
treating, stress relief, thermal cycling,
between sensitization and respirable
mechanical assembly, and chemical
exposure estimates were similarly
section, E. OSHA’s Exposure-Response
Analysis.
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milling/etching); and coatings (plasma
spray, anodizing, chromate conversion
coating, nickel sulfamate plate, nickel
plate, gold plate, black nickel plate,
copper plate/strike, passivation, and
painting). Most of the plant’s beryllium
operations involve machining beryllium
metal and high beryllium content
composite materials (beryllium metal/
beryllium oxide metal composites called
E-Metal or E-Material), with occasional
machining of beryllium oxide/metal
matrix (such as AlBeMet, aluminum
beryllium matrix) and berylliumcontaining alloys. E-Materials such as
E–20 and E–60 are currently processed
in the E-Cell department.
The 120,000 square-foot plant has two
main work areas: a front office area and
a large, open production shop.
Operations in the production shop
include inspection of materials,
machining, polishing, and quality
assurance. The front office is physically
separated from the production shop.
Office workers enter through the front of
the facility and have access to the
production shop through a change room
where they must don laboratory coats
and shoe covers to enter the production
area. Production workers enter the shop
area at the rear of the facility where a
change/locker room is available to
change into company uniforms and
work shoes. Support operations are
located in separate areas adjacent to the
production shop and include
management and administration, sales,
engineering, shipping and receiving,
and maintenance. Management and
administrative personnel include two
groups: those primarily working in the
front offices (front office management)
and those primarily working on the
shop floor (shop management).
In 1974, the company moved its
precision machining operations to the
plant’s current location in Cullman.
Workplace exposure controls reportedly
did not change much until the diagnosis
of an index case of CBD in 1995. Prior
to 1995, exposure controls for
machining operations primarily
included a low volume/high velocity
(LVHV) central exhaust system with
operator-adjusted exhaust pickups and
wet machining methods. Protective
clothing, gloves, and respiratory
protection were not required. After the
diagnosis, the facility established an inhouse target exposure level of 0.2 mg/m3,
installed change/locker rooms for
workers entering the production facility,
eliminated pressurized air hoses,
discouraged the use of dry sweeping,
initiated biennial medical surveillance
using the BeLPT, and implemented
annual beryllium hazard awareness
training.
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In 1996, the company instituted
requirements for work uniforms and
dedicated work shoes for production
workers, eliminated dry sweeping in all
departments, and purchased highefficiency particulate air (HEPA) filter
vacuum cleaners for workplace cleanup
and decontamination. Major engineering
changes were also initiated in 1996,
including the purchase of a new local
exhaust ventilation (LEV) system to
exhaust machining operations
producing finer aerosols (e.g., dust and
fume versus metal chips). The facility
also began installing mist eliminators
for each machine. Departments affected
by these changes included cutter grind
(tool and die), E-cell, electrical
discharge machining (EDM), flow lines,
grind, lapping, and optics. Dry
machining operations producing chips
were exhausted using the existing LVHV
exhaust system (ERG, 2004a). In the
course of making the ventilation system
changes, old ductwork and baghouses
were dismantled and new ductwork and
air cleaning devices were installed. The
company also installed Plexiglas
enclosures on machining operations in
1996–1997, including the lapping,
deburring, grinding, EDM, and tool and
die operations. In 1998, LEV was
installed in EDM and modified in the
lap, deburr, and grind departments.
Most exposure controls were
reportedly in place by 2000 (ERG,
2009a). In 2004, the plant industrial
hygienist reported that all machines had
LEV and about 65 percent were also
enclosed with either partial or full
enclosures to control the escape of
machining coolant (ERG, 2004b). Over
time, the facility has built enclosures for
operations that consistently produce
exposures greater than 0.2 mg/m3. The
company has never required workers to
use gloves or other PPE.
2. Air Sampling Database and Job
Exposure Matrix (JEM)
The NJMRC dataset includes
industrial hygiene sampling results
collected by the plant (1980–1984 and
1995–2005) and NJMRC researchers
(June 1996 to February 1997 and
September 1999), including 4,370
breathing zone (personal lapel) samples
and 712 area samples (ERG, 2004b).
Limited air sampling data is available
before 1980 and no exposure data
appears to be available for the 10-year
time period 1985 through 1994. A
review of the NJMRC air sampling
database from 1995 through 2005 shows
a significant increase in the number of
air samples collected beginning in 2000,
which the plant industrial hygienist
attributes to an increase in the number
of air sampling pumps (from 5 to 23)
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and the purchase of an automated
atomic absorption spectrophotometer.
ERG used the personal breathing zone
sampling results contained in the
sample database to quantify exposure
levels for each year and for several-year
periods. Separate exposure statistics
were calculated for each job included in
the job history database. For each job
included in the job history database,
ERG estimated the arithmetic mean,
geometric mean, median, minimum,
maximum, and 95th percentile value for
the available exposure samples. Prior to
generating these statistics ERG made
several adjustments. After consultation
with researchers at NJMRC, four
particularly high exposures were
identified as probably erroneous and
excluded from calculations. In addition,
a 1996 sample for the HS (Health and
Safety) process was removed from the
sample calculations after ERG
determined it was for a non-employee
researcher visiting the facility.
Most samples in the sample database
for which sampling times were recorded
were long-term samples: 2,503 of the
2,557 (97.9 percent) breathing zone
samples with sampling time recorded
had times greater than or equal to 400
minutes. No adjustments were made for
sampling time, except in the case of four
samples for the ‘‘maintenance’’ process
for 1995. These results show relatively
high values and exceptionally short
sampling times consistent with the
nature of much maintenance work,
marked by short-term exposures and
periods of no exposure. The four 1995
maintenance samples were adjusted for
an eight-hour sampling time assuming
that the maintenance workers received
no further beryllium exposure over the
rest of their work shift.
OSHA examined the database for
trends in exposure by reviewing sample
statistics for individual years and
grouping years into four time periods
that correspond to stages in the plant’s
approach to beryllium exposure control.
These were: 1980–1995, a period of
relatively minimal control prior to the
1995 discovery of a case of CBD among
the plant’s workers; 1996–1997, a period
during which some major engineering
controls were in the process of being
installed on machining equipment;
1998–1999, a period during which most
engineering controls on the machining
equipment had been installed; and
2000–2003, a period when installation
of all exposure controls on machining
equipment was complete and exposures
very low throughout the plant. Table
VI–4 below summarized the available
data for each time period. As the four
probable sampling errors identified in
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the original data set are excluded here,
arithmetic mean values are presented.
TABLE VI–4—EXPOSURE VALUES FOR MACHINING JOB TITLES, EXCLUDING PROBABLE SAMPLING ERRORS (μg/m3) IN
NJMRC DATA SET
1980–1995
1996–1997
1998–1999
2000–2003
Job title
Samples
Deburring .........................................................
Electrical Discharge Machining ........................
Grinding ............................................................
Lapping ............................................................
Lathe ................................................................
Milling ...............................................................
Reviewing the revised statistics for
individual years for different groupings,
OSHA noted that exposures in the
1996–1997 period were for some
machining jobs equivalent to, or even
higher than, exposure levels recording
during the 1980–1995 period. During
Mean
27
2
12
9
18
43
Samples
1.17
0.06
3.07
0.15
0.88
0.64
Mean
19
2
6
16
8
15
Samples
1.29
1.32
0.49
0.24
1.13
0.23
Mean
0
16
15
42
40
95
NA
0.08
0.24
0.21
0.17
0.17
Samples
Mean
67
63
68
103
200
434
0.1
0.1
0.1
0.1
0.1
0.1
These include jobs such as
administrative work, health and safety,
inspection, toolmaking (‘Tool’ and
‘Cgrind’), and others. A description of
jobs by title is available in the risk
assessment background document.
1996–1997, major engineering controls
were being installed, but exposure
levels were not yet consistently
reduced.
Table VI–5 below summarizes
exposures for the four time periods in
jobs other than beryllium machining.
TABLE VI–5—EXPOSURE VALUES FOR NON-MACHINING JOB TITLES (μg/m3) IN NJMRC DATA SET
1980–1995
1996–1997
1998–1999
2000–2003
Job title
Samples
mean
Samples
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0
0
0
1
0
0
1
0
0
0
0
0
4
0
0
1
1
0
3
0
FromTable VI–5, it is evident that
exposure samples are not available for
many non-machining jobs prior to 2000.
Where samples are available before
2000, sample numbers are small,
particularly prior to 1998. In jobs for
which exposure values are available in
1998–1999 and 2000–2003, exposures
appear either to decline from 1998–1999
to 2000–2003 (Assembly, Chem,
Inspection, Maintenance) or to be
roughly equivalent (Administration,
Cgrind, Engineering, Msupp, PCIC, and
Spec). Among the jobs with exposure
samples prior to 1998, most had very
few (1–5) samples, with the exception of
Ecell (13 samples in 1996–1997). Based
on this limited information, it appears
that exposures declined from the period
before the first dentification of a CBD
case to the period in which exposure
controls were introduced.
Because exposure results from 1996–
1997 were not found to be consistently
reduced in comparison to the 1985–
1995 period in primary machining jobs,
these two periods were grouped together
in the JEM. Exposure monitoring for
jobs other than the primary machining
operations were represented by a single
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0
0
0
0
1
13
0
0
0
0
0
0
1
0
0
0
0
0
0
0
Samples
Administration ..................................
Assembly .........................................
Cathode ...........................................
Cgrind ..............................................
Chem ...............................................
Ecell .................................................
Engineering ......................................
Flow Lines .......................................
Gas ..................................................
Glass ................................................
Health and Safety 8 ..........................
Inspection ........................................
Maintenance ....................................
Msupp ..............................................
Optics ...............................................
PCIC ................................................
Qroom ..............................................
Shop ................................................
Spec .................................................
Tool ..................................................
8 An exceptionally high result (0.845 mg/m3, not
shown in Table 5) for a 1996 sample for the HS
(Health and Safety) process was removed from the
sample calculations. OSHA’s contractor determined
this sample to be associated with a non-employee
researcher visiting the facility.
NA ..........
NA ..........
NA ..........
0.120 ......
NA ..........
NA ..........
0.065 ......
NA ..........
NA ..........
NA ..........
NA ..........
NA ..........
1.257 ......
NA ..........
NA ..........
0.040 ......
0.280 ......
NA ..........
0.247 ......
NA ..........
mean
Fmt 4701
NA ..........
NA ..........
NA ..........
NA ..........
0.529 ......
1.873 ......
NA ..........
NA ..........
NA ..........
NA ..........
NA ..........
NA ..........
0.160 ......
NA ..........
NA ..........
NA ..........
NA ..........
NA ..........
NA ..........
NA ..........
Sfmt 4702
39
8
0
14
21
0
49
0
0
0
0
32
16
47
0
13
0
4
24
0
mean
0.052 ......
0.136 ......
NA ..........
0.105 ......
0.277 ......
NA ..........
0.069 ......
NA ..........
NA ..........
NA ..........
NA ..........
0.101 ......
0.200 ......
0.094 ......
NA ..........
0.071 ......
NA ..........
0.060 ......
0.083 ......
NA ..........
Samples
74
2
9
76
91
26
125
113
121
38
5
150
70
68
41
42
2
0
19
1
mean
0.061
0.051
0.156
0.112
0.152
0.239
0.062
0.083
0.058
0.068
0.076
0.066
0.126
0.081
0.090
0.083
0.130
NA
0.087
0.070
mean exposure value for 1980–2003. As
respiratory protection was not routinely
used at the plant, there was no
adjustment for respiratory protection in
workers’ exposure estimates. The job
exposure matrix is presented in full in
the background document for the
quantitative risk assessment.
3. Worker Exposure Reconstruction
The work history database contains
job history records for 348 workers,
including start years, duration of
employment, and percentage of
worktime spent in each job. One
hundred ninety-eight of the workers had
been employed at some point in primary
machining jobs, including deburring,
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EDM, grinding, lapping, lathing, and
milling. The remainder worked only in
non-primary machining jobs, such as
administration, engineering, quality
control, and shop management. The
total number of years worked at each job
are presented as integers, leaving some
uncertainty regarding the worker’s exact
start and end date at the job.
Based on these records and the JEM
described previously, ERG calculated
cumulative and average exposure
estimates for each worker in the
database. Cumulative exposure was
calculated as, Si ei t i, where e(i) is the
exposure level for job (i), and t(i) is the
time spent in job (i). Cumulative
exposure was divided by total exposure
time to estimate each worker’s long-term
average exposure. These exposures were
computed in a time-dependent manner
for the statistical modeling. For workers
with beryllium sensitization or CBD,
exposure estimates excluded exposures
following diagnosis.
Workers who were employed for long
time periods in jobs with low-level
exposures tend to have low average and
cumulative exposures due to the way
these measures are constructed,
incorporating the worker’s entire work
history. As discussed in the Health
Effects chapter, higher-level exposures
or short-term peak exposures such as
those encountered in machining jobs
may be highly relevant to risk of
sensitization. Unfortunately, because it
is not possible to continuously monitor
individuals’ beryllium exposure levels
and sensitization status, it is not known
exactly when workers became sensitized
or what their ‘‘true’’ peak exposures
leading up to sensitization were. Only a
rough approximation of the upper levels
of exposure a worker experienced is
possible. ERG constructed a third type
of exposure estimate reflecting the
exposure level associated with the
highest-exposure job (HEJ) and time
period experienced by each worker.
This exposure estimate (HEJ), the
cumulative exposure estimate, and the
average exposure were used in the
quartile analysis and statistical analyses.
4. Prevalence of Sensitization and CBD
In the database provided to OSHA,
seven workers were reported as
sensitized only. Sixteen workers were
listed as sensitized and diagnosed with
CBD upon initial clinical evaluation.
Three workers, first shown to be
sensitized only, were later diagnosed
with CBD. Tables VI–6, VI–7, and VI–8
below present the prevalence of
sensitization and CBD cases across
several categories of lifetime-weighted
(LTW) average, cumulative, and highestexposed job (HEJ) exposure. Exposure
values were grouped by quartile. Note
that all workers with CBD are also
sensitized. Thus, the columns ‘‘Total
Sensitized’’ and ‘‘Total %’’ refer to all
sensitized workers in the dataset,
including workers with and without a
diagnosis of CBD.
TABLE VI–6—PREVALENCE OF SENSITIZATION AND CBD BY LTW AVERAGE EXPOSURE QUARTILE IN NJMRC DATA SET
Average exposure (μg/m3)
Group size
Sensitized
only
Total
sensitized
CBD
Total %
CBD %
0.0–0.080 .................................................
0.081–0.18 ...............................................
0.19–0.51 .................................................
0.51–2.15 .................................................
91
73
77
78
1
2
0
4
1
4
6
8
2
6
6
12
2.2
8.2
7.8
15.4
1.0
5.5
7.8
10.3
Total ..................................................
319
7
19
26
8.2
6.0
TABLE VI–7—PREVALENCE OF SENSITIZATION AND CBD BY CUMULATIVE EXPOSURE QUARTILE IN NJMRC DATA SET
Cumulative exposure (μg/m3-yrs)
Group size
Sensitized
only
Total
sensitized
CBD
Total %
CBD %
0.0–0.147 .................................................
0.148–1.467 .............................................
1.468–7.008 .............................................
7.009–61.86 .............................................
81
79
79
80
2
0
3
2
2
2
8
7
4
2
11
9
4.9
2.5
13.9
11.3
2.5
2.5
8.0
8.8
Total ..................................................
319
7
19
26
8.2
6.0
TABLE VI–8—PREVALENCE OF SENSITIZATION AND CBD BY HIGHEST-EXPOSED JOB EXPOSURE QUARTILE IN NJMRC
DATA SET
HEJ exposure (μg/m3)
Group size
Sensitized
only
Total
sensitized
CBD
Total %
CBD %
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0.0–0.086 .................................................
0.091–0.214 .............................................
0.387–0.691 .............................................
0.954–2.213 .............................................
86
81
76
76
1
1
2
3
0
6
9
4
1
7
11
7
1.2
8.6
14.5
9.2
0.0
7.4
11.8
5.3
Total ..................................................
319
7
19
26
8.2
6.0
Table VI–6 shows increasing
prevalence of total sensitization and
CBD with increasing LTW average
exposure, measured both as average and
cumulative exposure. The lowest
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prevalence of sensitization and CBD was
observed among workers with average
exposure levels less than or equal to
0.08 mg/m3, where two sensitized
workers (2.2 percent) including one case
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of CBD (1.0 percent) were found. The
sensitized worker in this category
without CBD had worked at the facility
as an inspector since 1972, one of the
lowest-exposed jobs at the plant.
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Because the job was believed to have
very low exposures, it was not sampled
prior to 1998. Thus, estimates of
exposures in this job are based on data
from 1998–2003 only. It is possible that
exposures earlier in this worker’s
employment history were somewhat
higher than reflected in his estimated
average exposure. The worker diagnosed
with CBD in this group had been hired
in 1996 in production control, and had
an estimated average exposure of 0.08
mg/m3. He was diagnosed with CBD in
1997.
The second quartile of LTW average
exposure (0.081—0.18 mg/m3) shows a
marked rise in overall prevalence of
beryllium-related health effects, with six
workers sensitized (8.2 percent), of
whom four (5.5 percent) were diagnosed
with CBD. Among six sensitized
workers in the third quartile (0.19—0.50
mg/m3), all were diagnosed with CBD
(7.8 percent). Another increase in
prevalence is seen from the third to the
fourth quartile, with 12 cases of
sensitization (15.4 percent), including
eight (10.3 percent) diagnosed with
CBD.
The quartile analysis of cumulative
exposure also shows generally
increasing prevalence of sensitization
and CBD with increasing exposure. As
shown in Table VI–7, the lowest
prevalences of CBD and sensitization
are in the first two quartiles of
cumulative exposure (0.0–0.147 mg/m3yrs, 0.148–1.467 mg/m3-yrs). The upper
bound on this cumulative exposure
range, 1.467 mg/m3-yrs, is the
cumulative exposure that a worker
would have if exposed to beryllium at
a level of 0.03 mg/m3 for a working
lifetime of 45 years; 0.15 mg/m3 for ten
years; or 0.3 mg/m3 for five years.
A sharp increase in prevalence of
sensitization and CBD and total
sensitization occurs in the third quartile
(1.468–7.008 mg/m3-yrs), with roughly
similar levels of both in the highest
group (7.009–61.86 mg/m3-yrs).
Cumulative exposures in the third
quartile would be experienced by a
worker exposed for 45 years to levels
between 0.03 and 0.16 mg/m3, for 10
years to levels between 0.15 and 0.7 mg/
m3, or for five years to levels between
0.3 and 1.4 mg/m3.
When workers’ exposures from their
highest-exposed job are considered, the
exposure-response pattern is similar to
that for LTW average exposure in the
lower quartiles (Table VI–8). The lowest
prevalence is observed in the first
quartile (0.0–0.86 mg/m3), with sharply
rising prevalence from first to second
and second to third exposure quartiles.
The prevalence of sensitization and CBD
in the top quartile (0.954–2.213 mg/m3)
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decreases relative to the third, with
levels similar to the overall prevalence
in the dataset. Many workers in the
highest exposure quartiles are long-time
employees, who were hired during the
early years of the shop when exposures
were highest. One possible explanation
for the drop in prevalence in the highest
exposure quartiles is that highlyexposed workers from early periods may
have developed CBD and left the plant
before sensitization testing began in
1995.
It is of some value to compare the
prevalence analysis of the Cullman
(NJMRC) data set with the results of the
Reading and Tucson studies discussed
previously. An exact comparison is not
possible, in part because the Reading
and Tucson exposure values are
associated with jobs and the NJMRC
values are estimates of lifetime weighted
average, cumulative, and highestexposed job (HEJ) exposures for
individuals in the data set.
Nevertheless, OSHA believes it is
possible to very roughly compare the
results of the Reading and Tucson
studies and the results of the NJMRC
prevalence analysis presented above. As
discussed in detail below, OSHA found
a general consistency between the
prevalence of sensitization and CBD in
the quartiles of average exposure in the
NJMRC data set and the prevalence of
sensitization and CBD at the Reading
and Tucson plants for similar exposure
values.
Personal lapel samples collected at
the Reading plant between 1995 and
2000 were relatively low overall
(median of 0.073 mg/m3), with higher
exposures (median of 0.149 mg/m3)
concentrated in the wire annealing and
pickling process (Schuler et al., 2005).
Exposures in the Reading plant in this
time period were similar to the secondquartile average (Table VI–6–0.081–0.18
mg/m3). The prevalence of sensitization
observed in the NJMRC second quartile
was 8.2 percent and appears roughly
consistent with the prevalence of
sensitization among Reading workers in
the mid-1990s (11.5 percent). The
reported prevalence of CBD (3.9
percent) among the Reading workforce
was also consistent with that observed
in the second NJMRC quartile (5.5
percent), After 2000, exposure controls
reduced exposures in most Reading jobs
to median levels below 0.03 mg/m3, with
a median value of 0.1 mg/m3 for the wire
annealing and pickling process. The
wire annealing and pickling process was
enclosed and stringent respirator and
skin protection requirements were
applied for workers in that area after
2002, essentially eliminating airborne
and dermal exposures for those workers.
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47637
Thomas et al. (2009) reported that one
of 45 workers (2.2 percent) hired after
the enclosure in 2002 was confirmed as
sensitized, a value in line with the
sensitization prevalence observed in the
lowest quartiles of average exposure (2.2
percent, 0.0–0.08 mg/m3).
As with Reading, the prevalence of
sensitization observed at Tucson and in
the NJMRC data set are not exactly
comparable due to the different natures
of the exposure estimates. Nevertheless,
in a rough sense the results of the
Tucson study and the NJMRC
prevalence analysis appear similar. In
Tucson, a 1998 BeLPT screening
showed that 9.5 percent of workers
hired after 1992 were sensitized
(Henneberger et al., 2001). Personal fullshift exposure samples collected in
production jobs between 1994 and 1999
had a median of 0.2 mg/m3 (0.1 mg/m3
for non-production jobs). In the NJMRC
data set, a sensitization prevalence of
8.2 percent was seen among workers
with average exposures between 0.081
and 0.18 mg/m3. At the time of the 1998
screening, workers hired after 1992 had
a median one year since first beryllium
exposure and, therefore, CBD
prevalence was only 1.4 percent. This
prevalence is likely an underestimate
since CBD often requires more than a
year to develop. Longer-term workers at
the Tucson plant with a median 14
years since first beryllium exposure had
a 9.1 percent prevalence of CBD. There
was a 5.5 percent prevalence of CBD
among the entire workforce
(Henneberger et al., 2001). As with the
Reading plant employees, this reported
prevalence is reasonably consistent with
the 5.5 percent CBD prevalence
observed in the second NJMRC quartile.
Beginning in 1999, the Tucson facility
instituted strict requirements for
respiratory protection and other PPE,
essentially eliminating airborne and
dermal exposure for most workers. After
these requirements were put in place,
Cummings et al. (2007) reported only
one case of sensitization (1 percent;
associated with a PPE failure) among 97
workers hired between 2000 and 2004.
This appears roughly in line with the
sensitization prevalence of 2.2 percent
observed in the lowest quartiles of
average exposure (0.0–0.08 mg/m3) in
the NJMRC data set.
While the literature analysis
presented here shows a clear reduction
in risk with well-controlled airborne
exposures (≤ 0.1 mg/m3 on average) and
protection from dermal exposure, the
level of detail presented in the
published studies limits the Agency’s
ability to characterize risk at all the
alternate PELs OSHA is considering. To
better understand these risks, OSHA
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Federal Register / Vol. 80, No. 152 / Friday, August 7, 2015 / Proposed Rules
used the NJMRC dataset to characterize
risk of sensitization and CBD among
workers exposed to each of the alternate
PELs under consideration in the
proposed beryllium rule.
F. OSHA’s Statistical Modeling
OSHA’s contractor performed a
complementary log-log proportional
hazards model using the NJMRC data
set. The proportional hazards model is
a generalization of logistic regression
that allows for time-dependent
exposures and differential time at risk.
The proportional hazards model
accounts for the fact that individuals in
the dataset are followed for different
amounts of time, and that their
exposures change over time. The
proportional hazards model provides
hazards ratios, which estimate the
relative risk of disease at a specified
time for someone with exposure level 1
compared to exposure level 2. To
perform this analysis, OSHA’s
contractor constructed exposure files
with time-dependent cumulative and
average exposures for each worker in
the data set in each year that a case of
sensitization or CBD was identified.
Workers were included in only those
years after they started working at the
plant and continued to be followed.
Sensitized cases were not included in
analysis of sensitization after the year in
which they were identified as being
sensitized, and CBD cases were not
included in analyses of CBD after the
year in which they were diagnosed with
CBD. Follow-up is censored after 2002
because work histories were deemed to
be less reliable after that date.
The results of the discrete
proportional hazards analyses are
summarized in Tables VI–9–12 below.
All coefficients used in the models are
displayed, including the exposure
coefficient, the model constant for
diagnosis in 1995, and additional
exposure-independent coefficients for
each succeeding year (1996–1999 for
sensitization and 1996–2002 for CBD) of
diagnosis that are fit in the discrete time
proportional hazards modeling
procedure. Model equations and
variables are explained more fully in the
companion risk assessment background
document.
Relative risk of sensitization increased
with cumulative exposure (p = 0.05). A
positive, but not statistically significant,
association was observed with LTW
average exposure (p = 0.09). The
association was much weaker for
exposure duration (p = 0.31), consistent
with the expected biological action of an
immune hypersensitivity response
where onset is believed to be more
dependent on the concentration of the
sensitizing agent at the target site rather
than the number of years of
occupational exposure. The association
was also much weaker for highestexposed job (HEJ) exposure (p = 0.3).
TABLE VI–9—PROPORTIONAL HAZARDS MODEL—CUMULATIVE EXPOSURE AND SENSITIZATION
Variable
Coefficient
Cumulative Exposure (μg/m3–yrs) ...............................
constant ........................................................................
1996 ..............................................................................
1997 ..............................................................................
1998 ..............................................................................
1999 ..............................................................................
0.031
¥3.48
¥1.49
¥0.29
¥1.56
¥1.57
95% Confidence interval
0.00 to 0.063 ................................................................
¥4.27 to ¥2.69 ...........................................................
¥3.04 to 0.06 ...............................................................
¥1.31 to 0.72 ...............................................................
¥3.11 to ¥0.01 ...........................................................
¥3.12 to ¥0.02 ...........................................................
P-value
0.05
<0.001
0.06
0.57
0.05
0.05
TABLE VI–10—PROPORTIONAL HAZARDS MODEL—LTW AVERAGE EXPOSURE AND SENSITIZATION
Variable
Coefficient
Average Exposure (μg/m3) ...........................................
constant ........................................................................
1996 ..............................................................................
1997 ..............................................................................
1998 ..............................................................................
1999 ..............................................................................
0.54
¥3.55
¥1.48
¥0.29
¥1.54
¥1.53
95% Confidence interval
¥0.09
¥4.42
¥3.03
¥1.31
¥3.09
¥3.08
to
to
to
to
to
to
1.17 ...............................................................
¥2.69 ...........................................................
0.07 ...............................................................
0.72 ...............................................................
0.01 ...............................................................
0.03 ...............................................................
P-value
0.09
<0.001
0.06
0.57
0.05
0.05
TABLE VI–11—PROPORTIONAL HAZARDS MODEL—EXPOSURE DURATION AND SENSITIZATION
Variable
Coefficient
mstockstill on DSK4VPTVN1PROD with PROPOSALS2
Exposure Duration (years) ...........................................
constant ........................................................................
1996 ..............................................................................
1997 ..............................................................................
1998 ..............................................................................
1999 ..............................................................................
0.03
¥3.55
¥1.48
¥0.30
¥1.59
¥1.62
95% Confidence interval
¥0.03
¥4.57
¥3.03
¥1.31
¥3.14
¥3.17
to
to
to
to
to
to
0.08 ...............................................................
¥2.53 ...........................................................
0.70 ...............................................................
0.72 ...............................................................
¥0.04 ...........................................................
¥0.72 ...........................................................
P-value
0.31
<0.001
0.06
0.57
0.05
0.04
TABLE VI–12—PROPORTIONAL HAZARDS MODEL—HEJ EXPOSURE AND SENSITIZATION
Variable
Coefficient
(μg/m3)
HEJ Exposure
.................................................
constant ........................................................................
1996 ..............................................................................
1997 ..............................................................................
1998 ..............................................................................
1999 ..............................................................................
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95% Confidence interval
0.31
¥3.42
¥1.49
¥0.31
¥1.59
¥1.60
¥0.27
¥4.27
¥3.04
¥1.33
¥3.14
¥3.15
Fmt 4701
Sfmt 4702
to
to
to
to
to
to
0.88 ...............................................................
¥2.56 ...........................................................
0.06 ...............................................................
0.70 ...............................................................
¥0.04 ...........................................................
¥0.05 ...........................................................
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P-value
0.30
<0.001
0.06
0.55
0.05
0.04
Federal Register / Vol. 80, No. 152 / Friday, August 7, 2015 / Proposed Rules
The proportional hazards models for
the CBD endpoint (Tables VI–13
through 16 below) showed positive
relationships with cumulative exposure
(p = 0.09) and duration of exposure (p
= 0.10). However, the association with
the cumulative exposure metric was not
as strong as that for sensitization,
47639
probably due to the smaller number of
CBD cases. LTW average exposure and
HEJ exposure were not closely related to
relative risk of CBD (p-values > 0.5).
TABLE VI–13—PROPORTIONAL HAZARDS MODEL—CUMULATIVE EXPOSURE AND CBD
Variable
Coefficient
Cumulative Exposure (μg/m3–yrs) ...............................
constant ........................................................................
1997 ..............................................................................
1998 ..............................................................................
1999 ..............................................................................
2002 ..............................................................................
0.03
¥3.77
¥0.59
¥2.01
¥0.63
¥2.13
95% Confidence interval
.00 to 0.07 ....................................................................
¥4.67 to ¥2.86 ...........................................................
¥1.86 to 0.68 ...............................................................
¥4.13 to 0.11 ...............................................................
¥1.90 to 0.64 ...............................................................
¥4.25 to ¥0.01 ...........................................................
P-value
0.09
<0.001
0.36
0.06
0.33
0.05
TABLE VI–14—PROPORTIONAL HAZARDS MODEL—LTW AVERAGE EXPOSURE AND CBD
Variable
Coefficient
(μg/m3)
Average Exposure
...........................................
constant ........................................................................
1997 ..............................................................................
1998 ..............................................................................
1999 ..............................................................................
2002 ..............................................................................
0.24
¥3.62
¥0.61
¥2.02
¥0.64
¥2.15
95% Confidence interval
¥0.59
¥4.60
¥1.87
¥4.14
¥1.92
¥4.28
to
to
to
to
to
to
1.06 ...............................................................
¥2.64 ...........................................................
0.66 ...............................................................
0.10 ...............................................................
0.63 ...............................................................
¥0.02 ...........................................................
P-value
0.58
<0.001
0.35
0.06
0.32
0.05
TABLE VI–15—PROPORTIONAL HAZARDS MODEL—EXPOSURE DURATION AND CBD
Variable
Coefficient
Exposure Duration (yrs) ...............................................
constant ........................................................................
1997 ..............................................................................
1998 ..............................................................................
1999 ..............................................................................
2002 ..............................................................................
0.05
¥4.18
¥0.53
¥2.01
¥0.67
¥2.22
95% Confidence interval
¥0.01 to 0.11 ...............................................................
¥5.40 to ¥2.96 ...........................................................
1.84 to 0.69 ..................................................................
¥4.13 to 0.11 ...............................................................
¥1.94 to 0.60 ...............................................................
¥4.34 to ¥0.10 ...........................................................
P-value
0.10
<0.001
0.38
0.06
0.30
0.04
TABLE VI–16—PROPORTIONAL HAZARDS MODEL—HEJ EXPOSURE AND CBD
Variable
Coefficient
mstockstill on DSK4VPTVN1PROD with PROPOSALS2
HEJ Exposure (μg/m3) .................................................
constant ........................................................................
1997 ..............................................................................
1998 ..............................................................................
1999 ..............................................................................
2002 ..............................................................................
In addition to the models reported
above, comparable models were fit to
the upper 95 percent confidence
interval of the HEJ exposure; logtransformed cumulative exposure; logtransformed LTW average exposure; and
log-transformed HEJ exposure. Each of
these measures was positively but not
significantly associated with
sensitization.
OSHA used the proportional hazards
models based on cumulative exposure,
shown in Tables VI–9 and VI–13, to
derive quantitative risk estimates. Of the
metrics related to exposure level, the
cumulative exposure metric showed the
most consistent association with
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0.03
¥3.49
¥0.62
¥2.05
¥0.68
¥2.21
95% Confidence interval
¥0.70
¥4.45
¥1.88
¥4.16
¥1.94
¥4.33
to
to
to
to
to
to
0.77 ...............................................................
¥2.53 ...........................................................
0.65 ...............................................................
0.07 ...............................................................
0.59 ...............................................................
¥0.09 ...........................................................
sensitization and CBD in these models.
Table VI–17 summarizes these risk
estimates for sensitization and the
corresponding 95 percent confidence
intervals separately for 1995 and 1999,
the years with the highest and lowest
baseline rates, respectively. The
estimated risks for CBD are presented in
VI–18. The expected number of cases is
based on the estimated conditional
probability of being a case in the given
year. The models provide time-specific
point estimates of risk for a worker with
any given exposure level, and the
corresponding interval is based on the
uncertainty in the exposure coefficient
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P-value
0.93
<0.001
0.34
0.06
0.30
0.04
(i.e., the predicted values based on the
95 percent confidence limits for the
exposure coefficient).
Each estimate represents the number
of sensitized workers the model predicts
in a group of 1000 workers at risk
during the given year with an exposure
history at the specified level and
duration. For example, in the exposure
scenario where 1000 workers are
occupationally exposed to 2 mg/m3 for
10 years in 1995, the model predicts
that about 56 (55.7) workers would be
sensitized that year. The model for CBD
predicts that about 42 (41.9) workers
would be diagnosed with CBD that year.
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TABLE VI–17a—PREDICTED CASES OF SENSITIZATION PER 1000 WORKERS EXPOSED AT CURRENT AND ALTERNATE
PELS BASED ON PROPORTIONAL HAZARDS MODEL, CUMULATIVE EXPOSURE METRIC, WITH CORRESPONDING INTERVAL BASED ON THE UNCERTAINTY IN THE EXPOSURE COEFFICIENT
[1995 Baseline]
Exposure duration
5 years
1995 Exposure level
(μg/m3)
Cumulative
(μg/m3-yrs)
2.0 ....................................
5.0
0.5 ....................................
2.5
0.2 ....................................
1.0
0.1 ....................................
cases/
1000
10.0
1.0 ....................................
10 years
0.5
μg/m3-yrs
41.1
30.3–56.2
35.3
30.3–41.3
32.7
30.3–35.4
31.3
30.3–32.3
30.8
30.3–31.3
20.0
10.0
5.0
2.0
1.0
20 years
cases/
1000
cases/
1000
μg/m3-yrs
55.7
30.3–102.9
41.1
30.3–56.2
35.3
30.3–41.3
32.2
30.3–34.3
31.3
30.3–32.3
45 years
40.0
101.0
30.3–318.1
55.7
30.3–102.9
41.1
30.3–56.2
34.3
30.3–38.9
32.2
30.3–34.3
20.0
10.0
4.0
2.0
cases/
1000
μg/m3-yrs
90.0
45.0
22.5
9.0
4.5
394.4
30.3–999.9
116.9
30.3–408.2
60.0
30.3–119.4
39.9
30.3–52.9
34.8
30.3–40.1
TABLE VI–17b—PREDICTED CASES OF SENSITIZATION PER 1000 WORKERS EXPOSED AT CURRENT AND ALTERNATE
PELS BASED ON PROPORTIONAL HAZARDS MODEL, CUMULATIVE EXPOSURE METRIC, WITH CORRESPONDING INTERVAL BASED ON THE UNCERTAINTY IN THE EXPOSURE COEFFICIENT
[1999 Baseline]
Exposure duration
1999 Exposure level
(μg/m3)
5 years
Cumulative
(μg/m3-yrs)
2.0 ....................................
5.0
0.5 ....................................
2.5
0.2 ....................................
1.0
0.1 ....................................
cases/
1000
10.0
1.0 ....................................
10 years
0.5
μg/m3-yrs
8.4
6.2–11.6
7.2
6.2–8.5
6.7
6.2–7.3
6.4
6.2–6.6
6.3
6.2–6.4
20 years
cases/
1000
20.0
10.0
5.0
2.0
1.0
cases/
1000
μg/m3-yrs
11.5
6.2–21.7
8.4
6.2–11.6
7.2
6.2–8.5
6.6
6.2–7.0
6.4
6.2–6.6
45 years
40.0
21.3
6.2–74.4
11.5
6.2–21.7
8.4
6.2–11.6
7.0
6.2–8.0
6.6
6.2–7.0
20.0
10.0
4.0
2.0
cases/
1000
μg/m3-yrs
90.0
45.0
22.5
9.0
4.5
96.3
6.2–835.4
24.8
6.2–100.5
12.4
6.2–25.3
8.2
6.2–10.9
7.1
6.2–8.2
TABLE VI–18a—PREDICTED NUMBER OF CASES OF CBD PER 1000 WORKERS EXPOSED AT CURRENT AND ALTERNATIVE
PELS BASED ON PROPORTIONAL HAZARDS MODEL, CUMULATIVE EXPOSURE METRIC, WITH CORRESPONDING INTERVAL BASED ON THE UNCERTAINTY IN THE EXPOSURE COEFFICIENT
[1995 baseline]
Exposure duration
5 years
1995 Exposure level
(μg/m3)
Cumulative
(μg/m3-yrs)
mstockstill on DSK4VPTVN1PROD with PROPOSALS2
2.0 ....................................
10.0
1.0 ....................................
5.0
0.5 ....................................
2.5
0.2 ....................................
1.0
0.1 ....................................
0.5
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10 years
Estimated
cases/1000
95% c.i.
μg/m3-yrs
30.9
22.8–44.0
26.6
22.8–31.7
24.6
22.8–26.9
23.5
22.8–24.3
23.1
22.8–23.6
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20.0
10.0
5.0
2.0
1.0
Fmt 4701
20 years
Estimated
cases/1000
95% c.i.
41.9
22.8–84.3
30.9
22.8–44.0
26.6
22.8–31.7
24.2
22.8–26.0
23.5
22.8–24.3
Sfmt 4702
μg/m3-yrs
Estimated
cases/1000
95% c.i.
40.0
20.0
10.0
4.0
2.0
E:\FR\FM\07AUP2.SGM
76.6
22.8–285.5
41.9
22.8–84.3
30.9
22.8–44.0
25.8
22.8–29.7
24.2
22.8–26.0
07AUP2
45 years
μg/m3-yrs
90.0
45.0
22.5
9.0
4.5
Estimated
cases/1000
95% c.i.
312.9
22.8–999.9
88.8
22.8–375.0
45.2
22.8–98.9
30.0
22.8–41.3
26.2
22.8–30.7
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Federal Register / Vol. 80, No. 152 / Friday, August 7, 2015 / Proposed Rules
TABLE VI–18b—PREDICTED NUMBER OF CASES OF CBD PER 1000 WORKERS EXPOSED AT CURRENT AND ALTERNATIVE
PELS BASED ON PROPORTIONAL HAZARDS MODEL, CUMULATIVE EXPOSURE METRIC, WITH CORRESPONDING INTERVAL BASED ON THE UNCERTAINTY IN THE EXPOSURE COEFFICIENT
[2002 baseline]
Exposure duration
5 years
2002 Exposure level
(μg/m3)
Cumulative
(μg/m3-yrs)
2.5
0.2 ....................................
1.0
0.1 ....................................
0.5
The statistical modeling analysis
predicts high risk of both sensitization
(96–394 cases per 1000, or 9.6–39.4
percent) and CBD (44–313 cases per
1000, or 4.4–31.3 percent) at the current
PEL of 2 mg/m3 for an exposure duration
of 45 years (90 mg/m3-yr). The predicted
risks of < 8.2–39.9 per 1000 (0.8–3.9
percent) cases of sensitization or 3.6 to
30.0 per 1000 (0.4–3 percent) cases of
CBD are substantially less for a 45-year
exposure at the proposed PEL, 0.2 mg/m3
(9 mg/m3-yr).
The model estimates are not directly
comparable to prevalence values
discussed in previous sections. They
assume a group without turnover and
are based on a comparison of unexposed
and hypothetically exposed workers at
specific points in time, whereas the
prevalence analysis simply reports the
percentage of workers at the Cullman
plant with sensitization or CBD in each
exposure category. Despite the difficulty
of direct comparison, the level of risk
seen in the prevalence analysis and
predicted in the modeling analysis
appear roughly similar at low
exposures. In the second quartile of
cumulative exposure (0.148–1.467 mg/
m3-yr), prevalence of sensitization and
CBD was 2.5 percent. This is roughly
congruent with the model predictions
for workers with cumulative exposures
between 0.5 and 1 mg/m3-yr: 6.3–31.3
cases of sensitization per 1000 workers
(0.6–3.1 percent) and 2.8 to 23.5 cases
of CBD per 1000 workers (0.28–2.4
percent). As discussed in the
background document for this analysis,
most workers in the data set had low
cumulative exposures (roughly half
below 1.5 mg/m3-years). It is difficult to
make any statement about the results at
higher levels, because there were few
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μg/m3-yrs
3.7
2.7–5.3
3.2
2.7–3.8
3.0
2.7–3.2
2.8
2.7–2.9
2.8
2.7–2.8
5.0
0.5 ....................................
Estimated
cases/1000
95% c.i.
10.0
1.0 ....................................
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2.0 ....................................
10 years
20.0
10.0
5.0
2.0
1.0
20 years
Estimated
cases/1000
95% c.i.
μg/m3-yrs
5.1
2.7–10.4
3.7
2.7–5.3
3.2
2.7–3.8
2.9
2.7–3.1
2.8
2.7–2.9
workers with high exposure levels and
the higher quartiles of cumulative
exposure include an extremely wide
range of exposures. For example, the
highest quartile of cumulative exposure
was 7.009–61.86 mg/m3-yr. This quartile,
which showed an 11.3 percent
prevalence of sensitization and 8.8
percent prevalence of CBD, includes the
cumulative exposure that a worker
exposed for 45 years at the proposed
PEL would experience (9 mg/m3-yr) near
its lower bound. Its upper bound
approaches the cumulative exposure
that a worker exposed for 45 years at the
current PEL would experience (90 mg/
m3-yr).
Due to limitations including the size
of the dataset, relatively limited
exposure data from the plant’s early
years, study size-related constraints on
the statistical analysis of the dataset,
and limited follow-up time on many
workers, OSHA must interpret the
model-based risk estimates presented in
Tables VI–17 and VI–18 with caution.
The Cullman study population is a
relatively small group and can support
only limited statistical analysis. For
example, its size precludes inclusion of
multiple covariates in the exposureresponse models or a two-stage
exposure-response analysis to model
both sensitization and the subsequent
development of CBD within the
subpopulation of sensitized workers.
The limited size of the Cullman dataset
is characteristic of studies on berylliumexposed workers in modern, lowexposure environments, which are
typically small-scale processing plants
(up to several hundred workers, up to
20–30 cases). However, these recent
studies also have important strengths:
They include workers hired after the
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45 years
Estimated
cases/1000
95% c.i.
40.0
20.0
10.0
4.0
2.0
9.4
2.7–39.2
5.1
2.7–10.4
3.7
2.7–5.3
3.1
2.7–3.6
2.9
2.7–3.1
μg/m3-yrs
90.0
45.0
22.5
9.0
4.5
Estimated
cases/1000
95% c.i.
43.6
2.7–679.8
11.0
2.7–54.3
5.5
2.7–12.3
3.6
2.7–5.0
3.1
2.7–3.7
institution of stringent exposure
controls, and have extensive exposure
sampling using full-shift personal lapel
samples. In contrast, older studies of
larger populations tend to have higher
exposures, less exposure data, and
exposure data collected in short-term
samples or outside of workers’ breathing
zones.
Another limitation of the Cullman
dataset, which is common to recent lowexposure studies, is the short follow-up
time available for many of the workers.
While in some cases CBD has been
known to develop in short periods (< 2
years), it more typically develops over a
longer time period. Sensitization occurs
in a typically shorter time frame, but
new cases of sensitization have been
observed in workers exposed to
beryllium for many years. Because the
data set is limited to individuals then
working at the plant, the Cullman data
set cannot capture CBD occurring
among workers who retire or leave the
plant. OSHA expects that the dataset
does not fully represent the risk of
sensitization, and is likely to
particularly under-represent CBD among
workers exposed to beryllium at this
facility. The Agency believes the short
follow-up time to be a significant source
of uncertainty in the statistical analysis,
a factor likely to lead to underestimation
of risk in this population.
A common source of uncertainty in
quantitative risk assessment is the series
of choices made in the course of
statistical analysis, such as model type,
inclusion or exclusion of additional
explanatory variables, and the
assumption of linearity in exposureresponse. Sensitivity analyses and
statistical checks were conducted to test
the validity of the choices and
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assumptions in the exposure-response
analysis and the impact of alternative
choices on the end results. These
analyses did not yield substantially
different results, adding to OSHA’s
confidence in the conclusions of its
preliminary risk assessment.
OSHA’s contractor examined whether
smoking and age were confounders in
the exposure-response analysis by
adding them as variables in the discrete
proportional hazards model. Neither
smoking status nor age was a
statistically significant predictor of
sensitization or CBD. The model
coefficients, 95 percent confidence
intervals, and p values can be found in
the background document. A sensitivity
analysis was done using the standard
Cox model that treats survival time as
continuous rather than discrete. The
model coefficients with the standard
Cox using cumulative exposure were
0.025 and very similar to the 0.03
reported in Tables VI–9 and VI–13
above. The interaction between
exposure and follow-up time was not
significant in these models, suggesting
that the proportional hazard assumption
should not be rejected. The proportional
hazards model assumes a linear
relationship between exposure level and
relative risk. The linearity assumption
was assessed using a fractional
polynomial approach. For both
sensitization and CBD, the best-fitting
fractional polynomial model did not fit
significantly better than the linear
model. This result supports OSHA’s use
of the linear model to estimate risk. The
details of these statistical analyses can
be found in the background document.
The possibility that the number of
times a worker has been tested for
sensitization might influence the
probability of a positive test was
examined (surveillance bias).
Surveillance bias could occur if workers
were tested because they showed some
sign of disease, and not tested
otherwise. It is also possible that the
original analysis included erroneous
assumptions about the dates of testing
for sensitization and CBD. OSHA’s
contractor performed a sensitivity
analysis, modifying the original analysis
to gauge the effect of different
assumptions about testing dates. In the
sensitivity analysis, the exposure
coefficients increased for all four
indices of exposure when the
sensitization analysis was restricted to
times when cohort members were
assumed to be tested. The exposure
coefficient was statistically significant
for duration of exposure but not for
cumulative, LTW average, or HEJ
exposure. The increase in exposure
coefficients suggests that the original
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models may have underestimated the
exposure-response relationship for
sensitization and CBD.
Errors in exposure measurement are a
common source of uncertainty in
quantitative risk assessments. Because
errors in high exposures can heavily
influence modeling results, OSHA’s
contractor performed sensitivity
analyses excluding the highest 5 percent
of cumulative exposures (those above
25.265 mg/m3-yrs) and the highest 10
percent of cumulative exposures (those
above 18.723 mg/m3-yrs). As discussed
in more detail in the background
document, exposure coefficients were
not statistically significant when these
exposures were dropped. This is not
surprising, given that the exclusion of
high exposure values reduced the size of
the data set. Prior to excluding high
exposure values, the data set was
already relatively small and many of the
exposure coefficients were nonsignificant or weakly significant in the
original analyses. As a result, the
sensitivity analyses did not provide
much information about uncertainty
due to exposure measurement error and
its effects on the modeling analysis.
Particle size, particle surface area, and
beryllium compound solubility are
believed to be important factors
influencing the risk of sensitization and
CBD among beryllium-exposed workers.
The workers at the Cullman machining
plant were primarily handling insoluble
beryllium compounds, such as
beryllium metal and beryllium metal/
beryllium oxide composites. Particle
size distributions from a limited number
of airborne beryllium samples collected
just after the 1996 installation of
engineering controls indicate worker
exposure to a substantial proportion of
respirable particulates. There was no
available particle size data for the 1980
to 1995 period prior to installation of
engineering controls when total
beryllium mass exposure levels were
greatest. Particle size data was also
lacking from 1998 to 2003 when
additional control measures were in
place and total beryllium mass
exposures were lowest. For these
reasons, OSHA was not able to
quantitatively account for the influence
of particle size and solubility in
developing the risk estimates based on
the Cullman data set. However, it is not
unreasonable to expect the CBD
experienced by this cohort to generally
reflect the risk from exposure to
beryllium that is relatively insoluble
and enriched with respirable particles.
As explained previously, the role of
particle size and surface area on risk of
sensitization is more difficult to predict.
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Additional uncertainty is introduced
when extrapolating the quantitative
estimates presented above to operations
that process beryllium compounds that
have different solubility and particle
characteristics than those encountered
at the Cullman machining plant. OSHA
does not have sufficient information to
quantitatively assess the degree to
which risks of beryllium sensitization
and CBD based on the NJMRC data may
be impacted in workplaces where such
beryllium forms and processes are used.
However, OSHA does not expect this
uncertainty to alter its qualitative
conclusions with regard to the risk at
the current PEL and at alternate PELs as
low as 0.1 mg/m3. The existing studies
provide clear evidence of sensitization
and CBD risk among workers exposed to
a number of beryllium forms as a result
of different processes such as beryllium
machining, beryllium-copper alloy
production, and beryllium ceramics
production. The Agency believes all of
these forms of beryllium exposure
contribute to the overall risk of
sensitization and CBD among berylliumexposed workers.
G. Lung Cancer
OSHA considers lung cancer to be an
important health endpoint for
beryllium-exposed workers. The
International Agency for Research on
Cancer (IARC), National Toxicology
Program (NTP), and American
Conference of Governmental Industrial
Hygienists (ACGIH) have all classified
beryllium as a known human
carcinogen. The National Academy of
Sciences (NAS), Environmental
Protection Agency, the Agency for Toxic
Substances and Disease Registry
(ATSDR), the National Institute of
Occupational Safety and Health
(NIOSH), and other reputable scientific
organizations have reviewed the
scientific evidence demonstrating that
beryllium is associated with an
increased incidence of cancer. OSHA
also has performed an extensive review
of the scientific literature regarding
beryllium and cancer. This includes an
evaluation of human epidemiological,
animal cancer, and mechanistic studies
described in the Health Effects section
of this preamble. Based on the weight of
evidence, the Agency has preliminarily
determined beryllium to be an
occupational carcinogen.
Although epidemiological and animal
evidence supports a conclusion of
beryllium carcinogenicity, there is
considerable uncertainty surrounding
the mechanism of carcinogenesis for
beryllium. The evidence for direct
genotoxicity of beryllium and its
compounds has been limited and
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inconsistent (NAS, 2008; IARC, 1993;
EPA, 1998; NTP, 2002; ATSDR, 2002).
One plausible pathway for beryllium
carcinogenicity described in the Health
Effects section of this preamble includes
a chronic, sustained neutrophilic
inflammatory response that induces
epigenetic alterations leading to the
neoplastic changes necessary for
carcinogenesis. The National Cancer
Institute estimates that nearly one-third
of all cancers are caused by chronic
inflammation (NCI, 2009). This
mechanism of action has also been
hypothesized for crystalline silica and
other agents that are known to be
human carcinogens but have limited
evidence of genotoxicity.
OSHA’s review of epidemiological
studies of lung cancer mortality among
beryllium workers found that most did
not characterize exposure levels
sufficiently for exposure-response
analysis. However, one NIOSH study
evaluated the association between
beryllium exposure and lung cancer
mortality based on data from a
beryllium processing plant in Reading,
PA (Sanderson et al., 2001a). As
discussed in the Health Effects section
of this preamble, this case-control study
evaluated lung cancer incidence in a
cohort of workers employed at the plant
from 1940 to 1969 and followed through
1992. For each lung cancer victim, 5
age- and race-matched controls were
selected by incidence density sampling,
for a total of 142 lung cancer cases and
710 controls.
Between 1971 and 1992, the plant
collected close to 7,000 high volume
filter samples consisting of both general
area and short-term, task-based
breathing zone measurements for
production jobs and exclusively area
measurements for office, lunch, and
laboratory areas (Sanderson et al.,
2001b). In addition, a few (< 200)
impinger and high-volume filter
samples were collected by other
organizations between 1947 and 1961,
and about 200 6-to-8-hour personal
samples were collected in 1972 and
1975. Daily-weighted-average (DWA)
exposure calculations based on the
impinger and high-volume samples
collected prior to the 1960s showed that
exposures in this period were extremely
high. For example, about half of
production jobs had estimated DWAs
ranging between 49 and 131 mg/m3 in
the period 1935–1960, and many of the
‘‘lower-exposed’’ jobs had DWAs of
approximately 20–30 mg/m3 (Table II,
Sanderson et al., 2001b). Exposures
were reported to have decreased
between 1959 and 1962 with the
installation of ventilation controls and
improved housekeeping and following
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the passage of the OSH Act in 1970.
While no exposure measurements were
available from the period 1961–1970,
measurements from the period 1971–
1980 showed a dramatic reduction in
exposures plant-wide. Estimated DWAs
for all jobs in this period ranged from
0.1 mg/m3 to 1.9 mg/m3. Calendar-timespecific beryllium exposure estimates
were made for every job based on the
DWA calculations and were used to
estimate workers’ cumulative, average,
and maximum exposures. Exposure
estimates were lagged by 10 and 20
years in order to account for exposures
that did not contribute to lung cancer
because they occurred after the
induction of cancer.
Results of a conditional logistic
regression analysis showed an increased
risk of lung cancer in workers with
higher exposures when dose estimates
were lagged by 10 and 20 years
(Sanderson et al., 2001a). The authors
noted that there was considerable
uncertainty in the estimation of
exposure in the 1940s and 1950s and
the shape of the dose-response curve for
lung cancer. NIOSH later reanalyzed the
data, adjusting for potential confounders
of hire age and birth year (SchubauerBerigan et al., 2008). The study reported
a significant increasing trend (p<0.05) in
the odds ratio when increasing quartiles
of average (log transformed) exposure
were lagged by 10 years. However, it did
not find a significant trend when
quartiles of cumulative (log
transformed) exposure were lagged by 0,
10, or 20 years.
OSHA is interested in lung cancer risk
estimates from a 45-year (i.e., working
lifetime) exposure to beryllium levels
between 0.1 mg/m3 and 2 mg/m3. The
majority of case and control workers in
the Sanderson et al. case-control
analysis were first hired during the
1940s when exposures were extremely
high (estimated DWAs > 20 mg/m3 for
most jobs). The cumulative, average,
and maximum beryllium exposure
concentration estimates for the 142
known lung cancer cases were: 46.06 ±
9.3mg/m3-days, 22.8 ± 3.4 mg/m3, and
32.4 ± 13.8 mg/m3, respectively. About
two-thirds of cases and half of controls
worked at the plant for less than a year.
Thus, a risk assessment based on this
exposure-response analysis would need
to extrapolate from very high to very
low exposures, based on a working
population with extremely short tenure.
While OSHA risk assessments must
often make extrapolations to estimate
risk within the range of exposures of
interest, the Agency acknowledges that
these issues of short tenure and
extremely high exposures would create
substantial uncertainty in a risk
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47643
assessment based on this study
population.
In addition, the relatively high
exposures of even the least-exposed
workers in the NIOSH study may create
methodological issues for the lung
cancer case-control study design.
Mortality risk is expressed as an odds
ratio that compares higher exposure
quartiles to the lowest quartile. It is
preferable that excess risks attributable
to occupational beryllium be
determined relative to an unexposed or
minimally exposed reference
population. However, in the NIOSH
study workers in the lowest quartile
were exposed well above the OSHA PEL
(average exposure <11.2 mg/m3) and may
have had a significant lung cancer risk.
This issue would introduce further
uncertainty in lung cancer risks
estimated from this epidemiological
study.
In 2010, researchers at NIOSH
published a quantitative risk assessment
based on an update of the Reading
cohort analyzed by Sanderson et al., as
well as workers from two smaller plants
(Schubauer-Berigan et al., 2010b). This
new risk assessment addresses several
of OSHA’s concerns regarding the
Sanderson et al. analysis. The new
cohort was exposed, on average, to
lower levels of beryllium and had fewer
short-term workers. Finally, the updated
cohorts followed the populations
through 2005, increasing the length of
follow-up time overall by an additional
17 years of observation. For these
reasons, OSHA considers the
Schubauer-Berigan risk analysis more
appropriate than the Sanderson et al.
analysis for its preliminary risk
assessment.
The cohort studied by SchubauerBerigan et al. included 5,436 male
workers who had worked for at least
two days at the Reading facility and
beryllium processing plants at Hazleton
PA and Elmore OH prior to 1970. The
authors developed job-exposure
matrices (JEMs) for the three plants
based on extensive historical exposure
data, primarily short-term general area
and personal breathing zone samples,
collected on a quarterly basis from a
wide variety of operations. These
samples were used to create daily
weighted average (DWA) estimates of
workers’ full-shift exposures, using
records of the nature and duration of
tasks performed by workers during a
shift. Details on the JEM and DWA
construction can be found in Sanderson
et al. (2001a), Chen et al. (2001), and
Couch et al. (2010).
Workers’ cumulative exposures (mg/
m3-days) were estimated by summing
daily average exposures (assuming five
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workdays per week). To estimate mean
exposure (mg/m3), cumulative exposure
was divided by exposure time (in days).
Maximum exposure (mg/m3) was
estimated as the highest annual DWA on
record for a worker prior to the study
cutoff date of December 31, 2005 and
accounting where appropriate for lag
time. Exposure estimates were lagged by
5, 10, 15, and 20 years in order to
account for exposures that may not have
contributed to lung cancer because of
the long latency required for
manifestation of the disease. The
authors also fit models with no lag time.
As shown in Table VI–19 below,
estimated exposure levels for workers
from the Hazleton and Elmore plants
were on average far lower than those for
workers from the Reading plant. The
median worker from Hazleton had a
mean exposure across his tenure of less
than 2 mg/m3, while the median worker
from Elmore had a mean exposure of
less than 1 mg/m3. The Elmore and
Hazleton worker populations also had
fewer short-term workers than the
Reading population. This was
particularly evident at Hazleton where
the median value for cumulative
exposure among cases was higher than
at Reading despite the much lower
mean and maximum exposure levels.
TABLE VI–19—COHORT DESCRIPTION AND DISTRIBUTION OF CASES BY EXPOSURE LEVEL
All plants
Number of cases ...............................
Number of non-cases .......................
Median value for mean exposure .....
(μg/m3) among cases .......................
Median value for cumulative exposure.
(μg/m3-days) among cases ...............
Median value for maximum exposure
(μg/m3) among cases .......................
Number of cases with potential asbestos exposure.
Number of cases who were professional workers.
Reading plant
Hazleton plant
Elmore plant
...........................................................
...........................................................
No lag ...............................................
10-year lag .......................................
No lag ...............................................
293
5143
15.42
15.15
2843
218
3337
25
25
2895
30
583
1.443
1.443
3968
45
1223
0.885
0.972
1654
10-year lag .......................................
No lag ...............................................
10-year lag .......................................
...........................................................
2583
25
25
100 (34%)
2832
25.1
25
68 (31%)
3648
3.15
3.15
16 (53%)
1449
2.17
2.17
16 (36%)
...........................................................
26 (9%)
21 (10%)
3 (10%)
2 (4%)
Table adapted from Schubauer-Berigan et al. 2011, Table 1.
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Schubauer-Berigan et al. analyzed the
data set using a variety of exposureresponse modeling approaches,
including categorical analyses and
continuous-variable piecewise log-linear
and power models, described in
Schubauer-Berigan et al. (2011). All
models adjusted for birth cohort and
plant. As exposure values were logtransformed for the power model
analyses, the authors added small
values to exposures of 0 in lagged
analyses (0.05 mg/m3 for mean and
maximum exposure, 0.05 mg/m3-days for
cumulative exposure). The authors used
restricted cubic spline models to assess
the shape of the exposure-response
curve and suggest appropriate
parametric model forms. The Akaike
Information Criterion (AIC) value was
used to evaluate the fit of different
model forms and lag times.
Because smoking information was
available for only about 25 percent of
the cohort, smoking could not be
controlled for directly in the models.
The authors reported that within the
subset with smoking information, there
was little difference in smoking by
cumulative or maximum exposure
category (p. 6), suggesting that smoking
was unlikely to act as a confounder in
the cohort. In addition to models based
on the full cohort, Schubauer-Berigan et
al. also prepared risk estimates based on
models excluding professional workers
and workers believed to have asbestos
exposure. These models were intended
to mitigate the potential impact of
smoking and asbestos as confounders. If
professional workers had both lower
beryllium exposures and lower smoking
rates than production workers, smoking
could be a confounder in the cohort
comprising both production and
professional workers. However, the
authors reasoned that smoking was
unlikely to be correlated with beryllium
exposure among production workers,
and would therefore probably not act as
a confounder in a cohort excluding
professional workers.
The authors found that lung cancer
risk was strongly and significantly
related to mean, cumulative, and
maximum measures of workers’
exposure (all models reported in
Schubauer-Berigan et al., 2011). They
selected the best-fitting categorical,
power, and monotonic piecewise loglinear (PWL) models with a 10-year lag
to generate hazard ratios for male
workers with a mean exposure of 0.5 mg/
m3 (the current NIOSH Recommended
Exposure Limit for beryllium).9 To
estimate excess lifetime risk of cancer,
they multiplied this hazard ratio by the
2004–2006 background lifetime lung
cancer rate among U.S. males who had
survived, cancer-free, to age 30. In
addition, they estimated the mean
exposure that would be associated with
an excess lifetime risk of one in 1000,
a value often used as a benchmark for
significant risk in OSHA regulations. At
OSHA’s request, they also estimated
excess lifetime risks for workers with
mean exposures at the current PEL of 2
mg/m3 each of the other alternate PELs
under consideration: 1 mg/m3, 0.2 mg/
m3, and 0.1 mg/m3 (Schubauer-Berigan,
4/22/11). The resulting risk estimates
are presented in Table VI–20 below.
9 Here, ‘‘monotonic PWL model’’ means a model
producing a monotonic exposure-response curve in
the 0–2 ug/m3 region.
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TABLE VI–20—EXCESS LIFETIME RISK PER 1000 [95% CONFIDENCE INTERVAL] FOR MALE WORKERS AT ALTERNATE
PELS
[NIOSH models]
Mean exposure
Exposure-response model
0.1
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Best monotonic PWL—all workers ........
Best monotonic PWL—excluding professional and asbestos workers .........
Best categorical—all workers ................
Best categorical—excluding professional and asbestos workers ..............
Power model—all workers .....................
Power model—excluding professional
and asbestos workers ........................
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0.2
μg/m3
0.5 μg/m3
1 μg/m3
2 μg/m3
7.3[2.0–13]
15[3.3–29]
45[9–98]
120[20–340]
200[29–370]
3.1[<0–11]
4.4[1.3–8]
6.4[<0–23]
9[2.7–17]
17[<0–74]
25[6–48]
39[39–230]
59[13–130]
61[<0–280]
170[29–530]
1.4[<0–6.0]
12[6–19]
2.7[<0–12]
19[9.3–29]
7.1[<0–35]
30[15–48]
15[<0–87]
40[19–66]
33[<0–290]
52[23–88]
19[8.6–31]
Schubauer-Berigan et al. discuss
several strengths, weaknesses, and
uncertainties of their analysis. Strengths
include long (> 30 years) follow-up time
for members of the cohort and the
extensive exposure and work history
data available for the development of
exposure estimates for workers in the
cohort. Among the weaknesses and
uncertainties of the study are the
limited information available on
workers’ smoking habits: smoking
information was available only for
workers employed in 1968, about 25
percent of the cohort. In addition, the
JEMs used did not account for possible
respirator use among workers in the
cohort. The authors note that workers’
exposures may therefore have been
overestimated, and that overestimation
may have been especially severe for
workers with high estimated exposures.
They suggest that overestimation of
exposures for workers in highly exposed
positions may have caused attenuation
of the exposure-response curve in some
models at higher exposures.
The NIOSH publication did not
discuss the reasons for basing risk
estimates on mean exposure rather than
cumulative exposure that is more
commonly used for lung cancer risk
analysis. OSHA believes the decision
may involve the nonmonotonic
relationship NIOSH observed between
cancer risk and cumulative exposure
level. As discussed previously, workers
from the Reading plant frequently had
very short tenures and high exposures
yielding lower cumulative exposures
compared to cohort workers from other
plants with longer employment. Despite
the low estimated cumulative exposures
among the short-term Reading workers,
they may be at high risk of lung cancer
due to the tendency of beryllium to
persist in the lung for long periods. This
exposure misclassification could lead to
the appearance of a nonmonotonic
relationship between cumulative
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49[21–87]
68[27–130]
90[34–180]
exposure and lung cancer risk. It is
possible that a dose-rate effect may exist
for beryllium, such that the risk from a
cumulative exposure gained by longterm, low-level exposure is not
equivalent to the risk from a cumulative
exposure gained by very short-term,
high-level exposure. In this case, mean
exposure level may better correlate with
the risk of lung cancer than cumulative
exposure level. For these reasons OSHA
considers the NIOSH choice of mean
exposure metric to be appropriate and
scientifically defensible for this
particular dataset.
H. Preliminary Conclusions
As described above, OSHA’s risk
assessment for beryllium sensitization
and CBD relied on two approaches: (1)
review of the literature and (2) analysis
of a dataset provided by NJRMC. First,
the Agency reviewed the scientific
literature to ascertain whether there is
substantial risk to workers exposed at
and below the current PEL and to
characterize the expected impact of
more stringent controls on workers’ risk
of sensitization and CBD. This review
focused on facilities where exposures
were primarily below the current PEL,
and where several rounds of BeLPT and
CBD screening had been conducted to
evaluate the effectiveness of various
exposure control measures. Second,
OSHA investigated the exposureresponse relationship for beryllium
sensitization and CBD by analyzing a
dataset that NJMRC provided on
workers at a prominent, longestablished beryllium machining
facility. Although exposure-response
studies have been published on
sensitization and CBD, OSHA believes
the nature and quality of their exposure
data significantly limits their value for
the Agency’s risk assessment. Therefore,
OSHA developed an independent
exposure-response analysis using the
NJMRC dataset, which was recently
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updated, includes workers exposed at
low levels, and includes extensive
exposure data collected in workers’
breathing zones, as is preferred by
OSHA.
OSHA’s review of the scientific
literature found substantial risk of both
sensitization and CBD in workplaces in
compliance with OSHA’s current PEL
(e.g., Kreiss et al., 1992; Schuler et al.,
2000; Madl et al., 2007). At these plants,
including a copper-beryllium processing
facility, a beryllia ceramics facility, and
a beryllium machining facility, exposure
reduction programs that primarily used
engineering controls to reduce airborne
exposures to median levels at or around
0.2 mg/m3 had only limited impact on
workers’ risk. Cases of sensitization
continued to occur frequently among
newly hired workers, and some of these
workers developed CBD within the
short follow-up time.
In contrast, industrial hygiene
programs that minimized both airborne
and dermal exposure substantially
lowered workers’ risk of sensitization in
the first years of employment. Programs
that drastically reduced respiratory
exposure via a combination of
engineering controls and respiratory
protection, minimized the potential for
skin exposure via dermal PPE, and
employed stringent housekeeping
methods to keep work areas clean and
prevent transfer of beryllium between
areas sharply curtailed new cases of
sensitization among newly-hired
workers. For example, studies
conducted at copper-beryllium
processing, beryllium production, and
beryllia ceramics facilities show that
reduction of exposures to below 0.1 mg/
m3 and protection from dermal
exposure, in combination, achieved a
substantial reduction in sensitization
risk among newly-hired workers.
However, even these stringent measures
did not protect all workers from
sensitization.
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The most recent epidemiological
literature on programs that have been
successful in reducing workers’ risk of
sensitization have had very short
follow-up time; therefore, they cannot
address the question of how frequently
workers sensitized in very low-exposure
environments develop CBD. Clinical
evaluation for CBD was not reported for
workers at the copper-beryllium
processing, beryllium production, and
ceramics facilities. However, cases of
CBD among workers exposed at low
levels at a machining plant and cases of
CA–CBD demonstrate that individuals
exposed to low levels of airborne
beryllium can develop CBD, and over
time, can progress to severe disease.
This conclusion is also supported by
case reports within the literature of
workers with CBD who may have been
minimally exposed to beryllium, such
as a worker employed only in
administration at a beryllium ceramics
facility (Kreiss et al., 1996).
The Agency’s analysis of the Cullman
dataset provided by NJMRC showed
strong exposure-response trends using
multiple analytical approaches,
including examination of sensitization
and disease prevalence by exposure
categories and a proportional hazards
modeling approach. In the prevalence
analysis, cases of sensitization and
disease were evident at all levels of
exposure. The lowest prevalence of
sensitization (2.0 percent) and CBD (1.0
percent) was observed among workers
with LTW average exposure levels
below 0.1 mg/m3, while those with LTW
average exposure between 0.1–0.2 mg/m3
showed a marked increase in overall
prevalence of sensitization (9.8 percent)
and CBD (7.3 percent). Prevalence of
sensitization and CBD also increased
with cumulative exposure.
OSHA’s proportional hazards analysis
of the Cullman dataset found increasing
risk of sensitization with both
cumulative exposure and average
exposure. OSHA also found a positive
relationship between risk of CBD and
cumulative exposure, but not between
CBD and average exposure. The Agency
used the cumulative exposure model
results to estimate hazards ratios and
risk of sensitization and CBD at the
current PEL of 2 mg/m3 and each of the
alternate PELs under consideration: 1
mg/m3, 0.5 mg/m3, 0.2 mg/m3, and 0.1 mg/
m3. To estimate risk of CBD from a
working lifetime of exposure, the
Agency calculated the cumulative
exposure associated with 45 years of
exposure at each level, for total
cumulative exposures of 90, 45, 22.5, 9,
and 4.5 mg/m3-years. The risk estimates
for sensitization and CBD ranged from
100–403 and 40–290 cases, respectively,
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per 1000 workers exposed at the current
PEL of 2 mg/m3. The risks are projected
to be substantially lower for both
sensitization and CBD at 0.1 mg/m3 and
range from 7.2–35 cases per 1000 and
3.1–26 cases per 1000, respectively. In
these ways, the modeling results are
similar to results observed from
published studies of the Reading,
Tucson, and Cullman plants and the
OSHA analysis of sensitization and CBD
prevalence within the Cullman plant.
OSHA has a high level of confidence
in the finding of substantial risk of
sensitization and CBD at the current
PEL, and the Agency believes that a
standard requiring a combination of
more stringent controls on beryllium
exposure will reduce workers’ risk of
both sensitization and CBD. Programs
that have reduced median levels to
below 0.1 mg/m3, tightly controlled both
respiratory and dermal exposure, and
incorporated stringent housekeeping
measures have substantially reduced
risk of sensitization within the first
years of exposure. These conclusions
are supported by the results of several
studies conducted in state-of-the-art
facilities dealing with a variety of
production activities and physical forms
of beryllium. In addition, these
conclusions are supported by OSHA’s
statistical analysis of a dataset with
highly detailed exposure and work
history information on several hundred
beryllium workers. While there is
uncertainty regarding the precision of
model-derived risk estimates, they
provide further evidence that there is
substantial risk of sensitization and CBD
associated with exposure at the current
PEL, and that this risk can be
substantially lessened by stringent
measures to reduce workers’ beryllium
exposure levels.
Furthermore, OSHA believes that
beryllium-exposed workers’ risk of lung
cancer will be reduced by more
stringent control of airborne beryllium
exposures. The risk estimates from
NIOSH’s recent lung cancer study,
described above, range from 33 to 140
excess lung cancers per 1000 workers
exposed at the current PEL of 2 mg/m3.
The NIOSH risk assessment’s six bestfitting models each predict substantial
reductions in risk with reduced
exposure, ranging from 3 to 19 excess
lung cancers per 1000 workers exposed
at the proposed PEL of 0.1 mg/m3. The
evidence of lung cancer risk from
NIOSH’s risk assessment provides
additional support for OSHA’s
preliminary conclusions regarding the
significance of risk to workers exposed
to beryllium levels at and below the
current PEL. However, the lung cancer
risks require a sizable low dose
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extrapolation below beryllium exposure
levels experienced by workers in the
NIOSH study. As a result, there is a
greater uncertainty in the lung cancer
risk estimates and lesser confidence in
their significance of risk below the
current PEL than with beryllium
sensitization and CBD. The preliminary
conclusions with regard to significance
of risk are presented and further
discussed in section VIII of the
preamble.
VII. Expert Peer Review of Health
Effects and Preliminary Risk
Assessment
In 2010, Eastern Research Group, Inc.
(ERG), under contract to the
Occupational Safety and Health
Administration (OSHA) ,10 conducted
an independent, scientific peer review
of (1) a draft Preliminary Beryllium
Health Effects Evaluation (OSHA,
2010a), (2) a draft Preliminary Beryllium
Risk Assessment (OSHA, 2010b), and (3)
two NIOSH study manuscripts
(Schubauer-Berigan et al., 2011 and
2011a). This section of the preamble
describes the review process and
summarizes peer reviewers’ comments
and OSHA’s responses.
ERG conducted a search for nationally
recognized experts in the areas of
occupational epidemiology,
occupational medicine, toxicology,
immunology, industrial hygiene/
exposure assessment, and risk
assessment/biostatistics as requested by
OSHA. ERG sought experts familiar
with beryllium health effects research
and who had no conflict of interest
(COI) or apparent bias in performing the
review. Interested candidates submitted
evidence of their qualifications and
responded to detailed COI questions.
ERG also searched the Internet to
determine whether qualified candidates
had made public statements or declared
a particular bias regarding beryllium
regulation.
From the pool of qualified candidates,
ERG selected five experts to conduct the
review, based on:
Æ Their qualifications, including their
degrees, years of relevant experience,
number of related peer-reviewed
publications, experience serving as a
peer reviewer for OSHA or other
government organizations, and
committee and association memberships
related to the review topic;
Æ Lack of any actual, potential, or
perceived conflict of interest; and
Æ The need to ensure that the panel
collectively was sufficiently broad and
10 Task Order No. DOLQ59622303, Contract No.
GS10F0125P, with a period of performance from
May, 2010 through December, 2010.
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diverse to fairly represent the relevant
scientific and technical perspectives
and fields of knowledge appropriate to
the review.
OSHA reviewed the qualifications of
the candidates proposed by ERG to
verify that they collectively represented
the technical areas of interest. ERG then
contracted the following experts to
perform the review.
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(1) John Balmes, MD, Professor of
Medicine, University of California-San
Francisco
Expertise: pulmonary and occupational
medicine, CBD, occupational lung disease,
epidemiology, occupational exposures,
medical surveillance.
(2) Patrick Breysse, Ph.D., Professor, Johns
Hopkins University Bloomberg School of
Public Health
Expertise: industrial hygiene,
occupational/environmental health
engineering, exposure monitoring/analysis,
biomarkers, beryllium exposure assessment
(3) Terry Gordon, Ph.D., Professor, New
York University School of Medicine.
Expertise: inhalation toxicology,
pulmonary disease, beryllium toxicity and
carcinogenicity, CBD genetic susceptibility,
mode of action, animal models.
(4) Milton Rossman, MD, Professor of
Medicine, Hospital of the University of
Pennsylvania School of Medicine.
Expertise: pulmonary and clinical
medicine, immunology, beryllium
sensitization, BeLPT, clinical diagnosis for
CBD.
(5) Kyle Steenland, Ph.D., Professor, Emory
University, Rollins School of Public Health.
Expertise: occupational epidemiology,
biostatistics, risk and exposure assessment,
lung cancer, CBD, exposure-response models.
Reviewers were provided with the
Technical Charge and Instructions (see
ERG, 2010), a Request for Peer Review
of NIOSH Manuscripts (see ERG, 2010),
the draft Preliminary OSHA Health
Effects Evaluation (OSHA, 2010a), the
draft Preliminary Beryllium Risk
Assessment (OSHA, 2010b), and access
to relevant references. Each reviewer
independently provided comments on
the Health Effects, Risk Assessment, and
NIOSH documents. A briefing call was
held early in the review to ensure that
reviewers understood the peer review
process. ERG organized the call and
OSHA representatives were available to
respond to technical questions of
clarification. Reviewers were invited to
submit any subsequent questions of
clarification.
The written comments from each
reviewer were received and organized
by ERG by charge questions. The
unedited individual and reorganized
comments were submitted to OSHA and
the reviewers in preparation for a
follow-up conference call. The
conference call, organized and
facilitated by ERG, provided an
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opportunity for OSHA to clarify
individual reviewer’s comments. After
the call, reviewers were given the
opportunity to revise their written
comments to include the clarifications
or additional information provided on
the call. ERG submitted the revised
comments to OSHA organized by both
individual reviewer and by charge
question. A final peer review report is
available in the docket (ERG, 2010).
Section VII.A of this preamble
summarizes the comments received on
the draft health effects document and
OSHA’s responses to those comments.
Section VII.B summarizes comments
received on the draft Preliminary Risk
Assessment and the OSHA response.
A. Peer Review of Draft Health Effects
Evaluation
The Technical Charge to peer
reviewers posed general questions on
the draft health effects document as well
as specific questions pertaining to
particle/chemical properties, kinetics
and metabolism, acute beryllium
disease, development of beryllium
sensitization and CBD, genetic
susceptibility, epidemiological studies
of sensitization and CBD, animal models
of chronic beryllium disease,
genotoxicity, lung cancer
epidemiological studies, animal cancer
studies, other health effects, and
preliminary conclusions drawn by
OSHA.
OSHA asked the peer reviewers to
generally comment on whether the draft
health effects evaluation included the
important studies, appropriately
addressed their strengths and
limitations, accurately described the
results, and drew scientifically sound
conclusions. Overall, the reviewers felt
that the studies were described in
sufficient detail, the interpretations
accurate, and the conclusions
reasonable. They agreed that the OSHA
document covered the significant health
endpoints related to occupational
beryllium exposure. However, several
reviewers requested that additional
studies and other specific information
be included in various sections of the
document and these are discussed
further below.
The reviewers had similar suggestions
to improve the section V.A of this
preamble on physical/chemical
properties and section V.B on kinetics/
metabolism. Dr. Balmes requested that
physical and chemical characteristics of
beryllium more clearly relate to
development of sensitization and
progression to CBD. Dr. Gordon
requested greater consistency in the
terminology used to describe particle
characteristics, sampling methodologies,
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and the particle deposition in the
respiratory tract. Dr. Breysse agreed and
requested that the respiratory deposition
discussion be better related to the onset
of sensitization and CBD. Dr. Rossman
suggested that the discussion of
particle/chemical characteristics might
be better placed after section V.D on the
immunobiology of sensitization and
CBD.
OSHA made a number of revisions to
sections V.A and V.B to address the peer
review comments above. Terminology
used to describe particle characteristics
in various studies was modified to be
more consistent and better reflect the
authors’ intent in the published research
articles. Section V.B.1 on respiratory
kinetics of inhaled beryllium was
modified to more clearly describe
particle deposition in the different
regions of the respiratory tract and their
influence on CBD. At the
recommendation of Dr. Gordon, a
confusing figure was removed since it
did not portray particle deposition in a
clear manner. Rather than relocate the
entire discussion of particle/chemical
characteristics, a new section V.B.5 was
added to specifically address the
influence of beryllium particle
characteristics and chemical form on the
development of sensitization and CBD.
Other section areas were shortened to
remove information that was not
necessarily relevant to the overall
disease process. Statements were added
on the effect of pre-existing diseases and
smoking on beryllium clearance from
the lung. It was made clear that the
precise role of dermal exposure in
beryllium sensitization is not
completely understood. These smaller
changes were made at the request of
individual reviewers.
There were a couple of comments
from reviewers pertaining to acute
beryllium disease (ABD). Dr. Rossman
commented that ABD did not make the
development of CBD more likely. He
requested that the document include a
reference to the Van Ordstrand et al.
(1943) article that first reported ABD in
the U.S. Dr. Balmes pointed out that
pathologists, rather than clinicians,
interpret ABD pathology from lung
tissue biopsy. Dr. Gordon commented
that ABD is of lesser importance than
CBD to the risk assessment and
suggested that discussion of ABD be
moved later in the document.
The Van Ordstrand reference was
included in section V.C on acute
beryllium diseases and statements were
modified to address the peer review
comments above. While OSHA agrees
that ABD does not have a great impact
on the Agency risk findings, the Agency
believes the current organization does
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not create confusion on this point and
decided not to move the ABD section
later in the document. A statement that
ABD is only relevant at exposures
higher than the current PEL has been
added to section V.C. Other reviewers
did not feel the ABD discussion needed
to be moved to a later section.
Most reviewers found the description
of the development and pathogenesis of
CBD in section V.D to be accurate and
understandable. Dr. Breysse felt the
section could better delineate the steps
in disease development (e.g.,
development of beryllium sensitization,
CBD progression) and recommended the
2008 National Academy of Sciences
report as a model. He and Dr. Gordon
felt the section overemphasized the role
of apoptosis in CBD development. Dr.
Breysse and Dr. Balmes recommended
avoiding the phrase ‘subclinical’ to
describe sensitization and asymptomatic
CBD, preferring the term ‘early stage’ as
a more appropriate description. Dr.
Balmes requested clarification regarding
accumulation of inflammatory cells in
the bronchoalveolar lavage (BAL) fluid
during CBD development. Dr. Rossman
suggested some additional description
of beryllium binding with the HLA-class
II receptor and subsequent interaction
¨
with the naıve CD4+ T cells in the
development of sensitization.
OSHA extensively reorganized section
V.D to clearly delineate the disease
process in a more linear fashion starting
with the formation of beryllium antigen
¨
complex, its interaction with naıve Tcells to trigger CD4+ T-cell proliferation,
and development of beryllium
sensitization. This is presented in
section V.D.1. A figure has been added
that schematically presents this process
in its entirety and the steps at which
dermal exposure and genetic factors are
believed to influence disease
development (Figure 2 in section V.D).
Section V.D.2 describes how subsequent
inhalation and the persistent residual
presence of beryllium in the lung leads
to CD4+ T cell differentiation, cytokine
production, accumulation of
inflammatory cells in the alveolar
region, granuloma formation, and
progression of CBD. The section was
modified to present apoptosis as only
one of the plausible mechanisms for
development/progression of CBD. The
‘early stage’ terminology was adopted
and the role of inflammatory cells in
BAL was clarified.
While peer reviewers felt genetic
susceptibility was adequately
characterized, Dr. Rossman, Dr. Gordon,
and Dr. Breysse suggested that
additional study data be discussed to
provide more depth on the subject,
particularly the role genetic
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polymorphisms in providing a
negatively charged HLA protein binding
site for the positively charged beryllium
ion. Section V.D.3 on genetic
susceptibility now includes more
information on the importance of geneenvironment interaction in the
development of CBD in low-exposed
workers. The section expands on HLA–
DPB1 alleles that influence berylliumhapten binding and its impact on CBD
risk.
All reviewers found the definition of
CBD to be clear and understandable.
However, several reviewers commented
on the document discussion of the
BeLPT which operationally defines
beryllium sensitization. Drs. Balmes and
Rossman requested a more clear
statement that two abnormal blood
BeLPT results were generally necessary
to confirm sensitization. Dr. Balmes and
Dr. Breysse requested more discussion
of historical changes in the BeLPT
method that have led to improvement in
test performance and reductions in
interlaboratory variability. These
comments were addressed in an
expanded document section V.D.5.b on
criteria for sensitization and CBD case
definition following development of the
BeLPT.
Reviewers made suggestions to
improve presentation of the many
epidemiological studies of sensitization
and CBD in the draft health effects
document. Dr. Breysse and Dr. Gordon
recommended that common weaknesses
that apply to multiple studies be more
rigorously discussed. Dr. Gordon
requested that the discussion of the
Beryllium Case Registry be modified to
clarify the case inclusion criteria. Most
reviewers called for the addition of
tables to assist in summarizing the
epidemiological study information.
A paragraph has been added near the
beginning of section V.D.5 that
identifies the common challenges to
interpreting the epidemiological
evidence that supports the occurrence of
sensitization and CBD at occupational
beryllium exposures below the current
PEL. These include studies with small
numbers of subjects and CBD cases,
potential exposure misclassification
resulting from lack of personal and
short-term exposure data prior to the
late 1990s, and uncertain dermal
contribution among other issues. Table
A.1 summarizing the key sensitization
and CBD epidemiological studies was
added to this preamble in appendix A
of section V. Subsection V.D.5.a on
studies conducted prior to the BeLPT
has been reorganized to more clearly
present the need for the Registry prior
to listing the inclusion criteria.
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Several reviewers requested that the
draft health effects document discuss
additional occupational studies on
sensitization and CBD. Dr. Balmes
suggested including Bailey et al. (2010)
on reduction in sensitization at a
beryllium production plant and
Arjomandi et al. (2010) on CBD among
workers in a nuclear weapons facility.
Dr. Breysse recommended adding a brief
discussion of Taiwo et al. (2008) on
sensitization in aluminum smelter
workers. Dr. Gordon and Dr. Rossman
suggested mention of Curtis, (1951) on
cutaneous hypersensitivity to beryllium
as important for the role of dermal
exposure. Dr. Rossman also provided a
reference to a number of other
sensitization and CBD articles of
historical significance.
The above studies have been
incorporated in several subsections of
V.D.5 on human epidemiological
evidence. The 1951 Curtis study is
mentioned in the introduction to section
V.D.5 as evidence of sensitization from
dermal exposure. The Bailey et al.
(2010) study is discussed in subsection
V.D.5.d on beryllium metal processing
and alloy production. The Arjomandi et
al. (2010) study is discussed subsection
V.D.5.h on nuclear weapons facilities
and cleanup of former facilities. The
Taiwo et al. (2008) study is discussed in
subsection V.D.5.i on aluminum
smelting. The other historical studies of
historical significance are referenced in
subsection V.D.5.a on studies conducted
prior to the BeLPT.
Dr. Gordon suggested that the draft
health effects document make clear that
limitations in study design and lack of
an appropriate model limited
extrapolation of animal findings to the
human immune-based respiratory
disease. Dr. Rossman also remarked on
the lack of a good animal model that
consistently demonstrates a specific
cell-mediated immune response to
beryllium. Section V.D.6 was modified
to include a statement that lack of a
dependable animal model combined
with studies that used single doses, few
animals or abbreviated observation
periods have limited the utility of the
data. Table A.2 was added that
summarizes important information on
key animal studies of beryllium-induced
immune response and lung
inflammation.
In general, peer reviewers considered
the preliminary conclusions with regard
to sensitization and CBD to be
reasonable and well presented in the
draft health effects evaluation. All
reviewers agreed that the scientific
evidence supports sensitization as a
necessary condition and an early
endpoint in the development of CBD.
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The peer reviewers did not consider the
presented evidence to convincingly
show lung burden to be an important
dose metric. Dr. Gordon explained that
some animal studies in dogs have
indicated that lung dose does influence
granuloma formation but the importance
of dose relative to genetic susceptibility,
and physical/chemical form is unclear.
He suggested the document indicate that
many factors, including lung burden,
affect the pulmonary tissue response to
beryllium particles in the workplace.
There were other suggested
improvements to the preliminary
conclusion section of the draft
document. Dr. Breysse felt that
presenting the range of observed
prevalence from occupational studies
would help support the Agency
findings. He also recommended that the
preliminary conclusions make clear that
CBD is a very complex disease and
certain steps involved in the onset and
progression are not yet clearly
understood. Dr. Rossman pointed out
that a report from Mroz et al. (2009)
updated information on the rate at
which beryllium sensitized individuals
progress to CBD.
A statement has been added to section
V.D.7 on the preliminary sensitization
and CBD conclusions to indicate that all
facets of development and progression
of sensitization and CBD are not fully
understood. Study references and
prevalence ranges were provided to
support the conclusion that
epidemiological evidence demonstrates
that sensitization and CBD occur from
present-day exposures below OSHA’s
PEL. Statements were modified to
indicate animal studies provide
important insights into the roles of
chemical form, genetic susceptibility,
and residual lung burden in the
development of beryllium lung disease.
Updated information on rate of
progression from sensitization to CBD
was also included.
Reviewers made suggestions to
improve presentation of the
epidemiological studies of lung cancer
that were similar to their comments on
the CBD studies. Dr. Steenland
requested that a table summarizing the
lung cancer studies be added. He also
recommended that more emphasis be
placed on the SMR results from the
Ward et al. (1992) study. Dr. Balmes felt
that more detail was presented on the
animal cancer studies than necessary to
convey the relevant message. All
reviewers thought that the SchubauerBerigan et al. (2010) cohort mortality
study that addressed some of the
shortcomings of earlier lung cancer
mortality studies should be discussed in
the health effects document.
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The recent Schubauer-Berigan et al.
(2010) study conducted by the NIOSH
Division of Surveillance, Hazard
Evaluations, and Field Studies is now
described and discussed in section
V.E.2 on human epidemiology studies.
Table A.3 summarizing the range of
exposure measurements, study strengths
and limitations, and other key lung
cancer epidemiological study
information was added to the health
effects preamble. Section V.E.3 on the
animal cancer studies already contained
several tables that present study data so
OSHA decided a summary table was not
needed in this section.
Reviewers were asked two questions
regarding the OSHA preliminary
conclusions on beryllium-induced lung
cancer: was the inflammation
mechanism presented in the lung cancer
section reasonable; and were there other
mechanisms or modes of action to be
considered? All reviewers agreed that
inflammation was a reasonable
mechanistic presentation as outlined in
the document. Dr. Gordon requested
OSHA clarify that inflammation may
not be the sole mechanism for
carcinogenicity. OSHA inserted
statements in section V.E.5 on the
preliminary lung cancer conclusions
clarifying that tumorigenesis secondary
to inflammation is a reasonable
mechanism of action but other plausible
mechanisms independent of
inflammation may also contribute to the
lung cancer associated with beryllium
exposure.
There were a few comments from
reviewers on health effects other than
sensitization/CBD and lung cancer in
the draft document. Dr. Balmes
requested that the term ‘‘beryllium
poisoning’’ not be used when referring
to the hepatic effects of beryllium. He
also offered language to clarify that the
cardiovascular mortality among
beryllium production workers in the
Ward study cohort was probably due to
ischemic heart disease and not the
result of impaired lung function. Dr.
Gordon requested removal of references
to hepatic studies from in vitro and
intravenous administration done at very
high dose levels of little relevance to the
occupational exposures of interest to
OSHA. These changes were made to
section V.F on other health effects.
B. Peer Review of the Draft Preliminary
Risk Assessment
The Technical Charge to peer
reviewers for review of the draft
preliminary risk assessment was to
ensure OSHA selected appropriate
study data, assessed the data in a
scientifically credible manner, and
clearly explained its analysis. Specific
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charge questions were posed regarding
choice of data sets, risk models, and
exposure metrics; the role of dermal
exposure and dermal protection;
construction of the job exposure matrix;
characterization of the risk estimates
and their uncertainties; and whether a
quantitative assessment of lung cancer
risk, in addition to sensitization and
CBD, was warranted.
Overall, the peer reviewers were
highly supportive of the Agency’s
approach and major conclusions. They
offered valuable suggestions for
revisions and additional analysis to
improve the clarity and certain
technical aspects of the risk assessment.
These suggestions and the steps taken
by OSHA to address them are
summarized here. A final peer review
report (ERG, 2010c) and a risk
assessment background document
(OSHA, 2014a) are available in the
docket.
OSHA asked peer reviewers a series of
questions regarding its selection of
surveys from a beryllium ceramics
facility, a beryllium machining facility,
and a beryllium alloy processing facility
as the critical studies that form the basis
of the preliminary risk assessment.
Research showed that these workplaces
had well characterized and relatively
low beryllium exposures and underwent
plant-wide screenings for sensitization
and CBD before and after
implementation of exposure controls.
The reviewers were requested to
comment on whether the study
discussions were clearly presented,
whether the role of dermal exposure and
dermal protection were adequately
addressed, and whether the preliminary
conclusions regarding the observed
exposure-related prevalence and
reduction in risk were reasonable and
scientifically credible. They were also
asked to identify other studies that
should be reviewed as part of the
sensitization/CBD risk assessment.
Every peer reviewer felt the key
studies were appropriate and their
selection clearly explained in the
document. Every peer reviewer regarded
the preliminary conclusions from the
OSHA review of these studies to be
reasonable and scientifically sound.
This conclusion stated that substantial
risk of sensitization and CBD were
observed in facilities where the highest
exposed processes had median full-shift
beryllium exposures around 0.2 mg/m3
or higher and that the greatest reduction
in risk was achieved when exposures for
all processes were lowered to 0.1 mg/m3
or below.
The reviewers suggested that three
additional studies be added to the risk
assessment review of the
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epidemiological literature. Dr. Balmes
felt the document would be
strengthened by including the Bailey et
al. (2010) investigation of sensitization
in a population of workers at the
beryllium metal, alloy, and oxide
production plant in Elmore, OH and the
Arjomandi et al. (2010) publication on
a group of 50 sensitized workers from a
nuclear plant. Dr. Breysse suggested the
study by Taiwo et al. (2008) on
sensitization among workers in four
aluminum smelters be considered.
A new subsection VI.A.3 was added
to the preliminary risk assessment that
describes the changes in beryllium
exposure measurements, prevalence of
sensitization and CBD, and
implementation of exposure controls
between 1992 and 2006 at the Elmore
plant. This subsection includes a
discussion of the Bailey et al. study. A
summary of the Taiwo et al. (2008)
study was added as subsection VI.A.5.
A discussion of the Arjomandi et al.
(2010) study was added in subsection
VI.B as evidence that sensitized workers
with primarily low beryllium exposure
go on to develop CBD. However, the low
rates of CBD among this group of
sensitized workers also suggest that low
beryllium exposure may reduce CBD
risk when compared to worker
populations with higher exposure
levels.
While the majority of reviewers stated
that OSHA adequately addressed the
role of dermal exposure in sensitization
and the importance of dermal protection
for workers, a few had additional
suggestions for OSHA’s discussion. Dr.
Breysse and Dr. Gordon pointed out that
because the beryllium exposure control
programs featured steps to reduce both
skin contact and inhalation, it was
difficult to distinguish between the
effects of reducing airborne and dermal
exposure. A statement was added to
subsection VI.B that concurrent
implementation of respirator use,
dermal protection and engineering
changes made it difficult to attribute
reduced risk to any single control
measure. Since the Cullman plant did
not require glove use, OSHA believes it
to be the best data set available for
evaluating the effects of airborne
exposure control on risk of
sensitization.
Dr. Breysse requested additional
discussion of the role of respiratory
protection in achieving reduction in
risk. Dr. Gordon suggested some
additional clarification regarding mean
and median exposure measures.
Additional information on respiratory
programs and exposure measures (e.g.,
median, arithmetic and geometric
means), where available, were presented
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for each of the studies discussed in
subsection VI.A.
The peer reviewers generally agreed
that it was reasonable to conclude that
community-acquired CBD (CA–CBD)
resulted from low beryllium exposures.
Drs. Breysse, Balmes and others noted
that higher short-term excursions could
not be ruled out. Dr. Gordon suggested
that genetic susceptibility may have a
role in cases of CA–CBD. Dr. Rossman
raised the possibility that some CA–CBD
cases could occur from contact with
beryllium workers. All these points
were added to subsection VI.C.
OSHA asked the peer reviewers to
evaluate the choice of the National
Jewish Medical and Research Center
(NJMRC) data set on the Cullman, AL
machinist population as a basis for
exposure-response analysis and the
reliance on cumulative exposure as the
basis for the exposure-response analysis
of sensitization and CBD. All peer
reviewers indicated that the choice of
the NJMRC data set for exposureresponse analysis was clearly explained
and reasonable and that they knew of no
better data set for the analysis. Dr.
Rossman commented that the NJMRC
data set was an excellent source of
exposures to different levels of
beryllium and testing and evaluation of
the workers. Dr. Steenland and Dr.
Gordon suggested that the results from
the OSHA analysis of the NJMRC data
be compared with the available data
from the studies of other beryllium
facilities discussed in the
epidemiological literature analysis.
While a rigorous quantitative
comparison (e.g., meta analysis) is
difficult due to differences in the study
designs and data types available for
each study, subsection VI.E.4 compares
the results of OSHA’s prevalence
analysis from the Cullman data with
results from studies of the Tucson and
Reading facilities.
OSHA asked the peer reviewers to
evaluate methods used to construct the
job exposure matrix (JEM) and to
estimate beryllium exposure for each
worker in the NJMRC data set. The JEM
procedure was briefly summarized in
the review document and described in
detail as part of a risk assessment
technical background document made
available to the reviewers (OSHA,
2014a). Dr. Balmes felt that a more
thorough discussion of the JEM would
strengthen the preamble document. Dr.
Gordon requested information about
values assigned exposures below the
limit of detection. Dr. Steenland
requested that both the preamble and
technical background document contain
additional information on aspects of the
JEM construction such as the job
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categories, job-specific exposure values,
how jobs were grouped, and how nonmachining jobs were handled in the
JEM. He suggested the entire JEM be
included in the technical background
document. OSHA greatly expanded
subsection VI.E.2 on air sampling and
JEM to include more detailed discussion
of the JEM construction. Exposure
values for machining and nonmachining job titles were provided in
Tables VI–4 and VI–5. The procedures
and rationale for grouping job-specific
measurements into four time periods
was explained. Jobs were not grouped in
the JEM; rather, individual exposure
estimates were created for each job in
the work history data set. The technical
background document further clarifies
the JEM construction and the full JEM
is included as an appendix to the
revised background document (OSHA,
2014a). Subsection VI.E.3 on worker
exposure reconstruction contains
further detail about the work histories.
Peer reviewers fully supported
OSHA’s choice of the cumulative
exposure metric to estimate risk of CBD
from the NJMRC data set. As explained
by Dr. Steenland, ‘‘cumulative exposure
is often the choice for many chronic
diseases as opposed to average or
highest exposure.’’ He pointed out that
the cumulative exposure metric also fit
the CBD data better than other metrics.
The reviewers generally felt that shortterm peak exposure was probably the
measure of airborne exposure most
relevant to risk of beryllium
sensitization. However, peer reviewers
agreed that data required to capture
workers’ short-term peak exposures and
to relate the peak exposure levels to
sensitization were not available. Dr.
Breysse explained that ‘‘short-term (hrs
to minutes) peak exposures may be
important to sensitization risk, while
long term averages are more important
for CBD risk. Unfortunately data for
short-term peak exposures may not
exist.’’ Dr. Steenland explained that of
the available metrics ‘‘cumulative
exposure fits the sensitization data
better than the two alternatives, and
hence is the best metric.’’ Statements
were added to subsection VI.E.3 to
indicate that while short-term exposures
may be highly relevant to risk of
sensitization, the individual peak
exposures leading up to onset of
sensitization was not able to be
determined in the NJRMC Cullman
study.
Peer reviewers found the methods
used in the statistical exposure-response
analysis to be clearly described. With
the exception of Dr. Steenland,
reviewers believed that a detailed
critique of the statistical approach was
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beyond their level of expertise. Dr.
Steenland supported OSHA’s overall
approach to the risk modeling and
recommended additional analyses to
explore the sensitivity of OSHA’s results
to alternate choices and to test the
validity of aspects of the analysis. Dr.
Steenland recommended that the
logistic regression used by OSHA as a
preliminary first analysis be dropped as
an inappropriate model for a situation
where it is important to account for
changing exposures and case onset over
time. Instead, he suggested a sensitivity
analysis in which exposure-response
coefficients generated using a traditional
Cox proportionate hazards model be
compared to the discrete time Cox
model analog (i.e., complementary loglog Cox model) used by OSHA. The
sensitivity analysis would facilitate
examination of the proportional hazard
assumption implied by the use of these
models. Dr. Steenland advocated that
OSHA include a table that displayed the
mean number of BeLPT tests for the
study population in order to address
whether the number of sensitization
tests introduced a potential bias. He
inquired about the possibility of
determining a sensitization incidence
rate using cumulative or average
exposure. Dr. Steenland suggested that
the model control for additional
potential confounders, such as age,
smoking status, race and gender. He
wanted a more complete explanation of
the model constant for the year of
diagnosis in Tables VI–9 through VI–12
to be included in the preamble as it was
in the technical background document.
Dr. Steenland recommended a
sensitivity analysis that excludes the
highest 5 to 10 percent of cumulative
exposures which might address
potential model uncertainty at the high
end exposures. He requested that the
results of statistical tests for nonlinearity be included and confidence
intervals for the risk estimates in Tables
VI–17 and VI–18 be determined.
Many of Dr. Steenland’s comments
were addressed in subsection VI.F on
the statistical modeling. The logistic
regression analysis was removed from
the section. A sensitivity analysis using
the standard Cox model that treats
survival time as continuous rather than
discrete was added to the risk
assessment background document and
results were described in subsection
VI.F. The interaction between exposure
and follow-up time was not significant
in the models suggesting that the
proportional hazard assumption should
not be rejected. The model coefficients
using the standard Cox model were
similar to model coefficients for the
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discrete model. Given this, OSHA did
not feel it necessary to further estimate
risks using the continuous Cox model at
specific exposure levels.
A table of the mean number of BeLPT
tests across the study population was
added to the risk assessment
background document. Subsection VI.F
describes the table results and its impact
on the statistical modeling. Smoking
status and age were included in the
discrete Cox proportional hazards
model and not found to be significant
predictors of beryllium sensitization.
However, the available study population
composition did not allow a confounder
analysis of race and gender. OSHA
chose not to include a detailed
explanation of the model constant for
the year of diagnosis in the preamble
section. OSHA agrees with Dr.
Steenland that the risk assessment
background document adequately
describes the model terms. For that
reason, OSHA prefers that the risk
assessment preamble focus on the
results and major points of the analysis
and refer the reader to the more
technical background document for an
explanation of model parameters. The
linearity assumption was assessed using
a fractional polynomial approach. The
best fitting polynomials did not fit
significantly better than the linear
model. The details of the analysis were
included in the risk assessment
background document. Tables VI–17
and VI–18 now include the upper 95
percent confidence limits on the modelpredicted cases of sensitization and CBD
for the current and alternative PELs.
Most peer reviewers felt the major
uncertainties of the risk assessment
were clearly and adequately discussed
in the documents they reviewed. Dr.
Breysse requested that the risk
assessment cover potential
underestimation of risk from exposure
misclassification bias. He requested
further discussion of the degree to
which the risk estimates from the
Cullman machining plant could be
extrapolated to workplaces that use
other physical (e.g., particle size) and
chemical forms of beryllium. He went
on to question the strength of evidence
that insoluble forms of beryllium cause
CBD. Dr. Breysse also suggested that the
assumptions used in the risk modeling
be consolidated and more clearly
presented. Dr. Steenland felt that there
was potential underestimation of CBD
risk resulting from exclusion of former
workers and case status of current
workers after employment.
Discussion of these uncertainties was
added in the final paragraphs of section
VI.F. The section was modified to more
clearly identify assumptions with regard
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to the risk modeling such as an assumed
linearity in exposure-response and
cumulative dose equivalency when
extrapolating risks over a 45-year
working lifetime. Section VI.F
recognizes the uncertainties in risk that
can result from reconstructing
individual exposures with very limited
sampling data prior to 1994. The
potential exposure misclassification can
limit the strength of exposure-response
relationships and result in the
underestimation of risk. A more
technical discussion of modeling
assumptions and exposure measurement
error are provided in the risk assessment
background document. Section VI.F
points out that the NJMRC data set does
not capture CBD that occurred among
workers who retired or left the Cullman
plant. This and the short follow-up time
is a source of uncertainty that likely
leads to underestimation of risk. The
section indicates that it is not
unreasonable to expect the risk
estimates to generally reflect onset of
sensitization and CBD from exposure to
beryllium forms that are relatively
insoluble and enriched with respirable
particles as encountered at the Cullman
machining plant. Additional uncertainty
is introduced when extrapolating the
risk estimates to beryllium compounds
of vastly different solubility and particle
characteristics. OSHA does not agree
with the comment suggesting that the
association between CBD and insoluble
forms of beryllium is weak. The
principle sources of beryllium
encountered at the Cullman machining
plant, the Reading copper beryllium
processing plant and the Tucson
ceramics plant where excessive CBD
was observed are insoluble forms of
beryllium, such as beryllium metal,
beryllium alloy, and beryllium oxide.
Finally, OSHA asked the peer
reviewers to evaluate its treatment of
lung cancer in the earlier draft
preliminary risk assessment (OSHA,
2010b). When that document was
prepared, OSHA had elected not to
conduct a lung cancer risk assessment.
The Agency believed that the exposureresponse data available to conduct a
lung cancer risk assessment from a
Sanderson et al. study of a Reading, PA
beryllium plant by was highly
problematic. The Sanderson study
primarily involved workers with
extremely high and short-term
exposures above airborne exposure
levels of interest to OSHA (2 mg/m3 and
below).
Just prior to arranging the peer
review, a NIOSH study was published
by Schubauer-Berigan et al. updating
the Reading, PA cohort studied by
Sanderson et al. and adding cohorts
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from two additional plants in Elmore,
OH and Hazleton, PA (SchubauerBerigan, 2011). At OSHA’s request, the
peer reviewers reviewed this study to
determine whether it could provide a
better basis for lung cancer risk analysis
than the Sanderson et al. study. The
reviewers found that the NIOSH update
addressed the major concerns OSHA
had expressed about the Sanderson
study. In particular, they pointed out
that workers in the Elmore and Hazleton
cohorts had longer tenure at the plants
and experienced lower exposures than
those at the Reading, PA plant. Dr.
Steenland recommended that ‘‘OSHA
consider the new NIOSH data and
develop risk estimates for lung cancer as
well as sensitization and CBD.’’ Dr.
Breysse believed that the NIOSH data
‘‘suggest that a risk assessment for lung
cancer should be conducted by OSHA
and the results be compared to the CBD/
sensitization risk assessment before
recommending an appropriate exposure
concentration.’’ While acknowledging
the improvements in the quality of the
data, other reviewers were more
restrained in their support for
quantitative estimates of lung cancer
risk. Dr. Gordon stated that despite
improvements, there was ‘‘still
uncertainty associated with the paucity
of data below the current PEL of 2 mg/
m3.’’ Dr. Rossman noted that the NIOSH
study ‘‘did not address the problem of
the uncertainty of the mechanism of
beryllium carcinogenicity.’’ He felt that
the updated NIOSH lung cancer
mortality data ‘‘should not change the
Agency’s rationale for choosing to
establish its risk findings for the
proposed rule on its analysis for
beryllium sensitization and CBD.’’ Dr.
Balmes agreed that ‘‘the agency will be
on firmer ground by focusing on
sensitization and CBD.’’
The preliminary risk assessment
preamble subsection VI.G on lung
cancer includes a discussion of the
quantitative lung cancer risk assessment
published by NIOSH researchers in
2010 (Schubauer-Berigan, 2011). The
discussion describes the lower exposure
levels, longer tenure, fewer short-term
workers and additional years of
observation that make the data more
suitable for risk assessment. NIOSH
relied on several modeling approaches
to show that lung cancer risk was
significantly related to both mean and
cumulative beryllium exposure.
Subsection VI.G provides the excess
lifetime lung cancer risks predicted
from several best-fitting NIOSH models
at beryllium exposures of interest to
OSHA (Table VI–20). Using the
piecewise log-linear proportional
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hazards model favored by NIOSH, there
is a projected drop in excess lifetime
lung cancer risks from approximately 61
cases per 1000 exposed workers at the
current PEL of 2.0 mg/m3 to
approximately 6 cases per 1000 at the
proposed PEL of 0.2 mg/m3. Subsection
VI.H on preliminary conclusions
indicates that these projections support
a reduced risk of lung cancer from more
stringent control of beryllium exposures
but that the lung cancer risk estimates
are more uncertain than those for
sensitization and CBD.
VIII. Significance of Risk
To promulgate a standard that
regulates workplace exposure to toxic
materials or harmful physical agents,
OSHA must first determine that the
standard reduces a ‘‘significant risk’’ of
‘‘material impairment.’’ The first part of
this requirement, ‘‘significant risk,’’
refers to the likelihood of harm, whereas
the second part, ‘‘material impairment,’’
refers to the severity of the
consequences of exposure.
The Agency’s burden to establish
significant risk is based on the
requirements of the OSH Act (29 U.S.C.
651 et seq). Section 3(8) of the Act
requires that workplace safety and
health standards be ‘‘reasonably
necessary or appropriate to provide safe
or healthful employment’’ (29 U.S.C.
652(8)). The Supreme Court, in the
Benzene decision, interpreted section
3(8) to mean that ‘‘before promulgating
any standard, the Secretary must make
a finding that the workplaces in
question are not safe’’ (Industrial Union
Department, AFL–CIO v. American
Petroleum Institute, 448 U.S. 607, 642
(1980) (plurality opinion)). Examining
section 3(8) more closely, the Court
described OSHA’s obligation to
demonstrate significant risk:
‘‘[S]afe’’ is not the equivalent of ‘‘risk-free.’’
A workplace can hardly be considered
‘‘unsafe’’ unless it threatens the workers with
a significant risk of harm. Therefore, before
the Secretary can promulgate any permanent
health or safety standard, he must make a
threshold finding that the place of
employment is unsafe in the sense that
significant risks are present and can be
eliminated or lessened by a change in
practices (Id).
As the Court made clear, the Agency
has considerable latitude in defining
significant risk and in determining the
significance of any particular risk. The
Court did not specify a means to
distinguish significant from
insignificant risks, but rather instructed
OSHA to develop a reasonable approach
to making a significant risk
determination. The Court stated that ‘‘it
is the Agency’s responsibility to
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determine in the first instance what it
considers to be a ’significant’ risk,’’ (448
U.S. at 655) and it did not express ‘‘any
opinion on the . . . difficult question of
what factual determinations would
warrant a conclusion that significant
risks are present which make
promulgation of a new standard
reasonably necessary or appropriate’’
(448 U.S. at 659). The Court also stated
that, while OSHA’s significant risk
determination must be supported by
substantial evidence, the Agency ‘‘is not
required to support the finding that a
significant risk exists with anything
approaching scientific certainty’’ (448
U.S. at 656). Furthermore:
A reviewing court [is] to give OSHA some
leeway where its findings must be made on
the frontiers of scientific knowledge . . . .
[T]he Agency is free to use conservative
assumptions in interpreting the data with
respect to carcinogens, risking error on the
side of overprotection rather than
underprotection [so long as such
assumptions are based on] a body of
reputable scientific thought (448 U.S. at 656).
Thus, to make the significance of risk
determination for a new or proposed
standard, OSHA uses the best available
scientific evidence to identify material
health impairments associated with
potentially hazardous occupational
exposures and to evaluate exposed
workers’ risk of these impairments.
The OSH Act also requires that the
Agency make a finding that the toxic
material or harmful physical agent at
issue causes material impairment to
worker health. In that regard, the Act
directs the Secretary of Labor to set
standards based on the available
evidence where no employee, over his/
her working life time, will suffer from
material impairment of health or
functional capacity, even if such
employee has regular exposure to the
hazard, to the exent feasible (29 U.S.C.
655(b)(5)).
As with significant risk, what
constitutes material impairment in any
given case is a policy determination for
which OSHA is given substantial
leeway. ‘‘OSHA is not required to state
with scientific certainty or precision the
exact point at which each type of [harm]
becomes a material impairment’’ (AFL–
CIO v. OSHA, 965 F.2d 962, 975 (11th
Cir. 1992)). Courts have also noted that
OSHA should consider all forms and
degrees of material impairment—not
just death or serious physical harm—
and that OSHA may act with a
‘‘pronounced bias towards worker
safety’’ (Id; Bldg & Constr. Trades Dep’t
v. Brock, 838 F.2d 1258, 1266 (D.C. Cir.
1988)). OSHA’s long-standing policy is
to consider 45 years as a ‘‘working life,’’
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over which it must evaluate material
impairment and risk.
In formulating this proposed
beryllium standard, OSHA has reviewed
the best available evidence pertaining to
the adverse health effects of
occupational beryllium exposure,
including lung cancer and chronic
beryllium disease (CBD), and has
evaluated the risk of these effects from
exposures allowed under the current
standard as well as the expected impact
of the proposed standard on risk. Based
on its review of extensive
epidemiological and experimental
research, OSHA has preliminarily
determined that long-term exposure at
the current Permissible Exposure Limit
(PEL) would pose a significant risk of
material impairment to workers’ health,
and that adoption of the new PEL and
other provisions of the proposed rule
will substantially reduce this risk.
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A. Material Impairment of Health
In this preamble at section V, Health
Effects, OSHA reviewed the scientific
evidence linking occupational beryllium
exposure to a variety of adverse health
effects, including CBD and lung cancer.
Based on this review, OSHA
preliminarily concludes that beryllium
exposure causes these effects. The
Agency’s preliminary conclusion was
strongly supported by a panel of
independent peer reviewers, as
discussed in section VII.
Here, OSHA discusses its preliminary
conclusion that CBD and lung cancer
constitute material impairments of
health, and briefly reviews other
adverse health effects that can result
from beryllium exposure. Based on this
preliminary conclusion and on the
scientific evidence linking beryllium
exposure to both CBD and lung cancer,
OSHA concludes that occupational
exposure to beryllium causes ‘‘material
impairment of health or functional
capacity’’ within the meaning of the
OSH Act.
1. Chronic Beryllium Disease
CBD is a respiratory disease in which
the body’s immune system reacts to the
presence of beryllium in the lung,
causing a progression of pathological
changes including chronic inflammation
and tissue scarring. CBD can also impair
other organs such as the liver, skin,
spleen, and kidneys and cause adverse
health effects such as granulomas of the
skin and lymph nodes and cor
pulmonale (i.e., enlargement of the
heart) (Conradi et al., 1971; ACCP, 1965;
Kriebel et al., 1988a and b). In early,
asymptomatic stages of CBD, small
granulomatous lesions and mild
inflammation occur in the lungs. Early
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stage CBD among some workers has
been observed to progress to more
serious disease even after the worker is
removed from exposure (Mroz, 2009),
probably because common forms of
beryllium have slow clearance rates and
can remain in the lung for years after
exposure. Sood et al. has reported that
cessation of exposure can sometimes
have beneficial effects on lung function
(Sood et al., 2004). However, this was
based on a small study of six patients
with CBD, and more research is needed
to better determine the relationship
between exposure duration and disease
progression. In general, progression of
CBD from early to late stages is
understood to vary widely, responding
differently to exposure cessation and
treatment for different individuals
(Sood, 2009; Mroz, 2009).
Over time, the granulomas can spread
and lead to lung fibrosis (scarring) and
moderate to severe loss of pulmonary
function, with symptoms including a
persistent dry cough and shortness of
breath (Saber and Dweik, 2000). Fatigue,
night sweats, chest and joint pain,
clubbing of fingers (due to impaired
oxygen exchange), loss of appetite, and
unexplained weight loss may occur as
the disease progresses. Corticosteroid
therapy, in workers whose beryllium
exposure has ceased, has been shown to
control inflammation, ease symptoms
(e.g., difficulty breathing, fever, cough,
and weight loss) and in some cases
prevent the development of fibrosis
(Marchand-Adam et al., 2008). Thus
early treatment can lead to CBD
regression in some patients, although
there is no cure (Sood, 2004). Other
patients have shown short-term
improvements from corticosteroid
treatment, but then developed serious
fibrotic lesions (Marchand-Adam et al.,
2008). Once fibrosis has developed in
the lungs, corticosteroid treatment
cannot reverse the damage (Sood, 2009).
Persons with late-stage CBD experience
severe respiratory insufficiency and may
require supplemental oxygen (Rossman,
1991). Historically, late-stage CBD often
ended in death (NAS, 2008).
While the use of steroid therapy has
mitigated CBD mortality, treatment with
corticosteroids has side effects that need
to be measured against the possibility of
progression of disease (Trikudanathan
and McMahon, 2008; Lipworth, 1999;
Gibson et al., 1996; Zaki et al., 1987).
Adverse effects associated with longterm corticosteroid use include, but are
not limited to, increased risk of
opportunistic infections (Lionakis and
Kontoyiannis, 2003; Trikudanathan and
McMahon, 2008); accelerated bone loss
or osteoporosis leading to increased risk
of fractures or breaks (Hamida et al.,
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2011; Lehouck et al., 2011; Silva et al.,
2011; Sweiss et al., 2011; Langhammer
et al., 2009); psychiatric effects
including depression, sleep
disturbances, and psychosis
(Warrington and Bostwick, 2006;
Brown, 2009); adrenal suppression
(Lipworth, 1999; Frauman, 1996); ocular
effects including cataracts, ocular
hypertension, and glaucoma (Ballonzolli
and Bourchier, 2010; Trikudanathan
and McMahon, 2008; Lipworth, 1999);
an increase in glucose intolerance
(Trikudanathan and McMahon, 2008);
excessive weight gain (McDonough et
al., 2008; Torres and Nowson, 2007;
Dallman et al., 2007; Wolf, 2002;
Cheskin et al., 1999); increased risk of
atherosclerosis and other cardiovascular
syndromes (Franchimont et al., 2002);
skin fragility (Lipworth, 1999); and poor
wound healing (de Silva and Fellows,
2010). Studies relating the long-term
effect of corticosteroid use for the
treatment of CBD need to be undertaken
to evaluate the treatment’s overall
effectiveness against the risk of adverse
side effects from continued usage.
OSHA considers late-stage CBD to be
a material impairment of health, as it
involves permanent damage to the
pulmonary system, causes additional
serious adverse health effects, can have
adverse occupational and social
consequences, requires treatment
associated with severe and lasting side
effects, and may in some cases be lifethreatening. Furthermore, OSHA
believes that material impairment
begins prior to the development of
symptoms of the disease.
Although there are no symptoms
associated with early-stage CBD, during
which small lesions and inflammation
appear in the lungs, the Agency has
preliminarily concluded that the earliest
stage of CBD is material impairment of
health. OSHA bases this conclusion on
evidence showing that early-stage CBD
is a measurable change in the state of
health which, with and sometimes
without continued exposure, can
progress to symptomatic disease. Thus,
prevention of the earliest stages of CBD
will prevent development of more
serious disease. The OSHA Lead
Standard established the Agency’s
position that a ‘subclinical’ health effect
may be regarded as a material
impairment of health. In the preamble to
that standard, the Agency said:
OSHA believes that while incapacitating
illness and death represent one extreme of a
spectrum of responses, other biological
effects such as metabolic or physiological
changes are precursors or sentinels of disease
which should be prevented . . . Rather than
revealing beginnings of illness the standard
must be selected to prevent an earlier point
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of measurable change in the state of health
which is the first significant indicator of
possibly more severe ill health in the future.
The basis for this decision is twofold—first,
pathophysiologic changes are early stages in
the disease process which would grow worse
with continued exposure and which may
include early effects which even at early
stages are irreversible, and therefore
represent material impairment themselves.
Secondly, prevention of pathophysiologic
changes will prevent the onset of the more
serious, irreversible and debilitating
manifestations of disease.11 (43 FR 52952,
52954, November 14, 1978)
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Since the Lead rulemaking, OSHA has
also found other non-symptomatic
health conditions to be material
impairments of health. In the
Bloodborne Pathogens (BP) rulemaking,
OSHA maintained that material
impairment includes not only workers
with clinically ‘‘active’’ hepatitis from
the hepatitis B virus (HBV) but also
includes asymptomatic HBV ‘‘carriers’’
who remain infectious and are able to
put others at risk of serious disease
through contact with body fluids (e.g.,
blood, sexual contact) (56 FR 64004,
December 6, 1991). OSHA stated:
‘‘Becoming a carrier [of Hepatitis B] is
a material impairment of health even
though the carrier may have no
symptoms. This is because the carrier
will remain infectious, probably for the
rest of his or her life, and any person
who is not immune to HBV who comes
in contact with the carrier’s blood or
certain other body fluids will be at risk
of becoming infected’’ (56 FR 64004,
64036).
OSHA preliminarily finds that earlystage CBD is the type of asymptomatic
health effect the Agency determined to
be a material impairment of health in
the lead standard. Early stage CBD
involves lung tissue inflammation
without symptomatology that can
worsen with—or without—continued
exposure. The lung pathology
progresses over time from a chronic
inflammatory response to tissue scarring
and fibrosis accompanied by moderate
to severe loss in pulmonary function.
Early stage CBD is clearly a precursor of
advanced clinical disease, prevention of
which will prevent symptomatic
11 Even if asymptomatic CBD were not itself a
material impairment of health, the D.C. Circuit
upheld OSHA’s authority to regulate to prevent
subclinical health effects as precursors to disease in
United Steelworkers of America, AFL–CIO v.
Marshall, 647 F.2d 1189, 1252 (D.C. Cir. 1980),
which reviewed the Lead standard. Without
deciding whether the early symptoms of disease
were themselves a material impairment, the court
concluded that OSHA may regulate subclinical
effects if it can demonstrate on the basis of
substantial evidence that preventing subclinical
effects would help prevent the clinical phase of
disease (Id.).
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disease. OSHA argued in the Lead
standard that such precursor effects
should be considered material health
impairments in their own right, and that
the Agency should act to prevent them
when it is feasible to do so. Therefore,
OSHA preliminarily finds all stages of
CBD to be material impairments of
health.
2. Lung Cancer
OSHA considers lung cancer, a
frequently fatal disease, to be a material
impairment of health. OSHA’s finding
that inhaled beryllium causes lung
cancer is based on the best available
epidemiological data, reflects evidence
from animal and mechanistic research,
and is consistent with the conclusions
of other government and public health
organizations (see this preamble at
section V, Health Effects). For example,
the International Agency for Research
on Cancer (IARC), National Toxicology
Program (NTP), and American
Conference of Governmental Industrial
Hygienists (ACGIH) have all classified
beryllium as a known human
carcinogen (IARC, 2009).
The Agency’s epidemiological
evidence comes from multiple studies of
U.S. beryllium workers (Sanderson et
al., 2001a; Ward et al., 1992; Wagoner
et al., 1980; Mancuso et al., 1979). Most
recently, a NIOSH cohort study found
significantly increased lung cancer
mortality among workers at seven
beryllium processing facilities
(Schubauer-Berigan et al., 2011). The
cohort was exposed, on average, to
lower levels of beryllium than those in
most previous studies, had fewer shortterm workers, and had sufficient followup time to observe lung cancer in the
population. OSHA considers the
Schubauer-Berigan study to be the best
available epidemiological evidence
regarding the risk of lung cancer from
beryllium at exposure levels near the
PEL.12
Supporting evidence of beryllium
carcinogenicity comes from various
animal studies as well as in vitro
genotoxicity and other studies (EPA,
1998; ATSDR, 2002; Gordon and
Bowser, 2003; NAS, 2008; Nickell-Brady
et al., 1994; NTP, 1999 and 2005; IARC,
1993 and 2009). Multiple mechanisms
may be involved in the carcinogenicity
of beryllium, and factors such as
epigenetics, mitogenicity, reactive
oxygen-mediated indirect genotoxicity,
and chronic inflammation may
contribute to the lung cancer associated
12 The scientific peer review panel for OSHA’s
Preliminary Risk Assessment agreed with the
Agency that the Schubauer-Berigan analysis
improves upon the previously available data for
lung cancer risk assessment.
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with beryllium exposure, although the
results of studies testing the direct
genotoxicity of beryllium are mixed
(EPA summary, 1998). While there is
uncertainty regarding the exact
mechanism of carcinogenesis for
beryllium, the overall weight of
evidence for the carcinogenicity of
beryllium is strong. Therefore, the
Agency has preliminarily determined
beryllium to be an occupational
carcinogen.
3. Other Impairments
While OSHA has relied primarily on
the relationship between occupational
beryllium exposure and CBD and lung
cancer to demonstrate the necessity of
the standard, the Agency has also
determined that several other adverse
health effects can result from exposure
to beryllium. Inhalation of high airborne
concentrations of beryllium (well above
the 2 mg/m3 OSHA PEL) can cause acute
beryllium disease, a severe (sometimes
fatal), rapid-onset inflammation of the
lungs. Hepatic necrosis, damage to the
heart and circulatory system, chronic
renal disease, mucosal irritation and
ulceration, and urinary tract cancer have
also reportedly been associated with
occupational exposures well above the
current PEL (see this preamble at
section V, Health Effects, subsection E,
Epidemiological Studies, and subsection
F, Other Health Effects). These adverse
systemic effects and acute beryllium
disease mostly occurred prior to the
introduction of occupational and
environmental standards set in 1970–
1972 (OSHA, 1971; ACGIH, 1971; ANSI,
1970) and 1974 (EPA, 1974) and
therefore are less relevant today than in
the past. Because they occur only rarely
in current-day occupational
environments, they are not addressed in
OSHA’s risk analysis or significance of
risk determination.
The Agency has also determined that
beryllium sensitization, a precursor
which occurs before early stage CBD
and is an essential step for worker
development of the disease, can result
from exposure to beryllium. The Agency
takes no position at this time on
whether sensitization constitutes a
material impairment of health, because
it was unnecessary to do so as part of
this rulemaking. As discussed in
Section V, Health Effects, only
sensitized individuals can develop CBD
(NAS, 2008). OSHA’s risk assessment
for sensitization informs the Agency’s
understanding of what exposure control
measures have been successful in
preventing sensitization, which in turn
prevents development of CBD.
Therefore sensitization is considered in
the next section on significance of risk.
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In AFL–CIO v. Marshall, 617 F.2d 636,
654 n.83 (D.C. Cir. 1979) (Cotton Dust),
the D.C. Circuit upheld OSHA’s
authority to regulate to prevent
precursors to a material impairment of
health without deciding whether the
precursors themselves constituted
material impairment of health.
B. Significance of Risk and Risk
Reduction
To evaluate the significance of the
health risks that result from exposure to
hazardous chemical agents, OSHA relies
on the best available epidemiological,
toxicological, and experimental
evidence. The Agency uses both
qualitative and quantitative methods to
characterize the risk of disease resulting
from workers’ exposure to a given
hazard over a working lifetime at levels
of exposure reflecting compliance with
current standards and compliance with
the new standards being proposed.
As discussed above, the Agency’s
characterization of risk is guided in part
by the Benzene decision. In Benzene,
the Court broadly describes the range of
risks OSHA might determine to be
significant:
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It is the Agency’s responsibility to
determine in the first instance what it
considers to be a ‘‘significant’’ risk. Some
risks are plainly acceptable and others are
plainly unacceptable. If, for example, the
odds are one in a billion that a person will
die from cancer by taking a drink of
chlorinated water, the risk clearly could not
be considered significant. On the other hand,
if the odds are one in a thousand that regular
inhalation of gasoline vapors that are 2
percent benzene will be fatal, a reasonable
person might well consider the risk
significant and take the appropriate steps to
decrease or eliminate it (Benzene, 448 U.S. at
655).
The Court further stated, ‘‘The
requirement that a ’significant’ risk be
identified is not a mathematical
straitjacket. . . . Although the Agency
has no duty to calculate the exact
probability of harm, it does have an
obligation to find that a significant risk
is present before it can characterize a
place of employment as ’unsafe’, ‘‘and
proceed to promulgate a regulation (Id.).
In this preamble at section VI,
Preliminary Risk Assessment, OSHA
finds that the available epidemiological
data are sufficient to evaluate risk for
beryllium sensitization, CBD, and lung
cancer among beryllium-exposed
workers. The preliminary findings from
this assessment are summarized below.
1. Risk of Beryllium Sensitization and
CBD
OSHA’s preliminary risk assessment
for CBD and beryllium sensitization
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relies on studies conducted at a Tucson,
AZ beryllium ceramics plant (Kreiss et
al., 1996; Henneberger et al., 2001;
Cummings et al., 2006); a Reading, PA
alloy processing plant (Schuler et al.,
2005; Thomas et al., 2009); a Cullman,
AL beryllium machining plant (Kelleher
et al., 2001; Madl et al., 2007); and an
Elmore, OH metal, alloy, and oxide
production plant (Kreiss et al., 1997;
Bailey et al., 2010; Schuler et al., 2012).
The Agency uses these studies to
demonstrate the significance of risk at
the current PEL and the significant
reduction in risk expected with
reduction of the PEL. In addition to the
effects OSHA anticipates from reduction
of airborne beryllium exposure, the
Agency expects that dermal protection
provisions in the proposed rule will
further reduce risk. Studies conducted
in the 1950s by Curtis et al. showed that
soluble beryllium particles could
penetrate the skin and cause beryllium
sensitization (Curtis 1951, NAS 2008).
Tinkle et al. established that 0.5- and
1.0-mm particles can penetrate intact
human skin surface and reach the
epidermis, where beryllium particles
would encounter antigen-presenting
cells and initiate sensitization (Tinkle et
al., 2003). Tinkle et al. further
demonstrated that beryllium oxide and
beryllium sulfate, applied to the skin of
mice, generate a beryllium-specific, cellmediated immune response similar to
human beryllium sensitization (Tinkle
et al., 2003). In the epidemiological
studies discussed below, the exposure
control programs that most effectively
reduced the risk of beryllium
sensitization and CBD incorporated both
respiratory and dermal protection.
OSHA has preliminarily determined
that an effective exposure control
program should incorporate both
airborne exposure reduction and dermal
protection provisions.
In the Tucson ceramics plant, 4,133
short-term breathing zone
measurements collected between 1981
and 1992 had a median of 0.3 mg/m3.
Kreiss et al. reported that eight (5.9
percent) of 136 workers tested for
beryllium sensitization in 1992 were
sensitized, six (4.4 percent) of whom
were diagnosed with CBD. Exposure
control programs were initiated in 1992
to reduce workers’ airborne beryllium
exposure, but the programs did not
address dermal exposure. Full-shift
personal samples collected between
1994 and 1999 showed a median
beryllium exposure of 0.2 mg/m3 in
production jobs and 0.1 mg/m3 in
production support (Cummings et al.,
2007). In 1998, a second screening
found that 6, (9 percent) of 69 tested
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47655
workers hired after the 1992 screening,
were sensitized, of whom 1 was
diagnosed with CBD. All of the
sensitized workers had been employed
at the plant for less than 2 years
(Henneberger et al., 2001), too short a
time period for most people to develop
CBD following sensitization. Of the 77
Tucson workers hired prior to 1992 who
were tested in 1998, 8 (10.4 percent)
were sensitized and all but 1 of these
(9.7 percent) were diagnosed with CBD
(Henneberger et al., 2001).
Kreiss et al., studied workers at a
beryllium metal, alloy, and oxide
production plant in Elmore, OH.
Workers participated in a BeLPT survey
in 1992 (Kreiss et al., 1997). Personal
lapel samples collected during 1990–
1992 had a median value of 1.0 mg/m3.
Kreiss et al. reported that 43 (6.9
percent) of 627 workers tested in 1992
were sensitized, 6 of whom were
diagnosed with CBD (4.4 percent).
Newman et al. conducted a series of
BeLPT screenings of workers at a
Cullman, AL precision machining
facility between 1995 and 1999
(Newman et al., 2001). Personal lapel
samples collected at this plant in the
early 1980s and in 1995 from all
machining processes combined had a
median of 0.33 mg/m3 (Madl et al.,
2007). After a sentinel case of CBD was
diagnosed at the plant in 1995, the
company implemented engineering and
administrative controls and PPE
designed to reduce workers’ beryllium
exposures in machining operations.
Personal lapel samples collected
extensively between 1996 and 1999 in
machining jobs have an overall median
of 0.16 mg/m3, showing that the new
controls reduced machinists’ exposures
during this period. However, the results
of BeLPT screenings conducted in
1995–1999 showed that the exposure
control program initiated in 1995 did
not sufficiently protect workers from
beryllium sensitization and CBD. In a
group of 60 workers who had been
employed at the plant for less than a
year, and thus would not have been
working there prior to 1995, 4 (6.7
percent) were found to be sensitized.
Two of these workers (3.35 percent)
were diagnosed with CBD. (Newman et
al., 2001).
Sensitization and CBD were studied
in a population of workers at a Reading,
PA copper beryllium plant, where alloys
containing a low level of beryllium were
processed (Schuler et al., 2005).
Personal lapel samples were collected in
production and production support jobs
between 1995 and May 2000. These
samples showed primarily very low
airborne beryllium levels, with a
median of 0.073 mg/m3. The wire
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annealing and pickling process had the
highest personal lapel sample values,
with a median of 0.149 mg/m3. Despite
these low exposure levels, a BeLPT
screening conducted in 2000 showed
that 5, (11.5 percent) workers of 43
hired after 1992 were sensitized
(evaluation for CBD not reported). Two
of the sensitized workers had been hired
less than a year before the screening
(Thomas et al., 2009).
In summary, the epidemiological
literature on beryllium sensitization and
CBD that OSHA’s risk assessment relied
on show sensitization prevalences
ranging from 6.5 percent to 11.5 percent
and CBD prevalences ranging from 1.3
percent to 9.7 percent among workers
who had full-shift exposures well below
the current PEL and median full-shift
exposures at or below the proposed PEL,
and whose follow-up time was less than
45 years. As referenced earlier, OSHA is
interested in the risk associated with a
45-year (i.e., working lifetime) exposure.
Because CBD often develops over the
course of years following sensitization,
the risk of CBD that would result from
45 years’ occupational exposure to
airborne beryllium is likely to be higher
than the prevalence of CBD observed
among these workers.13 In either case,
based on these studies, the risks to
workers appear to be significant.
The available epidemiological
evidence shows that reducing workers’
levels of airborne beryllium exposure
can substantially reduce risk of
beryllium sensitization and CBD. The
best available evidence on effective
exposure control programs comes partly
from studies of programs introduced
around 2000 at Reading, Tucson, and
Elmore that used a combination of
engineering controls, dermal and
respiratory PPE, and stringent
housekeeping measures to reduce
workers’ dermal exposures and airborne
exposures to levels well below the
proposed PEL of 0.2 mg/m3. These
programs have substantially lowered the
risk of sensitization among new
workers. As discussed earlier,
prevention of beryllium sensitization
prevents subsequent development of
CBD.
In the Reading, PA copper beryllium
plant, full-shift airborne exposures in all
jobs were reduced to a median of 0.1 mg/
m3 or below and dermal protection was
required for production-area workers
beginning in 2000–2001 (Thomas et al.,
2009). After these adjustments were
made, 2 (5.4 percent) of 37 newly hired
workers became sensitized. Thereafter,
13 This point was emphasized by members of the
scientific peer review panel for OSHA’s Preliminary
Risk Assessment (see this preamble at section VII).
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in 2002, the process with the highest
exposures (median 0.1 mg/m3) was
enclosed and workers involved in that
process were required to use respiratory
protection. As a result, the remaining
jobs had very low exposures (medians ∼
0.03 mg/m3). Among 45 workers hired
after the enclosure was built and
respiratory protection instituted, 1 was
found to be sensitized (2.2 percent).
This is a sharp reduction in
sensitization from the 11.5 percent of 43
workers, discussed above, who were
hired after 1992 and had been sensitized
by the time of testing in 2000.
In the Tucson beryllium ceramics
plant, respiratory and skin protection
was instituted for all workers in
production areas in 2000. BeLPT testing
done in 2000–2004 showed that only 1
(1 percent) worker had been sensitized
out of 97 workers hired during that time
period (Cummings et al., 2007; testing
for CBD not reported). This contrasts
with the prevalence of sensitization in
the 1998 Tucson BeLPT screening,
which found that 6 (9 percent) of 69
workers hired after 1992 were sensitized
(Cummings et al., 2007).
The modern Elmore facility provides
further evidence that combined
reductions in respiratory exposure (via
respirator use) and dermal exposure are
effective in reducing risk of beryllium
sensitization. In Elmore, historical
beryllium exposures were higher than in
Tucson, Reading, and Cullman. Personal
lapel samples collected at Elmore in
1990–1992 had a median of 1.0 mg/m3.
In 1996–1999, the company took steps
to reduce workers’ beryllium exposures,
including engineering and process
controls (Bailey et al., 2010; exposure
levels not reported). Skin protection was
not included in the program until after
1999. Beginning in 1999 all new
employees were required to wear loosefitting powered air-purifying respirators
(PAPR) in manufacturing buildings
(Bailey et al., 2010). Skin protection
became part of the protection program
for new employees in 2000, and glove
use was required in production areas
and for handling work boots beginning
in 2001. Bailey et al., (2010) compared
the occurrence of beryllium
sensitization and CBD in 2 groups of
workers: 1) 258 employees who began
work at the Elmore plant between
January 15, 1993 and August 9, 1999
(the ‘‘pre-program group’’) and were
tested in 1997 and 1999, and 2) 290
employees who were hired between
February 21, 2000 and December 18,
2006 and underwent BeLPT testing in at
least one of frequent rounds of testing
conducted after 2000 (the ‘‘program
group’’). They found that, as of 1999, 23
(8.9 percent) of the pre-program group
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were sensitized to beryllium. The
prevalence of sensitization among the
‘‘program group’’ workers, who were
hired after the respiratory protection
and PPE measures were put in place,
was around 2–3 percent. Respiratory
protection and skin protection
substantially reduced, but did not
eliminate, risk of sensitization.
Evaluation of sensitized workers for
CBD was not reported.
OSHA’s preliminary risk assessment
also includes analysis of a data set
provided to OSHA by the National
Jewish Research and Medical Center
(NJMRC). The data set describes a
population of 319 beryllium-exposed
workers at a Cullman, AL machining
facility. It includes exposure samples
collected between 1980 and 2005, and
has updated work history and screening
information for over three hundred
workers through 2003. Seven (2.2
percent) workers in the data set were
reported as sensitized only. Sixteen (5.0
percent) workers were listed as
sensitized and diagnosed with CBD
upon initial clinical evaluation. Three
(1.0 percent) workers, first shown to be
sensitized only, were later diagnosed
with CBD. The data set includes
workers exposed at airborne beryllium
levels near the proposed PEL, and
extensive exposure data collected in
workers’ breathing zones, as is preferred
by OSHA. Unlike the Tucson, Reading,
and Elmore facilities, respirator use was
not generally required for workers at the
Cullman facility. Thus, analysis of this
data set shows the risk associated with
varying levels of airborne exposure,
rather than the virtual elimination of
airborne exposure via respiratory PPE.
Also unlike the Tucson, Elmore, and
Reading facilities, glove use was not
reported to be mandatory in the
Cullman facility. Thus, OSHA believes
reductions in risk at the Cullman facility
to be the result of airborne exposure
control, rather than the combination of
airborne and dermal exposure controls
at the Tucson, Elmore, and Reading
facilities.
OSHA analyzed the prevalence of
beryllium sensitization and CBD among
workers at the Cullman facility who
were exposed to airborne beryllium
levels at and below the current PEL of
2 mg/m3. In addition, a statistical
modeling analysis of the NJMRC
Cullman data set was conducted under
contract with Dr. Roslyn Stone of the
University of Pittsburgh Graduate
School of Public Heath, Department of
Biostatistics. OSHA summarizes these
analyses briefly below, and in more
detail in this preamble at section VI,
Preliminary Risk Assessment.
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Tables 1 and 2 below present the
prevalence of sensitization and CBD
cases across several categories of
lifetime-weighted (LTW) average and
highest-exposed job (HEJ) exposure at
the Cullman facility. The HEJ exposure
is the exposure level associated with the
highest-exposure job and time period
experienced by each worker. The
columns ‘‘Total’’ and ‘‘Total percent’’
refer to all sensitized workers in the
dataset, including workers with and
without a diagnosis of CBD.
TABLE 1—PREVALENCE OF SENSITIZATION AND CBD BY LIFETIME WEIGHTED AVERAGE EXPOSURE QUARTILE, CULLMAN,
AL MACHINING FACILITY
LTW Average exposure (μg/m3)
Group size
Sensitized
only
CBD
Total
Total %
CBD %
0.0–0.080 .................................................
0.081–0.18 ...............................................
0.19–0.51 .................................................
0.51–2.15 .................................................
91
73
77
78
1
2
0
4
1
4
6
8
2
6
6
12
2.2
8.2
7.8
15.4
1.0
5.5
7.8
10.3
Total ..................................................
319
7
19
26
8.2
6.0
Source: Section VI, Preliminary Risk Assessment.
TABLE 2—PREVALENCE OF SENSITIZATION AND CBD BY HIGHEST-EXPOSED JOB EXPOSURE QUARTILE, CULLMAN, AL
MACHINING FACILITY
HEJ Exposure (μg/m3)
Group size
Sensitized
only
CBD
Total
Total %
CBD %
0.0–0.086 .................................................
0.091–0.214 .............................................
0.387–0.691 .............................................
0.954–2.213 .............................................
86
81
76
76
1
1
2
3
0
6
9
4
1
7
11
7
1.2
8.6
14.5
9.2
0.0
7.4
11.8
5.3
Total ..................................................
319
7
19
26
8.2
6.0
mstockstill on DSK4VPTVN1PROD with PROPOSALS2
Source: Section VI, Preliminary Risk Assessment.
The current PEL of 2 mg/m3 is close
to the upper bound of the highest
quartile of LTW average (0.51–2.15 mg/
m3) and HEJ (0.954–2.213) exposure
levels. In the highest quartile of LTW
average exposure, there were 12 cases of
sensitization (15.4 percent), including 8
(10.3 percent) diagnosed with CBD.
Notably, the Cullman workers had been
exposed to beryllium dust for
considerably less than 45 years at the
time of testing. A high prevalence of
sensitization (9.2 percent) and CBD (5.3
percent) is seen in the top quartile of
HEJ exposure as well, with even higher
prevalences in the third quartile (0.387–
0.691 mg/m3).14
The proposed PEL of 0.2 mg/m3 is
close to the upper bound of the second
quartile of LTW average (0.81–0.18 mg/
m3) and HEJ (0.091–0.214 mg/m3)
exposure levels and to the lower bound
of the third quartile of LTW average
(0.19–0.50 mg/m3) exposures. The
second quartile of LTW average
exposure shows a high prevalence of
beryllium-related health effects, with six
workers sensitized (8.2 percent), of
whom four (5.5 percent) were diagnosed
with CBD. The second quartile of HEJ
exposure also shows a high prevalence
of beryllium-related health effects, with
seven workers sensitized (8.6 percent),
of whom 6 (7.4 percent) were diagnosed
with CBD. Among six sensitized
workers in the third quartile of LTW
average exposures, all were diagnosed
with CBD (7.8 percent). The prevalence
of CBD among workers in these quartiles
was approximately 5–8 percent, and
overall sensitization (including workers
with and without CBD) was about 8
percent. OSHA considers these rates as
evidence that the risk of developing
CBD is significant among workers
exposed at and below the current PEL,
even down to the proposed PEL. Much
lower prevalences of sensitization and
CBD were found among workers with
exposure levels less than or equal to
about 0.08 mg/m3. Two sensitized
workers (2.2 percent), including 1 case
of CBD (1.0 percent), were found among
workers with LTW average exposure
levels and HEJ exposure levels less than
or equal to 0.08 mg/m3 and 0.086 mg/m3,
respectively. Strict control of airborne
exposure to levels below 0.1 mg/m3 can,
therefore, significantly reduce risk of
sensitization and CBD. Although OSHA
recognizes that maintaining exposure
levels below 0.1 mg/m3 may not be
feasible in some operations (see this
preamble at section IX, Summary of the
Preliminary Economic Analysis and
Initial Regulatory Flexibility Analysis),
the Agency believes that workers in
facilities that meet the proposed action
level of 0.1 mg/m3 will be at less risk of
sensitization and CBD than workers in
facilities that cannot meet the action
level.
Table 3 below presents the prevalence
of sensitization and CBD cases across
cumulative exposure quartiles, based on
the same Cullman data used to derive
Tables 1 and 2. Cumulative exposure is
the sum of a worker’s exposure across
the duration of his employment.
14 This exposure-response pattern is sometimes
attributed to a ‘‘healthy worker effect’’ or to
exposure misclassification, as discussed in this
preamble at section VI, Preliminary Risk
Assessment.
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TABLE 3—PREVALENCE OF SENSITIZATION AND CBD BY CUMULATIVE EXPOSURE QUARTILE CULLMAN, AL MACHINING
FACILITY
Cumulative exposure (μg/m3 yrs)
Group size
Sensitized
only
CBD
Total
Total %
CBD %
0.0–0.147 .................................................
0.148–1.467 .............................................
1.468–7.008 .............................................
7.009–61.86 .............................................
81
79
79
80
2
0
3
2
2
2
8
7
4
2
11
9
4.9
2.5
13.9
11.3
2.5
2.5
8.0
8.8
Total ..................................................
319
7
19
26
8.2
6.0
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Source: Section VI, Preliminary Risk Assessment.
A 45-year working lifetime of
occupational exposure at the current
PEL would result in 90 mg/m 3-years, a
value far higher than the cumulative
exposures of workers in this data set,
who worked for periods of time less
than 45 years and whose exposure
levels were mostly well below the PEL.
Workers with 45 years of exposure to
the proposed PEL would have a
cumulative exposure (9 mg/m 3-years) in
the highest quartile for this worker
population. As with the average and HEJ
exposures, the greatest risk of
sensitization and CBD appears at high
exposure levels (≤ 1.468 mg/m 3-years).
The third cumulative quartile, at which
a sharp increase in sensitization and
CBD appears, is bounded by 1.468 and
7.008 mg/m 3-years. This is equivalent to
0.73–3.50 years of exposure at the
current PEL of 2 mg/m 3, or 7.34–35.04
years of exposure at the proposed PEL
of 0.2 mg/m 3. Prevalence of both
sensitization and CBD is substantially
lower in the second cumulative quartile
(0.148–1.467 mg/m 3-years). This is
equivalent to approximately 0.7 to 7
years at the proposed PEL of 0.2 mg/m 3,
or 1.5 to 15 years at the proposed action
level of 0.1 mg/m 3. This supports that
maintaining exposure levels below the
proposed PEL, where feasible, will help
to protect long-term workers against risk
of beryllium sensitization and early
stage CBD.
As discussed in the Health Effects
section (V.D), CBD often worsens with
increased time and level of exposure. In
a longitudinal study, workers initially
identified as beryllium sensitized
through workplace surveillance
developed early stage CBD defined by
granulomatous inflammation but no
apparent physiological abnormalities
(Newman et al., 2005). A study of
workers with this early stage CBD
showed significant declines in breathing
capacity and gas exchange over the 30
years from first exposure (Mroz et al.,
2009). Many of the workers went on to
develop more severe disease that
required immunosuppressive therapy
despite being removed from exposure.
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While precise beryllium exposure levels
were not available on the individuals in
these studies, most started work in the
1980s and 1990s and were likely
exposed to average levels below the
current 2 mg/m 3 PEL. The evidence for
time-dependent disease progression
indicates that the CBD risk estimates for
a 45-year lifetime exposure at the
current PEL will include a higher
proportion of individuals with
advanced clinical CBD than found
among the workers in the NJMRC data
set.
Studies of community-acquired (CA)
CBD support the occurrence of
advanced clinical CBD from long-term
exposure to airborne beryllium
(Eisenbud, 1998; Maier et al., 2008). A
discussion of the study findings can be
found in this preamble at section VI.C,
Preliminary Risk Assessment. For
example, one study evaluated 16
potential cases of CA–CBD in
individuals that resided near a
beryllium production facility in the
years between 1943 and 2001 (Maier et
al., 2008). Five cases of definite CBD
and three cases of probable CBD were
found. Two of the subjects with
probable cases died before they could be
confirmed with the BeLPT; the third
had an abnormal BeLPT and
radiography consistent with CBD, but
granulomatous disease was not
pathologically proven. The individuals
with CA–CBD identified in this study
suffered significant health impacts from
the disease, including obstructive,
restrictive, and gas exchange pulmonary
defects. Six of the eight cases required
treatment with prednisone, a step
typically reserved for severe cases due
to the adverse side effects of steroid
treatment. Despite treatment, three had
died of respiratory impairment as of
2002. There was insufficient
information to estimate exposure to the
individuals, but the limited amount of
ambient air sampling in the 1950s
suggested that average beryllium levels
in the area where the cases resided were
below 2 mg/m 3. The authors concluded
that ‘‘low levels of exposures with
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significant disease latency can result in
significant morbidity and mortality’’
(Maier et al., 2008, p. 1017).
OSHA believes that the literature
review, prevalence analysis, and the
evidence for time-dependent
progression of CBD described above
provide sufficient information to draw
preliminary conclusions about
significance of risk, and that further
quantitative analysis of the NJMRC data
set is not necessary to support the
proposed rule. The studies OSHA used
to support its preliminary conclusions
regarding risk of beryllium sensitization
and CBD were conducted at modern
industrial facilities with exposure levels
in the range of interest for this
rulemaking, so a model is not needed to
extrapolate risk estimates from high to
low exposures, as has often been the
case in previous rules. Nevertheless, the
Agency felt further quantitative analysis
might provide additional insight into
the exposure-response relationship for
sensitization and CBD.
Using the NJMRC data set, Dr. Stone
ran a complementary log-log
proportional hazards model, an
extension of logistic regression that
allows for time-dependent exposures
and differential time at risk. Relative
risk of sensitization increased with
cumulative exposure (p = 0.05). A
positive, but not statistically significant
association was observed with LTW
average exposure (p = 0.09). There was
little association with highest-exposed
job (HEJ) exposure (p = 0.3). Similarly,
the proportional hazards models for the
CBD endpoint showed positive
relationships with cumulative exposure
(p = 0.09), but LTW average exposure
and HEJ exposure were not closely
related to relative risk of CBD (p-values
> 0.5). Dr. Stone used the cumulative
exposure models to generate risk
estimates for sensitization and CBD.
Tables 4 and 5 below present risk
estimates from these models, assuming
5, 10, 20, and 45 years of beryllium
exposure. The tables present
sensitization and CBD risk estimates
based on year-specific intercepts, as
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explained in the section on Risk
Assessment and the accompanying
background document. Each estimate
represents the number of sensitized
workers the model predicts in a group
of 1000 workers at risk during the given
year with an exposure history at the
specified level and duration. For
example, in the exposure scenario for
1995, if 1000 workers were
occupationally exposed to 2 mg/m 3 for
10 years, the model predicts that about
56 (55.7) workers would be identified as
sensitized. The model for CBD predicts
that about 42 (41.9) workers would be
diagnosed with CBD that year. The year
1995 shows the highest risk estimates
generated by the model for both
sensitization and CBD, while 1999 and
2002 show the lowest risk estimates
generated by the model for sensitization
and CBD, respectively. The
corresponding 95 percent confidence
intervals are based on the uncertainty in
the exposure coefficient.
TABLE 4a—PREDICTED CASES OF SENSITIZATION PER 1000 WORKERS EXPOSED AT CURRENT AND ALTERNATE PELS
BASED ON PROPORTIONAL HAZARDS MODEL, CUMULATIVE EXPOSURE METRIC, WITH CORRESPONDING INTERVAL
BASED ON THE UNCERTAINTY IN THE EXPOSURE COEFFICIENT. 1995 BASELINE.
1995
Exposure duration
5 years
Exposure level
(μg/m3)
10 years
Cumulative
(μg/m3-yrs)
cases/1000
2.0 ....................................
10.0
1.0 ....................................
5.0
0.5 ....................................
2.5
0.2 ....................................
1.0
0.1 ....................................
0.5
41.1
30.3–56.2
35.3
30.3–41.3
32.7
30.3–35.4
31.3
30.3–32.3
30.8
30.3–31.3
μg/m3-yrs
20.0
10.0
5.0
2.0
1.0
20 years
cases/1000
μg/m3-yrs
55.7
30.3–102.9
41.1
30.3–56.2
35.3
30.3–41.3
32.2
30.3–34.3
31.3
30.3–32.3
45 years
cases/1000
40.0
101.0
30.3–318.1
55.7
30.3–102.9
41.1
30.3–56.2
34.3
30.3–38.9
32.2
30.3–34.3
20.0
10.0
4.0
2.0
μg/m3-yrs
90.0
45.0
22.5
9.0
4.5
cases/1000
394.4
30.3–999.9
116.9
30.3–408.2
60.0
30.3–119.4
39.9
30.3–52.9
34.8
30.3–40.1
Source: Section VI, Preliminary Risk Assessment.
TABLE 4b—PREDICTED CASES OF SENSITIZATION PER 1000 WORKERS EXPOSED AT CURRENT AND ALTERNATE PELS
BASED ON PROPORTIONAL HAZARDS MODEL, CUMULATIVE EXPOSURE METRIC, WITH CORRESPONDING INTERVAL
BASED ON THE UNCERTAINTY IN THE EXPOSURE COEFFICIENT. 1999 BASELINE.
1999
Exposure duration
5 years
Exposure level (μg/m3)
10 years
Cumulative
(μg/m3-yrs)
cases/1000
2.0 ....................................
10.0
1.0 ....................................
5.0
0.5 ....................................
2.5
0.2 ....................................
1.0
0.1 ....................................
0.5
8.4
6.2–11.6
7.2
6.2–8.5
6.7
6.2–7.3
6.4
6.2–6.6
6.3
6.2–6.4
μg/m3-yrs
20 years
cases/1000
20.0
μg/m3-yrs
11.5
6.2–21.7
8.4
6.2–11.6
7.2
6.2–8.5
6.6
6.2–7.0
6.4
6.2–6.6
10.0
5.0
2.0
1.0
45 years
cases/1000
40.0
21.3
6.2–74.4
11.5
6.2–21.7
8.4
6.2–11.6
7.0
6.2–8.0
6.6
6.2–7.0
20.0
10.0
4.0
2.0
μg/m3-yrs
90.0
45.0
22.5
9.0
4.5
cases/1000
96.3
6.2–835.4
24.8
6.2–100.5
12.4
6.2–25.3
8.2
6.2–10.9
7.1
6.2–8.2
Source: Section VI, Preliminary Risk Assessment.
TABLE 5a—PREDICTED NUMBER OF CASES OF CBD PER 1000 WORKERS EXPOSED AT CURRENT AND ALTERNATIVE
PELS BASED ON PROPORTIONAL HAZARDS MODEL, CUMULATIVE EXPOSURE METRIC, WITH CORRESPONDING INTERVAL BASED ON THE UNCERTAINTY IN THE EXPOSURE COEFFICIENT. 1995 BASELINE.
mstockstill on DSK4VPTVN1PROD with PROPOSALS2
1995
Exposure duration
5 years
Exposure level
(μg/m3)
10 years
Cumulative
(μg/m3-yrs)
Estimated
cases/1000
(95% c.i.)
2.0 ....................................
10.0
1.0 ....................................
5.0
30.9
22.8–44.0
26.6
22.8–31.7
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Frm 00095
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10.0
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20 years
Estimated
cases/1000
(95% c.i.)
41.9
22.8–84.3
30.9
22.8–44.0
Sfmt 4702
μg/m3-yrs
Estimated
cases/1000
(95% c.i.)
40.0
20.0
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22.8–285.5
41.9
22.8–84.3
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45 years
μg/m3-yrs
90.0
45.0
Estimated
cases/1000
(95% c.i.)
312.9
22.8–999.9
88.8
22.8–375.0
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TABLE 5a—PREDICTED NUMBER OF CASES OF CBD PER 1000 WORKERS EXPOSED AT CURRENT AND ALTERNATIVE
PELS BASED ON PROPORTIONAL HAZARDS MODEL, CUMULATIVE EXPOSURE METRIC, WITH CORRESPONDING INTERVAL BASED ON THE UNCERTAINTY IN THE EXPOSURE COEFFICIENT. 1995 BASELINE.—Continued
1995
Exposure duration
5 years
Exposure level
(μg/m3)
10 years
Cumulative
(μg/m3-yrs)
Estimated
cases/1000
(95% c.i.)
0.5 ....................................
2.5
0.2 ....................................
1.0
0.1 ....................................
0.5
24.6
22.8–26.9
23.5
22.8–24.3
23.1
22.8–23.6
μg/m3-yrs
5.0
2.0
1.0
20 years
Estimated
cases/1000
(95% c.i.)
μg/m3-yrs
26.6
22.8–31.7
24.2
22.8–26.0
23.5
22.8–24.3
45 years
Estimated
cases/1000
(95% c.i.)
10.0
30.9
22.8–44.0
25.8
22.8–29.7
24.2
22.8–26.0
4.0
2.0
μg/m3-yrs
22.5
9.0
4.5
Estimated
cases/1000
(95% c.i.)
45.2
22.8–98.9
30.0
22.8–41.3
26.2
22.8–30.7
Source: Section VI, Preliminary Risk Assessment.
TABLE 5b—PREDICTED NUMBER OF CASES OF CBD PER 1000 WORKERS EXPOSED AT CURRENT AND ALTERNATIVE
PELS BASED ON PROPORTIONAL HAZARDS MODEL, CUMULATIVE EXPOSURE METRIC, WITH CORRESPONDING INTERVAL BASED ON THE UNCERTAINTY IN THE EXPOSURE COEFFICIENT. 2002 BASELINE.
2002
Exposure duration
5 years
Exposure level (μg/m3)
10 years
Cumulative
(μg/m3-yrs)
Estimated
cases/1000
(95% c.i.)
2.0 ....................................
10.0
1.0 ....................................
5.0
0.5 ....................................
2.5
0.2 ....................................
1.0
0.1 ....................................
0.5
3.7
2.7–5.3
3.2
2.7–3.8
3.0
2.7–3.2
2.8
2.7–2.9
2.8
2.7–2.8
μg/m3-yrs
20.0
10.0
5.0
2.0
1.0
20 years
Estimated
cases/1000
(95% c.i.)
μg/m3-yrs
5.1
2.7–10.4
3.7
2.7–5.3
3.2
2.7–3.8
2.9
2.7–3.1
2.8
2.7–2.9
45 years
Estimated
cases/1000
(95% c.i.)
40.0
20.0
10.0
4.0
2.0
9.4
2.7–39.2
5.1
2.7–10.4
3.7
2.7–5.3
3.1
2.7–3.6
2.9
2.7–3.1
μg/m3-yrs
90.0
45.0
22.5
9.0
4.5
Estimated
cases/1000
(95% c.i.)
43.6
2.7–679.8
11.0
2.7–54.3
5.5
2.7–12.3
3.6
2.7–5.0
3.1
2.7–3.7
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Source: Section VI, Preliminary Risk Assessment.
As shown in Tables 4 and 5, the
exposure-response models Dr. Stone
developed based on the Cullman data
set predict a high risk of both
sensitization (about 96–394 cases per
1000 exposed workers) and CBD (about
44–313 cases per 1000) at the current
PEL of 2 mg/m3 for an exposure duration
of 45 years (90 mg/m3-yr). For a 45-year
exposure at the proposed PEL of 0.2 mg/
m3, risk estimates for sensitization
(about 8–40 cases per 1000 exposed
workers) and CBD (about 4–30 per 1000
exposed workers) are substantially
reduced. Thus, the model predicts that
the risk of sensitization and CBD at a
PEL of 0.2 mg/m3 will be about 10
percent of the risk at the current PEL of
2 mg/m3.
OSHA does not believe the risk
estimates generated by these exposureresponse models to be highly accurate.
Limitations of the analysis include the
size of the dataset, relatively sparse
exposure data from the plant’s early
years, study size-related constraints on
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the statistical analysis of the dataset,
and limited follow-up time on many
workers. The Cullman study population
is a relatively small group and can
support only limited statistical analysis.
For example, its size precludes
inclusion of multiple covariates in the
exposure-response models or a twostage exposure-response analysis to
model both sensitization and the
subsequent development of CBD within
the subpopulation of sensitized workers.
The limited size of the Cullman dataset
is characteristic of studies on berylliumexposed workers in modern, lowexposure environments, which are
typically small-scale processing plants
(up to several hundred workers, up to
20–30 cases).
Despite these issues with the
statistical analysis, OSHA believes its
main policy determinations are well
supported by the best available
evidence, including the literature
review and careful examination of the
prevalence of sensitization and CBD
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among workers with exposure levels
comparable to the current and proposed
PELs in the NJMRC data set. The
previously described literature analysis
and prevalence analysis demonstrate
that workers with occupational
exposure to airborne beryllium at the
current PEL face a risk of becoming
sensitized to beryllium and progressing
to both early and advanced stages of
CBD that far exceeds the value of 1 in
1000 used by OSHA as a benchmark of
clearly significant risk. Furthermore,
OSHA’s preliminary risk assessment
indicates that risk of beryllium
sensitization and CBD can be
significantly reduced by reduction of
airborne exposure levels, along with
respiratory and dermal protection
measures, as demonstrated in facilities
such as the Tucson ceramics plant, the
Elmore beryllium production facility,
and the Reading copper beryllium
facility described in the literature
review.
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OSHA’s preliminary risk assessment
also indicates that despite the reduction
in risk expected with the proposed PEL,
the risk to workers with average
exposure levels of 0.2 mg/m3 is still
clearly significant (see this preamble at
section VI). In the prevalence analysis,
workers with LTW average or HEJ
exposures close to 0.2 mg/m3
experienced high levels of sensitization
and CBD. This finding is corroborated
by the literature analysis, which showed
that workers exposed to mean plantwide airborne exposures between 0.1
and 0.5 mg/m3 had a similarly high
prevalence of sensitization and CBD.
Given the significant risk at these levels
of exposure, the Agency believes that
the proposed action level of 0.1 mg/m3,
dermal protection requirements, and
other ancillary provisions of the
proposed rule are key to reducing the
risk of beryllium sensitization and CBD
among exposed workers. OSHA
preliminarily concludes that the
proposed standard, including the PEL of
0.2 mg/m3, the action level of 0.1 mg/m3,
and provisions to limit dermal exposure
to beryllium, together will significantly
reduce workers’ risk of beryllium
sensitization and CBD from
occupational beryllium exposure.
2. Risk of Lung Cancer
OSHA’s review of epidemiological
studies of lung cancer mortality among
beryllium workers found that most did
not characterize exposure levels
sufficiently to characterize risk of lung
cancer at the current and proposed
PELs. However, as discussed in this
preamble at section V, Health Effects
and section VI, Preliminary Risk
Assessment, NIOSH recently published
a quantitative risk assessment based on
beryllium exposure and lung cancer
mortality among 5436 male workers
employed at beryllium processing
plants in Reading, PA; Elmore, OH; and
Hazleton, PA, prior to 1970 (SchubauerBerigan et al., 2010b). This new risk
assessment addresses important sources
of uncertainty for previous lung cancer
analyses, including the sole prior
exposure-response analysis for
beryllium and lung cancer, conducted
by Sanderson et al. (2001) on workers
from the Reading plant alone. Workers
from the Elmore and Hazleton plants
who were added to the analysis by
Schubauer-Berigan et al. were, in
general, exposed to lower levels of
beryllium than those at the Reading
plant. The median worker from
Hazleton had a mean exposure across
his tenure of less than 2 mg/m3, while
the median worker from Elmore had a
mean exposure of less than 1 mg/m3. The
Elmore and Hazleton worker
populations also had fewer short-term
workers than the Reading population.
Finally, the updated cohorts followed
the worker populations through 2005,
increasing the length of follow-up time
compared to the previous exposureresponse analysis. For these reasons,
OSHA based its preliminary risk
assessment for lung cancer on the
Schubauer-Berigan risk analysis.
Schubauer-Berigan et al. (2011)
analyzed the data set using a variety of
exposure-response modeling
approaches, described in this preamble
at section VI, Preliminary Risk
Assessment. The authors found that
lung cancer mortality risk was strongly
and significantly related to mean,
cumulative, and maximum measures of
workers’ exposure to beryllium (all
models reported in Schubauer-Berigan
et al., 2011). They selected the bestfitting models to generate risk estimates
for male workers with a mean exposure
of 0.5 mg/m3 (the current NIOSH
Recommended Exposure Limit for
beryllium). In addition, they estimated
the mean exposure that would be
associated with an excess lung cancer
mortality risk of one in one thousand.
At OSHA’s request, the authors also
estimated excess risks for workers with
mean exposures at each of the other
alternate PELs under consideration: 1
mg/m3, 0.2 mg/m3, and 0.1 mg/m3. Table
6 presents the estimated excess risk of
lung cancer mortality associated with
various levels of beryllium exposure
allowed under the current rule, based
on the final models presented in
Schubauer-Berigan et al’s risk
assessment.
TABLE 6—EXCESS RISK OF LUNG CANCER MORTALITY PER 1000 MALE WORKERS AT ALTERNATE PELS (NIOSH
MODELS)
Mean exposure
Exposure-response model
0.1 μg/m3
Best monotonic PWL—all workers ......................................
Best monotonic PWL—excluding professional and asbestos workers .......................................................................
Best categorical—all workers ..............................................
Best categorical—excluding professional and asbestos
workers .............................................................................
Power model—all workers ...................................................
Power model—excluding professional and asbestos workers .....................................................................................
0.2 μg/m3
0.5 μg/m3
1 μg/m3
2 μg/m3
7.3
15
45
120
200
3.1
4.4
6.4
9
17
25
39
59
61
170
1.4
12
2.7
19
7.1
30
15
40
33
52
19
30
49
68
90
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Source: Section VI, Preliminary Risk Assessment.
The lowest estimate of excess lung
cancer deaths from the six final models
presented by Schubauer-Berigan et al. is
33 per 1000 workers exposed at a mean
level of 2 mg/m3, the current PEL. Risk
estimates as high as 200 lung cancer
deaths per 1000 result from the other
five models presented. Regardless of the
model chosen, the excess risk of about
33 to 200 per 1000 workers is clearly
significant, falling well above the level
of risk the Supreme Court indicated a
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reasonable person might consider
acceptable (See Benzene, 448 U.S. at
655). The proposed PEL of 0.2 mg/m3 is
expected to reduce these risks
significantly, to somewhere between
2.7–30 excess lung cancer deaths per
1000 workers. These risk estimates still
fall above the threshold of 1 in 1000 that
OSHA considers clearly significant.
However, the Agency believes the lung
cancer risks should be regarded with a
greater degree of uncertainty than the
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risk estimates for CBD discussed
previously. While the risk estimates for
CBD at the proposed PEL were
determined from exposure levels
observed in occupational studies, the
lung cancer risks are extrapolated from
much higher exposure levels.
C. Conclusions
As discussed above, OSHA used the
best available scientific evidence to
identify adverse health effects of
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occupational beryllium exposure, and to
evaluate exposed workers’ risk of these
impairments. The Agency reviewed
extensive epidemiological and
experimental research pertaining to
adverse health effects of occupational
beryllium exposure, including lung
cancer, immunological sensitization to
beryllium, and CBD, and has evaluated
the risk of these effects from exposures
allowed under the current and proposed
standards. The Agency has,
additionally, reviewed previous policy
determinations and case law regarding
material impairment of health, and has
preliminarily determined that CBD, in
all stages, and lung cancer constitute
material health impairments.
Furthermore, OSHA has preliminarily
determined that long-term exposure to
beryllium at the current PEL would pose
a risk of CBD and lung cancer greater
than the risk of 1 per 1000 exposed
workers the Agency considers clearly
significant. OSHA’s risk assessment for
beryllium indicates that adoption of the
new PEL, action level, and dermal
protection provisions of the proposed
rule will significantly reduce this risk.
OSHA therefore believes it has met the
statutory requirements pertaining to
significance of risk, consistent with the
OSH Act, Supreme Court precedent, and
the Agency’s previous policy decisions.
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IX. Summary of the Preliminary
Economic Analysis and Initial
Regulatory Flexibility Analysis
A. Introduction and Summary
OSHA’s Preliminary Economic
Analysis and Initial Regulatory
Flexibility Analysis (PEA) addresses
issues related to the costs, benefits,
technological and economic feasibility,
and the economic impacts (including
impacts on small entities) of this
proposed respirable beryllium rule and
evaluates regulatory alternatives to the
proposed rule. Executive Orders 13563
and 12866 direct agencies to assess all
costs and benefits of available regulatory
alternatives and, if regulation is
necessary, to select regulatory
approaches that maximize net benefits
(including potential economic,
environmental, and public health and
safety effects; distributive impacts; and
equity), unless a statute requires another
regulatory approach. Executive Order
13563 emphasized the importance of
quantifying both costs and benefits, of
reducing costs, of harmonizing rules,
and of promoting flexibility. The full
PEA has been placed in OSHA
rulemaking docket OSHA–H005C–
2006–0870. This rule is an economically
significant regulatory action under Sec.
3(f)(1) of Executive Order 12866 and has
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been reviewed by the Office of
Information and Regulatory Affairs in
the Office of Management and Budget,
as required by executive order.
The purpose of the PEA is to:
• Identify the establishments and
industries potentially affected by the
proposed rule;
• Estimate current exposures and the
technologically feasible methods of
controlling these exposures;
• Estimate the benefits resulting from
employers coming into compliance with
the proposed rule in terms of reductions
in cases of lung cancer and chronic
beryllium disease;
• Evaluate the costs and economic
impacts that establishments in the
regulated community will incur to
achieve compliance with the proposed
rule;
• Assess the economic feasibility of
the proposed rule for affected
industries; and
• Assess the impact of the proposed
rule on small entities through an Initial
Regulatory Flexibility Analysis (IRFA),
to include an evaluation of significant
regulatory alternatives to the proposed
rule that OSHA has considered.
The PEA contains the following
chapters:
Chapter I. Introduction
Chapter II. Assessing the Need for Regulation
Chapter III. Profile of Affected Industries
Chapter IV. Technological Feasibility
Chapter V. Costs of Compliance
Chapter VI. Economic Feasibility Analysis
and Regulatory Flexibility Determination
Chapter VII. Benefits and Net Benefits
Chapter VIII. Regulatory Alternatives
Chapter IX. Initial Regulatory Flexibility
Analysis
The PEA includes all of the economic
analyses OSHA is required to perform,
including the findings of technological
and economic feasibility and their
supporting materials required by the
OSH Act as interpreted by the courts (in
Chapters III, IV, V, and VI); those
required by EO 12866 and EO 13563
(primarily in Chapters III, V, and VII,
though these depend on material in
other chapters); and those required by
the Regulatory Flexibility Act (in
Chapters VI, VIII, and IX, though these
depend, in part, on materials presented
in other chapters).
Key findings of these chapters are
summarized below and in sections IX.B
through IX.I of this PEA summary.
Profile of Affected Industries
This proposed rule would affect
employers and employees in many
different industries across the economy.
As described in Section IX.C and
reported in Table IX–2 of this preamble,
OSHA estimates that a total of 35,051
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employees in 4,088 establishments are
potentially at risk from exposure to
beryllium.
Technological Feasibility
As described in more detail in Section
IX.D of this preamble and in Chapter IV
of the PEA, OSHA assessed, for all
affected sectors, the current exposures
and the technological feasibility of the
proposed PEL of 0.2 mg/m3.
Tables IX–5 in section IX.D of this
preamble summarizes all nine
application groups (industry sectors and
production processes) studied in the
technological feasibility analysis. The
technological feasibility analysis
includes information on current
exposures, descriptions of engineering
controls and other measures to reduce
exposures, and a preliminary
assessment of the technological
feasibility of compliance with the
proposed PELs.
The preliminary technological
feasibility analysis shows that for the
majority of the job groups evaluated,
exposures are either already at or below
the proposed PEL, or can be adequately
controlled with additional engineering
and work practice controls. Therefore,
OSHA preliminarily concludes that the
proposed PEL of 0.2 mg/m3 is
technologically feasible for most
operations most of the time.
Based on the currently available
evidence, it is more difficult to
determine whether an alternative PEL of
0.1 mg/m3 would also be feasible in most
operations. For some application
groups, a PEL of 0.1 mg/m3 would
almost certainly be feasible. In other
application groups, a PEL of 0.1 mg/m3
appears feasible, except for
establishments working with high
beryllium content alloys. For
application groups with the highest
exposure, the exposure monitoring data
necessary to more fully evaluate the
effectiveness of exposure controls
adopted after 2000 are not currently
available to OSHA, which makes it
difficult to determine the feasibility of
achieving exposure levels at or below
0.1 mg/m3.
OSHA also evaluated the feasibility of
a STEL of 2.0 mg/m3. The majority of the
available short-term measurements are
below 2.0 mg/m3; therefore OSHA
preliminarily concludes that the
proposed STEL of 2.0 mg/m3 can be
achieved for most operations most of the
time. OSHA recognizes that for a small
number of tasks, short-term exposures
may exceed the proposed STEL, even
after feasible control measures to reduce
TWA exposure to below the proposed
PEL have been implemented, and
therefore assumes that the use of
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respiratory protection will continue to
be required for some short-term tasks. It
is more difficult based on the currently
available evidence to determine whether
the alternative STEL of 1.0 mg/m3 would
also be feasible in most operations based
on lack of detail in the activities of the
workers presented in the data. OSHA
expects additional use of respiratory
protection would be required for tasks
in which peak exposures can be reduced
to less than 2.0 mg/m3 but not less than
1.0 mg/m3. Due to limitations in the
available sampling data and the higher
detection limits for short term
measurements, OSHA could not
determine the percentage of the STEL
measurements that are less than or equal
to 0.5 mg/m3.
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Costs of Compliance
As described in more detail in Section
IX.E and reported, by application group
and NAICS code, in Table IX–7 of this
preamble, the total annualized cost of
compliance with the proposed standard
is estimated to be about $37.6 million.
The major cost elements associated with
the revisions to the standard are
housekeeping ($12.6 million),
engineering controls ($9.5 million),
training ($5.8 million), and medical
surveillance ($2.9 million).
The compliance costs are expressed as
annualized costs in order to evaluate
economic impacts against annual
revenue and annual profits, to be able to
compare the economic impact of the
rulemaking with other OSHA regulatory
actions, and to be able to add and track
Federal regulatory compliance costs and
economic impacts in a consistent
manner. Annualized costs also represent
a better measure for assessing the
longer-term potential impacts of the
rulemaking. The annualized costs were
calculated by annualizing the one-time
costs over a period of 10 years and
applying a discount rate of 3 percent
(and an alternative discount rate of 7
percent).
The estimated costs for the proposed
beryllium standard represent the
additional costs necessary for employers
to achieve full compliance. They do not
include costs associated with current
compliance that has already been
achieved with regard to the new
requirements or costs necessary to
achieve compliance with existing
beryllium requirements, to the extent
that some employers may currently not
be fully complying with applicable
regulatory requirements.
Economic Impacts
To assess the nature and magnitude of
the economic impacts associated with
compliance with the proposed rule,
OSHA developed quantitative estimates
of the potential economic impact of the
new requirements on entities in each of
the affected industry sectors. The
estimated compliance costs were
compared with industry revenues and
profits to provide an assessment of the
economic feasibility of complying with
the revised standard and an evaluation
of the potential economic impacts.
As described in greater detail in
Section IX.F of this preamble and in
Chapter VI of the PEA, the costs of
compliance with the proposed
rulemaking are not large in relation to
the corresponding annual financial
flows associated with each of the
affected industry sectors. The estimated
annualized costs of compliance
represent about 0.11 percent of annual
revenues and about 1.52 percent of
annual profits, on average, across all
affected firms. Compliance costs do not
represent more than 1 percent of
revenues or more than 16.25 percent of
profits in any affected industry.
Based on its analysis of the relative
inelasticity of demand for berylliumcontaining inputs and products and of
possible international trade effects,
OSHA concluded that most or all costs
arising from this proposed beryllium
rule would be passed on in higher
prices rather than absorbed in lost
profits and that any price increases
would result in minimal loss of business
to foreign competition.
Given the minimal potential impact
on prices or profits in the affected
industries, OSHA has preliminarily
concluded that compliance with the
requirements of the proposed
rulemaking would be economically
feasible in every affected industry
sector.
Benefits, Net Benefits, and CostEffectiveness
As described in more detail in Section
VIII.G of this preamble, OSHA estimated
the benefits, net benefits, and
incremental benefits of the proposed
beryllium rule. That section also
contains a sensitivity analysis to show
how robust the estimates of net benefits
are to changes in various cost and
47663
benefit parameters. A full explanation of
the derivation of the estimates presented
there is provided in Chapter VII of the
PEA for the proposed rule.
OSHA estimated the benefits
associated with the proposed beryllium
PEL of 0.2 mg/m3 and, for analytical
purposes to comply with OMB Circular
A–4, with alternative beryllium PELs of
.1 mg/m3 and .5 mg/m3 by applying the
dose-response relationship developed in
the Agency’s preliminary risk
assessment—summarized in Section VI
of this preamble—to current exposure
levels. OSHA determined current
exposure levels by first developing an
exposure profile for industries with
workers exposed to beryllium, using
OSHA inspection and site-visit data,
and then applying this exposure profile
to the total current worker population.
The industry-by-industry exposure
profile is summarized in Table IX–3 in
Section IX.C of this preamble.
By applying the dose-response
relationship to estimates of current
exposure levels across industries, it is
possible to project the number of cases
of the following diseases expected to
occur in the worker population given
current exposure levels (the ‘‘baseline’’):
• fatal cases of lung cancer,
• fatal cases of chronic beryllium
disease (CBD), and
• morbidity related to chronic
beryllium disease.
Table IX–1 provides a summary of
OSHA’s best estimate of the costs and
benefits of the proposed rule. As shown,
the proposed rule, once it is fully
effective, is estimated to prevent 96
fatalities and 50 non-fatal berylliumrelated illnesses annually, and the
monetized annualized benefits of the
proposed rule are estimated to be $575.8
million using a 3-percent discount rate
and $255.3 million using a 7-percent
discount rate. Also as shown in Table
IX–1, the estimated annualized cost of
the rule is $37.6 million using a 3percent discount rate and $39.1 million
using a 7-percent discount rate. The
proposed rule is estimated to generate
net benefits of $538.2 million annually
using a 3-percent discount rate and
$216.2 million annually using a 7percent discount rate. The estimated
costs and benefits of the proposed rule,
disaggregated by industry sector, were
previously presented in Table I–1 in this
preamble.
TABLE IX–1—ANNUALIZED COSTS, BENEFITS AND NET BENEFITS OF OSHA’S PROPOSED BERYLLIUM STANDARD OF 0.2
μg/m3
Discount Rate ......................................................................................................................
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TABLE IX–1—ANNUALIZED COSTS, BENEFITS AND NET BENEFITS OF OSHA’S PROPOSED BERYLLIUM STANDARD OF 0.2
μg/m3—Continued
Annualized Costs
Engineering Controls ....................................................................................................
Respirators ...................................................................................................................
Exposure Assessment ..................................................................................................
Regulated Areas and Beryllium Work Areas ...............................................................
Medical Surveillance .....................................................................................................
Medical Removal ..........................................................................................................
Exposure Control Plan .................................................................................................
Protective Clothing and Equipment ..............................................................................
Hygiene Areas and Practices .......................................................................................
Housekeeping ...............................................................................................................
Training .........................................................................................................................
Total Annualized Costs (Point Estimate) .............................................................................
Annual Benefits: Number of Cases Prevented
Fatal Lung Cancer ........................................................................................................
CBD-Related Mortality ..................................................................................................
Total Beryllium Related Mortality .................................................................................
Morbidity .......................................................................................................................
Monetized Annual Benefits (midpoint estimate) ..................................................................
Net Benefits .........................................................................................................................
$9,540,189
249,684
2,208,950
629,031
2,882,076
148,826
1,769,506
1,407,365
389,241
12,574,921
5,797,535
37,597,325
4.0
92.0
96.0
49.5
$10,334,036
252,281
2,411,851
652,823
2,959,448
166,054
1,828,766
1,407,365
389,891
12,917,944
5,826,975
39,147,434
$572,981,864
2,844,770
575,826,633
538,229,308
$253,743,368
1,590,927
255,334,295
216,186,861
Source: OSHA, Directorate of Standards and Guidance, Office of Regulatory Analysis.
Initial Regulatory Flexibility Analysis
OSHA has prepared an Initial
Regulatory Flexibility Analysis (IRFA)
in accordance with the requirements of
the Regulatory Flexibility Act, as
amended in 1996. Among the contents
of the IRFA are an analysis of the
potential impact of the proposed rule on
small entities and a description and
discussion of significant alternatives to
the proposed rule that OSHA has
considered. The IRFA is presented in its
entirety both in Chapter IX of the PEA
and in Section IX.I of this preamble.
The remainder of this section (Section
IX) of the preamble is organized as
follows:
B. The Need for Regulation
C. Profile of Affected Industry
D. Technological Feasibility Analysis
E. Costs of Compliance
F. Economic Feasibility Analysis and
Regulatory Flexibility Determination
G. Benefits and Net Benefits
H. Regulatory Alternatives
I. Initial Regulatory Flexibility Analysis.
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B. Need for Regulation
Employees in work environments
addressed by the proposed beryllium
rule are exposed to a variety of
significant hazards that can and do
cause serious injury and death. As
described in Chapter II of the PEA in
support of the proposed rule, the risks
to employees are excessively large due
to the existence of various types of
market failure, and existing and
alternative methods of overcoming these
negative consequences—such as
workers’ compensation systems, tort
liability options, and information
dissemination programs—have been
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shown to provide insufficient worker
protection.
After carefully weighing the various
potential advantages and disadvantages
of using a regulatory approach to
improve upon the current situation,
OSHA preliminarily concludes that, in
the case of beryllium exposure, the
proposed mandatory standards
represent the best choice for reducing
the risks to employees. In addition,
rulemaking is necessary in this case in
order to replace older existing standards
with updated, clear, and consistent
health standards.
C. Profile of Affected Industries
1. Introduction
Chapter III of the PEA presents a
profile of industries that use beryllium,
beryllium oxide, and/or beryllium
alloys. The discussion below
summarizes the findings in that chapter.
For each industry sector identified, the
Agency describes the uses of beryllium
and estimates the number of
establishments and employees that may
be affected by this proposed rulemaking.
Employee exposure to beryllium can
also occur as a result of certain
processes such as welding that are
found in many industries. OSHA uses
the umbrella term ‘‘application group’’
to refer either to an industrial sector or
a cross-industry group with a common
process. These groups are all mutually
exclusive and are analyzed in separate
sections in Chapter III of the PEA. These
sections briefly describe each
application group and then explain how
OSHA estimated the number of
establishments working with beryllium
and the number of employees exposed
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to beryllium. Beryllium is rarely used by
all establishments in any particular
application group because its unique
properties and relatively high cost
typically result in only very specific and
limited usage within a portion of a
group.
The information in Chapter III of the
PEA is based on reports prepared under
task order by Eastern Research Group
(ERG), an OSHA contractor; information
collected during OSHA’s Small
Business Advocacy Review Panel
(OSHA 2008b); and Agency research
and analysis. Technological feasibility
reports (summarized in Chapter IV of
the PEA) for each beryllium-using
application group provide a detailed
presentation of processes and
occupations with beryllium exposure,
including available sampling exposure
measurements and estimates of how
many employees are affected in each
specific occupation.
OSHA has identified nine application
groups that would be potentially
affected by the proposed beryllium
standard:
1. Beryllium Production
2. Beryllium Oxide Ceramics and
Composites
3. Nonferrous Foundries
4. Secondary Smelting, Refining, and
Alloying
5. Precision Turned Products
6. Copper Rolling, Drawing, and
Extruding
7. Fabrication of Beryllium Alloy
Products
8. Welding
9. Dental Laboratories
These application groups are broadly
defined, and some include
establishments in several North
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American Industrial Classification
System (NAICS) codes. For example, the
Copper Rolling and Drawing, and
Extruding application group is made up
both of NAICS 331421 Copper Rolling,
Drawing, and Extruding and NAICS
331422 Copper Wire Drawing. While an
application group may contain
numerous NAICS six-digit industry
codes, in most cases only a fraction of
the establishments in any individual
six-digit NAICS industry use beryllium
and would be affected by the proposed
rule. For example, not all companies in
the above application group work with
copper that contains beryllium.
One application group, welding,
reflects industrial activities or processes
that take place in various industry
sectors. All of the industries in which a
given activity or process may result in
worker exposure to beryllium are
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identified in the sections on the
application group. The section on each
application group describes the
production processes where
occupational contact with beryllium can
occur and contains estimates of the total
number of firms, employees, affected
establishments, and affected employees.
Chapter III of the PEA presents
formulas in the text, usually in
parentheses, to help explain the
derivation of estimates. Because the
values used in the formulas shown in
the text are sometimes rounded, while
the actual spreadsheet formulas used to
create final costs are not, the calculation
using the presented formula will
sometimes differ slightly from the total
presented in the text—which is the
actual total as shown in the tables.
At the end of Chapter III in the PEA,
OSHA discusses other industry sectors
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47665
that have reportedly used beryllium in
the past or for which there are anecdotal
or informal reports of beryllium use.
The Agency was unable to verify
beryllium use in these sectors that
would be affected by the proposed
standard, and seeks further information
in this rulemaking on these or other
industries where there may be
significant beryllium use and employee
exposure.
2. Summary of Affected Establishments
and Employers
As shown in Table IX–2, OSHA
estimates that a total of 35,051 workers
in 4,088 establishments will be affected
by the proposed beryllium standard.
Also shown are the estimated annual
revenues for these entities.
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NAICS
Industry
Beryllium Production
331419 Primary Smelting and
Fmt 4701
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Nonferrous Foundnes
331521 Alum1num die-casting
331522 Nonferrous (except
331524 Alum1num foundries
Frm 00102
Beryllium Oxide Ceramics and Composites
327113a Porcelain electrical supply
327113b Porcelain electrical supply
334220 Cellular telephones
334310 Compact disc players
334411 Electron Tube
334415 Electronic resistor
334419 Other electronic
334510 Electromedical equipment
336322b Other motor vehicle
E:\FR\FM\07AUP2.SGM
07AUP2
EP07AU15.003
331 ~??~. Copp~~ .f?undn~~ .(~~cept
331525b Copperfoundnes (except
Secondary Smelt1ng, Refming, and Alloying
331314 Secondary smelt1ng &
331421b Copper rolling, dravvmg,
331423 Secondary smelting,
331492 Secondary Smelting,
Precision Machining
332721a Precision turned product
332721 b Precision turned product
Total Entitles [a]
Total Establishments [a]
Total Employees [a]
Affected Entitles [b]
Affected Establishments
Affected Employees
Total Revenues
Revenues/Entlt
Revenues/Establishment {$1,000)
140
161
8,943
1
1
616
58,524,863
$60,892
$52,949
94
94
4,310
4,310
79,732
2
12
9
5
16
10
8
8
9
2
14
10
5
21
12
9
9
10
83
168
120
60
252
144
108
108
120
789,731
789,731
$8,401
$8,401
$7,450
$7,450
3S,~75,3~3
$~8,999
$~3,797
460
62
50
1,058
555
585
106
106
810
464
79
61
1,133
629
636
3,975,351
$8,642
$19,685
$11,219
228
137
365
201
201
254
140
394
208
208
18,017
6
6,362
15,178
S,123
37
7
19
24
7
38
7
20
25
98
534
98
281
1,510,799
2,518,097
1,205,574
393
1,205,574
98
70
23
217
122
4,846
1
1
3
30
9
9
27
270
$49,358
$39,649
9,849
789
1
1
3
26
4,837,129
96
12,513,425
723,759
$178,763
$130,348
$31,468
$37,769
$30,157
$33,048
18
288
18
294
222
3,542
$4,338
$4,338
$4,245
$4,245
72~
24
248
8,858
4,884
3,722
,16,836
66,107
38,475
5,123
9,696
3,057
3,124
78,749
3,057
3,124
78,749
1,220,476
560,967
10,013,730
17,480,966
12,152,053
4,310,021
8,195,807
13,262,706
13,262,706
$8,568
$49,515
$20,773
$15,449
$9,195
$8,838
$43,690
$19,107
$18,904
$11,028
$5,880
$S,998
$5,998
$10,791
$6,391
$5,796
$5,796
$9,~65
$16,969
Federal Register / Vol. 80, No. 152 / Friday, August 7, 2015 / Proposed Rules
19:20 Aug 06, 2015
Table IX-2
CHARACTERISTICS OF INDUSTRIES AFFECTED BY OSHA'S PROPOSED STANDARD FOR BERYLLIUM-ALL ENTITIES
mstockstill on DSK4VPTVN1PROD with PROPOSALS2
VerDate Sep<11>2014
Jkt 235001
NAICS
Industry
Copper Rollmg, Drawng and Extrudmg
331422 Copper Wre (except
331421 a .Copper roll1ng, draWng,
PO 00000
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Stamping, Spring, and Connector Manufacturing
332612 ·Light gauge spring
332116 Metal stamping
334417. Electronic connector
336322a Other motor vehicle
Dental Laboratones
339116 ·Dental laboratories
62121 0 Offices of dent1sts
Fmt 4701
Sfmt 4725
E:\FR\FM\07AUP2.SGM
07AUP2
Arc and Gas Welding
331111 Iron and Steel Mills
331221 Rolled Steel Shape
331513 Steel Foundries (except
332117: POVI.der Metallurgy Part
332212 Hand and Edge Tool
332312 ·Fabricated Structural
332313 Plate Work Manufactunng
332322. Sheet Metal Work
332323 ·Ornamental and
332439 Other Metal Container
33291 9 ·Other Metal Valve and
332999 All Other Miscellaneous
333111 . Farm Machinery and
333414a Heating Equipment
333911 :Pump and Pumpmg
333922 Conveyor and Conveying
333924 ·Industrial Truck, Tractor,
333999 All Other Miscellaneous
336211 . Motor Vehicle Body
336214 ·Travel Trailer and Camper
336399a All Other Motor Vehicle
336510 ·Railroad Rolling Stock
336999 All Other Transportation
337215. ShoV\Case, Partition,
811310 Commercial and lndustnal
Total Entitles [a]
Total Establishments [a]
Total Employees [a]
Affected Establishments
Affected Employees
84
70
114
96
9,847
9,849
43
11
59
15
5,096
1,539
6,471,491
12,513,425
269
1,413
323
2,167,977
9,749,800
5,029,508
38,475
70
40
146
323
74
46
159
2,071
231
636
10,329
48,855
19,538
269
1,484
198
585
6,718
123,322
6,995
129,830
461
134
203
121
999
587
161
220
133
3,081
1,066
3,407
44,030
1,680
1,749
846,092
226
238
94,089
5
1
1
1
3
51
21
64
38
6
2
33
19
6
5
9
4
17
13
12
6
2
4
3
132
7
1
1
1
3
56
21
69
39
7
3
33
20
9,971
13,874
6,707
25,098
89,728
1,252
1,288
28,400
3,907
2,314
'1,173
2,354
321
240
3,195
975
433
445
737
347
370
265
3,262
91,3611
30,029
12,553
1,463
1,524
651
602
742
683
11156
1,350
157
366
226
374
95,1126
24,491
10,846
1,144
1,194
33,195
20,299
21,960
181,220
1,041
460
571
776
374
Affected Entitles [b]
14,688
65,821
53,133
16,768
31,272
26,970
19,974
43,401
38,587
30,803
6
7
9
4
18
15
14
7
3
4
3
143
Total Revenues
Revenues/Entlt
Revenues/Establishment l$1,000]
$77,042
$56,767
$178,763
$130,348
$6,712
$6,570
$21,773
$19,107
496
310
1,066
12,152,053
$8,059
$6,900
$15,402
$10,773
8,148
1,107
4,100,626
100,431,324
$610
$814
$586
$774
27
$92,726,004
$201,141
$157,966
6
5
4
12
224
85
270
155
8,376,271
$62,509
$10,945
$52,027
$19,327
$11,687
$10,632
$5,083
$8,478
$4,811
$4,604
$2,467
$19,100
$4,370
$24,684
$11,043
$27,855
$8,913
$4,763
$7,666
$4,677
$4,311
$2,425
$9,638
$17,198
$4,281
$23,119
$10,395
$21,708
$8,465
$21,454
$19,905
$7,500
$15,150
$12,400
$7,200
$13,312
$10,930
27
11
134
80
24
27
36
17
71
60
55
30
11
14
13
571
4,251,852
1,414,108
5,077,868
26,119,614
6,023,356
17,988,908
5,708,707
3,565,875
4,584,082
13,963,184
$24,067,145
4,781,561
12,395,387
6,569,120
7,444,451
10,972,258
$9,877,558
7,465,024
32,279,766
$11,927,191
5,250,368
5,815,404
31,650,469
$11,109
$27,92'1
$231911
$75,969
$52,775
$14,345
$14,038
$5,083
$1,559
$4,871
$1,441
Federal Register / Vol. 80, No. 152 / Friday, August 7, 2015 / Proposed Rules
19:20 Aug 06, 2015
Table IX-2 1 continued
CHARACTERISTICS OF INDUSTRIES AFFECTED BY OSHA'S PROPOSED STANDARD FOR BERYLLIUM-ALL ENTITIES
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NAICS
Industry
·Resistance Welding
333411
333412
333414b
333415
335211
335212
335221
335222
335224
335228
336311
336312
336321
336322c
336330
336340
336350
336360
336370
336391
336399b
Total
Air Purification Equipment
Industrial and Commercial
Heating Equipment
Air-Conditioning Warm
Electnc Housev,.ares and
Household Vacuum
Household Cook mg
Household Refrigerator
Household Laundry
Other MaJor Household
Carburetor, Piston, Piston
Gasol1ne Engine and
Vehicular Lighting
Other Motor Vehicle
Motor Vehicle Steer1ng
Motor Vehicle Brake
Motor Vehicle
Motor Vehicle Seatmg and
Motor Vehicle Metal
Motor Vehicle A1rAll Other Motor Vehicle
All Affected Industries
Total Entities [a]
Total Establishments [a]
Total Employees [a]
303
135
433
695
101
29
91
16
9
34
97
697
86
585
209
159
397
305
599
358
151
460
843
106
96
22
11
38
109
742
93
636
246
199
476
403
736
11,521
6,908
16,768
79,651
5,980
2,577
9,730
9,731
8,051
9,023
7,370
36,896
9,218
38,475
26,118
20,245
51,171
39,805
66,985
72
1,156
80
1,350
11,207
95,426
"
Affected Entities [b]
Affected Establishments
21
g
30
49
5
1
5
1
1
2
5
35
4
29
10
8
20
15
30
4
58
3,795
Affected Employees
Total Revenues
Revenues/Entit
Revenues/Establishment l$1,000]
10
24
20
37
379
160
487
893
80
26
73
17
8
29
82
561
70
481
186
150
360
305
557
3,060,71]1]
1,681,585
4,781,561
25,454,383
2,209,657
891,600
3,757,849
4,489,845
3,720,514
3,499,273
1,715,1]29
20,000,705
2,322,610
12,152,053
8,856,584
8,147,826
21,862,014
15,168,862
19,809,238
$10,101
$12,456
$11,043
$36,625
$21,878
$30,,5
$41,295
$280,615
$413,390
$102,920
$17,685
$28,695
$27,007
$20,773
$42,376
$51,244
$55,068
$49,734
$33,071
$8,550
$11,136
$10,395
$30,195
$20,846
$26,22,
$39,144
$204,084
$338,229
$92,086
$15,738
$26,955
$24,974
$19,107
$36,002
$40,944
$45,929
$37,640
$26,915
4
68
4,088
61
1,021
35,051
3,798,464
32,279,766
$52,756
$27,924
$47,481
$23,911
25
11
32
59
5
2
5
1
1
2
5
37
5
32
12
[a] US Census Bureau, Statistics of US Busmesses, 2010
[b] OSHA estimates of employees potentially exposed to beryllium and associated ent1t1es and establishments Affected ent1t1es and establishments constrained to be less than or equal to the number of affected employees.
·[c] Estimates based on 2007 receipts and payroll data from US Census Bureau, Statistics of US Businesses 2007, and payroll data from the US Census Bureau, Statistics of US Bus messes, 2010. Rece1pts are not reported for 2010
but V\ere estimated assum1ng the rat1o of rece1pts to payroll rema1ned unchanged from 2007 to 2010.
·Source: US Dept. of Labor, OSHA, Directorate of Evaluation and Analysis, Office of Regulatory Analysis, based on ERG, 2012
07AUP2
Federal Register / Vol. 80, No. 152 / Friday, August 7, 2015 / Proposed Rules
19:20 Aug 06, 2015
EP07AU15.005
Table IX-2! continued
CHARACTERISTICS OF INDUSTRIES AFFECTED BY OSHA'S PROPOSED STANDARD FOR BERYLLIUM-ALL ENTITIES
Federal Register / Vol. 80, No. 152 / Friday, August 7, 2015 / Proposed Rules
3. Beryllium Exposure Profile of At-Risk
Workers
mstockstill on DSK4VPTVN1PROD with PROPOSALS2
The technological feasibility analyses
presented in Chapter IV of the PEA
contain data and discussion of worker
exposures to beryllium throughout
industry. Exposure profiles, by job
category, were developed from
individual exposure measurements that
were judged to be substantive and to
contain sufficient accompanying
description to allow interpretation of
the circumstance of each measurement.
The resulting exposure profiles show
the job categories with current
overexposures to beryllium and, thus,
VerDate Sep<11>2014
19:20 Aug 06, 2015
Jkt 235001
the workers for whom beryllium
controls would be implemented under
the proposed rule.
Table IX–3 summarizes, from the
exposure profiles, the number of
workers at risk from beryllium exposure
and the distribution of 8-hour TWA
respirable beryllium exposures by
affected job category and sector.
Exposures are grouped into the
following ranges: Less than 0.1 mg/m3;
≥ 0.1 mg/m3 and ≤ 0.2 mg/m3; > 0.2 mg/
m3 and ≤ 0.5 mg/m3; > 0.5 mg/m3 and ≤
1.0 mg/m3; > 1.0 mg/m3 and ≤ 2.0 mg/m3;
and greater than 2.0 mg/m3. These
frequencies represent the percentages of
production employees in each job
PO 00000
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Sfmt 4702
47669
category and sector currently exposed at
levels within the indicated range.
Table IX–4 presents data by NAICS
code on the estimated number of
workers currently at risk from beryllium
exposure, as well as the estimated
number of workers at risk of beryllium
exposure above 0 mg/m3, at or above 0.1
mg/m3, at or above 0.2 mg/m3, at or above
0.5 mg/m3, at or above 1.0 mg/m3, and at
or above 2.0 mg/m3. As shown, an
estimated 12,101 workers currently have
beryllium exposures at or above the
proposed action level of 0.1 mg/m3; and
an estimated 8,091 workers currently
have beryllium exposures above the
proposed PEL of 0.2 mg/m3.
E:\FR\FM\07AUP2.SGM
07AUP2
mstockstill on DSK4VPTVN1PROD with PROPOSALS2
Sector
Beryllium Production
IX~3
Beryllium Exposure Range
Job Category/Activity
Administrative
Maintenance/Furnace& Tools
Other Production Support
Machining
Other Cold Work
Welding
PO 00000
Frm 00106
Jkt 235001
Alloy Arc Furnace
Alloy Induction Furnace
Vacuum Cast
Atomization
Beryllium Oxide Furnace
Material prepara_tions operators
_Formi,ng op_erators p_ress i ng
Forming operators -extruding
Kiln operators
Mac hi ning operators
Compact loadin&"/Sintering
NNS Operator
~hemical Oper~tipns
Be Oxide- Primary
Be Oxide- Secondary
Fmt 4701
Sfmt 4725
Sand foundries
Metallization Workers
Production support
Non Sand foundries
Administrative
Molder
Material Handler
Furnace operator
Pouri r!g operator.
Shakeout operator
Abrasive blaster
Grinding/finishing operator
E:\FR\FM\07AUP2.SGM
Maintenance
Molder
Material Handler
<0.1 U2/m 3
0.1-0.2 ue/m 1
0.2-0.5 ue/m 1
84.91%
58.70%
27.78%
35.42%
86.31%
27.45%
12.61%
10.34%
70.20%
55.48%
27.78%
25.00%
9.78%
1
17.65%
23.42%
8.62%
13.88%
21.23%
72.70%
19.23%
15.79%
0.00%
5.00%
0.00%
5.15%
0.00%
0.00%
31.58%:
22,22%;
10.00%
1
2.63%
13.40%
33.33%
0.00%.
18.44%
3.85%
20.00%
15.58%
0.00%
40.00%
55.56%
74.79%
93.51%
0.00%
0.00%
0.00%
0.00%
20.51%
0.00%
0.00%
1
0.00%
22.56%
13.89%
13.45%
4.32% 1
40.00%
0.00%
0.00%
0.00%
18~18%:
. Smelting- Be Alloys
Abrasive blaster
Grinding/finishing operator
. Smelti~g- ~recipu~ !!let, Mechanical p~~cess.i ng ~per~t~r
Furnace operator
Mechanical processing operator
Machining (high)
Machining (low}
Furnace operator
Machinist (high)
Ro_lling
07AUP2
:Drawing
Springs
:Stamping
Dental tabs
·we!ding_G!
. Resistance Welding
Machinist(low)
Administrative
Other Production support
Wastewater treatment operator
Production
Administrative
Other Production support
Wastewater treatment operator
Production
Assembly operator
Deburri ng Operator
Chemical process operator
Assembly opera to~
Deburri ng Operator
Chemic?! proc~ss operator
Mechanical processing operator
Dental technicians
Welder
Welder
Source: OSHA Office of Regulatory Analysis-Health
0.00%
6.25%
25.00%
0.00%
25.00%
50.00%
13.56%
73.75%
98.53%
97.96%
33.33%
92.81%
98.53%
97.96%
33.33%
85.71%
88.37%
92.86%
85.71%
88.37%
25.00%
30.43%
56.76%
100.00%
40.00%;
100.00%
31.25%,
75.00%,
0.00%
75.00%
0.00%
11.86%
11.25%
1.47%.
2.04%.
33.33%'
2.04%
33.33%
13.33%
7.14%
0.00%
6.98%
7.14%
75.00%
21.74%:
13.51%
0.00%
0.5 -1.0 U2/m 3
3.98%
19.57%
44.44%
14.58%
2.74%
33.33%
27.03%
27.59%
6.55%
15.53%
5.13%
40.00%
8.16%
23.08%
26.32%,
40.74%
50.00%
15.79%
31.96%
22.22%
0.00%
20.00%
31.17%
1.02%
4.35%
0.00%
14.58%
0.78%·
9.80%
3.59%
2.51%
0.71%
23.08%
0.00%
29.63%
20.00%
36.84%
26.80%
11.11%
30.77%
6.67%
19.48%
10.57%
10.57%
0.00%
10.26%
2.78%
2.52%
0.54%
25.00%
100.00%
18.18%
0.00%
100.00%
22.31%
1.08%
62.50%
0.00%
9.09%
0.00%
,0.00%
0.00%
31.25%
23.08%
62.503{,
14.10%
25.00%
100.00%
18.18%
0.00%
0.00%
6.25%
0.00%
0.00%
0.00%
0.00%
15.25%
2.50%
0.00%
0.00%
0.00%
0.00%
9.09%
0.00%
0.00%
31.25%
0.00%
0.00%
0.00%
50.00%
44.07%
7.50%
0.00%
0.00%
33.33%
1.88%
0.00%
0.00%
33.33%
0.00%
0.00%
14.29%
4.65%
0.00%
14.29%
4.65%
0.0~%
13.04%
16.22%
0.00%
c
0.00%
0.00%
0.0_0%.
0.00%
0.00%
0.00%
17.39%
10.81%
0.00%
1.0-2.0 Ui!/m 3
0.61%
0.00%
0.00%
9.80%
9.91%
8.62%
3.43%
3.20%
0.00%
26.92%
15.79%
3.70%
10-DO%
18.42%
13.40%
22.22%
0.00%
20.00%
10.39%;
0.00%
2.82%
0.00%
0.84%
0.54%
0.00%
0.00%
18.18%
20.00%
100.00%
0.00%
>2.0 Ui!/m 1
0.31%
0.00%
0.00%
4.17%
0.00%
1.96%
14.41%
24.14%
2.34%
2.05%
0.00%
3.85%
10.53%
3.70%
5.00%
26.32%
9.28%
11.11%
69.23%
13.33%
10.39%
1.47%
1.47%
0.00%
2.05%
0.00%
12.50%
0.00%
36.36%
40.00%,
0.00%
0.00%
0.00%
12.50%
0.00%
0.00%
6.25%'
0.00%
18.75%
ODD%
0.00%
6.78%
1.25%
0.00%
0.00%
0.00%
0.00%
8.47%
3.75%
0.00%
0.00%
0.00%
0.00%
0.00%
0.00%
0.00%
o.oo%:
0.00%
0.00%
0.00%
0.00%
0.00%
0.00%
0.00%
0.00%
0.00%
0.00%,
0.00%
0.00%
0.00%
O.DOo/o
4.35%
0.00%
0.00%
2.70%
0.00%
Total
100.00%
100.00%
100.00%
100.00%
100.00%
100.00%
100.00%
100.00%
100.00%
100.00%
100.00%
100.00%
100.00%
100.00%
100.00%
100.00%
100.00%
100.00%
100.00%
100.00%
100.00%
100.00%
100.00%
100.00%
100.00%
100.00%
100.00%
100.00%
100.00%
100.00%
100.00%
100.00%
100.00%
100.00%
100.00%
100.00%
100.00%
100.00%
100.00%
100.00%
100.00%
100.00%
100.00%,
100.00%
100.00%
100.00%
100.00%
100.00%
100.00%
100.00%
100.00%
100.00%
100.00%
100.00%
100.00%
100.00%
100.0%
100.0%
100.0%
100.0%
100.0%
100.0%
100.0%
100.0%
100.0%
100.0%
Federal Register / Vol. 80, No. 152 / Friday, August 7, 2015 / Proposed Rules
19:20 Aug 06, 2015
Wastewater Treatment
Boiler Operators
Decontamination
Other Site Support
Mix/Makeup
Scrap R~ycling
Other Hot Work
Impact Grinding
EP07AU15.006
47670
VerDate Sep<11>2014
Table
Distribution of Beryllium Exposures by Sector and Job Category or Activity
mstockstill on DSK4VPTVN1PROD with PROPOSALS2
VerDate Sep<11>2014
Numbers Exposed to Beryllium
NAICs
Jkt 235001
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E:\FR\FM\07AUP2.SGM
07AUP2
327113
331111
331221
331314
331419
331421
331422
331423
331492
331513
331521
331522
331524
331525
332116
332117
332212
332312
332313
332322
332323
332439
332612
332721
332919
332999
333111
333411
333412
333414
333415
333911
333922
333924
333999
334220
334310
334411
334415
334417
334419
334510
335211
335212
335221
Industry
Porcelain Electrical Supply
Iron and Steel Mills
Rolled Steel Shape Manufacturing
Secondary Smelting and Alloying of
Primary Smelting and Refining of
Copper Rolling, Drawing, and Extruding
Copper Wire (except Mechanical)
Secondary Smelting, Refining, and
Secondary Smelting, Refining, and
Steel Foundries (except Investment)
Aluminum Die-Casting Foundries
Nonferrous (exceptAiuminum) DieAluminum Foundries (except DieCopper Foundries (except Die-Casting)
Metal Stamping
Powder Metallurgy Part Manufacturing
Hand and Edge Tool Manufacturing
Fabricated Structural Metal
Plate Work Manufacturing
Sheet Metal Work Manufacturing
Ornamental and Architectural Metal
Other Metal Container Manufacturing
Spring (Light Gauge) Manufacturing
Precision Turned Product Manufacturing
Other Metal Valve and Pipe Fitting
All Other Miscellaneous Fabricated
Farm Machinery and Equipment
Air Purification Equipment
Industrial and Commercial Fan and
Heating Equipment (except Warm Air
Air-Conditioning, Warm Air Heating, and
Pump and Pumping Equipment
Conveyor and Conveying Equipment
Industrial Truck, Tractor, Trailer, and
All Other Miscellaneous General
Radio and Television Broadcasting and
Audio and Video Equipment
Electron Tube Manufacturing
Electronic Resistor Manufacturing
Electronic Connector Manufacturing
Other Electronic Component
Electromedical and Electrotherapeutic
Electric Housewares and Household Fan
Household Vacuum Cleaner
Household Cooking Applia nee
No. of Establishments
106
587
161
122
161
96
114
24
248
220
254
140
394
208
1,484
133
1,066
3,407
1,288
4,173
2,354
370
323
3,124
265
3,262
1,041
358
151
460
843
571
776
374
1,524
810
464
79
61
231
1,133
629
106
34
96
No. of Employees
4,310
94,089
9,971
4,846
8,943
9,849
9,847
789
9,696
13,874
18,017
6,362
15,178
5,123
48,855
6,707
25,098
89,728
28,400
91,364
30,029
12,553
10,329
78,749
14,688
65,821
53,133
14,521
6,908
16,768
79,651
31,272
26,970
19,974
43,401
79,732
8,858
4,884
3,722
19,538
46,836
66,107
5,980
2,577
9,730
>0
>=0.1 J.Jg/m
3
>=0.2 J.lg/m
3
>=0.5 J.Jg/m
3
>=1.0 J.Jg/m
3
>=2.0 J.lg/m
3
251
27
117
11
80
23
616
1,548
5,096
27
270
250
97
995
25
158
166
35
531
18
90
91
12
190
18
53
28
132
18
73
14
98
534
98
674
496
94
512
94
647
58
72
393
72
507
45
40
219
40
300
21
115
21
177
15
83
15
99
97
37
119
67
12
185
1,122
67
25
81
46
30
11
37
21
74
697
333
211
152
58
34
40
24
18
11
12
224
85
274
155
27
2,071
3,764
11
134
80
379
160
511
893
27
36
17
71
120
60
252
144
310
108
108
80
26
73
10
11
16
11
31
37
19
79
45
36
34
34
21
22
11
46
26
28
20
20
10
18
10
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Table IX-4
3
Numbers of Workers Exposed to Bervllium (by Affected Industry and Exposure level (1JQ/m )
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D. Technological Feasibility Analysis of
the Proposed Permissible Exposure
Limit to Beryllium Exposures
This section summarizes the
technological feasibility analysis
presented in Chapter IV of the PEA
(OSHA, 2014). The technological
feasibility analysis includes information
on current exposures, descriptions of
engineering controls and other measures
to reduce exposures, and a preliminary
assessment of the technological
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feasibility of compliance with the
proposed standard, including a
reduction in OSHA’s permissible
exposure limits (PELs) in nine affected
application groups. The current PELs for
beryllium are 2.0 mg/m3 as an 8-hour
time weighted average (TWA), and 5.0
mg/m3 as an acceptable ceiling
concentration. OSHA is proposing a PEL
of 0.2 mg/m3 as an 8-hour TWA and is
additionally considering alternative
TWA PELs of 0.1 and 0.5 mg/m3. OSHA
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is also proposing a 15-minute short-term
exposure limit (STEL) of 2.0 mg/m3, and
is considering alternative STELs of 0.5,
1.0 and 2.5 mg/m3.
The technological feasibility analysis
includes nine application groups that
correspond to specific industries or
production processes that OSHA has
preliminarily determined fall within the
scope of the proposed standard. Within
each of these application groups,
exposure profiles have been developed
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that characterize the distribution of the
available exposure measurements by job
title or group of jobs. Descriptions of
existing engineering controls for
operations that create sources of
beryllium exposure, and of additional
engineering and work practice controls
that can be used to reduce exposure are
also provided. For each application
group, a preliminary determination is
made regarding the feasibility of
achieving the proposed permissible
exposure limits. For application groups
in which the median exposures for some
jobs exceed the proposed TWA PEL, a
more detailed analysis is presented by
job or group of jobs within the
application group. The analysis is based
on the best information currently
available to the Agency, including a
comprehensive review of the industrial
hygiene literature, National Institute for
Occupational Safety and Health
(NIOSH) Health Hazard Evaluations and
case studies of beryllium exposure, site
visits conducted by an OSHA contractor
(Eastern Research Group (ERG)),
submissions to OSHA’s rulemaking
docket, and inspection data from
OSHA’s Integrated Management
Information System (IMIS). OSHA also
obtained information on production
processes, worker exposures, and the
effectiveness of existing control
measures from the primary beryllium
producer in the United States, Materion
Corporation, and from interviews with
industry experts.
The nine application groups included
in this analysis were identified based on
information obtained during
preliminary rulemaking activities that
included a SBRFA panel, a
comprehensive review of the published
literature, stakeholder input, and an
analysis of IMIS data collected during
OSHA workplace inspections where
detectable airborne beryllium was
found. The nine application groups and
their corresponding section numbers in
Chapter IV of the PEA are:
• Section 3—Beryllium Production,
• Section 4—Beryllium Oxide
Ceramics and Composites,
• Section 5—Nonferrous Foundries,
• Section 6—Secondary Smelting,
Refining, and Alloying,
• Section 7—Precision Turned
Products,
• Section 8—Copper Rolling,
Drawing, and Extruding,
• Section 9—Fabrication of Beryllium
Alloy Products,
• Section 10—Welding, and
• Section 11—Dental Laboratories.
OSHA developed exposure profiles by
job or group of jobs using exposure data
at the application, operation or task
level to the extent that such data were
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available. In those instances where there
were insufficient exposure data to create
a profile, OSHA used analogous
operations to characterize the
operations. The exposure profiles
represent baseline conditions with
existing controls for each operation with
potential exposure. For job groups
where exposures were above the
proposed TWA PEL of 0.2 mg/m3, OSHA
identified additional controls that could
be implemented to reduce employee
exposures to beryllium. These included
engineering controls, such as process
containment, local exhaust ventilation
and wet methods for dust suppression,
and work practices, such as improved
housekeeping and the prohibition of
compressed air for cleaning berylliumcontaminated surfaces.
For the purposes of this technological
feasibility assessment, these nine
application groups can be divided into
three general categories based on
current exposure levels:
(1) application groups in which
current exposures for most jobs are
already below the proposed PEL of 0.2
mg/m3;
(2) application groups in which
exposures for most jobs are below the
current PEL, but exceed the proposed
PEL of 0.2 mg/m3, and therefore
additional controls would be required;
and
(3) application groups in which
exposures in one or more jobs routinely
exceed the current PEL, and therefore
substantial reductions in exposure
would be required to achieve the
proposed PEL.
The majority of exposure
measurements taken in the application
groups in the first category are already
at or below the proposed PEL of 0.2 mg/
m3, and most of the jobs with exposure
to beryllium in these four application
groups have median exposures below
the alternative PEL of 0.1 mg/m3 (See
Table IX–5). These four application
groups include rolling, drawing, and
extruding; fabrication of beryllium alloy
products; welding; and dental
laboratories.
The two application groups in the
second category include: precision
turned products and secondary
smelting. For these two groups, the
median exposures in most jobs are
below the current PEL, but the median
exposure levels for some job groups
currently exceed the proposed PEL.
Additional exposure controls and work
practices could be implemented that the
Agency has preliminarily concluded
would reduce exposures to or below the
proposed PEL for most jobs most of the
time. One exception is furnace
operations in secondary smelting, in
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which the median exposure exceeds the
current PEL. Furnace operations involve
high temperatures that produce
significant amounts of fumes and
particulate that can be difficult to
contain. Therefore, the proposed PEL
may not be feasible for most furnace
operations involved with secondary
smelting, and in some cases, respiratory
protection would be required to
adequately protect furnace workers
when exposures exceed 0.2 mg/m3
despite the implementation of all
feasible controls.
Exposures in the third category of
application groups routinely exceed the
current PEL for several jobs. The three
application groups in this category
include: Beryllium production,
beryllium oxide ceramics production,
and nonferrous foundries. The
individual job groups for which
exposures exceed the current PEL are
discussed in the application group
specific sections later in this summary,
and described in greater detail in the
PEA. For the jobs that routinely exceed
the current PEL, OSHA identified
additional exposure controls and work
practices that the Agency preliminarily
concludes would reduce exposures to or
below the proposed PEL most of the
time, with three exceptions: Furnace
operations in primary beryllium
production and nonferrous foundries,
and shakeout operations at nonferrous
foundries. For these jobs, OSHA
recognizes that even after installation of
feasible controls, respiratory protection
may be needed to adequately protect
workers.
In conclusion, the preliminary
technological feasibility analysis shows
that for the majority of the job groups
evaluated, exposures are either already
at or below the proposed PEL, or can be
adequately controlled with additional
engineering and work practice controls.
Therefore, OSHA preliminarily
concludes that the proposed PEL of 0.2
mg/m3 is feasible for most operations
most of the time. The preliminary
feasibility determination for the
proposed PEL is also supported by
Materion Corporation, the sole primary
beryllium production company in the
U.S., and by the United Steelworkers,
who jointly submitted a draft proposed
standard that specified an exposure
limit of 0.2 mg/m3 to OSHA (Materion
and USW, 2012). The technological
feasibility analysis conducted for each
application group is briefly summarized
below, and a more detailed discussion
is presented in Sections 3 through 11 of
Chapter IV of the PEA (OSHA, 2014).
Based on the currently available
evidence, it is more difficult to
determine whether an alternative PEL of
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0.1 mg/m3 would also be feasible in most
operations. For some application
groups, such as fabrication of beryllium
alloy products, a PEL of 0.1 mg/m3
would almost certainly be feasible. In
other application groups, such as
precision turned products, a PEL of 0.1
mg/m3 appears feasible, except for
establishments working with high
beryllium content alloys. For
application groups with the highest
exposure, the exposure monitoring data
necessary to more fully evaluate the
effectiveness of exposure controls
adopted after 2000 are not currently
available to OSHA, which makes it
difficult to determine the feasibility of
achieving exposure levels at or below
0.1 mg/m3.
OSHA also evaluated the feasibility of
a STEL of 2.0 mg/m3, and alternative
STELs of 0.5 and 1.0 mg/m3. An analysis
of the available short-term exposure
measurements indicates that elevated
exposures can occur during short-term
tasks such as those associated with the
operation and maintenance of furnaces
at primary beryllium production
facilities, at nonferrous foundries, and at
secondary smelting operations. Peak
exposure can also occur during the
transfer and handling of beryllium oxide
powders. OSHA believes that in many
cases, reducing short-term exposures
will be necessary to reduce workers’
TWA exposures to or below the
proposed PEL. The majority of the
available short-term measurements are
below 2.0 mg/m3, therefore OSHA
preliminarily concludes that the
proposed STEL of 2.0 mg/m3 can be
achieved for most operations most of the
time. OSHA recognizes that for a small
number of tasks, short-term exposures
may exceed the proposed STEL, even
after feasible control measures to reduce
TWA exposure to below the proposed
PEL have been implemented, and
therefore assumes that the use of
respiratory protection will continue to
be required for some short-term tasks. It
is more difficult based on the currently
available evidence to determine whether
the alternative STEL of 1.0 mg/m3 would
also be feasible in most operations based
on lack of detail in the activities of the
workers presented in the data. OSHA
expects additional use of respiratory
protection would be required for tasks
in which peak exposures can be reduced
to less than 2.0 mg/m3 but not less than
1.0 mg/m3. Due to limitations in the
available sampling data and the higher
detection limits for short term
measurements, OSHA could not
determine the percentage of the STEL
measurements that are less than or equal
to 0.5 mg/m3. A detailed discussion of
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the STELs being considered by OSHA is
presented in Section 12 of Chapter IV of
the PEA (OSHA, 2014).
OSHA requests available exposure
monitoring data and comments
regarding the effectiveness of currently
implemented control measures and the
feasibility of the PELs under
consideration, particularly the proposed
TWA PEL of 0.2 mg/m3, the alternative
TWA PEL of 0.1 mg/m3, the proposed
STEL of 2.0 mg/m3, and the alternative
STEL of 1.0 mg/m3 to inform the
Agency’s final feasibility
determinations.
Application Group Summaries
This section summarizes the
technological feasibility analysis for
each of the nine application groups
affected by the proposed standard.
Chapter IV of the PEA, Technological
Feasibility Analysis, identifies specific
jobs or job groups with potential
exposure to beryllium, and presents
exposure profiles for each of these job
groups (OSHA, 2014). Control measures
and work practices that OSHA believes
can reduce exposures are described
along with preliminary conclusions
regarding the feasibility of the proposed
PEL. Table IX–5, located at the end of
this summary, presents summary
statistics for the personal breathing zone
samples taken to measure full-shift
exposures to beryllium in each
application group. For the five
application groups in which the median
exposure level for at least one job group
exceeds the proposed PEL, the sampling
results are presented by job group. Table
IX–5 displays the number of
measurements; the range, the mean and
the median of the measurement results;
and the percentage of measurements
less than 0.1 mg/m3, less than or equal
to the proposed PEL of 0.2 mg/m3, and
less than or equal to the current PEL of
2.0 mg/m3. A more detailed discussion
of exposure levels by job or job group
for each application group is provided
in Chapter IV of the PEA, sections 3
through 11, along with a description of
the available exposure measurement
data, existing controls, and additional
controls that would be required to
achieve the proposed PEL.
Beryllium Production
Only one primary beryllium
production facility is currently in
operation in the United States, a plant
owned and operated by Materion
Corporation,15 located in Elmore, Ohio.
15 Materion Corporation was previously named
Brush Wellman. In 2011, subsequent to the
collection of the information presented in this
chapter, the name changed. ‘‘Brush Wellman’’ is
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OSHA identified eight job groups at this
facility in which workers are exposed to
beryllium. These include: Chemical
operations, powdering operations,
production support, cold work, hot
work, site support, furnace operations,
and administrative work.
The Agency developed an exposure
profile for each of these eight job groups
to analyze the distribution of exposure
levels associated with primary
beryllium production. The job exposure
profiles are based primarily on full-shift
personal breathing zone (PBZ) (lapeltype) sample results from air monitoring
conducted by Brush Wellman’s primary
production facility in 1999 (Brush
Wellman, 2004). Starting in 2000, the
company developed the Materion
Worker Protection Program (MWPP), a
multi-faceted beryllium exposure
control program designed to reduce
airborne exposures for the vast majority
of workers to less than an internally
established exposure limit of 0.2 mg/m3.
According to information provided by
Materion, a combination of engineering
controls, work practices, and
housekeeping were used together to
reduce average exposure levels to below
0.2 mg/m3 for the majority of workers
(Materion Information Meeting, 2012).
Also, two operations with historically
high exposures, the wet plant and
pebble plants, were decommissioned in
2000, thereby reducing average
exposure levels. Therefore, the samples
taken prior to 2000 may overestimate
current exposures.
Additional exposure samples were
taken by NIOSH at the Elmore facility
from 2007 through 2008 (NIOSH, 2011).
This dataset, which was made available
to OSHA by Materion, contains fewer
samples than the 1999 survey. OSHA
did not incorporate these samples into
the exposure profile due to the limited
documentation associated with the
sampling data. The lack of detailed
information for individual samples has
made it difficult for OSHA to correlate
job classifications and identify the
working conditions associated with the
samples. Sampling data provided by
Materion for 2007 and 2008 were not
incorporated into the exposure profiles
because the data lacked specific
information on jobs and workplace
conditions. In a meeting in May 2012
held between OSHA and Materion
Corporation at the Elmore facility, the
Agency was able to obtain some general
information on the exposure control
modifications that Materion Corporation
made between 1999 and 2007, but has
been unable to determine what specific
used whenever the data being discussed pre-dated
the name change.
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controls were in place at the time
NIOSH conducted sampling (Materion
Information Meeting, 2012).
In five of the primary production job
groups (i.e., hot work, cold work,
production support, site support, and
administrative work), the baseline
exposure profile indicates that
exposures are already lower than the
proposed PEL of 0.2 mg/m3. Median
exposure values for these job groups
range from nondetectable to 0.08 mg/m3.
For three of the job groups involved
with primary beryllium production,
(i.e., chemical operations, powdering,
and furnace operations), the median
exposure level exceeds the proposed
PEL of 0.2 mg/m3. Median exposure
values for these job groups are 0.47,
0.37, and 0.68 mg/m3 respectively, and
only 17 percent to 29 percent of the
available measurements are less than or
equal to 0.2 mg/m3. Therefore, additional
control measures for these job groups
would be required to achieve
compliance with the proposed PEL.
OSHA has identified several
engineering controls that the Agency
preliminarily concludes can reduce
exposures in chemical processes and
powdering operations to less than or
equal to 0.2 mg/m3. In chemical
processes, these include fail-safe drumhandling systems, full enclosure of
drum-handling systems, ventilated
enclosures around existing drum
positions, automated systems to prevent
drum overflow, and automated systems
for container cleaning and disposal such
as those designed for hazardous
powders in the pharmaceutical
industry. Similar engineering controls
would reduce exposures in powdering
operations. In addition, installing
remote viewing equipment (or other
equally effective engineering controls)
to eliminate the need for workers to
enter the die-loading hood during die
filling will reduce exposures associated
with this powdering task and reduce
powder spills. Based on the availability
of control methods to reduce exposures
for each of the major sources of
exposure in chemical operations, OSHA
preliminarily concludes that exposures
at or below the proposed 0.2 mg/m3 PEL
can be achieved in most chemical and
powdering operations most of the time.
OSHA believes furnace operators’
exposures can be reduced using
appropriate ventilation, including fume
capture hoods, and other controls to
reduce overall beryllium levels in
foundries, but is not certain whether the
exposures of furnace operators can be
reduced to the proposed PEL with
currently available technology. OSHA
requests additional information on
current exposure levels and the
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effectiveness of potential control
measures for primary beryllium
production operations to further refine
this analysis.
Beryllium Oxide Ceramics Production
OSHA identified seven job groups
involved with beryllium oxide ceramics
production. These include: Material
preparation operator, forming operator,
machining operator, kiln operator,
production support, metallization, and
administrative work. Four of these jobs
(material preparation, forming operator,
machining operator and kiln operator)
work directly with beryllium oxides,
and therefore these jobs have a high
potential for exposure. The other three
job groups (production support work,
metallization, and administrative work)
have primarily indirect exposure that
occurs only when workers in these jobs
groups enter production areas and are
exposed to the same sources to which
the material preparation, forming,
machining and kiln operators are
directly exposed. However, some
production support and metallization
activities do require workers to handle
beryllium directly, and workers
performing these tasks may at times be
directly exposed to beryllium.
The Agency developed exposure
profiles for these jobs based on air
sampling data from four sources: (1)
Samples taken between 1994 and 2003
at a large beryllium oxide ceramics
facility, (2) air sampling data obtained
during a site visit to a primary beryllium
oxide ceramics producer, (3) a
published report that provides
information on beryllium oxide
ceramics product manufacturing for a
slightly earlier time period, and (4)
exposure data from OSHA’s Integrated
Management Information System
(OSHA, 2009). The exposure profile
indicates that the three job groups with
mostly indirect exposure (production
support work, metallization, and
administrative work) already achieve
the proposed PEL of 0.2 mg/m3. Median
exposure sample values for these job
groups did not exceed 0.06 mg/m3.
The four job groups with direct
exposure had higher exposures. In
forming operations and machining
operations, the median exposure levels
of 0.18 and 0.15 ug/m3, respectively, are
below the proposed PEL, while the
median exposure levels for material
preparation and kiln operations of 0.41
mg/m3 and 0.25 mg/m3, respectively,
exceed the proposed PEL.
The profile for the directly exposed
jobs may overestimate exposures due to
the preponderance of data from the mid1990s, a time period prior to the
implementation of a variety of exposure
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47675
control measures introduced after 2000.
In forming operations, 44 percent of
sample values in the exposure profile
exceeded 0.2 ug/m3. However, the
median exposure levels for some tasks,
such as small-press and large-press
operation, based on sampling conducted
in 2003 were below 0.1 mg/m3. The
exposure profile for kiln operation was
based on three samples taken from a
single facility in 1995, and are all above
0.2 ug/m3. Since then, exposures at the
facility have declined due to changes in
operations that reduced the amount of
time kiln operators spend in the
immediate vicinity of the kilns, as well
as the discontinuation of a nearby highexposure process. More recent
information communicated to OSHA
suggests that current exposures for kiln
operators at the facility are currently
below 0.1 ug/m3. Exposures in
machining operations, most of which
were already below 0.2 ug/m3 during
the 1990s, may have been further
reduced since then through improved
work practices and exposure controls
(PEA Chapter IV, Section 7). For
forming, kiln, and machining
operations, OSHA preliminarily
concludes that the installation of
additional controls such as machine
interlocks (for forming) and improved
enclosures and ventilation will reduce
exposures to or below the proposed PEL
most of the time. OSHA requests
information on recent exposure levels
and controls in beryllium oxide forming
and kiln operations to help the Agency
evaluate the effectiveness of available
exposure controls for this application
group.
In the exposure profile for material
preparation, 73 percent of sample values
exceeded 0.2 ug/m3. As with other parts
of the exposure profile, exposure values
from the mid-1990s may overestimate
airborne beryllium levels for current
operations. During most material
preparation tasks, such as material
loading, transfer, and spray drying,
OSHA preliminarily concludes that
exposures can be reduced to or below
0.2 mg/m3 with process enclosures,
ventilation hoods, and improved
housekeeping procedures. However,
OSHA acknowledges that peak
exposures from some short-term tasks
such as servicing of the spray chamber
might continue to drive the TWA
exposures above 0.2 mg/m3 on days
when these material preparation tasks
are performed. Respirators may be
needed to protect workers from
exposures above the proposed TWA PEL
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during these tasks.16 OSHA notes that
material preparation for production of
beryllium oxide ceramics currently
takes place at only two facilities in the
United States.
Nonferrous Foundries
OSHA identified eight job groups in
aluminum and copper foundries with
beryllium exposure: Molding, material
handling, furnace operation, pouring,
shakeout operation, abrasive blasting,
grinding/finishing, and maintenance.
The Agency developed exposure
profiles based on an air monitoring
survey conducted by NIOSH in 2007, a
Health Hazard Evaluation (HHE)
conducted by NIOSH in 1975, a site
visit by ERG in 2003, a site visit report
from 1999 by the California Cast Metals
Association (CCMA); and two sets of
data from air monitoring surveys
obtained from Materion in 2004 and
2010.
The exposure profile indicates that in
foundries processing beryllium alloys,
six of the eight job groups have median
exposures that exceed the proposed PEL
of 0.2 mg/m3 with baseline working
conditions. One exception is grinding/
finishing operations, where the median
value is 0.12 mg/m3 and 73 percent of
exposure samples are below 0.2 mg/m3.
The other exception is abrasive blasting.
The samples for abrasive blasting used
in the exposure profile were obtained
during blasting operations using
enclosed cabinets, and all 5 samples
were below 0.2 mg/m3. Exposures for
other job groups ranged from just below
to well above the proposed PEL,
including molder (all samples above 0.2
mg/m3), material handler (1 sample total,
above 0.2 mg/m3), furnace operator (81.8
percent of samples above 0.2 mg/m3),
pouring operator (60 percent of samples
above 0.2 mg/m3), shakeout operator (1
sample total, above 0.2 mg/m3), and
maintenance worker (50 percent of
samples above 0.2 mg/m3).
In some of the foundries at which the
air samples included in the exposure
profile were collected, there are
indications that the ventilation systems
were not properly used or maintained,
and dry sweeping or brushing and the
use of compressed air systems for
cleaning may have contributed to high
dust levels. OSHA believes that
exposures in foundries can be
substantially reduced by improving and
properly using and maintaining the
ventilation systems; switching from dry
brushing, sweeping and compressed air
to wet methods and use of HEPA16 One facility visited by ERG has reportedly
modified this process to reduce worker exposures,
but OSHA has no data to quantify the reduction.
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filtered vacuums for cleaning molds and
work areas; enclosing processes;
automation of high-exposure tasks; and
modification of processes (e.g.,
switching from sand-based to alternative
casting methods). OSHA preliminarily
concludes that these additional
engineering controls and modified work
practices can be implemented to achieve
the proposed PEL most of the time for
molding, material handling,
maintenance, abrasive blasting,
grinding/finishing, and pouring
operations at foundries that produce
aluminum and copper beryllium alloys.
The Agency is less confident that
exposure can be reliably reduced to the
proposed PEL for furnace and shakeout
operators. Beryllium concentrations in
the proximity of the furnaces are
typically higher than in other areas due
to the fumes generated and the difficulty
of controlling emissions during furnace
operations. The exposure profile for
furnace operations shows a median
beryllium exposure level of 1.14 mg/m3.
OSHA believes that furnace operators’
exposures can be reduced using local
exhaust ventilation and other controls to
reduce overall beryllium levels in
foundries, but it is not clear that they
can be reduced to the proposed PEL
with currently available technology. In
foundries that use sand molds, the
shakeout operation typically involves
removing the freshly cast parts from the
sand mold using a vibrating grate that
shakes the sand from castings. The
shakeout equipment generates
substantial amounts of airborne dust
that can be difficult to contain, and
therefore shakeout operators are
typically exposed to high dust levels.
During casting of beryllium alloys, the
dust may contain beryllium and
beryllium oxide residues dislodged from
the casting during the shakeout process.
The exposure profile for the shakeout
operations contains only one result of
1.3 mg/m3. This suggests that a
substantial reduction would be
necessary to achieve compliance with a
proposed PEL of 0.2 mg/m3. OSHA
requests additional information on
recent employee exposure levels and the
effectiveness of dust controls for
shakeout operations for copper and
aluminum alloy foundries.
Secondary Smelting, Refining, and
Alloying
OSHA identified two job groups in
this application group with exposure to
beryllium: Mechanical process operators
and furnace operations workers.
Mechanical operators handle and treat
source material, and furnace operators
run heating processes for refining,
melting, and casting metal alloy. OSHA
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developed exposure profiles for these
jobs based on exposure data from ERG
site visits to a precious/base metals
recovery facility and a facility that melts
and casts beryllium-containing alloys,
both conducted in 2003. The available
exposure data for this application group
are limited, and therefore, the exposure
profile is supplemented in part by
summary data presented in secondary
sources of information on beryllium
exposures in this application group.
The exposure profile for mechanical
processing operators indicates low
exposures (3 samples less than 0.2 mg/
m3), even though these samples were
collected at a facility where the
ventilation system was allowing visible
emissions to escape exhaust hoods.
Summary data from studies and reports
published in 2005–2009 showed that
mechanical processing operator
exposures averaged between 0.01 and
0.04 mg/m3 at facilities where mixed or
electronic waste including beryllium
alloy parts were refined. Based on these
results, OSHA preliminarily concludes
that the proposed PEL is already
achieved for most mechanical
processing operations most of the time,
and exposures could be further reduced
through improved ventilation system
design and other measures, such as
process enclosures.
As with furnace operations examined
in other application groups, the
exposure profile indicates higher worker
exposures for furnace operators in the
secondary smelting, refining, and
alloying application group (six samples
with a median of 2.15 mg/m3, and 83.3
percent above 0.2 mg/m3). The two
lowest samples in this job’s exposure
profile (0.03 and 0.5 mg/m3) were
collected at a facility engaged in
recycling and recovery of precious
metals where work with berylliumcontaining material is incidental. At this
facility, the furnace is enclosed and
fumes are ducted into a filtration
system. The four higher samples,
ranging from 1.92 to 14.08 mg/m3, were
collected at a facility engaged primarily
in beryllium alloying operations, where
beryllium content is significantly higher
than in recycling and precious metal
recovery activities, the furnace is not
enclosed, and workers are positioned
directly in the path of the exhaust
ventilation over the furnace. OSHA
believes these exposures could be
reduced by enclosing the furnace and
repositioning the worker, but is not
certain whether the reduction achieved
would be enough to bring exposures
down to the proposed PEL. Based on the
limited number of samples in the
exposure profile and surrogate data from
furnace operations, the proposed PEL
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may not be feasible for furnace work in
beryllium recovery and alloying, and
respirators may be necessary to protect
employees performing these tasks.
Precision Turned Products
OSHA’s preliminary feasibility
analysis for precision turned products
focuses on machinists who work with
beryllium-containing alloys. The
Agency also examined the available
exposure data for non-machinists and
has preliminarily concluded that, in
most cases, controlling the sources of
exposures for machinists will also
reduce exposures for other job groups
with indirect exposure when working in
the vicinity of machining operations.
OSHA developed exposure profiles
based on exposure data from four
NIOSH surveys conducted between
1976 and 2008; ERG site visits to
precision machining facilities in 2002,
2003, and 2004; case study reports from
six facilities machining copperberyllium alloys; and exposure data
collected between 1987 and 2001 by the
U.S. Navy Environmental Health Center
(NEHC). Analysis of the exposure data
showed a substantial difference between
the median exposure level for workers
machining pure beryllium and/or highberyllium alloys compared to workers
machining low-beryllium alloys. Most
establishments in the precision turned
products application group work only
with low-beryllium alloys, such as
copper-beryllium. A relatively small
number of establishments (estimated at
15) specialize in precision machining of
pure beryllium and/or high-beryllium
alloys.
The exposure profile indicates that
machinists working with low-beryllium
alloys have mostly low exposure to
airborne beryllium. Approximately 85
percent of the 80 exposure results are
less than or equal to 0.2 mg/m3, and 74
percent are less than or equal to 0.1 mg/
m3. Some of the results below 0.1 mg/m3
were collected at a facility where
machining operations were enclosed,
and metal cutting fluids were used to
control the release of airborne
contaminants. Higher results (0.1 mg/
m3–1.07 mg/m3) were found at a facility
where cutting and grinding operations
were conducted in partially enclosed
booths equipped with LEV, but some
LEV was not functioning properly. A
few very high results (0.77 mg/m3–24 mg/
m3) were collected at a facility where
exposure controls were reportedly
inadequate and poor work practices
were observed (e.g., improper use of
downdraft tables, use of compressed air
for cleaning). Based on these results,
OSHA preliminarily concludes that
exposures below 0.2 mg/m3 can be
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achieved most of the time for most
machinists at facilities dealing primarily
with low-beryllium alloys. OSHA
recognizes that higher exposures may
sometimes occur during some tasks
where exposures are difficult to control
with engineering methods, such as
cleaning, and that respiratory protection
may be needed at these times.
Machinists working with highberyllium alloys have higher exposure
than those working with low-beryllium
alloys. This difference is reflected in the
exposure profile for this job, where the
median of exposure is 0.31 mg/m3 and
75 percent of samples exceed the
proposed PEL of 0.2 mg/m3. The
exposure profile was based on two
machining facilities at which LEV was
used and machining operations were
performed under a liquid coolant flood.
Like most facilities where pure
beryllium and high-beryllium alloys are
machined, these facilities also used
some combination of full or partial
enclosures, as well as work practices to
minimize exposure such as prohibiting
the use of compressed air and dry
sweeping and implementing dust
migration control practices to prevent
the spread of beryllium contamination
outside production areas. At one facility
machining high-beryllium alloys, where
all machining operations were fully
enclosed and ventilated, exposures were
mostly below 0.1 mg/m3 (median 0.035
mg/m3, range 0.02–0.11 mg/m3).
Exposures were initially higher at the
second facility, where some machining
operations were not enclosed, existing
LEV system were in need of upgrades,
and some exhaust systems were
improperly positioned. Samples
collected there in 2003 and 2004 were
mostly below the proposed PEL in 2003
(median 0.1 mg/m3) but higher in 2004
(median 0.25 mg/m3), and high exposure
means in both years (1.65 and 0.68 mg/
m3 respectively) show the presence of
high exposure spikes in the facility.
However, the facility reported that
measures to reduce exposure brought
almost all machining exposures below
0.2 mg/m3 in 2006. With the use of fully
enclosed machines and LEV and work
practices that minimize worker
exposures, OSHA preliminarily
concludes that the proposed PEL is
feasible for the vast majority of
machinists working with pure beryllium
and high-beryllium alloys. OSHA
recognizes that higher exposures may
sometimes occur during some tasks
where exposures are difficult to control
with engineering methods, such as
machine cleaning and maintenance, and
that respiratory protection may be
needed at these times.
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47677
Copper Rolling, Drawing, and Extruding
OSHA’s exposure profile for copper
rolling, drawing, and extruding includes
four job groups with beryllium
exposure: strip metal production, rod
and wire production, production
support, and administrative work.
Exposure profiles for these jobs are
based on personal breathing zone lapel
sampling conducted at the Brush
Wellman Reading, Pennsylvania, rolling
and drawing facility from 1977 to 2000.
Prior to 2000, the Reading facility had
limited engineering controls in place.
Equipment in use included LEV in some
operations, HEPA vacuums for general
housekeeping, and wet methods to
control loose dust in some rod and wire
production operations. The exposure
profile shows very low exposures for all
four job groups. All had median
exposure values below 0.1 mg/m3, and in
strip metal production, production
support, and administrative work, over
90 percent of samples were below 0.1
mg/m3. In rod and wire production, 70
percent of samples were below 0.1 mg/
m3.
To characterize exposures in
extrusion, OSHA examined the results
of an industrial hygiene survey of a
copper-beryllium extruding process
conducted in 2000 at another facility.
The survey reported eight PBZ samples,
which were not included in the
exposure profile because of their short
duration (2 hours). Samples for three of
the four jobs involved with the
extrusion process (press operator,
material handler, and billet assembler)
were below the limit of detection (LOD)
(level not reported). The two samples
for the press operator assistant, taken
when the assistant was buffing, sanding,
and cleaning extrusion tools, were very
high (1.6 and 1.9 mg/m3). Investigators
recommended a ventilated workstation
to reduce exposure during these
activities.
In summary, exposures at or below
0.2 mg/m3 have already been achieved
for most jobs in rolling, drawing, and
extruding operations, and OSHA
preliminarily concludes that the
proposed PEL of 0.2 mg/m3 is feasible for
this application group. For jobs or tasks
with higher exposures, such as tool
refinishing, use of exposure controls
such as local exhaust ventilation can
help reduce workers’ exposures. The
Agency recognizes the limitations of the
available data, which were drawn from
two facilities and did not include fullshift PBZ samples for extrusion. OSHA
requests additional exposure data from
other facilities in this application group,
especially data from facilities where
extrusion is performed.
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Fabrication of Beryllium Alloy Products
This application group includes the
fabrication of beryllium alloy springs,
stampings, and connectors for use in
electronics. The exposure profile is
based on a study conducted at four
precision stamping companies; a NIOSH
report on a spring and stamping
company; an ERG site visit to a
precision stamping, forming, and
plating establishment; and exposure
monitoring results from a stamping
facility presented at the American
Industrial Hygiene Conference and
Exposition in 2007. The exposure
profiles for this application group
include three jobs: chemical processing
operators, deburring operators, and
assembly operators. Other jobs for
which all samples results were below
0.1 mg/m3 are not shown in the profile.
For the three jobs in the profile, the
majority of exposure samples were
below 0.1 mg/m3 (deburring operators,
79 percent; chemical processing
operators, 81 percent; assembly
operators, 93 percent). Based on these
results, OSHA preliminarily concludes
that the proposed PEL is feasible for this
application group. The Agency notes
that a few exposures above the proposed
PEL were recorded for the chemical
processing operator (in plating and
bright cleaning) and for deburring
(during corn cob deburring in an open
tumbling mill). OSHA believes the use
of LEV, improved housekeeping, and
work practice modifications would
reduce the frequency of excursions
above the proposed PEL.
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Welding
Most of the samples in OSHA’s
exposure profile for welders in general
industry were collected between 1994
and 2001 at two of Brush Wellman’s
alloy strip distribution centers, and in
1999 at Brush Wellman’s Elmore
facility. At these facilities, tungsten
inert gas (TIG) welding was conducted
on beryllium alloy strip. Seven samples
in the exposure profile came from a case
study conducted at a precision stamping
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facility, where airborne beryllium levels
were very low (see previous summary,
Fabrication of Beryllium Alloy
Products). At this facility, resistance
welding was performed on copperberyllium parts, and welding processes
were automated and enclosed.
Most of the sample results in the
welding exposure profile were below
0.2 mg/m3. Of the 44 welding samples in
the profile, 75 percent were below 0.2
mg/m3 and 64 percent were below 0.1
mg/m3, with most values between 0.01
and 0.05 mg/m3. All but one of the 16
exposure samples above 0.1 mg/m3 were
collected in Brush Wellman’s Elmore
facility in 1999. According to company
representatives, these higher exposure
levels may have been due to beryllium
oxide that can form on the surface of the
material as a result of hot rolling. All
seven samples from the precision
stamping facility were below the limit of
detection. Based on these results, OSHA
preliminarily concludes that the
proposed PEL of 0.2 mg/m3 is feasible for
most welding operations in general
industry.
Dental Laboratories
OSHA’s exposure profile for dental
technicians includes sampling results
from a site visit conducted by ERG in
2003; a study of six dental laboratories
published by Rom et al. in 1984; a data
set of exposure samples collected
between 1987 and 2001, on dental
technicians working for the U.S. Navy;
and a docket submission from CMP
Industries including two samples from a
large commercial dental laboratory
using nickel-beryllium alloy.
Information on exposure controls in
these facilities suggests that controls in
some cases may have been absent or
improperly used.
The exposure profile indicates that 52
percent of samples are less than or equal
to 0.2 mg/m3. However, the treatment of
nondetectable samples in the feasibility
analysis may overestimate many of the
sample values in the exposure profile.
Twelve of the samples in the profile are
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nondetectable for beryllium. In the
exposure profile, these were assigned
the highest possible value, the limit of
detection (LOD). For eight of the
nondetectable samples, the LOD was
reported as 0.2 mg/m3. For the other four
nondetectable samples, the LOD was
between 0.23 and 0.71 mg/m3. If the true
values for these four nondetectable
samples are actually less than or equal
to the assigned value of 0.2 mg/m3, then
the true percentage of profile sample
values less than or equal to 0.2 mg/m3
is between 52 and 70 percent. Of the
sample results with detectable
beryllium above 0.2 mg/m3, some were
collected in 1984 at facilities studied by
Rom et al., who reported that they
occurred during grinding with LEV that
was improperly used or, in one case, not
used at all. Others were collected at
facilities where little contextual
information was available to determine
what control equipment or work
practices might have reduced exposures.
Based on this information, OSHA
preliminarily concludes that beryllium
exposures for most dental technicians
are already below 0.2 mg/m3 most of the
time. OSHA furthermore believes that
exposure levels can be reduced to or
below 0.1 mg/m3 most of the time via
material substitution, engineering
controls, and work practices. Berylliumfree alternatives for casting dental
appliances are readily available from
commercial sources, and some alloy
suppliers have stopped carrying alloys
that contain beryllium. For those dental
laboratories that continue to use
beryllium alloys, exposure control
options include properly designed,
installed, and maintained LEV systems
(equipped with HEPA filters) and
enclosures; work practices that optimize
LEV system effectiveness; and
housekeeping methods that minimize
beryllium contamination in the
workplace. In summary, OSHA
preliminarily concludes that the
proposed PEL is feasible for dental
laboratories.
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E:\FR\FM\07AUP2.SGM
0.2 to 19.76
0.2 to 2.2
1.3
0.93
0.24 to 2.29
0.05 to 22.71
0.05 to 0.15
0.01 to 4.79
0.03 to 14.1
0.03 to 0.2
0.02 to 7.2
0.005 to 24
0.006 to 7.8
0.004 to 0.42
0.005 to 2.21
0.02 to 4.4
6
3
10.6
53.2
5.0
0.36
7.7
0.62
1.2
11
5
1
1
8
78
5
56
to
to
to
to
to
to
to
0.02
0.02
0.01
0.22
0.02
0.02
0.02
254
9.6
11.5
22.7
24.9
2.21
4.22
4.54
77
408
355
3
119
36
185
to
to
to
to
to
to
to
to
0.05
0.05
0.06
0.02
0.04
0.01
0.05
0.05
Range
172
20
72
861
555
297
879
981
80
59
650
71
44
23
Source: OSHA, Directorate of Standards and Guidance, Office of Regulatory Analysis.
Be Production Operations (Section 3)
Furnace Operations ........................................................................
Chemical Operations ......................................................................
Powdering Operations ....................................................................
Production Support .........................................................................
Cold Work .......................................................................................
Hot Work .........................................................................................
Site Support ....................................................................................
Administrative .................................................................................
Be Oxide Ceramics (Section 4)
Material Preparation Operator ........................................................
Forming Operator ...........................................................................
Machining Operator ........................................................................
Kiln Operator ...................................................................................
Production Support Worker ............................................................
Metallization Worker .......................................................................
Administrative .................................................................................
Aluminum and Copper Foundries (Section 5)
Furnace Operator ...........................................................................
Pouring Operator ............................................................................
Shakeout Operator .........................................................................
Material Handler .............................................................................
Molder .............................................................................................
Maintenance ...................................................................................
Abrasive Blasting Operator .............................................................
Grinding/finishing Operator .............................................................
Secondary Smelting (Section 6)
Furnace operations worker .............................................................
Mechanical processing operator .....................................................
Precision Turned Products (Section 7)
High Be Content Alloys ..................................................................
Low Be Content Alloys ...................................................................
Rolling, Drawing, and Extruding (Section 8)
Alloy Fabrication (Section 9)
Welding: Beryllium Alloy (Section 10)
Dental Laboratories (Section 11)
N
3.85
0.14
4.41
1.21
1.30
0.93
0.67
0.87
0.11
0.31
1.01
0.48
0.32
0.28
0.21
0.15
0.06
3.80
1.02
0.82
0.51
0.31
0.12
0.11
0.10
0.72
0.45
0.11
0.056
0.19
0.74
Mean
0.31
0.01
0.024
0.025
0.02
0.2
2.15
0.20
1.14
1.40
1.30
0.93
0.45
0.21
0.12
0.05
0.41
0.18
0.15
0.25
0.05
0.06
0.05
0.68
0.47
0.37
0.08
0.08
0.06
0.05
0.05
Median
%<0.1
TABLE IX–5—BERYLLIUM FULL-SHIFT PBZ SAMPLES BY APPLICATION/JOB GROUP (μg/m3)
Application/Job group
mstockstill on DSK4VPTVN1PROD with PROPOSALS2
14
74
86
83
64
13
17
33
0
0
0
0
0
15
40
59
13
27
37
0
68
55
93
5
5
11
56
61
69
81
85
%≤0.2
25
85
93
94
75
52
17
100
18
40
0
0
0
50
100
73
27
56
63
0
88
69
98
17
15
29
71
80
88
92
94
%≤2.0
92
96
99
100
98
87
50
100
64
60
100
100
88
96
100
95
90
99
98
100
98
100
100
82
95
94
94
98
99
99
99
Federal Register / Vol. 80, No. 152 / Friday, August 7, 2015 / Proposed Rules
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E. Costs of Compliance
Chapter V of the PEA in support of
the proposed beryllium rule provides a
detailed assessment of the costs to
establishments in all affected
application groups of reducing worker
exposures to beryllium to an eight-hour
time-weighted average (TWA)
permissible exposure limit (PEL) of 0.2
mg/m3 and to the proposed short-term
exposure limit (STEL) of 2.0 mg/m3, as
well as of complying with the proposed
standard’s ancillary provisions. OSHA
describes its methodology and sources
in more detail in Chapter V. OSHA’s
preliminary cost assessment is based on
the Agency’s technological feasibility
analysis presented in Chapter IV of the
PEA; analyses of the costs of the
proposed standard conducted by
OSHA’s contractor, Eastern Research
Group (ERG); and the comments
submitted to the docket in response to
the request for information (RFI) and as
part of the SBREFA process.
As shown in Table IX–7 at the end of
this section, OSHA estimates that the
proposed standard would have an
annualized cost of $37.6 million. All
cost estimates are expressed in 2010
dollars and were annualized using a
discount rate of 3 percent, which—along
with 7 percent—is one of the discount
rates recommended by OMB.17
Annualization periods for expenditures
on equipment are based on equipment
life, and one-time costs are annualized
over a 10-year period.
The estimated costs for the proposed
beryllium rule represent the additional
costs necessary for employers to achieve
full compliance. They do not include
costs associated with current
compliance that may already have been
achieved with regard to existing
beryllium requirements or costs
necessary to achieve compliance with
existing beryllium requirements, to the
extent that some employers may
currently not be fully complying with
applicable regulatory requirements.
Throughout this section and in the
PEA, OSHA presents cost formulas in
the text, usually in parentheses, to help
explain the derivation of cost estimates
for individual provisions. Because the
values used in the formulas shown in
the text are shown only to the second
decimal place, while the actual
spreadsheet formulas used to create
final costs are not limited to two
decimal places, the calculation using
the presented formula will sometimes
17 Appendix V–A of the PEA presents costs by
NAICS industry and establishment size categories
using, as alternatives, a 7 percent discount rate—
shown in Table V–A–1—and a 0 percent discount
rate—shown in Table V–A–2.
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differ slightly from the presented total
in the text, which is the actual and
mathematically correct total as shown in
the tables.
1. Compliance With the Proposed PEL/
STEL
OSHA’s estimate of the costs for
affected employers to comply with the
proposed PEL of 0.2 mg/m3 and the
proposed STEL of 2.0 mg/m3 consists of
two parts. First, costs are estimated for
the engineering controls, additional
studies and custom design requirements
to implement those controls, work
practices, and specific training required
for those work practices (as opposed to
general training in compliance with the
rule) needed for affected employers to
meet the proposed PEL and STEL, as
well as opportunity costs (lost
productivity) that may result from
working with some of the new controls.
In most cases, the PEA breaks out these
costs, but in other instances some or all
of the costs are shortened simply to
‘‘engineering controls’’ in the text, for
convenience. Second, for employers
unable to meet the proposed PEL and
STEL using engineering controls and
work practices alone, costs are
estimated for respiratory protection
sufficient to reduce worker exposure to
the proposed PEL and STEL or below.
In the technological feasibility
analysis presented in Chapter IV of the
PEA, OSHA concluded that
implementing all engineering controls
and work practices necessary to reach
the proposed PEL will, except for a
small residual group (accounting for
about 6 percent of all exposures above
the STEL), also reduce exposures below
the STEL. However, based on the nature
of the processes this residual group is
likely to be engaged in, the Agency
expects that employees would already
be using respirators to comply with the
PEL under the proposed standard.
Therefore, with the proposed STEL set
at ten times the proposed PEL, the
Agency has preliminarily determined
that engineering controls, work
practices, and (when needed)
respiratory protection sufficient to meet
the proposed PEL are also sufficient to
meet the proposed STEL. For that
reason, OSHA has taken no additional
costs for affected employers to meet the
proposed STEL. The Agency invites
comment and requests that the public
provide data on this issue.
a. Engineering Controls
For this preliminary cost analysis,
OSHA estimated the necessary
engineering controls and work practices
for each affected application group
according to the exposure profile of
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current exposures by occupation
presented in Chapter III of the PEA.
Under the requirements of the proposed
standard, employers would be required
to implement engineering or work
practice controls whenever beryllium
exposures exceed the proposed PEL of
0.2 mg/m3 or the proposed STEL of 2.0
mg/m3.
In addition, even if employers are not
exposed above the proposed PEL or
proposed STEL, paragraph (f)(2) of the
proposed standard would require
employers at or above the action level
to use at least one engineering or work
practice control to minimize worker
exposure. Based on the technological
feasibility analysis presented in Chapter
IV of the PEA, OSHA has determined
that, for only two job categories in two
application groups—chemical process
operators in the Stamping, Spring and
Connection Manufacture application
group and machinists in the Machining
application group—do the majority of
facilities at or above the proposed action
level, but below the proposed PEL, lack
the baseline engineering or work
controls required by paragraph (f)(2).
Therefore, OSHA has estimated costs,
where appropriate, for employers in
these two application groups to comply
with paragraph (f)(2).
By assigning controls based on
application group, the Agency is best
able to identify those workers with
exposures above the proposed PEL and
to design a control strategy for, and
attribute costs specifically to, these
groups of workers. By using this
approach, controls are targeting those
specific processes, emission points, or
procedures that create beryllium
exposures. Moreover, this approach
allows OSHA to assign costs for
technologies that are demonstrated to be
the most effective in reducing exposures
resulting from a particular process.
In developing cost estimates, OSHA
took into account the wide variation in
the size or scope of the engineering or
work practice changes necessary to
minimize beryllium exposures based on
technical literature, judgments of
knowledgeable consultants, industry
observers, and other sources. The
resulting cost estimates reflect the
representative conditions for the
affected workers in each application
group and across all work settings. In all
but a handful of cases (with the
exceptions noted in the PEA), all wage
costs come from the 2010 Occupational
Employment Statistics (OES) of the
Bureau of Labor Statistics (BLS, 2010a)
and utilize the median wage for the
appropriate occupation. The wages used
include a 30.35 percent markup for
fringe benefits as a percentage of total
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compensation, which is the average
percentage markup for fringe benefits
for all civilian workers from the 2010
Employer Costs for Employee
Compensation of the BLS (BLS, 2010b).
All descriptions of production processes
are drawn from the relevant sections of
Chapter IV of the PEA.
The specific engineering costs for
each of the applications groups, and the
NAICS industries that contain those
application groups, are discussed in
Chapter V of the PEA. Like the industry
profile and technological feasibility
analysis presented in other PEA
chapters, Chapter V of the PEA presents
engineering control costs for the
following application groups:
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Beryllium Production
Beryllium Oxide, Ceramics & Composites
Production
Nonferrous Foundries
Stamping, Spring and Connection
Manufacture
Secondary Smelting, Refining, and Alloying
Copper Rolling, Drawing, and Extruding
Secondary Smelting, Refining, and Alloying
Precision Machining
Welding
Dental Laboratories
The costs within these application
groups are estimated by occupation and/
or operation. One application group
could have multiple occupations,
operations, or activities where workers
are exposed to levels of beryllium above
the proposed PEL, and each will need
its own set of controls. The major types
of engineering controls needed to
achieve compliance with the proposed
PEL include ventilation equipment,
pharmaceutical-quality highcontainment isolators, decontainment
chambers, equipment with controlled
water sprays, closed-circuit remote
televisions, enclosed cabs, conveyor
enclosures, exhaust hoods, and portable
local-exhaust-ventilation (LEV) systems.
Capital costs and annual operation and
maintenance (O&M) costs, as well as
any other annual costs, are estimated for
the set of engineering controls estimated
to be necessary for limiting beryllium
exposures for each occupation or
operation within each application
group.
Tables V–2 through V–10 in Chapter
V of the PEA summarize capital,
maintenance, and operating costs for
each application group disaggregated by
NAICS code. Table IX–7 at the end of
this section breaks out the costs of
engineering controls/work practices by
application group and NAICS code.
Some engineering control costs are
estimated on a per-worker basis and
then multiplied by the estimated
number of affected workers—as
identified in Chapter III: Profile of
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Affected Industries in the PEA—to
arrive at a total cost for a particular
control within a particular application
group. This worker-based method is
necessary because—even though OSHA
has data on the number of firms in each
affected industry, the occupations and
industrial activities that result in worker
exposure to beryllium, and the exposure
profile of at-risk occupations—the
Agency does not have a way to match
up these data at the firm level. Nor does
the Agency have establishment-specific
data on worker exposure to beryllium
for all establishments, or even
establishment-specific data on the level
of activity involving worker exposure to
beryllium. Thus, OSHA could not
always directly estimate per-affectedestablishment costs, but instead first
had to estimate aggregate compliance
costs (using an estimated per-worker
cost multiplied by the number of
affected workers) and then calculate the
average per-affected-establishment costs
by dividing those aggregate costs by the
number of affected establishments. This
method, while correct on average, may
under- or over-state costs for certain
firms. For other controls that are
implemented on a fixed-cost basis per
establishment (e.g., creating a training
program, writing a control program), the
costs are estimated on an establishment
basis, and these costs were multiplied
by the number of affected
establishments in the given application
group to obtain total control costs.
In developing cost estimates, the
Agency sometimes had to make casespecific judgments about the number of
workers affected by each engineering
control. Because work environments
vary within occupations and across
establishments, there are no definitive
data on how many workers are likely to
have their exposures reduced by a given
set of controls. In the smallest
establishments, especially those that
might operate only one shift per day,
some controls would limit exposures for
only a single worker in one specific
affected occupation. More commonly,
however, several workers are likely to
benefit from each enhanced engineering
control. Many controls were judged to
reduce exposure for employees in multishift work or where workstations are
used by more than one worker per shift.
In general, improving work practices
involves operator training, actual work
practice modifications, and better
enforcement or supervision to minimize
potential exposures. The costs of these
process improvements consist of the
supervisor and worker time involved
and would include the time spent by
supervisors to develop a training
program.
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Unless otherwise specified, OSHA
viewed the extent to which exposure
controls are already in place to be
reflected in the distribution of
exposures at levels above the proposed
PEL among affected workers. Thus, for
example, if 50 percent of workers in a
given occupation are found to be
exposed to beryllium at levels above the
proposed PEL, OSHA judged this
equivalent to 50 percent of facilities
lacking adequate exposure controls. The
facilities may have, for example, the
correct equipment installed but without
adequate ventilation to provide
protection to workers exposed to
beryllium. In this example, the Agency
would expect that the remaining 50
percent of facilities to either have
installed the relevant controls to reduce
beryllium exposures below the PEL or
that they engage in activities that do not
require that the exposure controls be in
place (for example, they do not perform
any work with beryllium-containing
materials). To estimate the need for
incremental controls on a per-worker
basis, OSHA used the exposure profile
information as the best available data.
OSHA recognizes that a very small
percentage of facilities might have all
the relevant controls in place but are
still unable, for whatever reason, to
achieve the proposed PEL through
controls alone. ERG’s review of the
industrial hygiene literature and other
source materials (ERG, 2007b), however,
suggest that the large majority of
workplaces where workers are exposed
to high levels of beryllium lack at least
some of the relevant controls. Thus, in
estimating the costs associated with the
proposed standard, OSHA has generally
assumed that high levels of exposure to
beryllium occur due to the absence of
suitable controls. This assumption
likely results in an overestimate of costs
since, in some cases, employers may not
need to install and maintain new
controls in order to meet the proposed
PEL but merely need to upgrade or
better maintain existing controls, or to
improve work practices.
b. Respiratory Protection Costs
Based on the findings of the
technological feasibility analysis, a
small subset of employees working with
a few processes in a handful of
application groups will need to use
respirators, in addition to required
engineering controls and improved
work practices, to reduce employee
exposures to meet the proposed PEL.
Specifically, furnace operators—both in
non-ferrous foundries (both sand and
non-sand) and in secondary smelting,
refining, and alloying—as well as
welders in a few other processes, will
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need to wear half-mask respirators. In
beryllium production, workers who
rebuild or otherwise maintain furnaces
and furnace tools will need to wear fullface powered air-purifying respirators.
Finally, the Agency recognizes the
possibility that, after all feasible
engineering and other controls are in
place, there may still be a residual group
with potential exposure above the
proposed PEL and/or STEL. To account
for these residual cases, OSHA estimates
that 10 percent of the workers, across all
application groups and job categories,
who are above the proposed PEL before
the beryllium proposed standard is in
place (according to the baseline
exposure profile presented in Chapter III
of the PEA), would still be above the
PEL after all feasible controls are
implemented and, hence, would need to
use half-mask respirators to achieve
compliance with the proposed PEL.
There are five primary costs for
respiratory protection. First, there is a
cost per establishment to set up a
written respirator program in
accordance with the respiratory
protection standard (29 CFR 1910.134).
The respiratory protection standard
requires written procedures for the
proper selection, use, cleaning, storage,
and maintenance of respirators. As
derived in the PEA, OSHA estimates
that, when annualized over 10 years, the
annualized per-establishment cost for a
written respirator program is $207.
For reasons unrelated to the proposed
standard, certain establishments will
already have a respirator program in
place. Table V–11 in Chapter V of the
PEA presents OSHA’s estimates, by
application group, of current levels of
compliance with the respirator program
provision of the proposed rule.
The four other major costs of
respiratory protection are the peremployee costs for all aspects of
respirator use: equipment, training, fittesting, and cleaning. Table V–12 of
Chapter V in the PEA breaks out
OSHA’s estimate of the unit costs for the
two types of respirators needed: A halfmask respirator and a full-face powered
air-purifying respirator. As derived in
the PEA, the annualized per-employee
cost for a half-mask respirator would be
$524 and the annualized per-employee
cost for a full-face powered air-purifying
respirator would be $1,017.
Table V–13 in Chapter V of the PEA
presents the number of additional
employees, by application group and
NAICS code, that would need to wear
respirators to comply with the proposed
standard and the cost to industry to
comply with the respirator protection
provisions in the proposed rule. OSHA
judges that only workers in Beryllium
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Production work with processes that
would require a full-face respirator and
estimates that there are 23 of those
workers. Three hundred and eighteen
workers in other assorted application
groups are estimated to need half-mask
respirators. A total of 341 employees
would need to wear some type of
respirator, resulting in a total
annualized cost of $249,684 for affected
industries to comply with the
respiratory protection requirements of
the proposed standard. Table IX–7 at the
end of this section breaks out the costs
of respiratory protection by application
group and NAICS code.
2. Ancillary Provisions
This section presents OSHA’s
estimated costs for ancillary beryllium
control programs required under the
proposed rule. Based on the program
requirements contained in the proposed
standard, OSHA considered the
following cost elements in the following
employer duties: (a) Assess employees’
exposure to airborne beryllium, (b)
establish regulated areas, (c) develop a
written exposure control plan, (d)
provide protective work clothing, (e)
establish hygiene areas and practices, (f)
implement housekeeping measures, (g)
provide medical surveillance, (h)
provide medical removal for employees
who have developed CBD or been
confirmed positive for beryllium
sensitization, and (i) provide
appropriate training.
The worker population affected by
each program element varies by several
criteria discussed in detail in each
subsection below. In general, some
elements would apply to all workers
exposed to beryllium at or above the
action level. Other elements would
apply to a smaller set of workers who
are exposed above the PEL. The training
requirements would apply to all
employees who work in a beryllium
work area (e.g., an area with any level
of exposure to airborne beryllium). The
regulated area program elements
triggered by exposures exceeding the
proposed PEL of 0.2 mg/m3 would apply
to those workers for whom feasible
controls are not adequate. In the earlier
discussion of respiratory protection,
OSHA estimated that 10 percent of all
affected workers with current exposures
above the proposed PEL would fall in
this category.
Costs for each program requirement
are aggregated by employment and by
industry. For the most part, unit costs
do not vary by industry, and any
variations are specifically noted. The
estimated compliance rate for each
provision of the proposed standard by
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application group is presented in Table
V–15 of the PEA.
a. Exposure Assessment
Most establishments wishing to
perform exposure monitoring would
require the assistance of an outside
consulting industrial hygienist (IH) to
obtain accurate results. While some
firms might already employ or train
qualified staff, OSHA judged that the
testing protocols are fairly challenging
and that few firms have sufficiently
skilled staff to eliminate the need for
outside consultants.
The proposed standard requires that,
after receiving the results of any
exposure monitoring where exposures
exceed the TWA PEL or STEL, the
employer notify each such affected
employee in writing of suspected or
known sources of exposure, and the
corrective action(s) being taken to
reduce exposure to or below the PEL.
Those workers exposed at or above the
action level and at or below the PEL
must have their exposure levels
monitored annually.
For costing purposes, OSHA estimates
that, on average, there are four workers
per work area. OSHA interpreted the
initial exposure assessment as requiring
first-year testing of at least one worker
in each distinct job classification and
work area who is, or may reasonably be
expected to be, exposed to airborne
concentrations of beryllium at or above
the action level.
The proposed standard requires that
whenever there is a change in the
production, process, control equipment,
personnel, or work practices that may
result in new or additional exposures, or
when the employer has any reason to
suspect that a change may result in new
or additional exposures, the employer
must conduct additional monitoring.
The Agency has estimated that this
provision would require an annual
sampling of 10 percent of the affected
workers.
OSHA estimates that an industrial
hygienist (IH) would spend 1 day each
year to sample 2 workers, for a per
worker IH fee of $257. This exposure
monitoring requires that three samples
be taken per worker: One TWA and two
STEL for an annual IH fee per sample
of $86. Based on the 2000 EMSL
Laboratory Testing Catalog (ERG,
2007b), OSHA estimated that analysis of
each sample would cost $137 in lab
fees. When combined with the IH fee,
OSHA estimated the annual cost to
obtain a TWA sample to be $223 per
sampled worker and the annual cost to
obtain the two STEL samples to be $445
per sampled worker. The direct
exposure monitoring unit costs are
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summarized in Table V–16 in Chapter V
of the PEA.
The cost of the sample also
incorporates a productivity loss due to
the additional time for the worker to
participate in the sampling (30 minutes
per worker sampled) as well as for the
associated recordkeeping time incurred
by a manager (15 minutes per worker
sampled). The STEL samples are
assumed to be taken along with the
TWA sample and, thus, labor costs were
not added to both unit costs. Including
the costs related to lost productivity,
OSHA estimates the total annual cost of
a TWA sample to be $251, and 2 STEL
samples, $445. The total annual cost per
worker for all sampling taken is then
$696. OSHA estimates the total
annualized cost of this provision to be
$2,208,950 for all affected industries.
The annualized cost of this provision for
each affected NAICS industry is shown
in Table IX–6.
b. Beryllium Work Areas and Regulated
Areas
The proposed beryllium standard
requires the employer to establish and
maintain a regulated area wherever
employees are, or can reasonably
expected to be, exposed to airborne
beryllium at levels above the TWA PEL
or STEL. Regulated areas require
specific provisions that both limit
employee exposure within its
boundaries and curb the migration of
beryllium outside the area. The Agency
judged, based on the preliminary
findings of the technological feasibility
analysis, that companies can reduce
establishment-wide exposure by
ensuring that only authorized
employees wearing proper protective
equipment have access to areas of the
establishment where such higher
concentrations of beryllium exist, or can
be reasonably expected to exist. Workers
in other parts of the establishment are
also likely to see a reduction in
beryllium exposures due to these
measures since fewer employees would
be traveling through regulated areas and
subsequently carrying beryllium residue
to other work areas on their clothes and
shoes.
Requirements in the proposed rule for
a regulated area include: Demarcating
the boundaries of the regulated area as
separate from the rest of the workplace,
limiting access to the regulated area,
providing an appropriate respirator to
each person entering the regulated area
and other protective clothing and
equipment as required by paragraph (g)
and paragraph (h), respectively.
OSHA estimated that the total
annualized cost per regulated area,
including set-up costs ($76), respirators
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($1,768) and protective clothing
($4,500), is $6,344.
When establishments are in full
compliance with the standard, regulated
areas would be required only for those
workers for whom controls could not
feasibly reduce their exposures to or
below the 0.2 mg/m3 TWA PEL and the
2 mg/m3 STEL. Based on the findings of
the technological feasibility analysis,
OSHA estimated that 10 percent of the
affected workers would be exposed
above the TWA PEL or STEL after
implementation of engineering controls
and thus would require regulated areas
(with one regulated area, on average, for
every four workers exposed above the
proposed TWA PEL or STEL).
The proposed standard requires that
all beryllium work areas are adequately
established and demarcated. ERG
estimated that one work area would
need to be established for every 12 atrisk workers. OSHA estimates that the
annualized cost would be $33 per work
area.
OSHA estimates the total annualized
cost of the regulated areas and work
areas is $629,031 for all affected
industries. The cost for each affected
application group and NAICS code is
shown in Table IX–6.
c. Written Exposure Control Plan
The proposed standard requires that
employers must establish and maintain
a written exposure control plan for
beryllium work areas. The written
program must contain:
1. An inventory of operations and job
titles reasonably expected to have
exposure.
2. An inventory of operations and job
titles reasonably expected to have
exposure at or above the action level.
3. An inventory of operations and job
titles reasonably expected to have
exposure above the TWA PEL or STEL.
4. Procedures for minimizing crosscontamination, including but not
limited to preventing the transfer of
beryllium between surfaces, equipment,
clothing, materials and articles within
beryllium work areas.
5. Procedures for keeping surfaces in
the beryllium work area free as
practicable of beryllium.
6. Procedures for minimizing the
migration of beryllium from beryllium
work areas to other locations within or
outside the workplace.
7. An inventory of engineering and
work practice controls required by
paragraph (f)(2) of this standard.
8. Procedures for removal, laundering,
storage, cleaning, repairing, and
disposal of beryllium-contaminated
personal protective clothing and
equipment, including respirators.
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The unit cost estimates take into
account the judgment that (1) most
establishments have an awareness of
beryllium risks and, thus, should be
able to develop or modify existing
safeguards in an expeditious fashion,
and (2) many operations have limited
beryllium activities and these
establishments need to make only
modest changes in procedures to create
the necessary exposure control plan.
ERG’s experts estimated that managers
would spend eight hours per
establishment to develop and
implement such a written exposure
control plan, yielding a total cost per
establishment to develop and
implement the written control plan of
$563.53 and an annualized cost of $66.
In addition, because larger firms with
more affected workers will need to
develop more complicated written
control plans, the development of a plan
would require an extra thirty minutes of
a manager’s time per affected employee,
for a cost of $35 per affected employee
and an annualized cost of $4 per
employee. Managers would also need 12
minutes (0.2 hours) per affected
employee per quarter, or 48 minutes per
affected employee per year to review
and update the plan, for a recurring cost
of $56 per affected employee per year to
maintain and update the plan. Five
minutes of clerical time would also be
needed per employee for providing each
employee with a copy of the written
exposure control plan—yielding an
annualized cost of $2 per employee. The
total annual per-employee cost for
development, implementation, review,
and update of a written exposure
control plan is then $62. The Agency
estimates the total annualized cost of
this provision to be $1,769,506 for all
affected establishments. The breakdown
of these costs by application group and
NAICS code is presented in Table
IX–6.
d. Personal Protective Clothing and
Equipment
The proposed standard requires
personal protective clothing and
equipment for workers:
1. Whose exposure can reasonably be
expected to exceed the TWA PEL or
STEL.
2. When work clothing or skin may
become visibly contaminated with
beryllium, including during
maintenance and repair activities or
during non-routine tasks.
3. Where employees’ skin can
reasonably be expected to be exposed to
soluble beryllium compounds.
OSHA has determined that it would
be necessary for employers to provide
reusable overalls and/or lab coats at a
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cost of $284 and $86, respectively, for
operations in the following application
groups:
Beryllium Production
Beryllium Oxide, Ceramics & Composites
Nonferrous Foundries
Fabrication of Beryllium Alloy Products
Copper Rolling, Drawing & Extruding
Secondary Smelting, Refining and Alloying
Precision Turned Products
Dental Laboratories
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Chemical process operators in the
spring and stamping application group
would require chemical resistant
protective clothing at an annual cost of
$849. Gloves and/or shoe covers would
be required when performing operations
in several different application groups,
depending on the process being
performed, at an annual cost of $50 and
$78, respectively.
The proposed standard requires that
all reusable protective clothing and
equipment be cleaned, laundered,
repaired, and replaced as needed to
maintain their effectiveness. This
includes such safeguards as transporting
contaminated clothing in sealed and
labeled impermeable bags and
informing any third party businesses
coming in contact with such materials
of the risks associated with beryllium
exposure. OSHA estimates that the
lowest cost alternative to satisfy this
provision is for an employer to rent and
launder reusable protective clothing—at
an estimated annual cost per employee
of $49. Ten minutes of clerical time
would also be needed per establishment
with laundry needs to notify the
cleaners in writing of the potentially
harmful effects of beryllium exposure
and how the protective clothing and
equipment must be handled in
accordance with this standard—at a per
establishment cost of $3.
The Agency estimates the total
annualized cost of this provision to be
$1,407,365 for all affected
establishments. The breakdown of these
costs by application group and NAICS
code is shown in Table IX–6.
e. Hygiene Areas and Practices
The proposed standard requires
employers to provide readily accessible
washing facilities to remove beryllium
from the hands, face, and neck of each
employee working in a beryllium work
area and also to provide a designated
change room in workplaces where
employees would have to remove their
personal clothing and don the
employer-provided protective clothing.
The proposed standard also requires
that employees shower at the end of the
work shift or work activity if the
employee reasonably could have been
exposed to beryllium at levels above the
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PEL or STEL, and if those exposures
could reasonably be expected to have
caused contamination of the employee’s
hair or body parts other than hands,
face, and neck.
In addition to other forms of PPE
costed previously, for processes where
hair may become contaminated, head
coverings can be purchased at an annual
cost of $28 per employee. This could
satisfy the requirement to avoid
contaminated hair. If workers are
covered by protective clothing such that
no body parts (including their hair
where necessary, but not including their
hands, face, and neck) could reasonably
be expected to have been contaminated
by beryllium, and they could not
reasonably be expected to be exposed to
beryllium while removing their
protective clothing, they would not
need to shower at the end of a work
shift or work activity. OSHA notes that
some facilities already have showers,
and the Agency judges that all
employers either already have showers
where needed or will have sufficient
measures in place to ensure that
employees could not reasonably be
expected to be exposed to beryllium
while removing protective clothing.
Therefore, OSHA has preliminarily
determined that employers will not
need to provide any new shower
facilities to comply with the standard.
The Agency estimated the costs for
the addition of a change room and
segregated lockers based on the costs for
acquisition of portable structures. The
change room is presumed to be used in
providing a transition zone from general
working areas into beryllium-using
regulated areas. OSHA estimated that
portable building, adequate for 10
workers per establishment can be rented
annually for $3,251, and that lockers
could be procured for a capital cost of
$407—or $48 annualized—per
establishment. This results in an
annualized cost of $3,299 per facility to
rent a portable change room with
lockers. OSHA estimates that the 10
percent of affected establishments
unable to meet the proposed TWA PEL
would require change rooms. The
Agency estimated that a worker using a
change room would need 2 minutes per
day to change clothes. Assuming 250
days per year, this annual time cost for
changing clothes is $185 per employee.
The Agency estimates the total
annualized cost of the provision on
hygiene areas and practices to be
$389,241 for all affected establishments.
The breakdown of these costs by
application group and NAICS code can
be seen in Table IX–6.
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f. Housekeeping
The proposed rule specifies
requirements for cleaning and disposing
of beryllium-contaminated wastes. The
employer shall maintain all surfaces in
beryllium work areas as free as
practicable of accumulations of
beryllium and shall ensure that all spills
and emergency releases of beryllium are
cleaned up promptly, in accordance
with the employer’s written exposure
control plan and using a HEPA-filtered
vacuum or other methods that minimize
the likelihood and level of exposure.
The employer shall not allow dry
sweeping or brushing for cleaning
surfaces in beryllium work areas unless
HEPA-filtered vacuuming or other
methods that minimize the likelihood
and level of exposure have been tried
and were not effective.
ERG’s experts estimated that each
facility would need to purchase a single
vacuum at a cost of $2,900 for every five
affected employees in order to
successfully integrate housekeeping into
their daily routine. The per-employee
cost would be $580, resulting in an
annualized cost of $68 per worker.
ERG’s experts also estimated that all
affected workers would require an
additional five minutes per work day
(.083 hours) to complete vacuuming
tasks and to label and dispose of
beryllium-contaminated waste. While
this allotment is modest, OSHA judged
that the steady application of this
incremental additional cleaning, when
combined with currently conducted
cleaning, would be sufficient in average
establishments to address dust or
surface contamination hazards.
Assuming that these affected workers
would be working 250 days per year,
OSHA estimates that the annual labor
cost per employee for additional time
spent cleaning in order to comply with
this provision is $462.
The proposed standard requires each
disposal bag with contaminated
materials to be properly labeled. ERG
estimated a cost of 10 cents per label
with one label needed per day for every
five workers. With the disposal of one
labeled bag each day and 250 working
days, the per-employee annual cost
would be $5. The annualized cost of a
HEPA-filtered vacuum, combined with
the additional time needed to perform
housekeeping and the labeling of
disposal bags, results in a total
annualized cost of $535 per employee.
The Agency estimates the total
annualized cost of this provision to be
$12,574,921 for all affected
establishments. The breakdown of these
costs by application group and NAICS
code is shown in Table IX–6.
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g. Medical Surveillance
The proposed standard requires the
employer to make medical surveillance
available at no cost to the employee, and
at a reasonable time and place, for the
following employees:
1. Employees who have worked in a
regulated area for more than 30 days in
the last 12 months
2. Employees showing signs or
symptoms of chronic beryllium disease
(CBD)
3. Employees exposed to beryllium
during an emergency; and
4. Employees exposed to airborne
beryllium above 0.2 mg/m3 for more than
30 days in a 12-month period for 5 years
or more.
As discussed in the regulated areas
section of this analysis of program costs,
the Agency estimates that
approximately 10 percent of affected
employees would have exposure in
excess of the PEL after the standard goes
into effect and would therefore be
placed in regulated areas. The Agency
further estimates that a very small
number of employees will be affected by
emergencies in a given year, likely less
than 0.1 percent of the affected
population, representing a small
additional cost. The number of workers
who would suffer signs and symptoms
of CBD after the rule takes effect is
difficult to estimate, but would likely
substantially exceed those with actual
cases of CBD.
While the symptoms of CBD vary
greatly, the first to appear are usually
chronic dry cough (generally defined as
a nonproductive cough, without phlegm
or sputum, lasting two months or more)
and shortness of breath during exertion.
Ideally, in developing these costs
estimates, OSHA would first estimate
the percent of affected workers who
might be presenting with a chronic
cough and/or experiencing shortness of
breath.
Studies have found the prevalence of
a chronic cough ranging from 10 to 38
percent across various community
populations, with smoking accounting
for up to 18 percent of cough prevalence
(Irwin, 1990; Barbee, 1991). However,
these studies are over 20 years old, and
the number of smokers has decreased
substantially since then. It’s also not
clear whether the various segments of
the U.S. population studied are similar
enough to the population of workers
exposed to beryllium such that results
of these studies could be generalized to
the affected worker population.
A more recent study from a plant in
Cullman, Alabama that works with
beryllium alloy found that about five
percent of employees said they were
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current smokers, with roughly 52
percent saying they were previous
smokers and approximately 43 percent
stating they had never smoked
(Newman et al., 2001). This study does
not, however, report on the prevalence
of chronic cough in this workplace.
OSHA was unable to identify any
studies on the general prevalence of the
other common early symptom of CBD,
shortness of breath. Lacking any better
data to base an estimate on, the Agency
used the studies cited above (Irwin,
1990; Barbee, 1991) showing the
prevalence of chronic cough in the
general population, adjusted to account
for the long term decrease in smoking
prevalence (and hence, the amount of
overall cases of chronic cough), and
estimated that 15 percent of the worker
population with beryllium exposure
would exhibit a chronic cough or other
sign or symptom of CBD that would
trigger medical surveillance. The
Agency welcomes comment and further
data on this question.
According to the proposed rule, the
initial (baseline) medical examination
would consist of the following:
1. A medical and work history, with
emphasis on past and present exposure,
smoking history and any history of
respiratory system dysfunction;
2. A physical examination with
emphasis on the respiratory tract;
3. A physical examination for skin
breaks and wounds;
4. A pulmonary function test;
5. A standardized beryllium
lymphocyte proliferation test (BeLPT)
upon the first examination and within
every two years from the date of the first
examination until the employee is
confirmed positive for beryllium
sensitization;
6. A CT scan, offered every two years
for the duration of the employee’s
employment, if the employee was
exposed to airborne beryllium at levels
above 0.2 mg/m3 for more than 30 days
in a 12-month period for at least 5 years.
This obligation begins on the start-up
date of this standard, or on the 15th year
after the employee’s first exposure
above for more than 30 days in a 12month period, whichever is later; and
7. Any other test deemed appropriate
by the Physician or other Licensed
Health Care Professional (PLHCP).
Table V–17 in Chapter V of the PEA
lists the direct unit costs for initial
medical surveillance activities
including: Work and medical history,
physical examination, pulmonary
function test, BeLPT, CT scan, and costs
of additional tests. In OSHA’s cost
model, all of the activities will take
place during an employee’s initial visit
and on an annual basis thereafter and
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involve a single set of travel costs,
except that: (1) The BeLPT tests will
only be performed at two-year intervals
after the initial test, but will be
conducted in conjunction with the
annual general examination (no
additional travel costs); and (2) the CT
scans will typically involve different
specialists and are therefore treated as
separate visits not encompassed by the
general exams (therefore requiring
separate travel costs). Not all employees
would require CT scans, and employers
would only be required to offer them
every other year.
In addition to the fees for the annual
medical exam, employers may also
incur costs for lost work time when
their employees are unavailable to
perform their jobs. This includes time
for traveling, a health history review,
the physical exam, and the pulmonary
function test. Each examination would
require 15 minutes (or 0.25 hours) of a
human resource manager’s time for
recording the results of the exam and
tests and the PLHCP’s written opinion
for each employee and any necessary
post-exam consultation with the
employee. There is also a cost of 15
minutes of supervisor time to provide
information to the physician, five
minutes of supervisor time to process a
licensed physician’s written medical
opinion, and five minutes for an
employee to receive a licensed
physician’s written medical opinion.
The total unit annual cost for the
medical examinations and tests,
excluding the BeLPT test, and the time
required for both the employee and the
supervisor is $297.
The estimated fee for the BeLPT is
$259. With the addition of the time
incurred by the worker to undergo the
test, the total cost for a BeLPT is $261.
The standard requires a biennial BeLPT
for each employee covered by the
medical surveillance provision, so most
workers would receive between two and
five BeLPT tests over a ten year period
(including the BeLPT performed during
the initial examination), depending on
whether the results of these tests were
positive. OSHA therefore estimates a net
present value (NPV) of $1,417 for all
five tests. This NPV annualized over a
ten year period is $166.
Together, the annualized net present
value of the BeLPT and the annualized
cost of the remaining medical
surveillance produce an annual cost of
$436 per employee.
The proposed standard requires that a
helical tomography (CT scan) be offered
to employees exposed to airborne
beryllium above 0.2 mg/m3 for more than
30 days in a 12-month period, for a
period of 5 years or more. The five years
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do not need to be consecutive, and the
exposure does not need to occur after
the effective date of the standard. The
CT scan shall be offered every 2 years
starting on the 15th year after the first
year the employee was exposed above
0.2 mg/m3 for more than 30 days in a 12month period, for the duration of their
employment. The total yearly cost for
biennial CT scans consists of medical
costs totaling $1,020, comprised of a
$770 fee for the scan and the cost of a
specialist to review the results, which
OSHA estimates would cost $250. The
Agency estimates an additional cost of
$110 for lost work time, for a total of
$1,131. The annualized yearly cost for
biennial CT scans is $574.
Based on OSHA’s estimates explained
earlier in this section, all workers in
regulated areas, workers exposed in
emergencies, and an estimated 15
percent of workers not in regulated
areas who exhibit signs and symptoms
of CBD will be eligible for medical
surveillance other than CT scans. The
estimate for the number of workers
eligible to receive CT scans is 25 percent
of workers who are exposed above 0.2
in the exposure profile. The estimate of
25 percent is based on the facts that
roughly this percentage of workers have
15-plus years of job tenure in the
durable manufacturing sector and the
estimate that all those with 15-plus
years of job tenure and current exposure
over 0.2 would have had at least 5 years
of such exposure in the past.
The costs estimated for this provision
are likely to be significantly
overestimated, since not all affected
employees offered medical surveillance
would necessarily accept the offer. At
Department of Energy facilities, only
about 50 percent of eligible employees
participate in the voluntary medical
surveillance tests, and a report on an
initial medical surveillance program at
four aluminum manufacture facilities
found participation rates to be around
57 percent (Taiwo et al., 2008). Where
employers already offer equivalent
health surveillance screening, no new
costs are attributable to the proposed
standard.
Within 30 days after an employer
learns that an employee has been
confirmed positive for beryllium
sensitization, the employer’s designated
licensed physician shall consult with
the employee to discuss referral to a
CBD diagnostic center that is mutually
agreed upon by the employer and the
employee. If, after this consultation, the
employee wishes to obtain a clinical
evaluation at a CBD diagnostic center,
the employer must provide the
evaluation at no cost to the employee.
OSHA estimates this consultation will
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take 15 minutes, with an estimated total
cost of $33.
Table V–18 in Chapter V of the PEA
lists the direct unit costs for a clinical
evaluation with a specialist at a CBD
diagnostic center. To estimate these
costs, ERG contacted a healthcare
provider who commonly treats patients
with beryllium-related disease, and
asked them to provide both the typical
tests given and associated costs of an
initial examination for a patient with a
positive BeLPT test, presented in Table
V–18 in Chapter V of the PEA. Their
typical evaluation includes
bronchoscopy with lung biopsy, a
pulmonary stress test, and a chest CAT
scan. The total cost for the entire suite
of tests is $6,305.
In addition, there are costs for lost
productivity and travel. The Agency has
estimated the clinical evaluation would
take three days of paid time for the
worker to travel to and from one of two
locations: Penn Lung Center at the
Cleveland Clinic Foundation in
Cleveland, Ohio or National Jewish
Medical Center in Denver, Colorado.
OSHA estimates lost work time is 24
hours, yielding total cost for the 3 days
of $532.
OSHA estimates that roundtrip airfare would be available for most
facilities at $400, and the cost of a hotel
room would be approximately $100 per
night, for a total cost of $200 for the
hotel room. OSHA estimates a per diem
cost of $50 for three days, for a total of
$150. The total cost per trip for traveling
expenses is therefore $750.
The total cost of a clinical evaluation
with a specialist at a CBD diagnostic
center is equal to the cost of the
examination plus the cost of lost worktime and the cost for the employee to
travel to the CBD diagnostic center, or
$7,620.
Based on the data from the exposure
profile and the prevalence of beryllium
sensitization observed at various levels
of cumulative exposure,18 OSHA
estimated the number of workers
eligible for BeLPT testing (4,181) and
the percentage of workers who will be
confirmed positive for sensitization (two
positive BeLPT tests, as specified in the
proposed standard) and referred to a
CBD diagnostic center. During the first
year that the medical surveillance
provisions are in effect, OSHA estimates
that 9.4 percent of the workers who are
tested for beryllium sensitization will be
identified as sensitized. This percentage
is an average based on: (1) The number
of employees in the baseline exposure
profile that are in a given cumulative
18 See Table VI–6 in Section VI of the preamble,
Preliminary Risk Assessment.
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exposure range; (2) the expected
prevalence for a given cumulative
exposure range (from Table VI–6 in
Section VI of the preamble); and (3) an
assumed even distribution of employees
by cumulative years of exposure at a
given level—20 percent having
exposures at a given level for 5 years, 20
percent for 15 years, 20 percent for 25
years, 20 percent for 30 years, and 20
percent for 40 years.
OSHA did not assume that all workers
with confirmed sensitization would
choose to undergo evaluation at a CBD
diagnostic center, which may involve
invasive procedures and/or travel. For
purposes of this cost analysis, OSHA
estimates that approximately two-thirds
of workers who are confirmed positive
for beryllium sensitization will choose
to undergo evaluation for CBD. OSHA
requests comment on the CBD
evaluation participation rate. OSHA
estimates that about 264 of all nondental lab workers will go to a
diagnostic center for CBD evaluation in
the first year.
The calculation method described
above applies to all workers except
dental technicians, who were analyzed
with one modification. The rates for
dental technicians are calculated
differently due to the estimated 75
percent beryllium-substitution rate at
dental labs, where the 75 percent of labs
that eliminate all beryllium use are
those at higher exposure levels. None of
the remaining labs affected by this
standard had exposures above 0.1 mg/
m3. For the dental labs, the same
calculation was done as presented in the
previous paragraph, but only the
remaining 25 percent of employees
(2,314) who would still face beryllium
exposures were included in the baseline
cumulative exposure profile. With that
one change, and all other elements of
the calculation the same, OSHA
estimates that 9 percent of dental lab
workers tested for beryllium
sensitization will be identified as
sensitized. The predicted prevalence of
sensitization among those dental lab
workers tested in the first year after the
standard takes effect is slightly lower
than the predicted prevalence among all
other tested workers combined. This
slightly lower rate is not surprising
because only dental lab workers with
exposures below 0.1 mg/m3 are included
(after adjusting for substitution), and
OSHA’s exposure profile indicates that
the vast majority of non-dental workers
exposed to beryllium are also exposed at
0.1 mg/m3 or lower. OSHA estimates that
20 dental lab workers (out of 347 tested
for sensitization) would go to a
diagnostic center for CBD evaluation in
the first year.
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In each year after the first year, OSHA
relied on a 10 percent worker turnover
rate in a steady state (as discussed in
Chapter VII of the PEA) to estimate that
the annual sensitization incidence rate
is 10 percent of the first year’s incidence
rate. Based on that rate and the number
of workers in the medical surveillance
program, the CBD evaluation rate for
workers other than those in dental labs
would drop to 0.63 percent (.063 × .10).
The evaluation rate for dental labs
technicians is similarly estimated to
drop to 0.58 percent (.058 × .10).
Based on these unit costs and the
number of employees requiring medical
surveillance estimated above, OSHA
estimates that the medical surveillance
and referral provisions would result in
an annualized total cost of $2,882,706.
These costs are presented by application
group and NAICS code in Table IX–7.
h. Medical Removal Provision
Once a licensed physician diagnoses
an employee with CBD or the employee
is confirmed positive for sensitization to
beryllium, that employee is eligible for
medical removal and has two choices:
(a) Removal from current job, or
(b) Remain in a job with exposure
above the action level while wearing a
respirator pursuant to 29 CFR 1910.134.
To be eligible for removal, the
employee must accept comparable work
if such is available, but if not available
the employer would be required to place
the employee on paid leave for six
months or until such time as
comparable work becomes available,
whichever comes first. During that sixmonth period, whether the employee is
re-assigned or placed on paid leave, the
employer must continue to maintain the
employee’s base earnings, seniority and
other rights, and benefits that existed at
the time of the first test.
For purposes of this analysis, OSHA
has conservatively estimated the costs
as if all employees will choose removal,
rather than remaining in the current job
while wearing a respirator. In practice,
many workers may prefer to continue
working at their current job while
wearing a respirator, and the employer
would only incur the respirator costs
identified earlier in this chapter. The
removal costs are significantly higher
over the same six-month period, so this
analysis likely overestimates the total
costs for this provision.
OSHA estimated that the majority of
firms would be able to reassign the
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worker to a job at least at the clerical
level. The employer will often incur a
cost for re-assigning the worker because
this provision requires that, regardless
of the comparable work the medically
removed worker is performing, the
employee must be paid the full base
earnings for the previous position for six
months. The cost per hour of
reassigning a worker to a clerical job is
based on the wage difference of a
production worker of $22.16 and a
clerical worker of $19.97, for a
difference of $2.19. Over the six-month
period, the incremental cost of
reassigning a worker to a clerical
position would be $2,190 per employee.
This estimate is based on the employee
remaining in a clerical position for the
entire 6-month period, but the actual
cost would be lower if there is turnover
or if the employee is placed in any
alternative position (for any part of the
six-month period) that is compensated
at a wage closer to the employee’s
previous wage.
Some firms may not have the ability
to place the worker in an alternate job.
If the employee chooses not to remain
in the current position, the additional
cost to the employer would be at most
the cost of equipping that employee
with a respirator, which would be
required if the employee would
continue to face exposures at or above
the action level. Based on the earlier
discussion of respirator costs, that
option would be significantly cheaper
than the alternative of providing the
employee with six months of paid leave.
Therefore, in order to estimate the
maximum potential economic cost of
the remaining alternatives, the Agency
has conservatively estimated the cost
per worker based on the cost of 6
months paid leave.
Using the wage rate of a production
worker of $22.16 for 6 months (or 8
hours a day for 125 days), the total perworker cost for this provision when a
firm cannot place a worker in an
alternate job is $22,161.
OSHA has estimated an average
medical removal cost per worker
assuming 75 percent of firms are able to
find the employee an alternate job, and
the remaining 25 percent of firms would
not. The weighted average of these costs
is $7,183. Based on these unit costs,
OSHA estimates that the medical
removal provision would result in an
annualized total cost of $148,826. The
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breakdown of these costs by application
group and NAICS code is shown in
Table IX–6.
i. Training
As specified in the proposed standard
and existing OSHA standard 29 CFR
1910.1200 on hazard communication,
training is required for all employees
where there is potential exposure to
beryllium. In addition, newly hired
employees would require training before
starting work.
OSHA anticipates that training in
accordance with the requirements of the
proposed rule, which includes hazard
communication training, would be
conducted by in-house safety or
supervisory staff with the use of training
modules or videos. ERG estimated that
this training would last, on average,
eight hours. (Note that this estimate
does not include the time taken for
hazard communication training that is
already required by 29 CFR 1910.1200.)
The Agency judged that establishments
could purchase sufficient training
materials at an average cost of $2 per
worker, encompassing the cost of
handouts, video presentations, and
training manuals and exercises. For
initial and periodic training, ERG
estimated an average class size of five
workers with one instructor over an
eight hour period. The per-worker cost
of initial training totals to $239.
Annual retraining of workers is also
required by the standard. OSHA
estimates the same unit costs as for
initial training, so retraining would
require the same per-worker cost of
$239.
Finally, to calculate training costs, the
Agency needs the turnover rate of
affected workers to know how many
workers are receiving initial training
versus retraining. Based on a 26.3
percent new hire rate in manufacturing,
OSHA calculated a total net present
value (NPV) of ten years of initial and
annual retraining of $2,101 per
employee. Annualizing this NPV gives a
total annual cost for training of $246.
Based on these unit costs, OSHA
estimates that the training requirements
in the standard would result in an
annualized total cost of $5,797,535. The
breakdown of these costs by application
group and NAICS code is presented in
Table IX–6.
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NAICS
Code
lndustr
Be1ylliumPmcluction
331419 Pnmmy smeltmg and refinmg ofnonterrous metals
Beryllium Ohlde Ceranncs and Composites
327113a Porcelain electncal supply manufacturin,Q (prirrruy)
327113b Pmcelain electncal sup ply manu factming ( o;;econcl my)
334:220 Cellular telephones rnanutactunng
334310 Compact disc players manufacturing
334411
Electron tube manufacturing
334415 Electronic 1es1stmmanufuctming
334419 Other electromc component manu±actunng
334510 Electromedical equipment manufacturing
336322b Othermotorvelucle electncal and electromc eqmpment
manufacturing
Regulated Areas
and Beryllium
WorkAn•as
Exposure
Assessment
Pro~sed
Derl:!lium Standard !?l:· A~lication Groul! and Six-Digit NAICS lndustri ~in 2010 dollars2
1\Jedical
Surveillance
:Medical Remov.tl Written Exposure
Protective Work
Hygiene Areas
Control Plan
Clothing & Equipment and Practices
Pro"'sion
House-keeping
Total Program
Costs
Training
Sfmt 4725
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$0
$1,683
$11,121
$6,359
$0
$17,801
$8,112
$0
$0
$45,075
$6,959
$17,311
$12,365
$6,183
$25,967
$14,838
$11,129
$1U29
$12,365
$4,162
$5,303
$3,788
$1,894
$7,955
$4,545
$3,409
$3,409
$3,788
$9,205
$2C,,307
$14,505
$7252
$30,460
$17,406
$13,054
$13,054
$H,505
$1,912
$1,276
$911
$456
$1,914
$1,094
$820
$820
$911
$2,645
$11,365
$8,118
$4,059
$17,048
$9,742
$7,306
$7,306
$8,118
$2,761
$4,938
$8,526
$11,252
$6,346
$3,227
$8,193
$5,2!J3
$2,432
$1,959
$1,399
$864
$2,938
$1,679
$1,292
$1,292
$1,399
$22,189
$67,370
$48,122
$24,061
$101,055
$57,746
$43,309
$43,309
$!J8,122
$10,230
$3LOW
$22,186
$1LU93
$46590
$26,623
$19,967
$19.967
$22,186
$62,495
$160,889
$119,920
$56,692
$245,179
$140,019
$103,514
$108,480
$116,637
$18,965
$102,953
$18,965
$54,186
$11,764
$63,860
$11,764
$33,610
$22,386
$121,522
$22,386
$63,959
$2,948
$16,003
$2,948
$8,423
$6,580
$35,718
$6,580
$18,799
$14,421
$50,165
$7,835
$14,318
$3,882
$20,536
$3,882
$10,808
$39,473
$21,1,281
$39,473
$112,780
$18.199
$98,792
$18199
$51,996
$138,616
$723,831
$132,030
$368,879
$7),7(16
$4R,627
$91,1'0
$11,940
$26,047
$31,197
$1"',"'20
$1'57,416
$72,'57)
$'30,377
$1,687
$1,6R7
$1,926
$1,926
$5,779
$251
$2)1
$752
$625
$02)
$Ul76
$284
$733
$706
$294
$294
$3,609
$3,609
:R\~2
$10,~27
$L664
$1,664
$4,992
$11,325
$11,774
$5,tl62
$984
$984
$2,953
$38,355
$15,256
$40,496
$4,129
$18,761
$9,889
$4,411
$108,274
$49.918
$289,489
$830
A lumnnm cmd C'..0pper Founclries
331521
331522
331524
331525
Aluminum die-casting foundries
Nonferrous (except aluminum) die-casting foundries
Aluminumfoundnes (excepl die-cas ling)
a Copperfonndries (except dw-casting) (non-sand casting foundries)
11112
"'h Coppcrfonndncs (except dlC-castmg) (sand castmg foundncs)
Secondary Smelting, Refining, and Alloying
331314 Secondary smelting & alloying of aluminum
111421b l;opperrolling, drawmg, nnrl e-xtmrling
331423
331492
Secondary smeltmg, retinmg, & alloymg of copper
Secondary smelting, refinmg, & alloying of nonferrous metal (except
coppe1 & ahunimun)
Prcctston Turned Products
332721
a Precision turned product manufacturing (high beryllium content)
07AUP2
332721
b Precision turned product manufacturing (lowbe:rylltumcontent)
Copper Rolling, Drawing aml Exlrud:ing
331422 Copper wrre (except mechantcal) drawmg
331421a Copperrolling, dmwmg, illld extruding
$33,~29
$19,773
$20,306
$39,419
$6,022
$11,265
$22,809
$8,725
$59,373
$27.373
$215,066
$339,855
$93,938
$406,491
$22,244
$:239,550
$363,790
$35,735
$1,420,434
$654,876
$3,576,912
$330,266
$77,074
$77,096
$7,662
$426,151
$109,469
$23,234
$L983
$:240,458
$72,471
$349,147
$105,427
$27,975
$1,919
$2,043,664
$617,121
$942,210
$284.517
$4,460,202
$1,277,644
Federal Register / Vol. 80, No. 152 / Friday, August 7, 2015 / Proposed Rules
19:20 Aug 06, 2015
EP07AU15.009
Table IX-6
Annualized Cost of Program Reguirements for Industries Affected !?l: the
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Exposure
Assessment
NAICS
Code
PO 00000
Industry
Fabncat10n ofBerylliumAlloy Products
332612 Light gauge sp1ing IIIdltufacLUiing
112110 Metill stilmping
Frm 00125
334417 l::lcctromc conncctormanutactUilllg
336322a Other motor vehicle electrical & electronic equipment
A1c and Gas Welding
111111
Tmn <~nd steel mills
Fmt 4701
Sfmt 4725
E:\FR\FM\07AUP2.SGM
331221
331513
332117
112212
Kolicd steel shape manutacturmg
Steel form dries (except investment)
Powdei metallu1gy pml manufactuiing
Hnnrl cmrl edge tonl milnnfCJ.cturing
332312
332313
332322
112321
Fabncatcd structural metal manutacturmg
Plate v,-orkmanufacturing
33243SJ
332919
332999
other metal contamcr manutacturmg
Other metal valve and pipe fitting manufacturmg
333111
Farm machinery and equipment manufacturing
Regulated Areas
and Beryllium
\Vork Areas
Medical
Surwillance
Medical Remo,al
Pro,ision
Written Exposure
Contml Plan
$22,281
$9,640
$192,128
$51,182
$4,170
$1)))
$150,032
$:1),720
$80.612
$11,240
~46
$6,01~
$20,712
$32,079
$110,102
$2,911
$22,31)4
$76,762
$18014
$11,357
$1,107
$1,407
$1,792
$29)
$2,0R"'
$0
$1,0R"'
$14,171
$6,)1:1
$1"',19)
$65~
$305
$300
$201
$78~
$0
$0
$0
$0
$2,493
$9112
$3,053
$1,722
$3.379
$3,378
$3,352
$1,469
$21,713
S2,945
S2,897
S1,946
S0,2?i9
:1)119,636
$,15,228
:1)9,926
$32,010
$12,101
$39,207
$22,117
$433
$1126
$286
$918
$17,61)1
$1,35~
$775
$521
$1,6l'i9
$61
$60
$41
$BO
$617
$435
$1,194
$646
H681
$15,168
$R,'5'50
$3,206
$1,300
$16,000
$1,4~5
$3,83~
$602
$7,410
$1,556
$19,155
$299
$121
$1,492
333414a Heating equipment (except Wllim ai.r furnaces) manufactming
$9,531
$2,858
$4,414
$1,324
$11,411
$3,421
333911
333922
333921
$3,174
$4,314
$2,079
$1,470
$1,998
$963
$8,472
$7,157
333999
Pump and pumpmg eqmpment manu±ilcturmg
Conveyor 8lld conveying equipment manufacturmg
Industrial truck tmctm. tmile1-. and stacker machinety manufachuing
All othernnscellaneous general purpose machinery manufacturmg
07AUP2
336211
336214
336399a
3365W
Motorveh1de body manufacturmg
Travel trailer and campermanufacturmg
All other motorveh1ele parts rrn.nufacturing
Raihoad wiling stock
336999
337215
All other transportation eqmpment manu±ilcturmg
Showcase, part1tion, shelvmg, and lockermanufacturmg
811310
Corrrrncrc1al and mdustnal rnachmcty and cqmpmcnt rcparr
Tolal Program
Cost
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NAICS
Code
fu.lJOSure
Assessment
PO 00000
Jndustrv
Resistance Welding
333411 All pUiificalmn equipmenl HlllitufaclUiing
113412 TndustriCJ.l cmd wnnnerciCJl f
Table IX-6, continued
Annualized Cost of Pro~ram Requirements for btdustries Affected !!l· the
47691
Federal Register / Vol. 80, No. 152 / Friday, August 7, 2015 / Proposed Rules
Total Annualized Cost
As shown in Table IX–7, the total
annualized cost of the proposed rule is
estimated to be about $37.6 million. As
shown, at $27.8 million, the program
costs represent about 74 percent of the
total annualized costs of the proposed
rule. The annualized cost of complying
with the PEL accounts for the remaining
26 percent, almost all of which is for
engineering controls and work practices.
Respiratory protection, at about
$237,600, represents only 3 percent of
the annualized cost of complying with
the PEL and less than 1 percent of the
annualized cost of the proposed rule.
Table IX-7
Annualized Costs to Industries Affected by tbe Proposed Beryllium Standard, by Application Group and Six-DigitNAICS
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PO 00000
Total Costs
Frm 00127
Fmt 4701
Sfmt 4725
$1,188,758
$23,381
$45,075
$1,257,214
$175,546
$72,102
$51,502
$25,751
$108,154
$61,802
$46,352
$46,352
$2,702
$1,744
$1,246
$675
$2,617
$1,495
$1,132
$1,132
$62,495
$160,889
$119,920
$56,692
$245,179
$140,019
$103,514
$108,480
$240,744
$234,736
$172,668
$83,118
$355,950
$203,316
$150,998
$155,964
$51,502
$1,246
$116,637
$169,385
$182,887
$992,813
$182,887
$522,533
$682,229
$3,899
$20,999
$3,899
$11,052
$15,962
$138,616
$723,831
$132,030
$368,879
$530,377
$325,402
$1,737,643
$318,816
$902,464
$1,228,568
$19,186
$19,186
$57,558
$3,246
$3,246
$9,820
$11,325
$11,775
$33,831
$33,757
$34,207
$101,209
$287,789
$5,024
$289,489
$582,301
$162,739
$888,502
$8,864
$30,866
$215,066
$3,576,912
$386,669
$4,496,280
$23,656
$96,231
$1,677
$28,425
$1,277,644
$4,460,202
$1,302,977
$4,584,858
$588,200
$134,748
$84,126
$289,526
$8,874
$3,531
$2,204
$7,586
$2,218,314
$536,280
$345,805
$1,172,471
$2,815,387
$674,558
$432,136
$1,469,583
$18,123
$3,766
$679
$679
$35,195
$9,926
$53,997
$14,371
$679
$9,819
$14,203
$2,489
$7,979
$153,001
$57,841
$187,400
$105,713
$18,347
$7,438
$91,556
$54,540
Steel foundries (except investment)
Powder metallurgy part manufacturing
Hand and edge tool manufacturing
Fabricated structural metal manufacturing
Plate work manufacturing
Sheet metal work manufacturing
Ornamental and architectural metal work manufacturing
Other metal container manufacturing
Other metal valve and pipe fitting manufacturing
All other miscellaneous fabricated metal product manufacturing
Farm machinery and equipment manufacturing
19:20 Aug 06, 2015
Program Costs
$3,705
331513
332117
332212
332312
332313
332322
332323
332439
332919
332999
333111
VerDate Sep<11>2014
Fngineering Controls Respirator
and Work Practices
Costs
$679
$679
$4,352
$1,645
$5,330
$3,007
$679
$679
$2,604
$1,551
$7,679
$17,341
$287,730
$108,775
$352,421
$198,802
$35,589
$16,389
$172,178
$102,568
$10,846
$25,998
$445,083
$168,261
$545,151
$307,521
$54,614
$24,506
$266,338
$158,660
E:\FR\FM\07AUP2.SGM
07AUP2
EP07AU15.012
NAICS
code
Industr
Eery ilium Production
331419 Primary smelting and refming of nonferrous metals
Eery ilium Oxide Ceramics and Composites
327113a Porcelain electrical supply manufacturing (primary)
327113b Porcelain electrical supply manufacturing (secondary)
334220
Cellular telephones manufacturing
334310
Compact disc players manufacturing
Electron tube manufacturing
334411
334415
Electronic res is tor manufacturing
Other electronic component manufacturing
334419
334510 Electro medical equipment manufacturing
336322b Other motor vehicle electrical and electronic equipment
manufacturing
Nonferrous Foundries
331521
Alurnill.umdie-casting foundries
331522 Nonferrous (except aluminum) die-casting foundries
331524 Aluminum foundries (except die-casting)
331525a Copper foundries (except die-casting) (non-sand casting foundries)
331525b Copper foundries (except die-casting) (sand casting foundries)
Secondary Smelting, Refming, and Alloying
331314 Secondary smelting & alloying of aluminum
33142lb Copper rolling, drawing, and extruding
331423
Secondary smelting, refming, & alloying of copper
Secondary smelting, refming, & alloying of nonferrous metal
331492
(except copper & aluminum)
Precision Turned Products
33272la Precision turned product manufacturing (high beryllium content)
33272lb Precision turned product manufacturing (low bery ilium content)
Copper Rolling, Drawing and Extruding
33142la Copper rolling, drawing, and extruding
331422
Copper wire (except mechanical) drawing
Fabrication ofEerylliumAlloy Products
332612 Light gauge spring manufacturing
332116 Metal stamping
334417 Electronic connector manufacturing
336322a Other motor vehicle electrical & electronic equipment
Arc and Gas Welding
33llll
Iron and steel mills
331221
Rolled steel shape manufacturing
Federal Register / Vol. 80, No. 152 / Friday, August 7, 2015 / Proposed Rules
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F. Economic Feasibility Analysis and
Regulatory Flexibility Determination
Chapter VI of the PEA, summarized
here, investigates the economic impacts
of the proposed beryllium rule on
affected employers. This impact
investigation has two overriding
objectives: (1) To establish whether the
proposed rule is economically feasible
for all affected application groups/
industries, and (2) to determine if the
Agency can certify that the proposed
rule will not have a significant
economic impact on a substantial
number of small entities.
In the discussion below, OSHA first
presents its approach for achieving
these objectives and next applies this
approach to industries with affected
employers. The Agency invites
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19:20 Aug 06, 2015
Jkt 235001
comment on any aspect of the methods,
data, or preliminary findings presented
here or in Chapter VI of the PEA.
1. Analytic Approach
a. Economic Feasibility
Section 6(b)(5) of the OSH Act directs
the Secretary of Labor to set standards
based on the available evidence where
no employee, over his/her working life
time, will suffer from material
impairment of health or functional
capacity, even if such employee has
regular exposure to the hazard, ‘‘to the
exent feasible’’ (29 U.S.C. 655(b)(5)).
OSHA interpreted the phrase ‘‘to the
extent feasible’’ to encompass economic
feasibility and was supported in this
view by the U.S. Court of Appeals for
the D.C. Circuit, which has long held
PO 00000
Frm 00128
Fmt 4701
Sfmt 4702
that OSHA standards would satisfy the
economic feasibility criterion even if
they imposed significant costs on
regulated industries and forced some
marginal firms out of business, so long
as they did not cause massive economic
dislocations within a particular industry
or imperil the existence of that industry.
Am. Iron and Steel Inst. v. OSHA, 939
F.2d 975, 980 (D.C. Cir. 1991); United
Steelworkers of Am., AFL–CIO–CLC v.
Marshall, 647 F.2d 1189, 1265 (D.C. Cir.
1980); Indus. Union Dep’t v. Hodgson,
499 F.2d 467 (D.C. Cir. 1974).
b. The Price Elasticity of Demand and
Its Relationship to Economic Feasibility
In practice, the economic burden of
an OSHA standard on an industry—and
whether the standard is economically
feasible for that industry—depends on
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the magnitude of compliance costs
incurred by establishments in that
industry and the extent to which they
are able to pass those costs on to their
customers. That, in turn, depends, to a
significant degree, on the price elasticity
of demand for the products sold by
establishments in that industry.
The price elasticity of demand refers
to the relationship between the price
charged for a product and the demand
for that product: The more elastic the
relationship, the less an establishment’s
compliance costs can be passed through
to customers in the form of a price
increase and the more the establishment
has to absorb compliance costs in the
form of reduced profits. When demand
is inelastic, establishments can recover
most of the costs of compliance by
raising the prices they charge; under
this scenario, profit rates are largely
unchanged and the industry remains
largely unaffected. Any impacts are
primarily on those customers using the
relevant product. On the other hand,
when demand is elastic, establishments
cannot recover all compliance costs
simply by passing the cost increase
through in the form of a price increase;
instead, they must absorb some of the
increase from their profits. Commonly,
this will mean reductions both in the
quantity of goods and services produced
and in total profits, though the profit
rate may remain unchanged. In general,
‘‘[w]hen an industry is subjected to a
higher cost, it does not simply swallow
it; it raises its price and reduces its
output, and in this way shifts a part of
the cost to its consumers and a part to
its suppliers,’’ in the words of the court
in Am. Dental Ass’n v. Sec’y of Labor
(984 F.2d 823, 829 (7th Cir. 1993)).
The court’s summary is in accord
with microeconomic theory. In the long
run, firms can remain in business only
if their profits are adequate to provide
a return on investment that ensures that
investment in the industry will
continue. Over time, because of rising
real incomes and productivity increases,
firms in most industries are able to
ensure an adequate profit. As
technology and costs change, however,
the long-run demand for some products
naturally increases and the long-run
demand for other products naturally
decreases. In the face of additional
compliance costs (or other external
costs), firms that otherwise have a
profitable line of business may have to
increase prices to stay viable. Increases
in prices typically result in reduced
quantity demanded, but rarely eliminate
all demand for the product. Whether
this decrease in the total production of
goods and services results in smaller
output for each establishment within
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19:20 Aug 06, 2015
Jkt 235001
the industry or the closure of some
plants within the industry, or a
combination of the two, is dependent on
the cost and profit structure of
individual firms within the industry.
If demand is perfectly inelastic (i.e.,
the price elasticity of demand is zero),
then the impact of compliance costs that
are one percent of revenues for each
firm in the industry would be a one
percent increase in the price of the
product, with no decline in quantity
demanded. Such a situation represents
an extreme case, but might be observed
in situations in which there were few,
if any, substitutes for the product in
question, or if the products of the
affected sector account for only a very
small portion of the revenue or income
of its customers.
If the demand is perfectly elastic (i.e.,
the price elasticity of demand is
infinitely large), then no increase in
price is possible and before-tax profits
would be reduced by an amount equal
to the costs of compliance (net of any
cost savings—such as reduced workers’
compensation insurance premiums—
resulting from the proposed standard) if
the industry attempted to maintain
production at the same level as
previously. Under this scenario, if the
costs of compliance are such a large
percentage of profits that some or all
plants in the industry could no longer
operate in the industry with hope of an
adequate return on investment, then
some or all of the firms in the industry
would close. This scenario is highly
unlikely to occur, however, because it
can only arise when there are other
products—unaffected by the proposed
rule—that are, in the eyes of their
customers, perfect substitutes for the
products the affected establishments
make.
A commonly-discussed intermediate
case would be a price elasticity of
demand of one (in absolute terms). In
this situation, if the costs of compliance
amount to one percent of revenues, then
production would decline by one
percent and prices would rise by one
percent. As a result, industry revenues
would remain the same, with somewhat
lower production, but with similar
profit rates per unit of output (in most
situations where the marginal costs of
production net of regulatory costs
would fall as well). Customers would,
however, receive less of the product for
their (same) expenditures, and firms
would have lower total profits; this, as
the court described in Am. Dental Ass’n
v. Sec’y of Labor, is the more typical
case.
PO 00000
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Sfmt 4702
47693
c. Variable Costs Versus Fixed Costs
A decline in output as a result of an
increase in price may occur in a variety
of ways: individual establishments
could each reduce their levels of
production; some marginal plants could
close; or, in the case of an expanding
industry, new entry may be delayed
until demand equals supply. In some
situations, there could be a combination
of these three effects. Which possibility
is most likely depends on the form that
the costs of the regulation take. If the
costs are variable costs (i.e., costs that
vary with the level of production at a
facility), then economic theory suggests
that any reductions in overall output
will be the result of reductions in output
at each affected facility, with few, if any,
plant closures. If, on the other hand, the
costs of a regulation primarily take the
form of fixed costs (i.e., costs that do not
vary with the level of production at a
facility), then reductions in overall
output are more likely to take the form
of plant closures or delays in new entry.
Most of the costs of this regulation, as
estimated in Chapter V of the PEA, are
variable costs in the sense that they will
tend to vary by production levels and/
or employment levels. Almost all of the
major costs of program elements, such
as medical surveillance and training,
will vary in proportion to the number of
employees (which is a rough proxy for
the amount of production). Exposure
monitoring costs will vary with the
number of employees, but do have some
economies of scale to the extent that a
larger firm need only conduct
representative sampling rather than
sample every employee. Finally, the
costs of operating and maintaining
engineering controls tend to vary by
usage—which typically closely tracks
the level of production and are not fixed
costs in the strictest sense.
This leaves two kinds of costs that
are, in some sense, fixed costs—capital
costs of engineering controls and certain
initial costs. The capital costs of
engineering controls due to the
standard—many of which are scaled to
production and/or employment levels—
constitute a relatively small share of the
total costs, representing 10 percent of
total annualized costs (or approximately
$870 per year per affected
establishment).
Some ancillary provisions require
initial costs that are fixed in the sense
that they do not vary by production
activity or the number of employees.
Some examples are the costs to develop
a training plan for general training not
currently required and to develop a
written exposure control plan.
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As a result of these considerations,
OSHA expects it to be quite likely that
any reductions in total industry output
would be due to reductions in output at
each affected facility rather than as a
result of plant closures. However,
closures of some marginal plants or
poorly performing facilities are always
possible.
d. Economic Feasibility Screening
Analysis
To determine whether a rule is
economically feasible, OSHA begins
with two screening tests to consider
minimum threshold effects of the rule
under two extreme cases: (1) All costs
are passed through to customers in the
form of higher prices (consistent with a
price elasticity of demand of zero), and
(2) all costs are absorbed by the firm in
the form of reduced profits (consistent
with an infinite price elasticity of
demand).
In the former case, the immediate
impact of the rule would be observed in
increased industry revenues. While
there is no hard and fast rule, in the
absence of evidence to the contrary,
OSHA generally considers a standard to
be economically feasible for an industry
when the annualized costs of
compliance are less than a threshold
level of one percent of annual revenues.
Retrospective studies of previous OSHA
regulations have shown that potential
impacts of such a small magnitude are
unlikely to eliminate an industry or
significantly alter its competitive
structure,19 particularly since most
industries have at least some ability to
raise prices to reflect increased costs,
and normal price variations for products
typically exceed three percent a year.
In the latter case, the immediate
impact of the rule would be observed in
reduced industry profits. OSHA uses the
ratio of annualized costs to annual
profits as a second check on economic
feasibility. Again, while there is no hard
and fast rule, in the absence of evidence
to the contrary, OSHA generally
considers a standard to be economically
feasible for an industry when the
annualized costs of compliance are less
than a threshold level of ten percent of
annual profits. In the context of
economic feasibility, the Agency
believes this threshold level to be fairly
modest, given that normal year-to-year
variations in profit rates in an industry
can exceed 40 percent or more. OSHA
also considered whether this threshold
would be adequate to assure that
upfront costs would not create major
19 See OSHA’s Web page, https://www.osha.gov/
dea/lookback.html#Completed, for a link to all
completed OSHA lookback reviews.
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19:20 Aug 06, 2015
Jkt 235001
credit problems for affected employers.
To do this, OSHA examined a worst
case scenario in which annualized costs
were ten percent of profits and all of the
annualized costs were the result of
upfront costs. In this scenario, assuming
a three percent discount rate and a ten
year life of equipment, total costs would
be 85 percent of profits 20 in the year in
which these upfront costs were
incurred. Because upfront costs would
be less than one year’s profits in the
year they were incurred, this means that
an employer could pay for all of these
costs from that year’s profits and would
not necessarily have to incur any new
borrowing. As a result, it is unlikely that
these costs would create a credit crunch
or other major credit problems. It would
be true, however, that paying regulatory
costs from profits might reduce
investment from profits in that year.
OSHA’s choice of a threshold level of
ten percent of annual profits is low
enough that even if, in a hypothetical
worst case, all compliance costs were
upfront costs, then upfront costs—
assuming a three percent discount rate
and a ten-year time period—would be
no more than 85 percent of first-year
profits and thus would be affordable
from profits without resort to credit
markets. If the threshold level were firstyear costs of ten percent of annual
profits, firms could even more easily
expect to cover first-year costs at the
threshold level out of current profits
without having to access capital markets
and otherwise being threatened with
short-term insolvency.
In general, because it is usually the
case that firms would be able to pass on
to their customers some or all of the
costs of the proposed rule in the form
of higher prices, OSHA will tend to give
much more weight to the ratio of
industry costs to industry revenues than
to the ratio of industry costs to industry
profits. However, if costs exceed either
the threshold percentage of revenue or
the threshold percentage of profits for
an industry, or if there is other evidence
of a threat to the viability of an industry
because of the proposed standard,
OSHA will examine the effect of the
rule on that industry more closely. Such
an examination would include market
factors specific to the industry, such as
20 At a discount rate of 3 percent over a life of
investment of 10 years, the present value of that
stream of annualized costs would be 8.53 times a
single year’s annualized costs. Hence, if yearly
annualized costs are 10 percent of profits, upfront
costs would be 85 percent of the profits in that first
year. As a simple example, assume annualized costs
are $1 for each of the 10 years. If annualized costs
are 10 percent of profits, this translates to a yearly
profit of $10. The present value of that stream of
$1 for each year is $8.53. (The formula for this
calculation is ($1*(1.03∧10)¥1)/((.03)×(1.03)∧10).
PO 00000
Frm 00130
Fmt 4701
Sfmt 4702
normal variations in prices and profits,
and any special circumstances, such as
close domestic substitutes of equal cost,
which might make the industry
particularly vulnerable to a regulatory
cost increase.
The preceding discussion focused on
the economic viability of the affected
industries in their entirety. However,
even if OSHA found that a proposed
standard did not threaten the survival of
affected industries, there is still the
question of whether the industries’
competitive structure would be
significantly altered. For example, if the
annualized costs of an OSHA standard
were equal to 10 percent of an
industry’s annual profits, and the price
elasticity of demand for the products in
that industry were equal to one, then
OSHA would not expect the industry to
go out of business. However, if the
increase in costs were such that most or
all small firms in that industry would
have to close, it might reasonably be
concluded that the competitive
structure of the industry had been
altered. For this reason, OSHA also
calculates compliance costs by size of
firm and conducts its economic
feasibility screening analysis for small
and very small entities.
e. Regulatory Flexibility Screening
Analysis
The Regulatory Flexibility Act (RFA),
Public Law 96–354, 94 Stat. 1164
(codified at 5 U.S.C. 601), requires
Federal agencies to consider the
economic impact that a proposed
rulemaking will have on small entities.
The RFA states that whenever a Federal
agency is required to publish general
notice of proposed rulemaking for any
proposed rule, the agency must prepare
and make available for public comment
an initial regulatory flexibility analysis
(IRFA). 5 U.S.C. 603(a). Pursuant to
section 605(b), in lieu of an IRFA, the
head of an agency may certify that the
proposed rule will not have a significant
economic impact on a substantial
number of small entities. A certification
must be supported by a factual basis. If
the head of an agency makes a
certification, the agency shall publish
such certification in the Federal
Register at the time of publication of
general notice of proposed rulemaking
or at the time of publication of the final
rule. 5 U.S.C. 605(b).
To determine if the Assistant
Secretary of Labor for OSHA can certify
that the proposed beryllium rule will
not have a significant economic impact
on a substantial number of small
entities, the Agency has developed
screening tests to consider minimum
threshold effects of the proposed rule on
E:\FR\FM\07AUP2.SGM
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small entities. These screening tests do
not constitute hard and fast rules and
are similar in concept to those OSHA
developed above to identify minimum
threshold effects for purposes of
demonstrating economic feasibility.
There are, however, two differences.
First, for each affected industry, the
screening tests are applied, not to all
establishments, but to small entities
(defined as ‘‘small business concerns’’
by SBA) and also to very small entities
(as defined by OSHA as businesses with
fewer than 20 employees). Second,
although OSHA’s regulatory flexibility
screening test for revenues also uses a
minimum threshold level of annualized
costs equal to one percent of annual
revenues, OSHA has established a
minimum threshold level of annualized
costs equal to five percent of annual
profits for the average small entity or
very small entity. The Agency has
chosen a lower minimum threshold
level for the profitability screening
analysis and has applied its screening
tests to both small entities and very
small entities in order to ensure that
certification will be made, and an IRFA
will not be prepared, only if OSHA can
be highly confident that a proposed rule
will not have a significant economic
impact on a substantial number of small
entities or very small entities in any
affected industry.
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19:20 Aug 06, 2015
Jkt 235001
Furthermore, certification will not be
made, and an IRFA will be prepared, if
OSHA believes the proposed rule might
otherwise have a significant economic
impact on a substantial number of small
entities, even if the minimum threshold
levels are not exceeded for revenues or
profitability for small entities or very
small entities in all affected industries.
2. Impacts on Affected Industries
In this section, OSHA applies its
screening criteria and other analytic
methods, as needed, to determine (1)
whether the proposed rule is
economically feasible for all affected
industries within the scope of this
proposed rule, and (2) whether the
Agency can certify that the proposed
rule will not have a significant
economic impact on a substantial
number of small entities.
a. Economic Feasibility Screening
Analysis: All Establishments
To determine whether the proposed
rule’s projected costs of compliance
would threaten the economic viability
of affected industries, OSHA first
compared, for each affected industry,
annualized compliance costs to annual
revenues and profits per (average)
affected establishment. The results for
all affected establishments in all
affected industries are presented in
PO 00000
Frm 00131
Fmt 4701
Sfmt 4702
47695
Table IX–8. Shown in the table for each
affected industry are the total number of
establishments, the total number of
affected establishments, annualized
costs per affected establishment, annual
revenues per establishment, the profit
rate, annual profits per establishment,
annualized compliance costs as a
percentage of annual revenues, and
annualized compliance costs as a
percentage of annual profits.
The annualized costs per affected
establishment for each affected industry
were calculated by distributing the
industry-level (incremental) annualized
compliance costs among all affected
establishments in the industry, where
annualized compliance costs reflect a 3
percent discount rate. The annualized
cost of the proposed rule for the average
affected establishment is estimated at
$9,197 in 2010 dollars. It is clear from
Table IX–8 that the estimates of the
annualized costs per affected
establishment vary widely from
industry to industry. These estimates
range from $1,257,214 for NAICS
331419 (Beryllium Production) and
$120,372 for NAICS 327113a (Porcelain
Electrical Supply Manufacturing
(primary)) to $1,636 for NAICS 621210
(Offices of Dentists) and $1,632 for
NAICS 339116 (Dental Laboratories).
E:\FR\FM\07AUP2.SGM
07AUP2
mstockstill on DSK4VPTVN1PROD with PROPOSALS2
47696
VerDate Sep<11>2014
Table IX-8
Screening Analysis tOr Establislunents Atlected by the Proposed Beryllium Standard
With Costs Calculated Usi~a Three Percent Discount Rate
_l_
Revenues
_l
Profit
Per
Indusll]'_
Betyllium Productlon
331419
Primmy smelting and refining of nonferrous metals
Betyllium Ozjde Ceramics and Composites
Jkt 235001
327113a
Porcelain electrical supply mmufacturing (prirna:Iy)
327113b
Porcelain electrical supply mmufacturing (secondrny)
334220
Cellular telephones manufacturing
334310
Compact d1scplayers manufactunng
334411
Electron tube mmufacturing
334415
Electromc resistor manufacturing
PO 00000
334419
Other electronic component manufacturing
334510
Electrornedical equipment manufacturing
336322b
Other motor vehicle electncal and electronic eqmpment mmufacturing
Total
Establishments
Total Affected
Establishments
161
Establis lunent
To1al ($1,000)
($)
Rate
Frm 00132
2
$789,731
$35,475,343
5
79
61
1,133
629
21
12
9
9
$3,975,351
$1,220,476
636
10
254
140
7
38
$L257,214
$789,731
14
10
$560,967
$10,013,730
$27,480,966
$12,152,053
Costs
Per
Per
As a
As a
Establishment Establishment Percent of Percent of
($)
($)
Revenues
Profits
$8,524,863
106
106
810
464
Co~ance
$120,372
Fmt 4701
Sfmt 4725
7,450,295
43,796,720
8,567,567
5.01%
6.08%
4.39%
373,542
2,663,922
376,456
15,449,068
9,196,181
8,838,244
43,689,930
7.85%
7.85<}0
7.85%
6.75%
1,212,421
721,703
693,613
2,947,904
19,107,002
1.83%
348,832
16,968,585
10,791,418
5.22%
5.22%
885,603
563,212
6,391,108
5,796,031
5.22%
5.22%
333,557
302,499
5,796,031
5.22%
302,499
39,648,599
130,348,178
4.54%
4.79%
1,802,008
6,248,900
30,156,619
33,047,610
4.79%
4.79%
1,445,710
1,584,305
0.23~0
$16,767
$17,267
0.04%
$16,624
$16,950
0.11%
0.19~0
4.49%
0.65%
4.42o/o
$16,943
$16,778
0.19%
$17,329
$16,939
0.04~0
1.40%
2.35%
2.42%
0.59%
0.09%
4.86%
$46,486
0.27%
$45,727
$45,545
$45,123
$49,143
0.42~0
5.25%
8.12o/o
13.65%
14.92%
16.25%
0.18~0
Nonferrous Foundries
331521
Aluminum die-casting foundries
331522
Nonferrous (except aluminum) die-casting foundries
331524
331525a
Aluminumfmmdries (except die-casting)
Copper foundries (except die-casting) (non-sand castmg foundries)
394
208
7
20
331525b
Copper foundries (except die-casting) (sand casting foundries)
208
25
$4,310,021
$1,510,799
$2,518,097
$1,205,574
$1,205,574
0.71%
0.78~0
0.85%
Secondary Smelting, Refining, and Alloying
331314
Secondrny slll31ting & alloying of aluminum
331421b
Copper rolling, drawing, and extruding
331423
Secondrny slll31ting, refining, & alloying of copper
331492
Secondrny slll31ting, refining, & alloying ofnonfenuus Ill3tal (except copper & aluminum)
Precision Turned Products
$4,837,129
$12,513,425
$723,759
122
96
24
248
30
$8,195,807
E:\FR\FM\07AUP2.SGM
$33,757
$34,206
$33,639
0.09%
$19,410
0.06~0
0.49~0
8.49%
0.36%
6.19%
0.07%
0.14~0
1.39%
2.86%
0.13~0
2.31%
0.14%
0.04~0
2.71%
0.55%
0.05%
2.65%
0.10%
0.37%
0.03~0
0.11%
1.87%
0.55%
2.33%
1.23%
332721a
Precision turned product manufacturing (high berylliumcontent)
3,124
18
5.82%
247,032
Precision turned product manufacturing Gowbetylliumcontent)
3,124
294
$13,262,706
$13,262,706
4,245,425
332721b
4,245,425
5.82%
247,032
$20,979
$15,295
96
114
15
59
$12,513,425
$6,471,491
130,348,178
56,767,462
4.79%
4.79%
6,248,900
2,721,436
$86,865
$77,709
$2,167,977
$9,749,800
$5,029,508
$12,152,053
6,712,003
5.61%
376,763
6,569,946
21,772,761
5.12%
7.85%
336,300
1,708,696
19,107,002
1.83%
348,832
$8,716
$9,116
$9,354
$9,243
$92,726,004
$8,376,271
157,965,934
52,026,531
5.41%
5.41%
8,542,604
2,813,531
$8,149
$10,438
0.01%
0.02%
$4,251,852
$1,414,108
19,326,599
10,632,394
5.22%
1,008,670
544,246
$10,486
$11,921
0.05%
1.04%
0.11~&
2.19~0
Copper Rolling, Drmv:ing and Extruding
331421a
Copper rolling, drawing, and extruding
331422
Coppenvire (except mechanical) drawing
Fabrication ofBetyllmmAlloy Products
74
46
336322a
Other motor vehicle electncal & electronic equipment
Arc and Gas Welding
636
159
331111
331221
Iron and s tee! rrills
Rolled steel shape manufacturing
587
161
7
Steel foundries (except mvestlll3nt)
332117
Powder metallmgy pmt manufacturing
220
133
332212
Hand and edge tool manufacturing
1,066
3
$5,077,868
4,763,479
5.61%
267,387
$8,913
0.19%
3.33q'O
332312
Fabricated structural metal manufacturing
332313
Plate work manufacturing
3,407
1,288
56
21
$26,119,614
$6,023,356
7,666,455
4,676,519
4.74%
4.74%
363,273
221,596
$7,957
$7,957
0.10%
0.17%
2.19%
3.59q'O
332322
Sheet metal work manufacturing
4,173
332323
Ornamental and arch1tcctural tnJtal work manufacturing
2,354
69
39
$17,988,908
$5,708,707
4,310,786
2,425,109
4.74%
4.74%
204,266
114,913
$7,957
$7,957
0.18%
0.33%
3.90%
6.92q'O
332439
Other metal container manufactunng
332919
Other metal valve and pipe fitting manufacturing
9,637,500
17,298,424
4.30%
7.00%
414,839
1,211,086
$8,142
$9,012
0.08%
0.05%
1.96%
0.74q'O
332999
All other miscellaneous fabricated metal product manufacturing
Fannmachmcry and equipment mmufacturing
7
3
33
20
$3,565,875
$4,584,082
333111
07AUP2
323
331513
EP07AU15.014
323
1,484
231
$13,963,184
$24,067,145
4,280,559
23,119,255
7.00%
6.36%
299,688
1,471,196
$7,957
$7,957
0.19%
0.03%
2.66%
0.54q'O
332612
light gauge spnng manufactunng
332116
Metal stamping
334417
Electromc connector manufacturing
370
265
3,262
1,041
5.12~iJ
Federal Register / Vol. 80, No. 152 / Friday, August 7, 2015 / Proposed Rules
19:20 Aug 06, 2015
NAICS
Code
_l
mstockstill on DSK4VPTVN1PROD with PROPOSALS2
I
NAICS
Code
Industry
Total
Establishments
Total Affected
Establislnnents
Jkt 235001
Frm 00133
Fmt 4701
Sfmt 4702
07AUP2
8,549,565
11,136,327
10,394,697
30,194,998
20,845,825
26,223,543
39,144,257
204,083,854
338,228,505
92,086,126
15,737,881
26,955,128
4.68%
4.68%
4.68%
4.68%
4.03%
4.03%
4.03%
4.03%
4.03%
4.03%
1.83%
1.83%
400,062
521,106
486,402
1,412,924
840,119
1,056,849
1,577,573
8,224,892
13,631,126
3,711,212
287,323
492,114
$2,322,610
$12,152,053
24,974,299
19,107,002
1.~%
32
$g,g56,5g4
EP07AU15.015
1350
7
All other transportation equipment manufacturing
226
374
Ll94
21.960
3
4
3
143
358
151
460
843
106
34
96
22
11
38
109
742
25
11
32
59
Conveyor and conveying equipment manufacturing
333924
Industrial truck, tractor, trailer, and stacker machinery manufacturing
333999
All other miscellaneous general purpose machinery manufacturing
336211
Motor vehicle body manufacturmg
336214
337215
Showcase, partition, shelving, and locker manufacturing
811310
Commercial and mdustnalmachmery and eqmpment reparr
6
7
9
4
18
15
14
0.08%
0.04%
0.09%
0.04%
0.11%
0.06%
0.07%
O.O:l%
1.69%
0.70%
1.76%
0.79%
2.06%
3.27%
3.99%
l.S5%
0.31%
0.94%
0.02%
0.06%
0.18%
0.55%
10.19%
$15,044
$15,044
$15,044
$15,044
$15,044
$15,044
$15,044
$15,044
$15,044
$15,044
$15,044
$15,044
0.18%
0.14%
0.14%
0.05%
0.07%
0.06%
0.04%
0.01%
0.00%
0.02%
0.10%
0.06%
3.76%
2.89%
3.09%
1.06%
1.79%
1.42%
0.95%
0.18%
0.11%
0.41%
5.24%
3.06%
455,950
348,832
$15,044
$15,044
0.06%
0.08%
3.30%
4.31%
657,2g7
747,503
838,508
687,183
491,376
866,847
436,537
$15,044
$15,044
$15,044
$15,044
$15,044
$15,044
$15,044
0.04%
0.04%
0.03%
0.04%
006%
0.03%
0.06%
2.29%
2.01%
1.79%
2.19%
306%
1.74%
3.45%
4.23~'0
Resistance Welding
333411
Air purification equipment manufacturing
333412
Industrial and commercial fan and blower manufacturing
333414b
Heating eqmpment (except warm air furnaces) manufacturmg
333415
Air-conditioning, warm air heating, and industrial refrigeration equipment manufacturing
33<211
Electric housewares and household fan manufacturing
335212
Household vacuum cleaner manufacturing
335221
Household cooking appliance manufacturing
335222
Household refngerator and home freezer manufacturng
335224
Household laundry equipmentmanufacturmg
335228
336311
Other major household appliance manufacturmg
Carburetor, piston, piston ring, and valve manufacturing
336312
Gasoline engme and engine parts manufacturing
33G321
Vehicular lighting equipment manufactuting
336322c
Other motor vehicle electrical and electronic equipment manufacturing
336330
Motor vehicle steering and suspension components (except spring) manufacturmg
336340
Motor vehicle brake system manufacturing
336350
Motor vehicle transmission and power train parts manufacturir_g
336360
Motor vehicle seatmg and interior trim manufacturing
336370
Motor vehicle metal o;t3mping
336391
Motor vehicle air-conditioning manufacturing
336399b
All other motor vehicle parts manufacturing
93
636
2
2
1.~%
$8,147,826
$21,862,014
$15,168,862
$19,809,238
$3,798,464
$32,279,766
36,002,374
40,943,850
45,928,600
37,639,856
26,914,725
47,480,804
23,910,938
1.~%
1350
12
10
24
20
37
4
68
246
199
476
403
736
80
1.~%
1.~%
1.~%
1~%
1.~%
1.~%
Dental Laboratones
339116
Dental laboratories
Otlices of dentiSts
6,995
129,830
1,749
238
$4,100,626
$100,431,324
586,222
773,560
10. 55%
621210
8.47%
61,873
65,557
$1,632
$1,636
0.28%
0.21%
2.64%
2.50%
Totals I Averages
207.586
4,088
$877,101,106
8,145,219
7.42%
604,340
$9,197
0.11%
1.52%
11
--
11
indicates areas where data are not avmlah le (\\.-'hile the average revenues and implied profits for the Beryllium Production (T\AT\::S :l1141 9) and Beryllium Oxide (NA TC-::S 1271 Ba) industries can he
calculated, they would in no way reflect the actual revenues and profits of the affected facilities
Source: OSHA, Drcctoratc of Standards and Guidance, Office ofRcgulatory Analysis.
47697
annualized costs equal to 10 percent of
annual profits—below which the
E:\FR\FM\07AUP2.SGM
37
$3,060,744
$1,681,585
$4,781,561
$25,454,383
$2,209,657
$891,600
$3,757,849
$4,489,845
$3,720,514
$3,499,273
$1,715,429
$20,000,705
A II other motor vehicle p8rts manufrrctming
336999
of annualized costs equal to one percent
of annual revenues—and, secondarily,
PO 00000
$8,214
$8,148
$7,994
$8,464
$7,957
$7,957
$7,957
$8,0S7
$9,019
$8,660
$8,766
$7,957
Railroad rolling stock
333922
Compliance Costs
As a
As a
Eda~ishrnent Perct'nt of Pernnt of
($)
Rewnues
Profits
Per
486,402
1,163,538
453,735
1,066,885
385,894
243,036
199,542
436,5:17
2,887,552
921,324
207,405
78,080
336510
Pump and pumping equipment manufactunng
Rate
Per
Establishment
($)
4.68%
5.36%
5.36%
5.36%
5.36%
1.83%
1.83%
l.Kl%
5.47%
6.56%
4.26%
5.42%
Travel trailer and camper manufacturing
333911
Total ($1,000)
I
Profit
10,394,697
21,708,209
8,465,361
19,904,948
7,199,644
13,312,072
10,929,757
2:l,910,9.lS
52,775,180
14,038,417
4,870,523
1,441,278
336399a
Heating eqmpment (except warm air furnaces) manufacturmg
Per
E'!>tablishment
($)
$4,781,561
$12,395,387
$6,569,120
$7,444,451
$10,972,258
$9,877,558
$7,465,024
$:12,279,766
$11,927,191
$5,250,368
$5,815,404
$31,650,469
460
571
776
374
L524
742
683
333414a
I
Revenues
Federal Register / Vol. 80, No. 152 / Friday, August 7, 2015 / Proposed Rules
19:20 Aug 06, 2015
As previously discussed, OSHA has
established a minimum threshold level
VerDate Sep<11>2014
Table TX-R, continued
Screening Analysis for Establishments Affected by the Proposed Beryllium Standard
With Costs C:alculatedUdng a Three Percent Discount Rate
mstockstill on DSK4VPTVN1PROD with PROPOSALS2
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Federal Register / Vol. 80, No. 152 / Friday, August 7, 2015 / Proposed Rules
Agency has concluded that costs are
unlikely to threaten the economic
viability of an affected industry. The
results of OSHA’s threshold tests for all
affected establishments are displayed in
Table IX–8. For all affected
establishments, the estimated
annualized cost of the proposed rule is,
on average, equal to 0.11 percent of
annual revenue and 1.52 percent of
annual profit.
As Table IX–8 shows, there are no
industries in which the annualized costs
of the proposed rule exceed one percent
of annual revenues. However there are
three six-digit NAICS industries where
annualized costs exceed ten percent of
annual profits.
NAICS 331525 (Copper foundries
except die-casting) has the highest cost
impact as a percentage of profits. NAICS
331525 is made up of two types of
copper foundries: sand casting
foundries and non-sand casting
foundries, incurring an annualized cost
as a percent of profit of 16.25 percent
and 14.92 percent, respectively. The
other two six-digit NAICS industries
where annualized costs exceed ten
percent of annual profits are NAICS
331534: Aluminum foundries (except
die-casting), 13.65 percent; and NAICS
811310: Commercial and industrial
machinery and equipment repair, 10.19
percent.
OSHA believes that the berylliumcontaining inputs used by these
industries have a relatively inelastic
demand for three reasons. First,
beryllium has rare and unique
characteristics, including low mass,
high melting temperature, dimensional
stability over a wide temperature range,
strength, stiffness, light weight, and
high elasticity (‘‘springiness’’) that can
significantly improve the performance
of various alloys. These characteristics
cannot easily be replicated by other
materials. In economic terms, this
means that the elasticity of substitution
between beryllium and non-beryllium
inputs will be low. Second, products
which contain beryllium or berylliumalloy components typically have highperformance applications (whose
performance depends on the use of
higher-cost beryllium). The lack of
available competing products with these
performance characteristics suggests
that the price elasticity of demand for
products containing beryllium or
beryllium-alloy components will be
low. Third, components made of
beryllium or beryllium-containing
alloys typically account for only a small
portion of the overall cost of the
finished goods that these parts are used
to make. For example, the cost of brakes
made of a beryllium-alloy used in the
VerDate Sep<11>2014
20:43 Aug 06, 2015
Jkt 235001
production of a jet airplane represents a
trivial percentage of the overall cost to
produce that airplane. As economic
theory indicates, the elasticity of
derived demand for a factor of
production (such as beryllium) varies
directly with the elasticity of
substitution between the input in
question and other inputs; the price
elasticity of demand for the final
product that the input is used to
produce; and, in general, the share of
the cost of the final product that the
input accounts for. Applying these three
conditions to beryllium points to the
relative inelastic derived demand for
this factor of production and the
likelihood that cost increases resulting
from the proposed rule would be passed
on to the consumer in the form of higher
prices.
A secondary point is that the
establishments in an industry that use
beryllium may be more profitable than
those that don’t. This follows from the
prior arguments about beryllium’s rare
and desirable characteristics and its
valuable applications. For example, of
the 208 establishments that make up
NAICS 331525, OSHA estimated that 45
establishments (or 21 percent) work
with beryllium. Of the 394
establishments that make up NAICS
331524, OSHA estimated that only 7
establishments (less than 2 percent)
work with beryllium. Of the 21,960
establishments that make up NAICS
811310, OSHA estimated that 143 (0.7
percent) work with beryllium. However,
when OSHA calculated the cost-toprofit ratio, it used the average profit per
firm for the entire NAICs industry, not
the average profit per firm for firms
working with beryllium.
(1) Normal Year-to-Year Variations in
Prices and Profit Rates
The United States has a dynamic and
constantly changing economy in which
an annual percentage increase in
industry revenues or prices of one
percent or more are common. Examples
of year-to-year changes in an industry
that could cause such an increase in
revenues or prices include increases in
fuel, material, real estate, or other costs;
tax increases; and shifts in demand.
To demonstrate the normal year-toyear variation in prices for all the
manufacturers in general industry
affected by the proposed rule, OSHA
developed in the PEA year-to-year
producer price indices and year-to-year
percentage changes in producer prices,
by industry, for the years 1999–2010.
For all of the industries estimated to be
affected by this proposed standard over
the 12-year period, the average change
in producer prices was 4.4 percent a
PO 00000
Frm 00134
Fmt 4701
Sfmt 4702
year—which is over 4 times as high as
OSHA’s 1 percent cost-to-revenue
threshold. For the industries found to
have the largest estimated potential
annual cost impact as a percentage of
revenue shown in Chapter VI of the PEA
are—NAICS 331524: Aluminum
Foundries (except Die-Casting), (0.71
percent); NAICS 331525(a and b):
Copper Foundries (except Die-Casting)
(average of 0.81 percent); NAICS
332721a: Precision Turned Product
Manufacturing of high content
beryllium (0.49 percent); 21 and NAICS
811310: Commercial and Industrial
Machinery and Equipment (Except
Automotive and Electronic) Repair and
Maintenance (0.55 percent)—the
average annual changes in producer
prices in these industries over the 12year period analyzed were 3.1 percent,
8.2 percent, 3.6 percent and 2.3 percent,
respectively.
Based on these data, it is clear that the
potential price impacts of the proposed
rule in affected industries are all well
within normal year-to-year variations in
prices in those industries. The
maximum cost impact of the proposed
rule as a percentage of revenue in any
affected industry is 0.84 percent, while,
as just noted, the average annual change
in producer prices for affected
industries was 4.4 percent for the period
1999–2010. In fact, Chapter VI of the
PEA shows two of the industries within
the secondary smelting, refining, and
alloying group, for example, the prices
rose over 60 percent in one year without
imperiling the existence of those
industries. Thus, OSHA preliminarily
concludes that the potential price
impacts of the proposal would not
threaten the economic viability of any
industries affected by this proposed
standard.
Profit rates are also subject to the
dynamics of the U.S. economy. A
recession, a downturn in a particular
industry, foreign competition, or the
increased competitiveness of producers
of close domestic substitutes are all
easily capable of causing a decline in
profit rates in an industry of well in
excess of ten percent in one year or for
several years in succession.
To demonstrate the normal year-toyear variation in profit rates for all the
manufacturers affected by the proposed
rule, OSHA presented data in the PEA
on year-to-year profit rates and year-toyear percentage changes in profit rates,
by industry, for the years 2002–2009.
For the industries that OSHA has
estimated will be affected by this
21 By contrast, NAICS 332721b: Precision Turned
Product Manufacturing of low content beryllium
alloys has a cost to revenue ratio below 0.4 percent.
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Federal Register / Vol. 80, No. 152 / Friday, August 7, 2015 / Proposed Rules
mstockstill on DSK4VPTVN1PROD with PROPOSALS2
proposed standard over the 8-year
period, the average change in profit
rates is calculated to be 39 percent per
year. For the industries with the largest
estimated potential annual cost impacts
as a percentage of profit—NAICS
331524: Aluminum foundries (except
die-casting), (14 percent); NAICS
331525(a and b): Copper foundries
(except die-casting) (16 percent); NAICS
332721a: Precision Turned Product
Manufacturing of high content
beryllium (8 percent); 22 and NAICS
811310 Commercial and Industrial
Machinery and Equipment (Except
Automotive and Electronic) Repair and
Maintenance (10 percent)—the average
annual changes in profit rates in these
industries over the eight-year period
were 35 percent, 35 percent, 11 percent,
and 5 percent, respectively.
A longer-term loss of profits in excess
of 10 percent a year could be more
problematic for some affected industries
and might conceivably, under
sufficiently adverse circumstances,
threaten an industry’s economic
viability. However, as previously
discussed, OSHA’s analysis indicates
that affected industries would generally
not absorb the costs of the proposed rule
in reduced profits but, instead, would
be able to pass on most or all of those
costs in the form of higher prices (due
to the relative price inelasticity of
demand for beryllium and berylliumcontaining inputs). It is possible that
such price increases will result in some
reduction in output, and the reduction
in output might be met through the
closure of a small percentage of the
plants in the industry. The only realistic
circumstance where an entire industry
would be significantly affected by small
potential price increases would be
where there is a very close or perfect
substitute product available not subject
to OSHA regulation. In most cases
where beryllium is used, there is no
substitute product that could be used in
place of beryllium and achieve the same
level of performance. The main
potential concern would be substitution
by foreign competition, but the
following discussion reveals why such
competition is not likely.
(2) International Trade Effects
World production of beryllium is a
thin market, with only a handful of
countries known to process beryllium
ores and concentrates into beryllium
products, and characterized by a high
degree of variation and uncertainty. The
United States accounts for
22 By contrast, NAICS 332721b: Precision Turned
Product Manufacturing of low content beryllium
alloys has a cost to profit ratio of 6 percent.
VerDate Sep<11>2014
19:20 Aug 06, 2015
Jkt 235001
approximately 65 percent of world
beryllium deposits and 90 percent of
world production, but there is also a
significant stockpiling of beryllium
materials in Kazakhstan, Russia, China,
and possibly other countries (USGS,
2013a). For the individual years 2008–
2012, the United States’ net import
reliance as a percentage of apparent
consumption (that is, imports minus
exports net of industry and government
stock adjustments) ranged from 10
percent to 61 percent (USGS, 2013b). To
assure an adequate stockpile of
beryllium materials to support national
defense interests, the U.S. Department
of Defense, in 2005, under the Defense
Production Act, Title III, invested in a
public-private partnership with the
leading U.S. beryllium producer to
build a new $90.4 million primary
beryllium facility in Elmore, Ohio.
Construction of that facility was
completed in 2011 (USGS, 2013b).
One factor of importance to firms
working with beryllium and beryllium
alloys is to have a reliable supply of
beryllium materials. U.S. manufacturers
can have a relatively high confidence in
the availability of beryllium materials
relative to manufacturers in many
foreign countries, particularly those that
do not have economic or national
security partnerships with the United
States.
Firms using beryllium in production
must consider not just the cost of the
chemical itself but also the various
regulatory costs associated with the use,
transport, and disposal of the material.
For example, for marine transport,
metallic beryllium powder and
beryllium compounds are classified by
the International Maritime Organization
(IMO) as poisonous substances,
presenting medical danger. Beryllium is
also classified as flammable. The United
Nations classification of beryllium and
beryllium compounds for the transport
of dangerous goods is ‘‘poisonous
substance’’ and, for packing, a
‘‘substance presenting medium danger’’
(WHO, 1990). Because of beryllium’s
toxicity, the material is subject to
various workplace restrictions as well as
international, national, and State
requirements and guidelines regarding
beryllium content in environmental
media (USGS, 2013a).
As the previous discussion indicates,
the production and use of beryllium and
beryllium alloys in the United States
and foreign markets appears to depend
on the availability of production
facilities; beryllium stockpiles; national
defense and political considerations;
regulations limiting the shipping of
beryllium and beryllium products;
international, national, and State
PO 00000
Frm 00135
Fmt 4701
Sfmt 4702
47699
regulations and guidelines regarding
beryllium content in environmental
media; and, of course, the special
performance properties of beryllium and
beryllium alloys in various applications.
Relatively small changes in the price of
beryllium would seem to have a minor
effect on the location of beryllium
production and use. In particular, as a
result of this proposed rule, OSHA
would expect that, if all compliance
costs were passed through in the form
of higher prices, a price increase of 0.11
percent, on average, for firms
manufacturing or using beryllium in the
United States—and not exceeding 1
percent in any affected industry—would
have a negligible effect on foreign
competition and would therefore not
threaten the economic viability of any
affected domestic industries.
(b) Economic Feasibility Screening
Analysis: Small and Very Small
Businesses
The preceding discussion focused on
the economic viability of the affected
industries in their entirety. Even though
OSHA found that the proposed standard
did not threaten the survival of these
industries, there is still the possibility
that the competitive structure of these
industries could be significantly altered
such as by small entities exiting from
the industry as a result of the proposed
standard.
To address this possibility, OSHA
examined the annualized costs of the
proposed standard per affected small
entity, and per affected very small
entity, for each affected industry. Again,
OSHA used a minimum threshold level
of annualized compliance costs equal to
one percent of annual revenues—and,
secondarily, annualized compliance
costs equal to ten percent of annual
profits—below which the Agency has
concluded that the costs are unlikely to
threaten the survival of small entities or
very small entities or, consequently, to
alter the competitive structure of the
affected industries.
Based on the results presented in
Table IX–9, the annualized cost of
compliance with the proposed rule for
the average affected small entity is
estimated to be $8,108 in 2010 dollars.
Based on the results presented in Table
IX–10, the annualized cost of
compliance with the proposed rule for
the average affected very small entity is
estimated to be $1,955 in 2010 dollars.
These tables also show that there are no
industries in which the annualized costs
of the proposed rule for small entities or
very small entities exceed one percent
of annual revenues. NAICS 331525b:
Sand Copper Foundries (except diecasting) has the highest estimated cost
E:\FR\FM\07AUP2.SGM
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Federal Register / Vol. 80, No. 152 / Friday, August 7, 2015 / Proposed Rules
impact as a percentage of revenues for
small entities, 0.95 percent, and NAICS
336322b: Other motor vehicle electrical
and electronic equipment has the
highest estimated cost impact as a
percentage of revenues for very small
entities, 0.70 percent.
Small entities in four industries—
NAICS 331525: Sand and non-sand
foundries (except die-casting); NAICS
331524(a and b): Aluminum foundries
(except die-casting); NAICS 811310:
Commercial and Industrial Machinery
and Equipment; and NAICS 331522:
Nonferrous (except aluminum) diecasting foundries—have annualized
costs in excess of 10 percent of annual
profits (17.45 percent, 16.12 percent,
11.68 percent, and 10.64 percent,
respectively). Very small entities in 7
industries are estimated to have
annualized costs in excess of 10 percent
of annual profit; NAICS 336322b: Other
motor vehicle electrical and electronic
equipment (38.49 percent); 23 NAICS
336322a: Other motor vehicle electrical
and electronic equipment, (18.18
percent); NAICS 327113: Porcelain
electrical Supply Manufacturing (13.82
percent); NAICS 811310: Commercial
and Industrial Machinery and
Equipment (Except Automotive and
Electronic) Repair and Maintenance
(12.76 percent); NAICS 332721a:
Precision turned product manufacturing
mstockstill on DSK4VPTVN1PROD with PROPOSALS2
23 NAICS 336322 contains entities that fall into
three separate application groups. NAICS 336322b
is in the Beryllium Oxide Ceramics and Composites
application group. NAICS 336322a (which follows
in the text) is in the Fabrication of Beryllium Alloy
Products application group.
VerDate Sep<11>2014
19:20 Aug 06, 2015
Jkt 235001
(10.50 percent); NAICS 336214: Travel
trailer and camper manufacturing (10.75
percent); and NAICS 336399: All other
motor vehicle parts manufacturing
(10.38 percent).
In general, cost impacts for affected
small entities or very small entities will
tend to be somewhat higher, on average,
than the cost impacts for the average
business in those affected industries.
That is to be expected. After all, smaller
businesses typically suffer from
diseconomies of scale in many aspects
of their business, leading to less revenue
per dollar of cost and higher unit costs.
Small businesses are able to overcome
these obstacles by providing specialized
products and services, offering local
service and better service, or otherwise
creating a market niche for themselves.
The higher cost impacts for smaller
businesses estimated for this rule—other
than very small entities in NAICS
336322b: Other motor vehicle electrical
and electronic equipment—generally
fall within the range observed in other
OSHA regulations and, as verified by
OSHA’s lookback reviews, have not
been of such a magnitude to lead to the
economic failure of regulated small
businesses.
The ratio of annualized costs to
annual profit is a sizable 38.49 percent
in NAICS 336322b: Other motor vehicle
electrical and electronic equipment.
However, OSHA believes that the actual
ratio is significantly lower. There are
386 very small entities in NAICS
336322, of which only 6, or 1.5 percent,
are affected entities using beryllium.
When OSHA calculated the cost-to-
PO 00000
Frm 00136
Fmt 4701
Sfmt 4702
profit ratio, it used the average profit per
firm for the entire NAICs industry, not
the average profit rate for firms working
with beryllium. The profit rate for all
establishments in NAICS 336322b was
estimated at 1.83 percent. If, for
example, the average profit rate for a
very small entity in NAICS 336322b
were equal to 5.95 percent, the average
profit rate for its application group,
Beryllium Oxide Ceramics and
Composites, then the ratio of the very
small entity’s annualized cost of the
proposed rule to its annual profit would
actually be 11.77 percent. OSHA
tentatively concludes the 6
establishments in the NAICS
specializing in beryllium production
will have a higher than average profit
rate and will be able to pass much of the
cost onto the consumer for three main
reasons: (1) The absence of substitutes
containing the rare performance
characteristics of beryllium; (2) the
relative price insensitivity of (other)
motor vehicles containing the special
performance characteristics of beryllium
and beryllium alloys; and (3) the fact
that electrical and electronic
components made of beryllium or
beryllium-containing alloys typically
account for only a small portion of the
overall cost of the finished (other) motor
vehicles. The annualized compliance
cost to annual revenue ratio for NAICS
336332b is 0.70 percent, 0.30 percent
below the 1 percent threshold. Based on
OSHA’s experience, price increases of
this magnitude have not historically
been associated with the economic
failure of small businesses.
E:\FR\FM\07AUP2.SGM
07AUP2
mstockstill on DSK4VPTVN1PROD with PROPOSALS2
VerDate Sep<11>2014
TableiX-9
Jkt 235001
PO 00000
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334411
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disc
460
62
$326.127
9
5
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0.65°o
4.420.)
14JJD/(.
2.29qt,
5.01%
$35.475,343
$48.999,093
6.08~0
4.39g0
$2,980,355
$379,730
$19318
7.85%
7.85%
33cl415
0.27~(,
3.41~(,
0.12q-o
L72'}o
4.86°&
Sfmt 4725
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0.84°/o
l0.64q.•i}
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1
11
0.95%
7.85~-Q
8
7
9
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$18.415
6
o.07ofi
0.02<:·n
16.12°•o
16.6"1°(,
18.22%
I. 50°6
0.40%;
2.33q··O
07AUP2
331-!22
Federal Register / Vol. 80, No. 152 / Friday, August 7, 2015 / Proposed Rules
19:20 Aug 06, 2015
85
85
327113h
332612
176
585
.336312a
EP07AU15.016
o.o?~o
2.91%
0.83%..
0.05%
2.65~l:.
136"'
33cl4!7
Othermoior vehicle electrical & electronic equ'
l-f6
20.772 7 -lO
1.83q··b
379.243
$10,048
47701
332116
mstockstill on DSK4VPTVN1PROD with PROPOSALS2
47702
VerDate Sep<11>2014
Table IX -9. continued
PO 00000
Fabricated
3323.13
Plate workmanufaduring
33232:..:
Sheet metal \;;to1X nm1u:tScturing
33:3.23
Omamcnlal and architec:uml metal worl: manu!
331-.09
Other metal
332919
Other metal valw and pipe fithng
207
-
333111
Fanntmchll:tely
941
18
353414<1
Heating equiptn::nt (except wannair furnaces)
707
5
8
4
Frm 00138
Jkt 235001
332312
332117
Hand and edge tool rnanufacturing
975
3,001
L220
~287
5,622,904
9.799,278
5
nnnufa cturi:ng
~
4 30'1o
Fmt 4701
.B391l
rn'l!Himcturing
Sfmt 4725
33392~
<;
and
333922
Industrial
E:\FR\FM\07AUP2.SGM
333999
}.1otor ,·ehide body mmufacturing
3.\6214
652
585
336399a
336510
Railroad
336999
All other transportation equipment tmnufactut
337215
Sho'\\rase.
157
349
5.454.538
6.30Ll51
$3.348.262
$7,444,451
All other miscellaneous general purpose rnachi
336211
$5.132720
4.68%
5.36%
6,744,933
21.453. 748
4,04-l-,530
15.149.628
12
6
1
24L034
7.00%
33.:999
07AUP2
33341411
333415
283
118
410
33521.2
Household ·vacuutn cleaner 11Bnuf3.ctu.t1ng
335.221
Household cooL-ing appliance !m::tufactming
335211
5.369&
5.36%
L839o
33522S
036~-ll
0.10%
2.42~o
o.o6~o
229,602
347.100
294.852
449,783
$5,769
$4.457
0.05~A)
0.100\J
1.88%,
1.149$99
$9J22
o.o4~o
$5~282
0.13'}•{,
2:76.583
$9.055
0.06~il
0.21%
0.10°o
0.03%
o.02"·"
0.16%
5.47~6
2,698.100
8A90,124
8
29
6.56%1
4,156,603
177.073
140,227
$12,983
$4.339
$6,966
$
4.68~\J
219,418
397.281
$8,363
$11,780
o.:mo.
0.18%
3.Sl~o
2.97~··0
3.45~·o
21,877,797
29
91
5
$89L600
$3,757,849
9
24
l
1
1
$185~373,
Household Iefrigemtorand honr fi·eeZCTlnanu.
35522-t
O.l8°o
0.2]<;;,
1.83%
$941,637
1
$7379
$7,010
$6.548
$5,858
$6.301
3.980,&
2.50"&
3.88%
4.50°o
7.670•(;
1
5
335211
2.04~&
0.22~·b
5.36~h
s he!vin~. and lo~ker n1<1ni
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0.10%1
o.92'lo
2.95°&
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l. 96°'o
0.99'%
19,857
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$8,278
$7m'
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33.2212
4 03~o
4.03%>
4.03%
o.o5q·o
0.07%
1.06q&
881,709
L239JJ64
1.664,253
$15,789
$15,870
0.04Qil
o.Ol?o
0.95qo
15Qi<)
0.050,'0
31L284
$1,7-ID
o.02"·o
0.56~&
L42~&
4.03%
4.03~.;)
1. 79"&
Federal Register / Vol. 80, No. 152 / Friday, August 7, 2015 / Proposed Rules
19:20 Aug 06, 2015
0.37%
1.14%
!34
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336322c
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209'
159
397
29
10
8
20
273
14
..,..,
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58
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transmission and
and
pov;,~er
train
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lll.::.'lllllfac ttuin.£
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are not
calculated, thev would in no way ret1ec: the actual revenues and pror!ts ofthe affected fucilities
Sour~c:
OSHI\. Directorate ofStmHlards and Guidance. otlice
1. 83°1J
L83Q0
1.83%
1.83%
1.83%
1.83%
13,448,854
523.886
163,568
379.243
935,554
1.005.365
2:_<2.903
$16.015
3.06%
3.71q,,(i
$16.355'
$17.
$18,828
0.08"-o
$3.156.130
$687,134,666
470.853
764,
4.31%
1.29~~o
2.0l~o
0.03%
0.05%
i.
1.83~0
$16.715
225
Totai/Awrage
28,695.417
umo
")"'7
Offices of de:ntis ts
areas \Vhere
$20.000.705
10.55~0
49.696
0.03"-<>
0.06°/o
SL394
0.30":"
0.21"-o
SL630
7.55°/o
550,848
2.81%t
2.51%
1.47%
32"1
Federal Register / Vol. 80, No. 152 / Friday, August 7, 2015 / Proposed Rules
19:20 Aug 06, 2015
Table IX-9, continued
47703
EP07AU15.018
mstockstill on DSK4VPTVN1PROD with PROPOSALS2
47704
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Jkt 235001
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$192368
Porcelain electlical
rmnufucruring \seconda!J'L
CeUuiar telephon;;s nRnnfucturi:ng
445
4
Con~ act
373
4
.38
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discplaversn11nufucturitcg
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$379,730
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7.85%
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$6,8~8
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$6,962
$6,171
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$247,7~0
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$2.980,355
6.85%,
5.78~:¢
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Alunlinum di~-ca3ting foundrhs
3315:24
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Ahtrnlnum foundries (except die--::asting)
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6
349,811
217
alurninun:l) di2-cas tm~g foundrie-s
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1
35;
18
2.2og_,9
332612
li~ht,gau~e sp~g. n:anufu.cturin,g
164
164
332116
:Metal
807
40
5~LB··&
$288,086
$3.5-B
334417
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Othertmtorvehicle el~trical & electrm1k' equipn1ent
106
ll
7 .85~'0
$694211
386
60
1.83%
$379,.H3
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3-19,811
$906,::-16
SAO%,
$3.Ql4:
0.28%
0.25('./Q
$3,007
0.33%
HUS%
3.1:5~/Q
Federal Register / Vol. 80, No. 152 / Friday, August 7, 2015 / Proposed Rules
19:20 Aug 06, 2015
53
3C!7113h
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VerDate Sep<11>2014
Table lX-Hl. COIItin!led
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0
$100,643
$68!375
332~12
~51
~
332312
.1,1 '9
35
845
14
2~778
5.12q-s·
406J6l
176,.878
$3.171
0.35~%J
243.251
$2.299
0.16%
3.29~elmo!alworlcmamd3clurillg
Oman::en!aland archliecrr:ral n::etal worlcrr,ru::ufactming.
332323
nunufacturing
907290
L~/4,043
$1.00~.308
1.192.1}80
5.61%
7..f'!/('h
.+. 74q,·s
$2,620
Fmt 4701
O:her:m::-tal ccntainer1mnnfaeturinF£
203
33;919
331.99'9
Othern::etalval\·e and pipe fitting manufacturing
ns:
333111
Fann nncllh:e:Ty at:d equ_ipilll"11t manufacturing
othernUscella.ne-ous
""
924.1 ~4
242~03-4
S2.'17!
0.27~~
7.00%
686,061
$4.302
0.27%>
6.21%
3.90(YO
899,831
24
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1575,580
$187,.607
l
7.00%
0.28~'&
4.06%.
$2,299
0.20%
3.100,0
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$365551
1,167,103
$.t97
!,981,660
5.369'fL
$541.532
1.33054"7
5.36%1
$213,335
1,G9·1,026
673
~
283
2
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$Ll5U52
Ll80.669
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mdusttial tmek, !1nc:or. !railer, and s!ackerulll.cl:ine1y manufac1
195
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4
l
333999
All other miscellaneous
975
10
336211
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Tm~:el
5
294$52
0.10~,c{l
4.2oo,;,
H9,783
0.12%
l.33{h)
4
336214
333911
333912
fu~
and purrping -equipme!:t rnanufucturing
conveyiEg equipr:.1e11t
-107
trail2-r and canpernnnufa.:nuatg
653
307
07AUP2
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333414b
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l
$189,164.
i..
189
13
60
r:e,xrept sarmairfu1naces! manufuctu1~E
283
wannairheati11g,aud indumia!refrigemtbn'
395
1
0 ..25%
0.19%
1.83%
1.839-'0
5A7;;Ya'
78..t.l5
$2.300
509.796
$2,424
0.19%
lO.JS%
46.622
$3,949
0.69%
12.76%
219.+18
~2506
$253,916
4
20
28
~quipment
333415
$.2.761
$2.298
5.-t2~~o
333411
$2.335
Ul9,899
0.17%
1.171958
0
336510
333412
5.84%1
9.70~/o
32
332439
623~-·~
10
Household vactnlmcleantt· manufacturing
18
House]:old cooking appliance rnauufacturing
:)i'
2
335:222
Housel:: old
6
335224
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Othenmiorhm;sehold aoolianre mmufacrurina
!5
0
~.68'~{,
357ft/()
3.91~,6
3.84%,
294.852
0.05~/{}
0
335228
1.291.699
$806,99-1
0
335:211
$365.551
L500,678
O.J7%,
0.18%
$.2S3.62R
4
335.:!12
.:1.156.603.
335211
ru:d household fan n1anufacturing
hon:e
equ.iprr:et~t
1T1[tllt:fachuing-
0
$1.151
Federal Register / Vol. 80, No. 152 / Friday, August 7, 2015 / Proposed Rules
19:20 Aug 06, 2015
331513
332117
!.417.419
0.08°"0
!,239,064
$66.863
$1.831
1.66-1253
1,1 i3.037
-L03~}"[,
$1.056
2.23%;
16.660266
4.03%>
47705
EP07AU15.020
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19
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116
5
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:ivlotorvehicle transmission. and po,Yer train parts manufacrnrin.
2-1.0
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9
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!67
7
3JG370
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225
336391
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-1,.55%·
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0.21%
1.52%·
0.291?,·0
3..18%
$1.329
34
339116
Dental labcm:ories
6:.::1:::10
$283.285
128.3-17.342
TOO!J/Average
$6i9.421
10.55%)
$-19,696
$922
8A79,Q
1.807,075
Offices ofdt:11tists
$64,809
$1A6-l
8.27~·'0
$56,189
07AUP2
Beryl!iumProd·Gction (NAICS 331419) a"d Beavlli:umO;tide(NAICS 317113a)bduslries can
'.;:-ayrefle-ct
Source: OSHA. Directorate ofStandardsru:d 0Jidance. OfficeofRegulato:y Anatysi>.
EP07AU15.021
0.08?·0
0.06%
$1.056
Federal Register / Vol. 80, No. 152 / Friday, August 7, 2015 / Proposed Rules
19:20 Aug 06, 2015
Table IX-10, continued
Federal Register / Vol. 80, No. 152 / Friday, August 7, 2015 / Proposed Rules
(c) Regulatory Flexibility Screening
Analysis
To determine if the Assistant
Secretary of Labor for OSHA can certify
that the proposed beryllium standard
will not have a significant economic
impact on a substantial number of small
entities, the Agency has developed
screening tests to consider minimum
threshold effects of the proposed
standard on small entities. The
minimum threshold effects for this
purpose are annualized costs equal to
one percent of annual revenues, and
annualized costs equal to five percent of
annual profits, applied to each affected
industry. OSHA has applied these
screening tests both to small entities and
to very small entities. For purposes of
certification, the threshold level cannot
be exceeded for affected small entities
or very small entities in any affected
industry.
Tables IX–9 and Table IX–10,
presented above, show that the
annualized costs of the proposed
standard do not exceed one percent of
annual revenues for affected small
entities or affected very small entities in
any affected industry. These tables also
show that the annualized costs of the
proposed standard exceed five percent
of annual profits for affected small
entities in 12 industries and for affected
very small entities in 30 industries.
OSHA is therefore unable to certify that
the proposed standard will not have a
significant economic impact on a
substantial number of small entities and
must prepare an Initial Regulatory
Flexibility Analysis (IRFA). The IRFA is
presented in Chapter IX of the PEA and
is reproduced in Section IX.I of this
preamble.
mstockstill on DSK4VPTVN1PROD with PROPOSALS2
G. Benefits and Net Benefits
In this section, OSHA presents a
summary of the estimated benefits and
net benefits of the proposed beryllium
rule. This section proceeds in five steps.
The first step estimates the numbers of
diseases and deaths prevented by
comparing the current (baseline)
situation to a world in which the
proposed PEL is adopted in a final
standard to a world in which employees
are exposed at the level of the proposed
PEL throughout their working lives. The
second step also assumes that the
proposed PEL is adopted, but uses the
results from the first step to estimate
what would happen under a more
realistic scenario in which employees
have been exposed for varying periods
of time to the baseline situation and will
thereafter be exposed to the new PEL.
The third step covers the
monetization of benefits. Then, in the
VerDate Sep<11>2014
19:20 Aug 06, 2015
Jkt 235001
fourth step, OSHA estimates the net
benefits and incremental benefits of the
proposed rule by comparing the
monetized benefits to the costs
presented in Chapter V of the PEA. The
models underlying each step inevitably
need to make a variety of assumptions
based on limited data. In the fifth step,
OSHA provides a sensitivity analysis to
explore the robustness of the estimates
of net benefits with respect to many of
the assumptions made in developing
and applying the underlying models. A
full explanation of the derivation of the
estimates presented here is provided in
Chapter VII of the PEA for the proposed
rule. OSHA invites comments on any
aspect of the data and methods used to
estimate the benefits and net benefits of
this proposed rule. Because dental labs
constitute a significant source of both
costs and benefits to the rule (over 40
percent), OSHA is particularly
interested in comments regarding the
appropriateness of the model,
assumptions, and data to estimating the
benefits to workers in that industry.
OSHA has added to the docket the
spreadsheets used to calculate the
estimates of benefits outlined below
(OSHA, 2015a). Those interested in
exploring the details and methodology
of OSHA’s benefits analysis, such as
how the life table referred to below was
developed and applied, should consult
those spreadsheets.
Step 1—Estimation of the Steady-State
Number of Beryllium-Related Diseases
Avoided
Methods of Estimation
The first step in OSHA’s development
of the benefits analysis compares the
situation in which employees continue
to be at baseline exposure levels for
their entire working lives to the
situation in which all employees have
been exposed at a given PEL for their
entire working lives. This is a
comparison of two steady-state
situations. To do this, OSHA must
estimate both the risk associated with
the baseline exposure levels and the risk
following the promulgation of a new
beryllium standard. OSHA’s approach
assumes for inputs such as the turnover
rate and the exposure response function
that they are similar across all workers
exposed to beryllium, regardless of
industry.
An exposure-response model,
discussed below, is used to estimate a
worker’s risk of beryllium-related
disease based on the worker’s
cumulative beryllium exposure. The
Agency used a lifetime risk model to
estimate the baseline risk and the
associated number of cases for the
PO 00000
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Fmt 4701
Sfmt 4702
47707
various disease endpoints. A lifetime
risk model explicitly follows a worker
each year, from work commencement
onwards, accumulating the worker’s
beryllium exposure in the workplace
and estimating outcomes each year for
the competing risks that can occur. To
go from exposure to number of cases,
the Agency needs to estimate an
exposure-response relationship, and this
is discussed below. The possible
outcomes are no change, or the various
health endpoints OSHA has considered
(beryllium sensitization, CBD, lung
cancer, and the mortality associated
with these endpoints). As part of the
estimation discussion, OSHA will
mention specific parameters used in
some of the estimation methods, but
will further discuss how these
parameters were derived later in this
section.
The baseline lifetime risk model is the
most complicated part of the analysis.
The Agency only needs to make
relatively simple adjustments to this
model to reflect changes in activities
and conditions due to the standard,
which, working through the model, then
lead to changes in relevant health
outcomes. There are three channels by
which the standard generates benefits.
First are estimated benefits due to the
lowering of the PEL. Second are
estimated benefits with further exposure
reductions from the substitution of nonberyllium for beryllium-containing
materials, ending workers’ beryllium
exposures entirely. This potential
source of benefits is particularly
significant with respect to OSHA’s
assumptions for how dental labs are
likely to reduce exposures (see below).
Finally, the model estimates benefits
due to the ancillary programs that are
required by the proposed standard. The
last channel affects CBD and
sensitization, endpoints which may be
mitigated or prevented with the help of
ancillary provisions such as dermal
protection and medical surveillance for
early detection, and for which the
Agency has some information on the
effects on risk of ancillary provisions.
The benefits of ancillary provisions are
not estimated for lung cancer because
the benefits from reducing lung cancer
are considered to be the result of
reducing airborne exposure only and
thus the ancillary provisions will have
no separable effect on airborne
exposures. The discussion here will
concentrate on CBD as being the most
important and complex endpoint, and
most illustrative of other endpoints: The
structure for other endpoints is the
same; only the exposure response
functions are different. Here OSHA will
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07AUP2
mstockstill on DSK4VPTVN1PROD with PROPOSALS2
47708
Federal Register / Vol. 80, No. 152 / Friday, August 7, 2015 / Proposed Rules
discuss first the exposure-response
model, then the structure of the year-toyear changes for a worker, then the
estimated exposure distribution in the
affected population and the risk model
with the lowering of the PEL, and, last,
the other adjustments for the ancillary
benefits and the substitution benefits.
The exposure response model is
designed to translate beryllium
exposure to risk of adverse health
endpoints. In the case of beryllium
sensitization and CBD, the Agency uses
the cumulative exposure data from a
beryllium manufacturing facility.
Specifically, OSHA uses the quartile
data from the Cullman plant that is
presented in Table VI–7 of the
Preliminary Risk Assessment in the
preamble. The raw data from this study
show cases of CBD with cumulative
exposures that would represent an
average exposure level of less than 0.1
mg/m3 if exposed for 10 years; show
cases of CBD with exposures lasting less
than one year; and show cases of CBD
with actual average exposure of less
than 0.1 mg/m3.
Prevalence is defined as the
percentage of persons with a condition
in a population at a given point in time.
The quartile data in Table VI–7 of the
Preliminary Risk Assessment are
prevalence percentages (the number of
cases of illness documented over several
years in the 319 person cohort from the
Cullman plant) at different cumulative
exposure levels. The Cullman data do
not cover persons who left the work
force or what happened to persons who
remained in the workforce after the
study was completed. For the lifetime
risk model, the prevalence percentages
will be translated into incidence
percentages—the estimated number of
new cases predicted to occur each year.
For this purpose OSHA assumed that
the incidence for any given cumulative
exposure level is constant from year to
year and continues after exposure
ceases.
To calculate incidence from
prevalence, OSHA assumed a steady
state in which both the size of the
beryllium-exposed affected population,
exposure concentrations during
employment and prevalence are
constant over time. If these conditions
are met, and turnover among workers
with a condition is equal to turnover for
workers without a condition, then the
incidence rate will be equal to the
turnover rate multiplied by the
prevalence rate. If the turnover rate
among persons with a condition is
higher than the turnover rate for
workers without the condition, then this
assumption will underestimate
incidence. This might happen if, in
VerDate Sep<11>2014
19:20 Aug 06, 2015
Jkt 235001
addition to other reasons for leaving
work, persons with a condition leave a
place of employment more frequently
because their disabilities cause them to
have difficulty continuing to do the
work. If the turnover rate among persons
with a condition is lower than the
turnover rate for workers without the
condition, then this assumption will
overestimate incidence. This could
happen if an employer provides special
benefits to workers with the condition,
and the employer would cease to
provide these benefits if the employee
left work.
To illustrate, if 10 percent of the work
force (including 10 percent of those
with the condition) leave each year and
if the overall prevalence is at 20 percent,
then a 2 percent (10 percent times 20
percent) incidence rate will be needed
in order to keep a steady 20 percent
group prevalence rate each year.
OSHA’s model assumes a constant 10
percent turnover rate (see later in this
section for the rationale for this
particular turnover rate). While turnover
rates are not available for the specific set
of employees in question, for
manufacturing as a whole, the turnover
rates are greater than 20 percent, and
greater than 30 percent for the economy
as a whole (BLS, 2013). For this
analysis, OSHA assumed an effective
turnover rate of 10 percent. Different
turnover rates will result in different
incidence rates. The lower the turnover
rate the lower the estimated incidence
rate. This is a conservative assumption
for the industries where turnover rates
may be higher. However, some
occupations/industries, such as dental
lab technicians, may have lower
turnover rates than manufacturing
workers. Additionally, the typical
dental technician even if leaving one
workplace, has significant likelihood of
continuing to work as a dental
technician and going to another
workplace that uses beryllium. OSHA
welcomes comments on its turnover
estimates and on sectors, such as dental
laboratories, where turnover may be
lower than ten percent.
Using Table VI–7 of the Preliminary
Risk Assessment, when a worker’s
cumulative exposure is below 0.147 (mg/
m3-years), the prevalence of CBD is 2.5
percent and so the derived annual risk
would be 0.25 percent (0.10 × 2.5
percent). It will stay at this level until
the worker has reached a cumulative
exposure of 1.468, where it will rise to
0.80 percent.
The model assumes a maximum 45year (250 days per year) working life
(ages 20 through 65 or age of death or
onset of CBD, whichever is earlier) and
follows workers after retirement through
PO 00000
Frm 00144
Fmt 4701
Sfmt 4702
age 80. The 45-year working life is based
on OSHA’s legal requirements and is
longer than the working lives of most
exposed workers. A shorter working life
will be examined later in this section.
While employed, the worker
accumulates beryllium exposure at a
rate depending on where the worker is
in the empirical exposure profile
presented in Chapter IV of the PEA (i.e.,
OSHA calculates a general risk model
which depends on the exposure level
and then plug in our empirical exposure
distribution to estimate the final number
of cases of various health outcomes).
Following a worker’s retirement, there is
no increased exposure, just a constant
annual risk resulting from the worker’s
final cumulative exposure.
OSHA’s model follows the population
of workers each year, keeping track of
cumulative exposure and various health
outcomes. Explicitly, each year the
model calculates: The increased
cumulative exposure level for each
worker versus last year, the incidence at
the new exposure level, the survival rate
for this age bracket, and the percentage
of workers who have not previously
developed CBD in earlier years.
For any individual year, the equation
for predicting new cases of CBD for
workers at age t is:
New CBD cases rate(t) = modeled
incidence rate(t) * survival rate(t) * (1currently have CBD rate(t)), where the
variables used are:
New CBD cases rate(t) is the output
variable to be calculated;
cumulative exposure(t) = cumulative
exposure(t-1) + current exposure;
modeled incidence rate(t) is a function of
cumulative exposure; and
survival rate(t) is the background survival
rate from mortality due to other causes in the
national population.
Then for the next year the model
updates the survival rate (due to an
increase in the worker’s age), incidence
rate (due to any increased cumulative
exposure), and the rate of those
currently having CBD, which increases
due to the new CBD case rate of the year
before. This process then repeats for all
60 years.
It is important to note that this model
is based on the assumption that
prevalence is explained by an
underlying constant incidence, and as a
result, prevalence will be different
depending on the average number of
years of exposure in the population
examined and (though a sensitivity
analysis is provided later) on the
assumption of a maximum of 45 years
of exposure. OSHA also examined
(OSHA 2015c) a model in which
prevalence is constant at the levels
shown in Table VI–7 of the preliminary
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risk assessment, with a population age
(and thus exposure) distribution
estimated based on an assumed constant
turnover rate. OSHA solicits comment
on this and other alternative approaches
to using the available prevalence data to
develop an exposure-response function
for this benefits analysis.
In the next step, OSHA uses its model
to take into account the adoption of the
lower proposed PEL. OSHA uses the
exposure profile for workers as
estimated in Chapter IV of the PEA for
each of the various application groups.
These exposure profiles estimate the
number of workers at various exposure
levels, specifically the ranges less than
0.1 mg/m3, 0.1 to 0.2, 0.2 to 0.5, 0.5 to
1.0, 1.0 to 2.0, and greater than 2.0 mg/
m3. Translating these ranges into
exposure levels for the risk model, the
model assumes an average exposure
equal to the midpoint of the range,
except for the lower end, where it was
assumed to be equal to 0.1 mg/m3, and
the upper end, where it was assumed to
be equal to 2.0 mg/m3.
The model increases the workers’
cumulative exposure each year by these
midpoints and then plugs these new
values into the new case equation. This
alters the incidence rate as cumulative
exposure crosses a threshold of the
quartile data. So then using the
exposure profiles by application group
from Chapter IV of the PEA, the baseline
exposure flows through the life time risk
model to give us a baseline number of
cases. Next OSHA calculated the
number of cases estimated to occur after
the implementation of the proposed PEL
of 0.2 mg/m3. Here OSHA simply takes
the number of workers with current
average exposure above 0.2 mg/m3 and
set their exposure level at 0.2 mg/m3; all
exposures for workers exposed below
0.2 mg/m3 stay the same. After adjusting
the worker exposure profile in this way,
OSHA goes through all the same
calculations and obtains a post-standard
number of CBD cases. Subtracting
estimated post-standard CBD cases from
estimated pre-standard CBD cases gives
us the number of CBD cases that would
be averted due to the proposed change
in the PEL.
Based on these methods, OSHA’s
estimate of benefits associated with the
proposed rule does not include benefits
associated with current compliance that
have already been achieved with regard
to the new requirements, or benefits
obtained from future compliance with
existing beryllium requirements.
However, available exposure data
indicate that few employees are
currently exposed above the existing
standard’s PEL of 2.0 mg/m3. To achieve
consistency with the cost estimation
method in chapter V, all employees in
the exposure profile that are above 2.0
mg/m3 are assumed to be at the 2.0 mg/
m3 level.
There is also a component that
applies only to dental labs. OSHA has
preliminarily assumed, based on the
estimates of higher costs for engineering
controls than using substitutes
presented in the cost chapter, that rather
than incur the costs of compliance with
the proposed standard, many dental labs
are likely to stop using berylliumcontaining materials after the
promulgation of the proposed
standard.24 OSHA estimated earlier in
this PEA that, for the baseline, only 25
percent of dental lab workers still work
with beryllium. OSHA estimates that, if
OSHA adopts the proposed rule, 75
percent of the 25 percent still using
beryllium will stop working with
beryllium; their beryllium exposure
level will therefore drop to zero. OSHA
estimates that the 75 percent of workers
will not be a random sample of the
dental lab exposure profile but instead
will concentrate among workers who are
currently at the highest exposure levels
because it would cost more to reduce
those higher exposures into compliance
with the proposed PEL. Under this
judgment OSHA is estimating that the
rule would eliminate all cases of CBD in
the 75 percent of dental lab workers
with the highest exposure levels. As
discussed in the sensitivity analysis
below, dental labs constitute a
significant source of both costs and
benefits to the rule (over 40 percent),
and the extent to which dental
laboratories substitute other materials
for beryllium has significant effects on
the benefits and costs of the rule. To
derive its baseline estimate of cases of
CBD in dental laboratories, OSHA (1)
estimated baseline cases of CBD using
the existing rate of beryllium use in
dental labs without a projection of
further substitution; (2) estimated cases
of CBD with the proposed regulation
using an estimate that 75 percent of the
dental labs with higher exposure would
switch to other materials and thus
eliminate exposure to beryllium; and (3)
estimated that the turnover rate in the
industry is 10 percent. OSHA welcomes
comments on all aspects of the analysis
of substitution away from beryllium in
the dental laboratories sector.
Estimation results for both dental labs
and non-dental workplaces appear in
the table below.
CBD CASE ESTIMATES, 45-YEAR TOTALS, BASELINE AND WITH PEL OF 0.2 μg/m3
Current beryllium exposure
(μg/m3)
< 0.1
0.1–0.2
0.2–0.5
0.5–1.0
Total
1.0–2.0
> 2.0
Dental labs ...................
Non-dental ...................
827
5,912
636
631
432
738
608
287
155
112
466
214
3,124
7,893
PEL = 0.2 μg/m3 ..........
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Baseline .......................
Total ......................
Dental labs ...................
Non-dental ...................
6,739
679
5,912
1,267
0
631
1,171
0
693
895
0
255
267
0
98
679
0
186
11,017
679
7,774
Total ......................
Dental labs ...................
6,591
148
631
636
693
432
255
608
98
155
186
466
8,454
2,444
Non-dental ...................
0
0
45
32
14
27
119
Total ......................
148
636
478
640
169
493
2,563
Prevented by PEL reduction.
24 In Chapter V (Costs) of the PEA, OSHA
explored the cost of putting in LEV instead of
substitution. The Agency costed an enclosure for 2
technicians: The Powder Safe Type A Enclosure, 32
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inch wide with HEPA filter, AirClean Systems
(2011), which including operating and
maintenance, was annualized at $411 per worker.
This is significantly higher than the annual cost for
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substitution of $166 per worker, shown later in this
section.
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In contrast to this PEL component of
the benefits, both the ancillary program
benefits calculation and the substitution
benefits calculation are relatively
simple. Both are percentages of the
lifetime-risk-model CBD cases that still
occur in the post-standard world. OSHA
notes that in the context of existing CBD
prevention programs, some ancillaryprovision programs similar to those
included in OSHA’s proposal have
eliminated a significant percentage of
the remaining CBD cases (discussed
later in this chapter). If the ancillary
provisions reduce remaining CBD cases
by 90 percent for example, and if the
estimated baseline contains 120 cases of
CBD, and post-standard compliance
with a lower PEL reduces the total to
100 cases of CBD, then 90 of those
remaining 100 cases of CBD would be
averted due to the ancillary programs.
OSHA assumed, based on the clinical
experience discussed further below, that
approximately 65 percent of CBD cases
ultimately result in death. Later in this
chapter, OSHA provides a sensitivity
analysis of the effects of different values
for assuming this percentage at 50
percent and 80 percent on the number
of CBD deaths prevented. OSHA
welcomes comment on this assumption.
OSHA’s exposure-response model for
lung cancer is based on lung cancer
mortality data. Thus, all of the estimated
cases of lung cancer in the benefits
analysis are cases of premature death
from beryllium-related lung cancer.
Finally, in recognition of the
uncertainty in this aspect of these
models, OSHA presents a ‘‘high’’
estimate, a ‘‘low’’ estimate, and uses the
midpoint of these two as our ‘‘primary’’
estimate. The low estimate is simply
those CBD fatalities prevented due to
everything except the ancillary
provisions, i.e., both the reduction in
the PEL and the substitution by dental
labs. The high estimate includes both of
these factors plus all the ancillary
benefits calculated at an effectiveness
rate of 90 percent in preventing cases of
CBD not averted by the reduction of the
PEL. The midpoint is the combination
of reductions attributed to adopting the
proposed PEL, substitution by dental
labs, and the ancillary provisions
calculated at an effectiveness rate of
only 45 percent.
a. Chronic Beryllium Disease
CBD is a respiratory disease in which
the body’s immune system reacts to the
presence of beryllium in the lung,
causing a progression of pathological
changes including chronic inflammation
and tissue scarring. Immunological
sensitization to beryllium (BeS) is a
precursor that occurs before early-stage
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CBD. Only sensitized individuals can go
on to develop CBD. In early,
asymptomatic stages of CBD, small
granulomatous lesions and mild
inflammation occur in the lungs. As
CBD progresses, the capacity and
function of the lungs decrease, which
eventually affects other organs and
bodily functions as well. Over time the
spread of lung fibrosis (scarring) and
loss of pulmonary function cause
symptoms such as: A persistent dry
cough, shortness of breath, fatigue, night
sweats, chest and join pain, clubbing of
fingers due to impaired oxygen
exchange, and loss of appetite. In these
later stages CBD can also impair the
liver, spleen, and kidneys, and cause
health effects such as granulomas of the
skin and lymph nodes, and cor
pulmonale (enlargement of the heart).
The speed and extent of disease
progression may be influenced by the
level and duration of exposure,
treatment with corticosteroids, and
genetics, but these effects are not fully
understood.
Corticosteroid therapy, in workers
whose beryllium exposure has ceased,
has been shown to control
inflammation, ease symptoms, and in
some cases prevent the development of
fibrosis. However, corticosteroid use can
have adverse effects, including
increased risk of infections; accelerated
bone loss or osteoporosis; psychiatric
effects such as depression, sleep
disturbances, and psychosis; adrenal
suppression; ocular effects; glucose
intolerance; excessive weight gain;
increased risk of cardiovascular disease;
and poor wound healing. The effects of
CBD, and of common treatments for
CBD, are discussed in detail in this
preamble at Section V, Health Effects,
and Section VIII, Significance of Risk.
OSHA’s review of the literature on
CBD suggests three broad types of CBD
progression (see this preamble at
Section V, Health Effects). In the first,
individuals progress relatively directly
toward death related to CBD. They
suffer rapidly advancing disability and
their death is significantly premature.
Medical intervention is not applied, or
if it is, does little to slow the
progression of disease. In the second
type, individuals live with CBD for an
extended period of time. The
progression of CBD in these individuals
is naturally slow, or may be medically
stabilized. They may suffer significant
disability, in terms of loss of lung
function—and quality of life—and
require medical oversight their
remaining years. They would be
expected to lose some years of normal
lifespan. As discussed previously,
advanced CBD can involve organs and
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systems beyond the respiratory system;
thus, CBD can contribute to premature
death from other causes. Finally,
individuals with the third type of CBD
progression do not die prematurely from
causes related to CBD. The disease is
stabilized and may never progress to a
debilitating state. These individuals
nevertheless may experience some
disability or loss of lung function, as
well as side effects from medical
treatment, and may be affected by the
disease in many areas of their lives:
Work, recreation, family, etc.25
In the analysis that follows, OSHA
assumes, based on the clinical
experience discussed below, that 35
percent of workers who develop CBD
experience the third type of progression
and do not die prematurely from CBD.
The remaining 65 percent were
estimated to die prematurely, whether
from rapid disease progression (type 1)
or slow (type 2). Although the
proportion of CBD patients who die
prematurely as a result of the disease is
not well understood or documented at
this time, OSHA believes this
assumption is consistent with the
information submitted in response to
the RFI. Newman et al. (2003) presented
a scenario for what they considered to
be the ‘‘typical’’ CBD patient:
We have included an example of a life care
plan for a typical clinical case of CBD. In this
example, the hypothetical case is diagnosed
at age 40 and assumed to live an additional
33.7 years (approximately 5% reduced life
expectancy in this model). In this
hypothetical example, this individual would
be considered to have moderate severity of
chronic beryllium disease at the time of
initial diagnosis. They require treatment with
prednisone and treatment for early cor
pulmonale secondary to CBD. They have
experienced some, but not all, of the side
effects of treatment and only the most
common CBD-related health effects.
In short, most workers diagnosed with
CBD are expected to have shortened life
expectancy, even if they do not progress
rapidly and directly to death. It should
be emphasized that this represents the
Agency’s best estimate of the mortality
related to CBD based upon the current
available evidence. As described in
Section V, Health Effects, there is a
substantial degree of uncertainty as to
the prognosis for those contracting CBD,
particularly as the relatively less severe
25 As indicated in the Health Effects section of
this preamble: ‘‘It should be noted, however, that
treatment with corticosteroids has side-effects of
their own that need to be measured against the
possibility of progression of disease (Gibson et al.,
1996; Zaki et al., 1987). Alternative treatments such
as azathiopurine and infliximab, while successful at
treating symptoms of CBD, have been demonstrated
to have side-effects as well (Pallavicino et al., 2013;
Freeman, 2012)’’.
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cases are likely not to be studied closely
for the remainder of their lives.
As mentioned previously, OSHA used
the Cullman data set for empirical
estimates of beryllium sensitization and
CBD prevalence in its exposure
response model, which translates
beryllium exposure to risk of adverse
health endpoints for the purpose of
determining the benefits that could be
achieved by preventing those adverse
health endpoints.
OSHA chose the cumulative exposure
quartile data as the basis for this
benefits analysis. The choice of
cumulative quartiles was based in part
on the need to use the cumulative
exposure forecast developed in the
model, and in part on the fact that in
statistically fitted models for CBD, the
cumulative exposure tended to fit the
CBD data better than other exposure
variables. OSHA also chose the quartile
model because the outside expert who
examined the logistic and proportional
hazards models believed statistical
modeling of the data set to be unreliable
due to its small size. In addition, the
proportional hazards model with its
dummy variables by year of detection is
difficult to interpret for purposes of this
section. Of course regression analyses
are often useful in empirical analysis.
They can be a useful compact
representation of a set of data, allow
investigations of various variable
interactions and possible causal
relationships, have added flexibility due
to covariate transformations, and under
certain conditions can be shown to be
statistically ‘‘optimal.’’ However, they
are only useful when used in the proper
setting. The possibility of
misspecification of functional form,
endogeneity, or incorrect distributional
assumptions are just three reasons to be
cautious about using regression
analyses.
On the other hand, the use of results
produced by a quartile analysis as
inputs in a benefits assessment implies
that the analytic results are being
interpreted as evidence of an exposureresponse causal relationship. Regression
analysis is a more sophisticated
approach to estimating causal
relationships (or even correlations) than
quartile or other quantile analysis, and
any data limitations that may apply to
a particular regression-based exposureresponse estimation also apply to
exposure-response estimation
conducted with a quartile analysis using
the same data set. In this case, OSHA
adopted the quartile analysis because
the logistic regression analysis yielded
extremely high prevalence rates for
higher level of exposure over long time
periods that some might not find
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credible. Use of the quartile analysis
serves to show that there are significant
benefits even without using an
extremely high estimate of prevalence
for long periods of exposure at high
levels. As a check on the quartile model,
the Agency performed the same benefits
calculation using the logit model
estimated by the Agency’s outside
expert, and these benefit results are
presented in a separate OSHA
background document (OSHA, 2015b).
The difference in benefits between the
two models is slight, and there is no
qualitative change in final outcomes.
The Agency solicits comment on these
issues.
(1) Number of CBD Cases Prevented by
the Proposed PEL
To examine the effect of simply
changing the PEL, including the effect of
the standard on some dental labs to
discontinue their use of beryllium,
OSHA compared the number of CBDrelated deaths (mortality) and cases of
non-fatal CBD (morbidity) that would
occur if workers were exposed for a 45year working life to PELs of 0.1, 0.2, or
0.5 mg/m3 to the number of cases that
would occur at levels of exposure at or
below the current PEL. The number of
avoided cases over a hypothetical
working life of exposure for the current
population at a lower PEL is then equal
to the difference between the number of
cases at levels of exposure at or below
the current PEL for that population
minus the number of cases at the lower
PEL. This approach represents a steadystate comparison based on what would
hypothetically happen to workers who
received a specific average level of
occupational exposure to beryllium
during an entire working life. (Chapter
VII in the PEA modifies this approach
by introducing a model that takes into
account the timing of benefits before
steady state is reached.)
As indicated in Table IX–11, the
Agency estimates that there would be
16,240 cases of beryllium sensitization,
from which there would be 11,017, or
about 70 percent, progressing to CBD.
The Agency arrived at these estimates
by using the CBD and BeS prevalence
values from the Agency’s preliminary
risk analysis, the exposure profile at
current exposure levels (under an
assumption of full, or fixed, compliance
with the existing beryllium PEL), and
the model outlined in the previous
methods of estimation section after a
working lifetime of exposure. Applying
the prior midpoint estimate, as
explained above, that 65 percent of CBD
cases cause or contribute to premature
death, the Agency predicts a total of
7,161 cases of mortality and 3,856 cases
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of morbidity from exposure at current
levels; this translates, annually, to 165
cases of mortality and 86 cases of
morbidity. At the proposed PEL,
OSHA’s base model estimates that, due
to the airborne factor only, a total of
2,563 CBD cases would be avoided from
exposure at current levels, including
1,666 cases of mortality and 897 cases
of morbidity—or an average of 37 cases
of mortality and 20 cases of morbidity
annually. OSHA has not estimated the
quantitative benefits of sensitization
cases avoided.
OSHA requests comment on this
analysis, including feedback on the data
relied on and the approach and
assumptions used. As discussed earlier,
based on information submitted in
response to the RFI, the Agency
estimates that most of the workers with
CBD will progress to an early death,
even if it comes after retirement, and
has quantified those cases prevented.
However, given the evolving nature of
science and medicine, the Agency
invites public comment on the current
state of CBD-related mortality.
The proposed standard also includes
provisions for medical surveillance and
removal. The Agency believes that to
the extent the proposal provides
medical surveillance sooner and to more
workers than would have been the case
in the absence of the proposed standard,
workers will be more likely to receive
appropriate treatment and, where
necessary, removal from beryllium
exposure. These interventions may
lessen the severity of beryllium-related
illnesses, and possibly prevent
premature death. The Agency requests
public comment on this issue.
(2) CBD Cases Prevented by the
Ancillary Provisions of the Proposed
Standard
The nature of the chronic beryllium
disease process should be emphasized.
As discussed in this preamble at Section
V, Heath Effects, the chronic beryllium
disease process involves two steps.
First, workers become sensitized to
beryllium. In most epidemiological
studies of CBD conducted to date, a
large percentage of sensitized workers
have progressed to CBD. A certain
percentage of the population has an
elevated risk of this occurring, even at
very low exposure levels, and
sensitization can occur from dermal as
well as inhalation exposure to
beryllium. For this reason, the threat of
beryllium sensitization and CBD persist
to a substantial degree, even at very low
levels of airborne beryllium exposure. It
is therefore desirable not only to
significantly reduce airborne beryllium
exposure, but to avoid nearly any source
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of beryllium exposure, so as to prevent
beryllium sensitization.
The analysis presented above
accounted only for CBD-prevention
benefits associated with the proposed
reduction of the PEL, from 2 ug/m3 to
0.2 ug/m3. However, the proposed
standard also includes a variety of
ancillary provisions—including
requirements for respiratory protection,
personal protective equipment (PPE),
housekeeping procedures, hygiene
areas, medical surveillance, medical
removal, and training—that the Agency
believes would further reduce workers’
risk of disease from beryllium exposure.
These provisions were described in
Chapter I of the PEA and discussed
extensively in Section XVIII of this
preamble, Summary and Explanation of
the Proposed Standard.
The leading manufacturer of
beryllium in the U.S., Materion
Corporation (Materion), has
implemented programs including these
types of provisions in several of its
plants and has worked with NIOSH to
publish peer-reviewed studies of their
effectiveness in reducing workers’ risk
of sensitization and CBD. The Agency
used the results of these studies to
estimate the health benefits associated
with a comprehensive standard for
beryllium.
The best available evidence on
comprehensive beryllium programs
comes from studies of programs
introduced at Materion plants in
Reading, PA; Tucson, AZ; and Elmore,
OH. These studies are discussed in
detail in this preamble at Section VI,
Preliminary Risk Assessment, and
Section VIII, Significance of Risk. All
three facilities were in compliance with
the current PEL prior to instituting
comprehensive programs, and had taken
steps to reduce airborne levels of
beryllium below the PEL, but their
medical surveillance programs
continued to identify cases of
sensitization and CBD among their
workers. Beginning around 2000, these
facilities introduced comprehensive
beryllium programs that used a
combination of engineering controls,
dermal and respiratory PPE, and
stringent housekeeping measures to
reduce workers’ dermal exposures and
airborne exposures. These
comprehensive beryllium programs
have substantially lowered the risk of
sensitization among workers. At the
times that studies of the programs were
published, insufficient follow-up time
had elapsed to report directly on the
results for CBD. However, since only
sensitized workers can develop CBD,
reduction of sensitization risk
necessarily reduces CBD risk as well.
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In the Reading, PA copper beryllium
plant, full-shift airborne exposures in all
jobs were reduced to a median of 0.1 ug/
m3 or below, and dermal protection was
required for production-area workers,
beginning in 2000–2001 (Thomas et al.,
2009). In 2002, the process with the
highest exposures (with a median of 0.1
ug/m3) was enclosed, and workers
involved in that process were required
to use respiratory protection. Among 45
workers hired after the enclosure was
built and respiratory protection
instituted, one was found to be
sensitized (2.2 percent). This is more
than an 80 percent reduction in
sensitization from a previous group of
43 workers hired after 1992, 11.5
percent of whom had been sensitized by
the time of testing in 2000.
In the Tucson beryllium ceramics
plant, respiratory and skin protection
was instituted for all workers in
production areas in 2000 (Cummings et
al., 2007). BeLPT testing in 2000–2004
showed that only 1 (1 percent) of 97
workers hired during that time period
was sensitized to beryllium. This is a 90
percent reduction from the prevalence
of sensitization in a 1998 BeLPT
screening, which found that 6
(9 percent) of 69 workers hired after
1992 were sensitized.
In the Elmore, OH beryllium
production and processing facility, all
new workers were required to wear
loose-fitting powered air-purifying
respirators (PAPRs) in manufacturing
buildings, beginning in 1999 (Bailey et
al., 2010). Skin protection became part
of the protection program for new
workers in 2000, and glove use was
required in production areas and for
handling work boots, beginning in 2001.
Bailey et al. (2010) found that 23 (8.9
percent) of 258 workers hired between
1993 and 1999, before institution of
respiratory and dermal protection, were
sensitized to beryllium. The prevalence
of sensitization among the 290 workers
who were hired after the respiratory
protection and PPE measures were put
in place was about 2 percent, close to an
80 percent reduction in beryllium
sensitization.
In a response to OSHA’s 2002 Request
for Information (RFI), Lee Newman et al.
from National Jewish Medical and
Research Center (NJMRC) summarized
results of beryllium program
effectiveness from several sources. Said
Dr. Newman (in response to Question
#33):
Q. 33. What are the potential impacts of
reducing occupational exposures to
beryllium in terms of costs of controls, costs
for training, benefits from reduction in the
number or severity of illnesses, effects on
revenue and profit, changes in worker
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productivity, or any other impact measures
than you can identify?
A: From experience in [the Tucson, AZ
facility discussed above], one can infer that
approximately 90 percent of beryllium
sensitization can be eliminated. Furthermore,
the preliminary data would suggest that
potentially 100 percent of CBD can be
eliminated with appropriate workplace
control measures.
In a study by Kelleher 2001, Martyny 2000,
Newman, JOEM 2001) in a plant that
previously had rates of sensitization as high
as 9.7 percent, the data suggests that when
lifetime weighted average exposures were
below 0.02 mg per cu meter that the rate of
sensitization fell to zero and the rate of CBD
fell to zero as well.
In an unpublished study, we have been
conducting serial surveillance including
testing new hires in a precision machining
shop that handles beryllium and beryllium
alloys in the Southeast United States. At the
time of the first screening with the blood
BeLPT of people tested within the first year
of hire, we had a rate of 6.7 percent (4/60)
sensitization and with 50 percent of these
individuals showing CBD at the time of
initial clinical evaluation. At that time, the
median exposures in the machining areas of
the plant was 0.47 mg per cu meter.
Subsequently, efforts were made to reduce
exposures, further educate the workforce,
and increase monitoring of exposure in the
plant. Ongoing testing of newly hired
workers within the first year of hire
demonstrated an incremental decline in the
rate of sensitization and in the rate of CBD.
For example, at the time of most recent
testing when the median airborne exposures
in the machining shop were 0.13 mg per cu
meter, the percentage of newly hired workers
found to have beryllium sensitization or CBD
was now 0 percent (0/55). Notably, we also
saw an incremental decline in the percentage
of longer term workers being detected with
sensitization and disease across this time
period of exposure reduction and improved
hygiene practices.
Thus, in calculating the potential economic
benefit, it’s reasonable to work with the
assumption that with appropriate efforts to
control exposures in the work place, rates of
sensitization can be reduced by over 90
percent. (NJMRC, RFI Ex. 6–20)
OSHA has reviewed these papers and
is in agreement with Dr. Newman’s
testimony. OSHA judges Dr. Newman’s
estimate to be an upper bound of the
effectiveness of ancillary programs and
examined the results of using Dr.
Newman’s estimate that beryllium
ancillary programs can reduce BeS by
90 percent, and potentially eliminate
CBD where sensitization is reduced,
because CBD can only occur where
there is sensitization. OSHA applied
this 90 percent reduction factor to all
cases of CBD remaining after application
of the reductions due to lowering the
PEL alone. OSHA applied this reduction
broadly because the proposed standard
would require housekeeping and PPE
related to skin exposure (18,000 of
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28,000 employees will need PPE
because of possible skin exposure) to
apply to all or most employees likely to
come in contact with beryllium and not
just those with exposure above the
action level. Table IX–11 shows that
there are 11,017 baseline cases of CBD
and that the proposed PEL of 0.2 mg/m3
would prevent 2,563 cases through
airborne prevention alone. The
remaining number of cases of CBD is
then 8,454 (11,017 minus 2,563). If
OSHA applies the full ninety percent
reduction factor to account for
prevention of skin exposure (‘‘nonairborne’’ protections), then 7,609 (90
percent of 8,454 cases) additional cases
of CBD would be prevented.
The Agency recognizes that there are
significant differences between the
comprehensive programs discussed
above and the proposed standard. While
the proposed standard includes many of
the same elements, it is generally less
stringent. For example, the proposed
standard’s requirements for respiratory
protection and PPE are narrower, and
many provisions of the standard apply
only to workers exposed above the
proposed TWA PEL or STEL. However,
many provisions, such as housekeeping
and beryllium work areas, apply to all
employers covered by the proposed
standard. To account for these
differences, OSHA has provided a range
of benefits estimates (shown in Table
IX–11), first, assuming that there are no
ancillary provisions to the standard,
and, second, assuming that the
comprehensive standard achieves the
full 90-percent reduction in risk
documented in existing programs. The
Agency is taking the midpoint of these
two numbers as its main estimate of the
benefits of avoided CBD due to the
ancillary provisions of the proposed
standard. The results in Table IX–11
suggest that approximately 60 percent of
the beryllium sensitization cases and
the CBD cases avoided would be
attributable to the ancillary provisions
of the standard. OSHA solicits comment
on all aspects of this approach to
analyzing ancillary provisions and
solicits additional data that might serve
to make more accurate estimates of the
effects of ancillary provisions. OSHA is
interested in the extent of the effects of
ancillary provisions and whether these
apply to all exposed employees or only
those exposed above or below a given
exposure level.
(3) Morbidity Only Cases
As previously indicated, the Agency
does not believe that all CBD cases will
ultimately result in premature death.
While currently strong empirical data
on this are lacking, the Agency
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estimates that approximately 35 percent
of cases would not ultimately be fatal,
but would result in some pain and
suffering related to having CBD, and
possible side effects from steroid
treatment, as well as the dread of not
knowing whether the disease will
ultimately lead to premature death.
These would be described as ‘‘mild’’
cases of CBD relative to the others.
These are the residual cases of CBD after
cases with premature mortality have
been counted. As indicated in Table IX–
11, the Agency estimates the standard
will prevent 2,228 such cases
(midpoint) over 45 years, or an
estimated 50 cases annually.
b. Lung Cancer
In addition to the Agency’s
determinations with respect to the risk
of chronic beryllium disease, the
Agency has preliminarily determined
that chronic beryllium exposure at the
current PEL can lead to a significantly
elevated risk of (fatal) lung cancer.
OSHA used the estimation methodology
outlined at the beginning of this section.
However, unlike with chronic beryllium
disease, the underlying data were based
on incidence of lung cancer and thus
there was no need to address the
possible limitations of prevalence data.
The Agency also used lifetime excess
risk estimates of lung cancer mortality,
presented in Table VI–20 in Section VI
of this preamble, Preliminary Risk
Assessment, to estimate the benefits of
avoided lung cancer mortality. The lung
cancer risk estimates are derived from
one of the best-fitting models in a
recent, high-quality NIOSH lung cancer
study, and are based on average
exposure levels. The estimates of excess
lifetime risk of lung cancer were taken
from the line in Table VI–20 in the risk
assessment labeled PWL (piecewise loglinear) not including professional and
asbestos workers. This model avoids
possible confounding from asbestos
exposure and reduces the potential for
confounding due to smoking, as
smoking rates and beryllium exposures
can be correlated via professional
worker status. Of the three estimates in
the NIOSH study that excluded
professional workers and those with
asbestos exposure, this model was
chosen because it was at the midpoint
of risk results.
Table IX–11 shows the number of
avoided fatal lung cancers for PELs of
0.2 mg/m3, 0.1 mg/m3, and 0.5 mg/m3. At
the proposed PEL of 0.2 mg/m3, an
estimated 180 lung cancers would be
prevented over the lifetime of the
current worker population. This is the
equivalent of 4.0 cases avoided
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annually, given a 45-year working life of
exposure.
Combining the two major fatal health
endpoints—for lung cancer and CBDrelated mortality—OSHA estimates that
the proposed PEL would prevent
between 1,846 and 6,791 premature
fatalities over the lifetime of the current
worker population, with a midpoint
estimate of 4,318 fatalities prevented.
This is the equivalent of between 41 and
151 premature fatalities avoided
annually, with a midpoint estimate of
96 premature fatalities avoided
annually, given a 45-year working life of
exposure.
Note that the Agency based its
estimates of reductions in the number of
beryllium-related diseases over a
working life of constant exposure for
workers who are employed in a
beryllium-exposed occupation for their
entire working lives, from ages 20 to 65.
In other words, workers are assumed not
to enter or exit jobs with beryllium
exposure mid-career or to switch to
other exposure groups during their
working lives. While the Agency is
legally obligated to examine the effect of
exposures from a working lifetime of
exposure and set its standard
accordingly,26 in an alternative analysis
purely for informational purposes, using
the same underlying risk model for
CBD, the Agency examined, in Chapter
VII of the PEA, the effect of assuming
that workers are exposed for a
maximum of only 25 working years, as
opposed to the 45 years assumed in the
main analysis. While all workers are
assumed to have less cumulative
exposure under the 25-years-ofexposure assumption, the effective
exposed population over time is
proportionately increased.
A comparison of exposures over a
maximum of 25 working years versus
over a potentially 45-year working life
shows variations in the number of
estimated prevented cases by health
outcome. For chronic beryllium disease,
there is a substantial increase in the
number of estimated baseline and
prevented cases if one assumes that the
typical maximum exposure period is 25
years, as opposed to 45. This reflects the
26 Section (6)(b)(5) of the OSH Act states: ‘‘The
Secretary, in promulgating standards dealing with
toxic materials or harmful physical agents under
this subsection, shall set the standard which most
adequately assures, to the extent feasible, on the
basis of the best available evidence, that no
employee will suffer material impairment of health
or functional capacity even if such employee has
regular exposure to the hazard dealt with by such
standard for the period of his working life.’’ Given
that it is necessary for OSHA to reach a
determination of significant risk over a working life,
it is a logical extension to estimate what this
translates into in terms of estimated benefits for the
affected population over the same period.
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relatively flat CBD risk function within
the relevant exposure range, given
varying levels of airborne beryllium
exposure—shortening the average
tenure and increasing the exposed
population over time translates into
larger total numbers of people sensitized
to beryllium. This, in turn, results in
larger populations of individuals
contracting CBD. Since the lung cancer
model itself is based on average, as
opposed to cumulative, exposure, it is
not adaptable to estimate exposures over
a shorter period of time. As a practical
matter, however, over 90 percent of
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illness and mortality attributable to
beryllium exposure in this analysis
comes from CBD.
Overall, the 45-year-maximumworking-life assumption yields smaller
estimates of the number of cases of
avoided fatalities and illnesses than
does the maximum-25-years-of-exposure
assumption. For example, the midpoint
estimates of the number of avoided
fatalities and illnesses related to CBD
under the proposed PEL of 0.2 mg/m3
increases from 92 and 50, respectively,
under the maximum-45-year-workinglife assumption to 145 and 78,
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respectively, under the maximum-25year-working-life assumption—or
approximately a 57 to 58 percent
increase.27
27 Technically, this analysis assumes that workers
receive 25 years’ worth of beryllium exposure, but
that they receive it over 45 working years, as is
assumed by the risk models in the risk assessment.
It also accounts for the turnover implied by 25, as
opposed to 45, years of work. However, it is
possible that an alternate analysis, which accounts
for the larger number of post-exposure worker-years
implied by workers departing their jobs before the
end of their working lifetime, might find even larger
health effects for workers receiving 25 years’ worth
of beryllium exposure.
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Table IX-11
Prevented Mortality and Morbidity by PEL Option (45-Year Working Life Case)
(Quartile Model)
Airborne Factor Only
Baseline
PEL Option (1Jg/m 3 )
Total Cases Total Number of Avoided Cases
0.1
0.2
0.5
PEL Option (1Jg/m3 )
Baseline
Annual Cases Annual Number of Avoided Cases
0.1
0.2
0.5
361
245
85.0
61.4
79.9
56.9
77.9
54.7
163
6.2
4.3
4.0
3.6
1,666
1,601
159
39.9
37.0
35.6
1,988
1,846
1,764
165
44.2
41.0
39.2
967
897
862
86
21.5
19.9
19.2
Total Cases
Be S
CBD
16,240
11,017
3,826
2,763
3,594
2,563
3,503
2,463
Mortality
Lung Cancer
279
192
180
CBD-Related
7,161
1,796
Total Mortality
7,440
Morbidity
3,856
Non-Airborne Factor Included
3
Baseline
PEL Option (1Jg/m )
Total Cases Total Number of Avoided Cases
0.1
0.2
0.5
3
Baseline
PEL Option (1Jg/m )
Annual Cases Annual Number of Avoided Cases
0.1
0.2
0.5
361
245
333.3
226.5
332.8
226.0
205.2
140.3
163
6
4.3
4.0
3.6
6,611
4,103
159
147.2
146.9
91.2
6,816
6,791
4,266
165
151.5
150.9
94.8
3,567
3,560
2,209
86
79.3
79.1
49.1
Total Cases
Be S
CBD
16,240
11,017
14,998
10,191
14,975
10,171
9,235
6,312
Mortality
Lung Cancer
279
192
180
CBD-Related
7,161
6,624
Total Mortality
7,440
Morbidity
3,856
Midpoint Estimates
3
3
Baseline
PEL Option (1Jg/m )
Baseline
PEL Option (1Jg/m )
Total Cases Total Number of Avoided Cases
Annual Cases Annual Number of Avoided Cases
0.1
0.2
0.5
0.1
0.2
0.5
Total Cases
Be S- Total
16,240
11,017
9,412
6,477
9,284
6,367
6,369
4,387
361
245
209.2
143.9
206.3
141.5
141.5
97.5
Mortality
Lung Cancer
279
192
180
163
6
4.3
4.0
3.6
CBD-Related
7,161
4,210
4,139
2,852
159
93.6
92.0
63.4
Total Mortality
7,440
4,402
4,318
3,015
165
97.8
96.0
67.0
Morbidity
3,856
2,267
2,228
1,536
86
50.4
49.5
34.1
Source: Office of Regulatory Analysis, Directorate of Standards and Guidance
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Step 2—Estimating the Stream of
Benefits Over Time
Risk assessments in the occupational
environment are generally designed to
estimate the risk of an occupationally
related illness over the course of an
individual worker’s lifetime. As
demonstrated previously in this section,
the current occupational exposure
profile for a particular substance for the
current cohort of workers can be
matched up against the expected profile
after the proposed standard takes effect,
creating a ‘‘steady state’’ estimate of
benefits. However, in order to annualize
the benefits for the period of time after
the beryllium rule takes effect, it is
necessary to create a timeline of benefits
for an entire active workforce over that
period.
While there are various approaches
that could be taken for modeling the
workforce, there seem to be two polar
extremes. At one extreme, one could
assume that none of the benefits occur
until after the worker retires, or at least
45 years in the future. In the case of lung
cancer, that period would effectively be
at least 55 years, since the 45 years of
exposure must be added to a 10-year
latency period during which it is
assumed that lung cancer does not
develop.28 At the other extreme, one
could assume that the benefits occur
immediately, or at least immediately
after a designated lag. However, based
on the various risk models discussed in
this preamble at Section VI, Risk
Assessment, which reflect real-world
experience with development of disease
over an extended period of time, it
appears that the actual pattern occurs at
some point between these two extremes.
At first glance, the simplest
intermediate approach would be to
follow the pattern of the risk
assessments, which are based in part on
life tables, and observe that typically the
risk of the illness grows gradually over
the course of a working life and into
retirement. Thus, the older the person
exposed to beryllium, the higher the
odds that that person will have
developed the disease.
However, while this is a good working
model for an individual exposed over a
working life, it is not very descriptive of
the effect of lowering exposures for an
entire working population. In the latter
case, in order to estimate the benefits of
the standard over time, one has to
consider that workers currently being
exposed to beryllium are going to vary
considerably in age. Since the
calculated health risks from beryllium
28 This
assumption is consistent with the 10-year
lag incorporated in the lung cancer risk models
used in OSHA’s preliminary risk assessment.
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exposure depend on a worker’s
cumulative exposure over a working
lifetime, the overall benefits of the
proposed standard will phase in over
several decades, as the cumulative
exposure gradually falls for all age
groups, until those now entering the
workforce reach retirement and the
annual stream of beryllium-related
illnesses reaches a new, significantly
lowered ‘‘steady state.’’ 29 That said, the
near-term impact of the proposed rule
estimated for those workers with similar
current levels of cumulative exposure
will be greater for workers who are now
middle-aged or older. This conclusion
follows in part from the structure of the
relative risk model used for lung cancer
in this analysis and the fact that the
background mortality rates for lung
cancer increase with age.
In order to characterize the magnitude
of benefits before the steady state is
reached, OSHA created a linear phasein model to reflect the potential timing
of benefits. Specifically, OSHA
estimated that, for all non-cancer cases,
while the number of cases of berylliumrelated disease would gradually decline
as a result of the proposed rule, they
would not reach the steady-state level
until 45 years had passed. The
reduction in cases estimated to occur in
any given year in the future was
estimated to be equal to the steady-state
reduction (the number of cases in the
baseline minus the number of cases in
the new steady state) times the ratio of
the number of years since the standard
was implemented and a working life of
45 years. Expressed mathematically:
Nt = (C¥S) × (t/45),
Where 10 ≤ t ≤ 55 and Lt is the number of
lung cancer cases avoided in year t as a
result of the proposed rule; Cm is the
current annual number of berylliumrelated lung cancers; and Sm is the
steady-state annual number of berylliumrelated lung cancers.
Where Nt is the number of non-malignant
beryllium-related diseases avoided in
year t; C is the current annual number of
non-malignant beryllium-related
diseases; S is the steady-state annual
number of non-malignant berylliumrelated diseases; and t represents the
number of years after the proposed
standard takes effect, with t ≤ 45.
Separating the Timing of Mortality
In previous sections, OSHA modeled
the timing and incidence of morbidity.
OSHA’s benefit estimates are based on
an underlying CBD-related mortality
rate of 65 percent. However, this
mortality is not simultaneous with the
onset of morbidity. Although mortality
from CBD has not been well studied,
OSHA believes, based on discussions
with experienced clinicians, that the
average lag for a larger population has
a range of 10 to 30 years between
morbidity and mortality. The Agency’s
review of Workers Compensation data
related to beryllium exposure from the
Office of Worker Compensation
Programs (OWCP) Division of Energy
Employees Occupational Illness
Compensation is consistent with this
range. Hence, for the purposes of this
In the case of lung cancer, the
function representing the decline in the
number of beryllium-related cases as a
result of the proposed rule is similar,
but there would be a 10-year lag before
any reduction in cancer cases would be
achieved. Expressed mathematically, for
lung cancer:
Lt = (Cm¥Sm) × ((t¥10)/45)),
29 Technically, the RA lung cancer model is based
on average exposure, Nonetheless, as noted in the
RA, the underlying studies found lung cancer to be
significantly related to cumulative exposure.
Particularly since the large majority of the benefits
are related to CBD, the Agency considers this fairly
descriptive of the overall phase-in of benefits from
the standard.
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This model was extended to 60 years
for all the health effects previously
discussed in order to incorporate the 10year lag, in the case of lung cancer, and
a maximum-45-year working life, as
well as to capture some occupationallyrelated disease that manifests itself after
retirement.30 As a practical matter,
however, there is no overriding reason
for stopping the benefits analysis at 60
years. An internal analysis by OSHA
indicated that, both in terms of cases
prevented, and even with regard to
monetized benefits, particularly when
lower discount rates are used, the
estimated benefits of the standard are
larger on an annualized basis if the
analysis extends further into the future.
The Agency welcomes comment on the
merit of extending the benefits analysis
beyond the 60-years analyzed in the
PEA.
In order to compare costs to benefits,
OSHA assumes that economic
conditions remain constant and that
annualized costs—and the underlying
costs—will repeat for the entire 60-year
time horizon used for the benefits
analysis (as discussed in Chapter V of
the PEA). OSHA welcomes comments
on the assumption for both the benefit
and cost analysis that economic
conditions remain constant for sixty
years. OSHA is particularly interested in
what assumptions and time horizon
should be used instead and why.
30 The left-hand columns in the tables in
Appendix VII–A of the PEA provide estimates using
this model of the stream of prevented fatalities and
illnesses due to the proposed beryllium rule.
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proposal, OSHA estimates that mortality
occurs on average 20 years after the
onset of CBD morbidity. Thus, for
example, the prevented deaths that
would have occurred in year 21 after the
promulgation of the rule are associated
with the CBD morbidity cases prevented
in year one. OSHA requests comment on
this estimate and range.
The Agency invites comment on each
of these elements of the analysis,
particularly on the estimates of the
expected life expectancy of a patient
with CBD.
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Step 3—Monetizing the Benefits of the
Proposed Rule
To estimate the monetary value of the
reductions in the number of berylliumrelated fatalities, OSHA relied, as OMB
recommends, on estimates developed
from the willingness of affected
individuals to pay to avoid a marginal
increase in the risk of fatality. While a
willingness-to-pay (WTP) approach
clearly has theoretical merit, it should
be noted that an individual’s
willingness to pay to reduce the risk of
fatality would tend to underestimate the
total willingness to pay, which would
include the willingness of others—
particularly the immediate family—to
pay to reduce that individual’s risk of
fatality.
For estimates using the willingnessto-pay concept, OSHA relied on existing
studies of the imputed value of fatalities
avoided based on the theory of
compensating wage differentials in the
labor market. These studies rely on
certain critical assumptions for their
accuracy, particularly that workers
understand the risks to which they are
exposed and that workers have
legitimate choices between high- and
low-risk jobs. These assumptions are far
from obviously met in actual labor
markets.31 A number of academic
studies, as summarized in Viscusi &
Aldy (2003), have shown a correlation
between higher job risk and higher
wages, suggesting that employees
demand monetary compensation in
return for a greater risk of injury or
fatality. The estimated trade-off between
lower wages and marginal reductions in
fatal occupational risk—that is, workers’
willingness to pay for marginal
reductions in such risk—yields an
imputed value of an avoided fatality:
The willingness-to-pay amount for a
31 On the former assumption, see the discussion
in Chapter II of the PEA on imperfect information.
On the latter, see, for example, the discussion of
wage compensation for risk for union versus
nonunion workers in Dorman and Hagstrom (1998).
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reduction in risk divided by the
reduction in risk.32
OSHA has used this approach in
many recent proposed and final rules.
Although this approach has been
criticized for yielding results that are
less than statistically robust (see, for
example, Hintermann, Alberini and
Markandya, 2010), a more recent WTP
analysis, by Kniesner et al. (2012), of the
trade-off between fatal job risks and
wages, using panel data, seems to
address many of the earlier econometric
criticisms by controlling for
measurement error, endogeneity, and
heterogeneity. In conclusion, the
Agency views the WTP approach as the
best available and will rely on it to
monetize benefits.33 OSHA welcomes
comments on the use of willingness-topay measures and estimates based on
compensating wage differentials.
Viscusi & Aldy (2003) conducted a
meta-analysis of studies in the
economics literature that use a
willingness-to-pay methodology to
estimate the imputed value of lifesaving programs and found that each
fatality avoided was valued at
approximately $7 million in 2000
dollars. Using the GDP Deflator (U.S.
BEA, 2010), this $7 million base number
in 2000 dollars yields an estimate of
$8.7 million in 2010 dollars for each
fatality avoided.34
In addition to the benefits that are
based on the implicit value of fatalities
avoided, workers also place an implicit
value on occupational injuries or
illnesses avoided, which reflect their
willingness to pay to avoid monetary
costs (for medical expenses and lost
wages) and quality-of-life losses as a
result of occupational illness. Chronic
beryllium disease and lung cancer can
adversely affect individuals for years, or
even decades, in non-fatal cases, or
before ultimately proving fatal. Because
measures of the benefits of avoiding
32 For example, if workers are willing to pay $90
each for a 1/100,000 reduction in the probability of
dying on the job, then the imputed value of an
avoided fatality would be $90 divided by 1/100,000,
or $9,000,000. Another way to consider this result
would be to assume that 100,000 workers made this
trade-off. On average, one life would be saved at a
cost of $9,000,000.
33 Note that, consistent with the economics
literature, these estimates would be for reducing the
risk of an acute (immediate) fatality. They do not
include an individual’s willingness to pay to avoid
a higher risk of illness prior to fatality, which is
separately estimated in the following section.
34 An alternative approach to valuing an avoided
fatality is to monetize, for each year that a life is
extended, an estimate from the economics literature
of the value of that statistical life-year (VSLY). See,
for instance, Aldy and Viscusi (2007) for discussion
of VSLY theory and FDA (2003), pp. 41488–9, for
an application of VSLY in rulemaking. OSHA has
not investigated this approach, but welcomes
comment on the issue.
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these illnesses are rare and difficult to
find, OSHA has included a range based
on a variety of estimation methods.
For both CBD and lung cancer, there
is typically some permanent loss of lung
function and disability, on-going
medical treatments, side effects of
medicines, and major impacts on one’s
ability to work, marry, enjoy family life,
and quality of life.
While diagnosis with CBD is evidence
of material impairment of health,
placing a precise monetary value on this
condition is difficult, in part because
the severity of symptoms may vary
significantly among individuals. For
that reason, for this preliminary
analysis, the Agency employed a broad
range of valuation, which should
encompass the range of severity these
individuals may encounter.
Using the willingness-to-pay
approach, discussed in the context of
the imputed value of fatalities avoided,
OSHA has estimated a range in
valuations (updated and reported in
2010 dollars) that runs from
approximately $62,000 per case—which
reflects estimates developed by Viscusi
and Aldy (2003), based on a series of
studies primarily describing simple
accidents—to upwards of $5 million per
case—which reflects work developed by
Magat, Viscusi, and Huber (1996) for
non-fatal cancer. The latter number is
based on an approach that places a
willingness-to-pay value to avoid
serious illness that is calibrated relative
to the value of an avoided fatality.
OSHA previously used this approach in
the Preliminary Economic Analysis
(PEA) supporting its respirable
crystalline silica proposal (2013) and in
the Final Economic Analysis (FEA)
supporting its hexavalent chromium
final rule (2006), and EPA (2003) used
this approach in its Stage 2 Disinfection
and Disinfection Byproducts Rule
concerning regulation of primary
drinking water. Based on Magat,
Viscusi, and Huber (1996), EPA used
studies on the willingness to pay to
avoid nonfatal lymphoma and chronic
bronchitis as a basis for valuing a case
of nonfatal cancer at 58.3 percent of the
value of a fatal cancer. OSHA’s estimate
of $5 million for an avoided case of nonfatal cancer is based on this 58.3 percent
figure.
The Agency believes this range of
estimates, between $62,000 and $5
million, is descriptive of the value of
preventing morbidity associated with
moderate to severe CBD that ultimately
results in premature death. 35
35 There are several benchmarks for valuation of
health impairment due to beryllium exposure, using
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While the Agency has estimated that
65 percent of CBD cases will result in
premature mortality, the Agency has
also estimated that approximately 35
percent of CBD cases will not result in
premature mortality. However, the
Agency acknowledges that it is possible
there have been new developments in
medicine and industrial hygiene related
to the benefits of early detection,
medical intervention, and greater
control of exposure achieved within the
past decade. For that reason, as
elsewhere, the Agency requests
comment on these issues.
Also not clear are the negative effects
of the illness in terms of lost
productivity, medical costs, and
potential side-effects of a lifetime of
immunosuppressive medication.
Nonetheless, the Agency is assigning a
valuation of $62,000 per case, to reflect
the WTP value of a prevented injury not
estimated to precede premature
mortality. The Agency believes this is
conservative, in part because, with any
given case of CBD, the outcome is not
known in advance, certainly not at the
point of discovery; indeed much of the
psychic value of preventing the cases
may come from removing the threat of
premature mortality. In addition, as
previously noted, some of these cases
could involve relatively severe forms of
CBD where the worker died of other
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a variety of techniques, which provide a number of
mid-range estimates between OSHA’s high and low
estimates. For a fuller discussion of these
benchmarks, see Chapter VII of the PEA.
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causes; however, in those cases, the
duration of the disease would be
shortened. While beryllium
sensitization is a critical precursor of
CBD, this preliminary analysis does not
attempt to assign a separate value to
sensitization itself.
Particularly given the uncertainties in
valuation on these questions, the
Agency is interested in public input on
the issue of valuing the cost to society
of morbidity associated with CBD, both
in cases preceding mortality, and those
that may not result in premature
mortality. The Agency is also interested
in comments on whether it is
appropriate to assign a separate
valuation to prevented sensitization
cases in their own right, and if so, how
such cases should be valued.
a. Summary of Monetized Benefits
Table IX–12 presents the estimated
annualized (over 60 years, using a 0
percent discount rate) benefits from
each of these components of the
valuation, and the range of estimates,
based on uncertainty of the prevention
factor (i.e., the estimated range of
prevented cases, depending on how
large an impact the rule has on cases
beyond an airborne-only effect), and the
range of uncertainty regarding valuation
of morbidity. (Mid-point estimates of
the undiscounted benefits for each of
the first 60 years are provided in the
middle columns of Table VII–A–1 in
Appendix VII–A at the end of Chapter
VII in the PEA. The estimates by year
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reach a peak of $3.5 billion in the 60th
year. Note that, by using a 60-year timeperiod, OSHA is not including any
monetized fatality benefits associated
with reduced worker CBD cases
originating after year 40 because the 20year lag takes these CBD fatalities
beyond the 60-year time horizon. To
this extent, OSHA will have
underestimated benefits.)
As shown in Table IX–12, the full
range of monetized benefits,
undiscounted, for the proposed PEL of
0.2 mg/m3 runs from $291 million
annually, in the case of the lowest
estimate of prevented cases of CBD, and
the lowest valuation for morbidity, up to
$2.1 billion annually, for the highest of
both. Note that the value of total
benefits is more sensitive to the
prevention factor used (ranging from
$430 million to $1.6 billion, given
estimates at the midpoint of the
morbidity valuation) than to the
valuation of morbidity (ranging from
$666 million to $1.3 billion, given
estimates at the midpoint of prevention
factor).
Also, the analysis illustrates that most
of the morbidity benefits are related to
CBD and lung cancer cases that are
ultimately fatal. At the valuation and
case frequency midpoint, $663 million
in benefits are related to mortality, $226
million are related to morbidity
preceding mortality, and $4.3 million
are related to morbidity not preceding
mortality.
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Estimated Annualized Undiscounted Monetized Benefits of the Beryllium Proposal for Morbidity and Mortality
PEL
Low
I
0.1 ~g/m 3
Valuation
Midpoint
I
High
Low
I
0.2 ~g/m 3
Valuation
Midpoint
I
High
Low
I
0.5 ~g/m 3
Valuation
Midpoint
I
High
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07AUP2
Fatalities- Total
Low
Midpoint
High
$308,027,593
$666,610,424
$1,025,193,255
$308,027,593
$666,610,424
$1,025,193,255
$308,027,593
$666,610,424
$1,025,193,255
$285,909,109
$653,373,439
$1,020,660,530
$285,909,109
$653,373,439
$1,020,660,530
$285,909,109
$653,373,439
$1,020,660,530
$272,760,749
$458,581,095
$644,401,440
$272,760,749
$458,581,095
$644,401,440
$272,760,749
$458,581,095
$644,401,440
Morbidity Preceding Mortality- CBD and lung cancer deaths
Low
Midpoint
High
$3,765,360
$8,431,448
$13,097,537
$153,711,707
$344,193,474
$534,675,242
$303,658,053
$679,955,500
$1,056,252,947
$3,495,142
$8,274,496
$13,053,849
$142,680,735
$337,786,267
$532,891,800
$281,866,327
$667,298,039
$1,052,729,751
$3,343,232
$5,761,234
$8,179,237
$136,479,355
$235, 188,453
$333,897, 551
$269,615,478
$464,615,672
$659,615,865
Morbidity Not Preceding Mortality
Low
Midpoint
High
$1,869,166
$4,381,675
$7,320,735
$1,869,166
$4,381,675
$7,320,735
$1,869,166
$4,381,675
$7,320,735
$1,733,636
$4,307,133
$7,306,343
$1,733,636
$4,307,133
$7,306,343
$1,733,636
$4,307,133
$7,306,343
$1,665,847
$2,967,849
$4,321,800
$1,665,847
$2,967,849
$4,321,800
$1,665,847
$2,967,849
$4,321,800
TOTAL
Low
Midpoint
High
$313,662,119
$679,423,547
$1,045,611,526
$463,608,465
$1,015,185,573
$1,567,189,232
$613,554,812
$1,350,947,599
$2,088,766,937
$291, 137,887
$665,955,068
$1,041,020,722
$430,323,479
$995,466,840
$1,560,858,673
$569,509,072
$1,324,978,612
$2,080,696,625
$277,769,829
$467,310,178
$656,902,477
$410,905,952
$696,737,396
$982,620,791
$544,042,075
$926, 164,615
$1,308,339,106
Source: Office of Regulatory Analysis, Directorate of Standards & Guidance
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avoid a fatality (with an imputed value
per fatality avoided of $8.7 million in
2010 dollars) and to avoid a berylliumrelated disease (with an imputed value
per disease avoided of between $62,000
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on the imputed value of each avoided
fatality and each avoided berylliumrelated disease. As previously
discussed, these, in turn, are derived
from a worker’s willingness to pay to
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OSHA’s estimates of the monetized
benefits of the proposed rule are based
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and $5 million in 2010 dollars). To this
point, these imputed values have been
assumed to remain constant over time.
However, two related factors suggest
that these values will tend to increase
over time.
First, economic theory indicates that
the value of reducing life-threatening
and health-threatening risks—and
correspondingly the willingness of
individuals to pay to reduce these
risks—will increase as real per capita
income increases. With increased
income, an individual’s health and life
becomes more valuable relative to other
goods because, unlike other goods, they
are without close substitutes and in
relatively fixed or limited supply.
Expressed differently, as income
increases, consumption will increase
but the marginal utility of consumption
will decrease. In contrast, added years
of life (in good health) is not subject to
the same type of diminishing returns—
implying that an effective way to
increase lifetime utility is by extending
one’s life and maintaining one’s good
health (Hall and Jones, 2007).
Second, real per capita income has
broadly been increasing throughout U.S.
history, including recent periods. For
example, for the period 1950 through
2000, real per capita income grew at an
average rate of 2.31 percent a year (Hall
and Jones, 2007),36 although real per
capita income for the recent 25-year
period 1983 through 2008 grew at an
average rate of only 1.3 percent a year
(U.S. Census Bureau, 2010). More
important is the fact that real U.S. per
capita income is projected to grow
significantly in future years. For
example, the Annual Energy Outlook
(AEO) projections, prepared by the
Energy Information Administration
(EIA) in the Department of Energy
(DOE), show an average annual growth
rate of per capita income in the United
States of 2.7 percent for the period
2011–2035.37 The U.S. Environmental
Protection Agency prepared its
economic analysis of the Clean Air Act
using the AEO projections. OSHA
believes that it is reasonable to use the
same AEO projections employed by
DOE and EPA, and correspondingly
projects that per capita income in the
36 The results are similar if the historical period
includes a major economic downturn (such as the
United States has recently experienced). From 1929
through 2003, a period in U.S. history that includes
the Great Depression, real per capita income still
grew at an average rate of 2.22 percent a year
(Gomme and Rupert, 2004).
37 The EIA used DOE’s National Energy Modeling
System (NEMS) to produce the Annual Energy
Outlook (AEO) projections (EIA, 2011). Future per
capita GDP was calculated by dividing the projected
real gross domestic product each year by the
projected U.S. population for that year.
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United States will increase by 2.7
percent a year.
On the basis of the predicted increase
in real per capita income in the United
States over time and the expected
resulting increase in the value of
avoided fatalities and diseases, OSHA
has adjusted its estimates of the benefits
of the proposed rule to reflect the
anticipated increase in their value over
time. This type of adjustment has been
recognized by OMB (2003), supported
by EPA’s Science Advisory Board (EPA,
2000), and applied by EPA 38. OSHA
proposes to accomplish this adjustment
by modifying benefits in year i from [Bi]
to [Bi * (1 + k)i], where ‘‘k’’ is the
estimated annual increase in the
magnitude of the benefits of the
proposed rule.
What remains is to estimate a value
for ‘‘k’’ with which to increase benefits
annually in response to annual
increases in real per capita income,
where ‘‘k’’ is equal to ‘‘(1+g) * (h)’’, ‘‘g’’
is the expected annual percentage
increase in real per capita income, and
‘‘h’’ is the income elasticity of the value
of a statistical life. Probably the most
direct evidence of the value of ‘‘k’’
comes from the work of Costa and Kahn
(2003, 2004). They estimate repeated
labor market compensating wage
differentials from cross-sectional
hedonic regressions using census and
fatality data from the Bureau of Labor
Statistics for 1940, 1950, 1960, 1970,
and 1980. In addition, with the imputed
income elasticity of the value of life on
per capita GNP of 1.7 derived from the
1940–1980 data, they then predict the
value of an avoided fatality in 1900,
1920, and 2000. Given the change in the
value of an avoided fatality over time,
it is possible to estimate a value of ‘‘k’’
of 3.4 percent a year from 1900–2000; of
4.3 percent a year from 1940–1980; and
of 2.5 percent a year from 1980–2000.
Other, more indirect evidence comes
from estimates in the economics
literature of ‘‘h’’, the income elasticity of
the value of a statistical life. Viscusi and
Aldy (2003) performed a meta-analysis
on 0.2 wage-risk studies and concluded
that the confidence interval upper
bound on the income elasticity did not
exceed 1.0 and that the point estimates
across a variety of model specifications
ranged between 0.5 and 0.6. Applied to
a long-term increase in per capita
income of about 2.7 percent a year, this
would suggest a value of ‘‘k’’ of about
1.5 percent a year.
More recently, Kniesner, Viscusi, and
Ziliak (2010), using panel data quintile
regressions, developed an estimate of
the overall income elasticity of the value
38 See,
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of a statistical life of 1.44. Applied to a
long-term increase in per capita income
of about 2.7 percent a year, this would
suggest a value of ‘‘k’’ of about 3.9
percent a year.
Based on the preceding discussion of
these three approaches for estimating
the annual increase in the value of the
benefits of the proposed rule and the
fact that the projected increase in real
per capita income in the United States
has flattened in recent years and could
flatten in the long run, OSHA suggests
a conservative value for ‘‘k’’ of
approximately two percent a year. The
Agency invites comment on this
estimate and on estimates of the income
elasticity of the value of a statistical life.
The Agency believes that the rising
value, over time, of health benefits is a
real phenomenon that should be taken
into account in estimating the
annualized benefits of the proposed
rule. Table IX–13, in the following
section on discounting benefits, shows
estimates of the monetized benefits of
the proposed rule (under alternative
discount rates) with this estimated
increase in monetized benefits over
time. The Agency invites comment on
this adjustment to monetized benefits.
c. The Discounting of Monetized
Benefits
As previously noted, the estimated
stream of benefits arising from the
proposed beryllium rule is not constant
from year to year, both because of the
45-year delay after the rule takes effect
until all active workers obtain reduced
beryllium exposure over their entire
working lives and because of, in the
case of lung cancer, a 10-year latency
period between reduced exposure and a
reduction in the probability of disease.
An appropriate discount rate 39 is
needed to reflect the timing of benefits
over the 60-year period after the rule
takes effect and to allow conversion to
an equivalent steady stream of
annualized benefits.
1. Alternative Discount Rates for
Annualizing Benefits
Following OMB (2003) guidelines,
OSHA has estimated the annualized
benefits of the proposed rule using
separate discount rates of 3 percent and
7 percent. Consistent with the Agency’s
own practices in recent rulemakings,
OSHA has also estimated, for
benchmarking purposes, undiscounted
benefits—that is, benefits using a zero
percent discount rate.
39 Here and elsewhere throughout this section,
unless otherwise noted, the term ‘‘discount rate’’
always refers to the real discount rate—that is, the
discount rate net of any inflationary effects.
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The question remains, what is the
‘‘appropriate’’ or ‘‘preferred’’ discount
rate to use to monetize health benefits?
The choice of discount rate is a
controversial topic, one that has been
the source of scholarly economic debate
for several decades. However, in
simplest terms, the basic choices
involve a social opportunity cost of
capital approach or social rate of time
preference approach.
The social opportunity cost of capital
approach reflects the fact that private
funds spent to comply with government
regulations have an opportunity cost in
terms of foregone private investments
that could otherwise have been made.
The relevant discount rate in this case
is the pre-tax rate of return on the
foregone investments (Lind, 1982, pp.
24–32).
The rate of time preference approach
is intended to measure the tradeoff
between current consumption and
future consumption, or in the context of
the proposed rule, between current
benefits and future benefits. The
individual rate of time preference is
influenced by uncertainty about the
availability of the benefits at a future
date and whether the individual will be
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alive to enjoy the delayed benefits. By
comparison, the social rate of time
preference takes a broader view over a
longer time horizon—ignoring
individual mortality and the riskiness of
individual investments (which can be
accounted for separately).
The usual method for estimating the
social rate of time preference is to
calculate the post-tax real rate of return
on long-term, risk-free assets, such as
U.S. Treasury securities (OMB, 2003, p.
33). A variety of studies have estimated
these rates of return over time and
reported them to be in the range of
approximately 1–4 percent.
In accordance with OMB Circular A–
4 (2003), OSHA presents benefits and
net benefits estimates using discount
rates of 3 percent (representing the
social rate of time preference) and 7
percent (a rate estimated using the
social cost of capital approach). The
Agency is interested in any evidence,
theoretical or applied, that would
inform the application of discount rates
to the costs and benefits of a regulation.
2. Summary of Annualized Benefits
under Alternative Discount Rates
Table IX–13 presents OSHA’s
estimates of the sum of the annualized
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47721
benefits of the proposed rule, using
alternative discount rates of 0, 3, and 7
percent, with the suggested adjustment
for increasing monetized benefits in
response to annual increases in per
capita income over time.
Given that the stream of benefits
extends out 60 years, the value of future
benefits is sensitive to the choice of
discount rate. The undiscounted
benefits in Table IX–13 range from $291
million to $2.1 billion annually. Using
a 7 percent discount rate, the
annualized benefits range from $60
million to $591 million. As can be seen,
going from undiscounted benefits to a 7
percent discount rate has the effect of
cutting the annualized benefits of the
proposed rule by about 74 percent.
Taken as a whole, the Agency’s best
preliminary estimate of the total
annualized benefits of the proposed
rule—using a 3 percent discount rate
with an adjustment for the increasing
value of health benefits over time—is
between $158 million and $1.2 billion,
with a mid-point value of $576 million.
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Step 4: Net Benefits of the Proposed
Rule
OSHA has estimated, in Table IX–14,
the monetized and annualized net
benefits of the proposed rule (with a
PEL of 0.2 mg/m3), based on the benefits
and costs previously presented. Table
IX–14 also provides estimates of
annualized net benefits for alternative
PELs of 0.1 and 0.5 mg/m3. Both the
proposed rule and the alternatives PEL
options have the same ancillary
provisions and an action level equal to
half of the PEL in both cases.
Table IX–14 is being provided for
informational purposes only. As
previously noted, the OSH Act requires
the Agency to set standards based on
eliminating significant risk to the extent
feasible. An alternative criterion of
maximizing net (monetized) benefits
may result in very different regulatory
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outcomes. Thus, this analysis of net
benefits has not been used by OSHA as
the basis for its decision concerning the
choice of a PEL or of other ancillary
requirements for the proposed beryllium
rule.
Table IX–14 shows net benefits using
alternative discount rates of 0, 3, and 7
percent for benefits and costs, having
previously included an adjustment to
monetized benefits to reflect increases
in real per capita income over time.
OSHA has relied on a uniform discount
rate applied to both costs and benefits.
The Agency is interested in any
evidence, theoretical or applied, that
would support or refute the application
of differential discount rates to the costs
and benefits of a regulation.
As previously noted in this section,
the choice of discount rate for
annualizing benefits has a significant
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effect on annualized benefits. The same
is true for net benefits. For example, the
net benefits using a 7 percent discount
rate for benefits are considerably smaller
than the net benefits using a 3 percent
discount rate, declining by over half
under all scenarios. (Conversely, as
noted in Chapter V of the PEA, the
choice of discount rate for annualizing
costs has a relatively minor effect on
annualized costs.)
Based on the results presented in
Table IX–14, OSHA finds:
• While the net benefits of the
proposed rule vary considerably—
depending on the choice of discount
rate used to annualize benefits and on
whether the benefits being used are in
the high, midpoint, or low range—
benefits exceed costs for the proposed
0.2 mg/m3 PEL in all cases that OSHA
considered.
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47723
between $120 million and $1.2 billion,
with a midpoint value of $538 million.
• The alternative of a 0.5 mg/m3 PEL
has lower net benefits under all
assumptions, whereas the effect on net
benefits of the 0.1 mg/m3 PEL is mixed,
relative to the proposed 0.2 mg/m3 PEL.
However, for these alternative PELs,
benefits were also found to exceed costs
in all cases that OSHA considered.
Incremental Benefits of the Proposed
Rule
Incremental costs and benefits are
those that are associated with increasing
the stringency of the standard. A
comparison of incremental benefits and
costs provides an indication of the
relative efficiency of the proposed PEL
and the alternative PELs. Again, OSHA
has conducted these calculations for
informational purposes only and has not
used these results as the basis for
selecting the PEL for the proposed rule.
OSHA provides, in Table IX–15,
estimates of the net benefits of the
alternative 0.1 and 0.5 mg/m3 PELs. The
incremental costs, benefits, and net
benefits of meeting a 0.5mg/m3 PEL and
then going to a 0.2 mg/m3 PEL (as well
as meeting a 0.2 mg/m3 PEL and then
going to a 0.1 mg/m3 PEL—which the
Agency has not yet determined is
feasible), for alternative discount rates
of 3 and 7 percent, are presented in
Table IX–15. Table IX–15 breaks out
costs by provision and benefits by type
of disease and by morbidity/mortality.
As Table IX–15 shows, at a discount rate
of 3 percent, a PEL of 0.2 mg/m3, relative
to a PEL of 0.5 mg/m3, imposes
additional costs of $4.4 million per year;
additional benefits of $172.7 million per
year; and additional net benefits of
$168.2 million per year. The proposed
PEL of 0.2 mg/m3 also has higher net
benefits, relative to a PEL of 0.5 mg/m3,
using a 7 percent discount rate.
Table IX–15 demonstrates that,
regardless of discount rate, there are net
benefits to be achieved by lowering
exposures from the current PEL of 2.0
mg/m3 to 0.5 mg/m3 and then, in turn,
lowering them further to 0.2 mg/m3.
However, the majority of the benefits
and costs attributable to the proposed
rule are from the initial effort to lower
exposures to 0.5 mg/m3. Consistent with
the previous analysis, net benefits
decline across all increments as the
discount rate for annualizing benefits
increases. As also shown in Table IX–
15, there is a slight positive net
incremental benefit from going from a
PEL of 0.2 mg/m3 to 0.1 mg/m3 for a
discount rate of 3 percent, and a slight
negative net increment for a discount
rate of 7 percent. (Note that these results
are for OSHA’s midpoint estimate of
benefits, although as indicated in Table
IX–14, this is not universal across all
estimation parameters.)
In addition to examining alternative
PELs, OSHA also examined alternatives
to other provisions of the standard.
These regulatory alternatives are
discussed Section IX.H of this preamble.
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• The Agency’s best estimate of the
net annualized benefits of the proposed
rule—using a uniform discount rate for
both benefits and costs of 3 percent—is
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Millions ($2010)
Alternative 4
Alternative 5
Incremental Costs/Benefits
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Alternative 5
(PEL= 0.5 ~g/m 3 , AL = 0.25 ~g/m 3 )
Incremental Costs/Benefits
3%
7%
------
3%
7%
$9.5
$0.2
$2.2
$0.6
$2.9
$0.1
$1.8
$1.4
$0.4
$12.6
3%
$10.3
$0.3
$2.4
$0.7
$3.0
$0.2
$1.8
$1.4
$0.4
$12.9
7%
3%
7%
Annualized Costs
$12.9
$0.7
$3.8
$0.9
$3.0
$0.4
$1.8
$1.4
$0.6
$12.6
Contrd Costs
Respiratcrs
Exposure Assessment
Regulated Areas
Medical Surveillance
Medical Removal
Exposure Contrd Plan
Prdective Cldhing and Equipment
Hygiene Areas and Practices
Housekeeping
$13.9
$0.7
$3.9
$0.9
$3.1
$0.5
$1.8
$1.4
$0.6
$12.9
$3.3
$0.4
$1.6
$0.3
$0.1
$0.3
$0.0
$0.0
$0.2
$0.0
~~
Training
$43.7
Total Annualized Costs (point estimate)
07AUP2
EP07AU15.026
Annual Benefits: Number of Cases Prevented
$3.5
$0.5
$1.5
$0.3
$0.1
$0.3
$0.0
$0.0
$0.2
$0.0
~~
$45.5
$6.1
~
$6.3
$37.6
$3.6
$0.1
$0.3
$0.3
$0.1
$0.1
$0.0
$0.0
$0.0
$0.0
~
$39.1
~
$4.8
$33.2
$34.4
Cases
Fatal Chronic Beryllium Disease
4
94
0
2
98
$584.4
$258.8
2
$11.1
$4.9
96
$573.0
$253.7
29
$171.8
$76.1
67
$401.2
$177.7
Beryllium rvbrbidity
50
$2.9
$1.6
1
$0.0
$0.0
50
$2.8
$1.6
15
$0.9
$0.5
34
$2.0
$1.1
Monetized Annual Benefits (midpoint estimate)
$587.3
$260.4
$11.2
$5.1
$575.8
$255.3
$172.7
$76.6
$403.1
$178.8
I
$543.5
$214.9
$5.3
-$1.3
$538.2
$216.2
$168.2
$71.8
$370.0
$144.4
Net Benefits
Soorce: OSHA, Directorate of Standards and Guidance, Office of Regulatcry Analysis
Cases
$6.0
$0.1
$1.9
$0.3
$2.8
$0.1
$1.8
$1.4
$0.4
$12.6
Cases
Fatal Lung Cancers (midpoint estimate)
Cases
~
$6.5
$0.1
$2.1
$0.4
$2.9
$0.1
$1.8
$1.4
$0.4
$12.9
$5.8
$4.4
~
$3.9
$0.1
$0.3
$0.3
$0.1
$0.1
$0.0
$0.0
$0.0
$0.0
Beryllium-Related Matality
cost and benefit input parameters in
order to determine their effects on the
Agency’s estimates of annualized costs,
annualized benefits, and annualized net
benefits. In the second type of
E:\FR\FM\07AUP2.SGM
robust the estimates of net benefits are
to changes in various cost and benefit
parameters. In the first type of
sensitivity analysis, OSHA made a
series of isolated changes to individual
PO 00000
3%
7%
------
Discount Rate
Proposed PEL
Alternative 4
(PEL= 0.1 ~g/m 3 , AL = 0.05 ~g/m 3 )
4
92
Cases
0
29
4
63
Federal Register / Vol. 80, No. 152 / Friday, August 7, 2015 / Proposed Rules
Step 5: Sensitivity Analysis
19:20 Aug 06, 2015
In this section, OSHA presents the
results of two different types of
sensitivity analysis to demonstrate how
VerDate Sep<11>2014
Table IX-15: Annualized Costs, Benefits and Incremental Benefits of OSHA's Proposed Beryllium Standard of of 0.1 1Jg/m3 and 0.51Jg/m3 PEL Alternative
Federal Register / Vol. 80, No. 152 / Friday, August 7, 2015 / Proposed Rules
sensitivity analysis—a so-called ‘‘breakeven’’ analysis—OSHA also investigated
isolated changes to individual cost and
benefit input parameters, but with the
objective of determining how much they
would have to change for annualized
costs to equal annualized benefits. For
both types of sensitivity analyses, OSHA
used the annualized costs and benefits
obtained from a three-percent discount
rate as the reference point.
Again, the Agency has conducted
these calculations for informational
purposes only and has not used these
results as the basis for selecting the PEL
for the proposed rule.
mstockstill on DSK4VPTVN1PROD with PROPOSALS2
a. Analysis of Isolated Changes to Inputs
The methodology and calculations
underlying the estimation of the costs
and benefits associated with this
rulemaking are generally linear and
additive in nature. Thus, the sensitivity
of the results and conclusions of the
analysis will generally be proportional
to isolated variations in a particular
input parameter. For example, if the
estimated time that employees need to
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19:20 Aug 06, 2015
Jkt 235001
travel to (and from) medical screenings
were doubled, the corresponding labor
costs would double as well.
OSHA evaluated a series of such
changes in input parameters to test
whether and to what extent the general
conclusions of the economic analysis
held up. OSHA first considered changes
to input parameters that affected only
costs and then changes to input
parameters that affected only benefits.
Each of the sensitivity tests on cost
parameters had only a very minor effect
on total costs or net costs. Much larger
effects were observed when the benefits
parameters were modified; however, in
all cases, net benefits remained
significantly positive. On the whole,
OSHA found that the conclusions of the
analysis are reasonably robust, as
changes in any of the cost or benefit
input parameters still show significant
net benefits for the proposed rule. The
results of the individual sensitivity tests
are summarized in Table IX–16 and are
described in more detail below.
In the first of these sensitivity tests,
where OSHA doubled the estimated
PO 00000
Frm 00161
Fmt 4701
Sfmt 4702
47725
portion of employees in need of
protective clothing and equipment
(PPE), essentially doubling the
estimated baseline non-compliance rate
(e.g., from 10 to 20 percent), and
estimates of other input parameters
remained unchanged, Table IX–16
shows that the estimated total costs of
compliance would increase by $1.4
million annually, or by about 3.7
percent, while net benefits would also
decline by $1.4 million annually, from
$538.2 million to $536.8 million
annually.
In a second sensitivity test, OSHA
increased the estimated unit cost of
ventilation from $13.18 per cfm for most
sectors to $25 per cfm for most sectors.
As shown in Table IX–16, if OSHA’s
estimates of other input parameters
remained unchanged, the total
estimated costs of compliance would
increase by $2.0 million annually, or by
about 5.3 percent, while net benefits
would also decline by $2.0 million
annually, from $538.2 million to $536.2
million annually.
E:\FR\FM\07AUP2.SGM
07AUP2
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47726
Uncertainty Scenarios
Percentage Impact
Jkt 235001
Frm 00162
Fmt 4701
Sfmt 4702
07AUP2
annually, or by about 4.1 percent, while
net benefits would also decline by $1.5
million annually, from $538.2 million to
$536.7 million annually.
In a fourth sensitivity test, OSHA
increased its estimated incremental time
per workers for housekeeping by 50
E:\FR\FM\07AUP2.SGM
Difference From
Estimate
Primary Estimate
NA
$0
0.0%
$37,597,325
$538,229, 309
$1,385,575
3.7%
$38,982,900
$536,843,733
$1,993,863
5.3%
$39, 591, 188
$536,235,445
$1,545,310
4.1%
$39,142,635
$536,683,999
$5,429,113
14.4%
$43,026,437
$532,800,196
$4,483,148
11.9%
$42,080,472
$533,7 46, 161
$0
0.0%
$575,826,633
$538,229, 309
-$216,839,627
-37.7%
$358,987,006
$321,389,682
$443,411,757
77.0%
$1,019,238,390
$981,641,066
-$314,319,477
-54.6%
$261,507,156
$223,909,831
on Costs or
Benefits
Total Annualized
Cost or Benefit
Net Benefit
Cost Scenarios
Proposed Rule- OSHA's best estimate
Reduced PPE Compliance Rates
Double PPE non-compliance
rates
Increased CFM Unit Cost
Increase CFM Unit Cost to $25
for most sectors
another reason (working in a regulated
area, exposed during an emergency,
etc.). As shown in Table IX–16, if
OSHA’s estimates of other input
parameters remained unchanged, the
total estimated costs of compliance
would increase by $1.5 million
PO 00000
Change from OSHA's Primary
EP07AU15.027
Increased share of workers showing signs and symptoms
Increase share of workers
showing signs and symtoms to
25%
Increased housekeeping
Increase the estimated
incremental time per worker
for housekeeping by 50"/o
Increased establishment-based costs
For establishment-based costs,
increased the number of
affected establishments by up
to 100"/o
Benefit Secnarios
Proposed Rule- OSHA's best estimate
Low morbidity valuation
NA
Benefits estimated using low
morbidity value
High morbidity valuation
Benefits estimated using high
morbidity value
Remove adjustment for future valuation of benefits (due to
Set the growth in future
positive income elasticity of health benefits
benefits to 0.0"/o
Source: OSHA, Directorate of Standards and Guidance, Office of Regulatory Analysis
Federal Register / Vol. 80, No. 152 / Friday, August 7, 2015 / Proposed Rules
19:20 Aug 06, 2015
In a third sensitivity test, OSHA
increased the estimated share of workers
showing signs and symptoms of CBD
from 15 to 25 percent, thereby adding
these workers to the group eligible for
medical surveillance and assuming that
they would not be otherwise eligible for
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Table IX-16 Sensitivity Tests
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Federal Register / Vol. 80, No. 152 / Friday, August 7, 2015 / Proposed Rules
percent. As shown in Table IX–16, if
OSHA’s estimates of other input
parameters remained unchanged, the
total estimated costs of compliance
would increase by $5.4 million
annually, or by about 14.4 percent,
while net benefits would also decline by
$5.4 million annually, from $538.2
million to $532.8 million annually.
In a fifth sensitivity test, OSHA
increased the estimated number of
establishments needing engineering
controls. For this sensitivity test, if less
than 50 percent of the establishments in
an industry needed engineering
controls, OSHA doubled the percentage
of establishments needing engineering
controls. If more than 50 percent of
establishments in an industry needed
engineering controls, then OSHA
increased the percentage of
establishment needing engineering
control to 100 percent. The purpose of
this sensitivity analysis was to check the
importance of using a methodology that
treated 50 percent of workers in a given
occupation exposed above the PEL as
equivalent to 50 percent of facilities
lacking adequate exposure controls. As
shown in Table IX–16, if OSHA’s
estimates of other input parameters
remained unchanged, the total
estimated costs of compliance would
increase by $4.5 million, or by about
11.9 percent, while net benefits would
also decline by $4.5 million, from
$538.2 million to $533.7 million
annually.
The Agency also performed
sensitivity tests on several input
parameters used to estimate the benefits
of the proposed rule. In the first two
tests, in an extension of results
previously presented in Table IX–12,
the Agency examined the effect on
annualized net benefits of employing
the high-end estimate of the benefits, as
well as the low-end estimate,
specifically examining the effect on
undiscounted benefits of varying the
valuation of individual morbidity cases.
Table IX–16 presents the effect on
annualized net benefits of using the
extreme values of these ranges: the high
morbidity valuation case and the low
morbidity valuation case. For the low
estimate of valuation, the benefits
decline by 37.7 percent, to $359 million
annually, yielding net benefits of $321
million annually. As shown, using the
high estimate of morbidity valuation,
the benefits rise by 77.0 percent to $1.0
billion annually, yielding net benefits of
$982 million annually.
In a third sensitivity test of benefits,
the Agency examined the effect of
removing the component for the
estimated rising value of health and
safety over time. This would reduce the
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19:20 Aug 06, 2015
Jkt 235001
benefits by 54.6 percent, or $314 million
annually, lowering the net benefits to
$224 million annually.
In Chapter VII of the PEA the Agency
examined the effect of raising the
discount rate for costs and benefits to 7
percent. Raising the discount rate to 7
percent would increase costs by $1.5
million annually and lower benefits by
$320.5 million annually, yielding
annualized net benefits of $216.2
million.
Also in Chapter VII of the PEA the
Agency performed a sensitivity analysis
of dental lab substitution. In the PEA,
OSHA estimates that 75 percent of the
dental laboratory industry will react to
a new standard on beryllium by
substituting away from using beryllium
to the use of other materials.
Substitution is not costless, and Chapter
V of the PEA estimates the increased
cost due to the higher costs of using
non-beryllium alloys. These costs are
smaller than the avoided costs of the
ancillary provisions and engineering
controls. Thus, as indicated in Table
VII–8 of the PEA, the benefits of the
proposal would be lower and the costs
higher if there were less substitution out
of beryllium in dental labs. The lowest
net benefits would occur if labs were
unable to substitute out berylliumcontaining materials at all, and had to
use ventilation to control exposures. In
this case, the proposal would yield only
$420 million in net benefits. The highest
net benefits, larger than assumed for
OSHA’s primary estimate, would be if
all dental labs substituted out of
beryllium-containing materials as a
result of the proposal; as a result, the
proposal would yield $573 million in
net benefits. Another possibility is a
scenario is which technology and the
market move along rapidly away from
using beryllium-containing materials,
independently of an OSHA rule, and the
proposal itself would therefore produce
neither costs nor benefits in this sector.
If dental labs are removed from the PEA,
the net benefits for the proposal—for the
remaining industry sectors—decline to
$284 million. This analysis
demonstrates, however, that regardless
of any assumption regarding
substitution in dental labs, the proposal
would generate substantially more
monetized benefits than costs.
Finally, the Agency examined in
Chapter VII of the PEA the effects of
changes in two important inputs to the
benefits analysis: the factor that
transforms CBD prevalence rates into
incidence rates, needed for the
equilibrium lifetime risk model, and the
percentage of CBD cases that eventually
lead to a fatality.
PO 00000
Frm 00163
Fmt 4701
Sfmt 4702
47727
From the Cullman dataset, the Agency
has estimated the prevalence of CBD
cases at any point in time as a function
of cumulative beryllium exposure. In
order to utilize the lifetime risk model,
which tracks workers over their working
life in a job, OSHA has turned these
prevalence rates into an incidence rate,
which is the rate of contracting CBD at
a point in time. OSHA’s baseline
estimate of the turnover rate in the
model is 10 percent. In Table VII–10 in
the PEA, OSHA also presented
alternative turnover rates of 5 percent
and 20 percent. A higher turnover rate
translates into a higher incidence rate,
and the table shows that, from a
baseline midpoint estimate with 10
percent turnover the number of CBD
cases prevented is 6,367, while raising
the turnover rate to 20 percent causes
this midpoint estimate to rise to 11,751.
Conversely, a rate of 5 percent lowers
the number of CBD cases prevented to
3,321. Translated into monetary
benefits, the table shows that the
baseline midpoint estimate of $575.8
million now ranges from $314.4 million
to $1,038 million.
Also in TableVII–10 of the PEA, the
Agency looked at the effects of varying
the percentage of CBD cases that
eventuate in fatality. The Agency’s
baseline estimate of this outcome is 65
percent, with half of this occurring
relatively soon, and the other half after
an extended debilitating condition. The
Agency judged that a reasonable range
to investigate was a low of 50 percent
and a high of 80 percent, while
maintaining the shares of short-term and
long-term endpoint fatality. At a
baseline of 65 percent, the midpoint
estimate of total CBD cases prevented is
4,139. At the low end of 50 percent
mortality this estimate lowers to 3,183
while at the high end of 80 percent
mortality this estimate rises to 5,094.
Translated into monetary benefits, the
table shows that the baseline midpoint
estimate of $575.8 million now ranges
from $500.1 million to $651.5 million.
b. ‘‘Break-Even’’ Analysis
OSHA also performed sensitivity tests
on several other parameters used to
estimate the net costs and benefits of the
proposed rule. However, for these, the
Agency performed a ‘‘break-even’’
analysis, asking how much the various
cost and benefits inputs would have to
vary in order for the costs to equal, or
break even with, the benefits. The
results are shown in Table IX–17.
In one break-even test on cost
estimates, OSHA examined how much
total costs would have to increase in
order for costs to equal benefits. As
shown in Table IX–17, this point would
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07AUP2
47728
Federal Register / Vol. 80, No. 152 / Friday, August 7, 2015 / Proposed Rules
mstockstill on DSK4VPTVN1PROD with PROPOSALS2
be reached if costs increased by $538.2
million, or by 1,431 percent.
In a second test, looking specifically
at the estimated engineering control
costs, the Agency found that these costs
would need to increase by $566.7
million, or 6,240 percent, for costs to
equal benefits.
In a third sensitivity test, on benefits,
OSHA examined how much its
estimated monetary valuation of an
avoided illness or an avoided fatality
would need to be reduced in order for
the costs to equal the benefits. Since the
total valuation of prevented mortality
and morbidity are each estimated to
exceed the estimated costs of $38
million, an independent break-even
point for each is impossible. In other
words, for example, if no value is
attached to an avoided illness associated
with the rule, but the estimated value of
an avoided fatality is held constant, the
rule still has substantial net benefits.
Only through a reduction in the
estimated net value of both components
is a break-even point possible.
The Agency, therefore, examined how
large an across-the-board reduction in
VerDate Sep<11>2014
19:20 Aug 06, 2015
Jkt 235001
the monetized value of all avoided
illnesses and fatalities would be
necessary for the benefits to equal the
costs. As shown in Table IX–17, a 94
percent reduction in the monetized
value of all avoided illnesses and
fatalities would be necessary for costs to
equal benefits, reducing the estimated
value to $733,303 per fatality prevented,
and an equivalent percentage reduction
to about $4,048 per illness prevented.
In a fourth break-even sensitivity test,
OSHA estimated how many fewer
beryllium-related fatalities and illnesses
would be required for benefits to equal
costs. Paralleling the previous
discussion, eliminating either the
prevented mortality or morbidity cases
alone would be insufficient to lower
benefits to the break-even point. The
Agency therefore examined them as a
group. As shown in Table IX–17, a
reduction of 96 percent, for both
simultaneously, is required to reach the
break-even point—90 fewer fatalities
prevented annually, and 46 fewer
beryllium-related illnesses-only cases
prevented annually.
PO 00000
Frm 00164
Fmt 4701
Sfmt 4702
Taking into account both types of
sensitivity analysis the Agency
performed on its point estimates of the
annualized costs and annualized
benefits of the proposed rule, the results
demonstrate that net benefits would be
positive in all plausible cases tested. In
particular, this finding would hold even
with relatively large variations in
individual input parameters.
Alternately, one would have to imagine
extremely large changes in costs or
benefits for the rule to fail to produce
net benefits. OSHA concludes that its
finding of significant net benefits
resulting from the proposed rule is a
robust one.
OSHA welcomes input from the
public regarding all aspects of this
sensitivity analysis, including any data
or information regarding the accuracy of
the preliminary estimates of compliance
costs and benefits and how the
estimates of costs and benefits may be
affected by varying assumptions and
methodological approaches. OSHA also
invites comment on the risk analysis
and risk estimates from which the
benefits estimates were derived.
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Break-Even Sensitivity Analysis
Frm 00165
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07AUP2
Factor
Factor Value at Which
Benefits Equal Costs
Required Factor
Dollar/Number
Change
Percentage
Factor Change
Total Costs
$37,597,325
$575,826,633
$538,229,309
1431.6%
Engineering Control Costs
$9,082,884
$575,826,633
$566,743,749
6239.7%
$11,231,000
$62,000
$733,303
$4,048
-$10,497,697
-$57,952
-93.5%
-93.5%
96
50
6
3
-90
-46
-93.5%
-93.5%
Benefits Valuation per Case Avoided
Monetized Benefit per Fatality Avoided
Monetized Benefit per Illness Avoided
Cases Avoided
Deaths Avoided
Illnesses Avoided
Source: OSHA, Directorate of Standards and Guidance, Office of Regulatory Analysis
47729
distributive impacts; and equity), unless
a statute requires another regulatory
approach.’’ The OSH Act, as interpreted
by the courts, requires health
regulations to reduce significant risk to
E:\FR\FM\07AUP2.SGM
Order 12866 instructs agencies to
‘‘select those approaches that maximize
net benefits (including potential
economic, environmental, public health
and safety, and other advantages;
PO 00000
OSHA's Best Estimate of
Annualized Cost or Benefit
Federal Register / Vol. 80, No. 152 / Friday, August 7, 2015 / Proposed Rules
H. Regulatory Alternatives
19:20 Aug 06, 2015
This section discusses various
regulatory alternatives to the proposed
OSHA beryllium standard. Executive
VerDate Sep<11>2014
EP07AU15.028
Table IX-17
47730
Federal Register / Vol. 80, No. 152 / Friday, August 7, 2015 / Proposed Rules
mstockstill on DSK4VPTVN1PROD with PROPOSALS2
the extent feasible. Nevertheless OSHA
has examined possible regulatory
alternatives that may not meet its
statutory requirements.
Each regulatory alternative presented
here is described and analyzed relative
to the proposed rule. Where
appropriate, the Agency notes whether
the regulatory alternative, to be a
legitimate candidate for OSHA
consideration, requires evidence
contrary to the Agency’s preliminary
findings of significant risk and
feasibility. To facilitate comment, OSHA
has organized some two dozen specific
regulatory alternatives into five
categories: (1) Scope; (2) exposure
limits; (3) methods of compliance; (4)
ancillary provisions; and (5) timing.
1. Scope Alternatives
The first set of regulatory alternatives
would alter scope of the proposed
standard—that is, the groups of
employees and employers covered by
the proposed standard. The scope of the
current beryllium proposal applies only
to general industry work, and does not
apply to employers when engaged in
construction or maritime activities. In
addition, the proposed rule provides an
exemption for those working with
materials that contain beryllium only as
a trace contaminant (less than
0.1percent composition by weight).40
As discussed in the explanation of
paragraph (a) in Section XVIII of this
preamble, Summary and Explanation of
the Proposed Standard, OSHA is
considering alternatives to the proposed
scope that would increase the range of
employers and employees covered by
the standard. OSHA’s review of several
industries indicates that employees in
some construction and maritime
industries, as well as some employees
who deal with materials containing less
than 0.1 percent beryllium, may be at
significant risk of CBD and lung cancer
as a result of their occupational
exposures. Regulatory Alternatives #1a,
#1b, #2a, and #2b would increase the
scope of the proposed standard to
provide additional protection to these
workers.
Regulatory Alternative #1a would
expand the scope of the proposed
standard to also include all operations
in general industry where beryllium
exists only as a trace contaminant; that
is, where the materials used contain less
than 0.1 percent beryllium by weight.
Regulatory Alternative #1b is similar to
Regulatory Alternative #1a, but exempts
40 Employers engaged in general industry
activities exempted from the proposed rule must
still ensure that their employees are protected from
beryllium exposure above the current PEL, as listed
in 29 CFR 1910.1000 Table Z–2.
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operations where beryllium exists only
as a trace contaminant and the employer
can show that employees’ exposures
will not meet or exceed the action level
or exceed the STEL. Where the
employer has objective data
demonstrating that a material containing
beryllium or a specific process,
operation, or activity involving
beryllium cannot release beryllium in
concentrations at or above the proposed
action level or above the proposed STEL
under any expected conditions of use,
that employer would be exempt from
the proposed standard except for
recordkeeping requirements pertaining
to the objective data. Alternative #1a
and Alternative #1b, like the proposed
rule, would not cover employers or
employees in construction or shipyards.
OSHA has identified two industries
with workers engaged in general
industry work that would be excluded
under the proposed rule but would fall
within the scope of the standard under
Regulatory Alternatives #1a and #1b:
Primary aluminum production and coalfired power generation. Beryllium exists
as a trace contaminant in aluminum ore
and may result in exposures above the
proposed permissible exposure limits
(PELs) during aluminum refining and
production. Coal fly ash in coalpowered power plants is also known to
contain trace amounts of beryllium,
which may become airborne during
furnace and baghouse operations and
might also result in worker exposures.
See Appendices VIII–A and VIII–B at
the end of Chapter VIII in the PEA for
a discussion of beryllium exposures and
available controls in these two
industries.
As discussed in Appendix IV–B of the
PEA, beryllium exposures from fly ash
high enough to exceed the proposed
PEL would usually be coupled with
arsenic exposures exceeding the arsenic
PEL. Employers would in that case be
required to implement all feasible
engineering controls, work practices,
and necessary PPE (including
respirators) to comply with the OSHA
Inorganic Arsenic standard (29 CFR
1910.1018)—which would be sufficient
to comply with those aspects of the
proposed beryllium standard as well.
The degree of overlap between the
applicability of the two standards and,
hence, the increment of costs
attributable to this alternative are
difficult to gauge. To account for this
uncertainty, the Agency at this time is
presenting a range of costs for
Regulatory Alternative #1a: From no
costs being taken for ancillary
provisions under Regulatory Alternative
#1a to all such costs being included. At
the low end, the only additional costs
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Fmt 4701
Sfmt 4702
under Regulatory Alternative #1a are
due to the engineering control costs
incurred by the aluminum smelters (see
Appendix VIII–A).
Similarly, the proposed beryllium
standard would not result in additional
benefits from a reduction in the
beryllium PEL or from ancillary
provisions similar to those already in
place for the arsenic standard, but
OSHA does anticipate some benefits
will flow from ancillary provisions
unique to the proposed beryllium
standard. To account for significant
uncertainty in the benefits that would
result from the proposed beryllium
standard for workers in primary
aluminum production and coal-fired
power generation, OSHA estimated a
range of benefits for Regulatory
Alternative #1a. The Agency estimated
that the proposed ancillary provisions
would avert between 0 and 45 percent 41
of those baseline CBD cases not averted
by the proposed PEL. Though the
Agency is presenting a range for both
costs and benefits for this alternative,
the Agency judges the degree of overlap
with the arsenic standard is likely to be
substantial, so that the actual costs and
benefits are more likely to be found at
the low end of this range. The Agency
invites comment on all these issues.
Table IX–18 presents, for
informational purposes, the estimated
costs, benefits, and net benefits of
Regulatory Alternative #1a using
alternative discount rates of 3 percent
and 7 percent. In addition, this table
presents the incremental costs,
incremental benefits, and incremental
net benefits of this alternative relative to
the proposed rule. Table IX–18 also
breaks out costs by provision, and
benefits by type of disease and by
morbidity/mortality.
As shown in Table IX–18, Regulatory
Alternative #1a would increase the
annualized cost of the rule from $37.6
million to between $39.6 and $56.0
million using a 3 percent discount rate
and from $39.1 million to between $41.3
and $58.1 million using a 7 percent
discount rate. OSHA estimates that
regulatory Alternative #1a would
prevent as few as an additional 0.3 (i.e.,
almost one fatality every 3 years) or as
many as an additional 31.8 berylliumrelated fatalities annually, relative to the
proposed rule. OSHA also estimates that
Regulatory Alternative #1a would
prevent as few as an additional 0.002 or
as many as an additional 9 berylliumrelated non-fatal illnesses annually,
relative to the proposed rule. As a
result, annualized benefits in monetized
41 As discussed in Chapter VII of the PEA, OSHA
used 45 percent to develop its best estimate.
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Federal Register / Vol. 80, No. 152 / Friday, August 7, 2015 / Proposed Rules
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terms would increase from $575.8
million to between $578.0 and $765.2
million, using a 3 percent discount rate,
and from $255.3 million to between
$256.3 and $339.3 million using a 7
percent discount rate. Net benefits
would increase from $538.2 million to
between $538.4 and $709.2 million
using a 3 percent discount rate and from
$216.2 million to somewhere between
$215.1 to $281.2 million using a 7
percent discount rate. As noted in
Appendix VIII–B of Chapter VIII in the
PEA, the Agency emphasizes that these
estimates of benefits are subject to a
significant degree of uncertainty, and
the benefits associated with Regulatory
Alternative #1a arguably could be a
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19:20 Aug 06, 2015
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small fraction of OSHA’s best estimate
presented here.
OSHA estimates that the costs and the
benefits of Regulatory Alternative #1b
will be somewhat lower than the costs
of Regulatory Alternative #1a, because
most—but not all—of the provisions of
the proposed standard are triggered by
exposures at the action level, 8-hour
time-weighted average (TWA) PEL, or
STEL. For example, where exposures
exist but are below the action level and
at or below the STEL, Alternative #1a
would require employers to establish
work areas; develop, maintain, and
implement a written exposure control
plan; provide medical surveillance to
employees who show signs or
PO 00000
Frm 00167
Fmt 4701
Sfmt 4702
47731
symptoms of CBD; and provide PPE in
some instances. Regulatory Alternative
#1b would not require employers to take
these measures in operations where they
can produce objective data
demonstrating that exposures are below
the action level and at or below the
STEL. OSHA only analyzed costs, not
benefits, for this alternative, consistent
with the Agency’s treatment of
Regulatory Alternatives in the past.
Total costs for Regulatory Alternative
#1b versus #1a, assuming full ancillary
costs, drop from to $56.0 million to
$49.9 million using a 3 percent discount
rate, and from $58.1 million to $51.8
million using a 7 percent discount rate.
BILLING CODE 4510–26–P
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47732
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Millions ($2010)
Alternative 1a
(Include trace contaminants)
Frm 00168
Fmt 4701
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(PEL= 0.2 ~9Im 3 , AL = 0.10 ~9Im 3 )
3%
$11.7-$11.7
$0.3- $0.3
$2.5- $4.1
$0.7- $0.7
$3.1- $4.5
$0.2- $0.3
$1.8- $2.8
$0.0- $0.0
$0.4- $0.4
$13.3- $22.0
$6.0- $9.9
$1.3-$1.3
$0.0- $0.0
$0.1-$1.5
$0.0- $0.1
$0.1-$1.5
$0.0- $0.1
$0.0- $1.0
$0.0- $0.0
$0.0- $0.0
$0.4- $8.8
$0.2- $4.1
$20-$184
$01-$179
Cases
$10.3
$0.3
$2.4
$0.7
$3.0
$0.2
$1.8
$1.4
$0.4
$12.9
__
$5.8
~
$37.6
$39.1
Cases
Cases
4.1-41
92.1- 123.7
______lli.
$9.5
$0.2
$2.2
$0.6
$2.9
$0.1
$1.8
$1.4
$0.4
$12.6
$1.3-$1.3
$0.0- $0.0
$0.1-$2.1
$0.0- $0.1
$0.7-$2.7
$0.0- $0.1
$0.0-$1.3
$0.2- $0.2
$0.0- $0.0
$0.4-$10.9
$0.2- $4.9
$413-$581
~
7%
$396-$560
Total Annualized Costs(point estimate)
Annual Benefits: Number of Cases Prevented
Fatal Lung Cancers (midpoint estimate)
Fatal Chronic Beryllium Disease
3%
$10.8-$10.8
$0.3-$0.3
$2.3-$3.8
$0.7-$0.7
$3.0-$4.3
$0.2-$0.3
$1.8-$2.8
$1.4-$1.4
$0.4- $0.4
$12.9-$21.4
$6.0-$9.9
Annualized Costs
Control Costs
Respi raters
Exposure Assessment
Regulated Areas and Beryllium Work Areas
Medical Surveillance
Medical Removal
Exposure Control Plan
Protective Clothing and Equipment
Hygiene Areas and Practices
Housekeeping
Training
7%
0.1-0.1
0.2-31.7
4
~
Beryllium-Related Mortality
96.3- 127.8
$575.0- $761.4
$254.6- $337.2
0.3-31.8
$2 0-$188.4
$0.9- $83.4
96
$573.0
$253.7
Bery11ium Morbidity
49.5- 58.5
$3.0-$3.8
$1.7- $2.1
0.0- 9.0
$0.2- $1.0
$0.1 - $0.5
50
$2.8
$1.6
Monetized Annual Benefits (midpoint estimate)
07AUP2
example, this alternative would cover
abrasive blasters, pot tenders, and
E:\FR\FM\07AUP2.SGM
standard to include employers in
construction and maritime. For
PO 00000
Discount Rate
Proposed PEL
Alternative 1a
Incremental Costs/Benefits
EP07AU15.029
I
$578.0-$765.2
$256.3 - $339.3
$2.2-$189.4
$1.0-$84.0
$575.8
$255.3
Net Benefits
I
$538.4-$709.2
$215.1-$281.2
$0.2-$171.0
$-1.1-$65.0
$538.2
$216.2
Source: OSHA, Directorate of Standards and Guidance, Office of Regulatory Analysis
*Benefits are assessed over a 60-year time horizon, during VV'hich it is assumed that economic conditions remain constant. Costs are annualized over ten years, vvith the exception of
equipment expenditures, VV'hich are annualized over the life of the equipment. Annualized costs are assumed to continue at the same level for sixty years, VV'hich is consistent vvith
assuming that economic conditions remain constant for the sixty year time horizon.
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19:20 Aug 06, 2015
Regulatory Alternative #2a would
expand the scope of the proposed
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Federal Register / Vol. 80, No. 152 / Friday, August 7, 2015 / Proposed Rules
cleanup staff working in construction
and shipyards who have the potential
for airborne beryllium exposure during
blasting operations and during cleanup
of spent media. Regulatory Alternative
#2b would update 29 CFR 1910.1000
Tables Z–1 and Z–2, 1915.1000 Table Z,
and 1926.55 Appendix A so that the
proposed TWA PEL and STEL would
apply to all employers and employees in
general industry, shipyards, and
construction, including occupations
where beryllium exists only as a trace
contaminant. For example, this
alternative would cover abrasive
blasters, pot tenders, and cleanup staff
working in construction and shipyards
who have the potential for significant
airborne exposure during blasting
operations and during cleanup of spent
media. The changes to the Z tables
would also apply to workers exposed to
beryllium during aluminum refining
and production, and workers engaged in
maintenance operations at coal-powered
utility facilities. All provisions of the
standard other than the PELs, such as
exposure monitoring, medical removal,
and PPE, would be in effect only for
employers and employees that fall
within the scope of the proposed rule.42
Alternative #2b would not be as
protective as Alternative #1a or
Alternative #1b for employees in
aluminum refining and production or
coal-powered utility facilities because
the other provisions of the proposed
standard would not apply.
As discussed in the explanation of
proposed paragraph (a) in this preamble
at Section XVIII, Summary and
Explanation of the Proposed Standard,
abrasive blasting is the primary
application group in construction and
maritime industries where workers may
be exposed to beryllium. OSHA has
judged that abrasive blasters and their
helpers in construction and maritime
industries have the potential for
significant airborne exposure during
blasting operations and during cleanup
of spent media. Airborne concentrations
of beryllium have been measured above
the current TWA PEL of 2 mg/m3 when
blast media containing beryllium are
used as intended (see Appendix IV–C in
the PEA for details).
To address high concentrations of
various hazardous chemicals in abrasive
blasting material, employers must
42 However, many of the occupations excluded
from the scope of the proposed beryllium standard
receive some ancillary provision protections from
other rules, such as Personal Protective Equipment
(29 CFR 1910 subpart I, 1915 subpart I, 1926.28,
also 1926 subpart E), Ventilation (including
abrasive blasting) (§§ 1926.57 and 1915.34), Hazard
Communication (§ 1910.1200), and specific
provisions for welding (parts 1910 subpart Q, 1915
subpart D, and 1926 subpart J).
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already be using engineering and work
practice controls to limit workers’
exposures and must be supplementing
these controls with respiratory
protection when necessary. For
example, abrasive blasters in the
construction industry fall under the
protection of the Ventilation standard
(29 CFR 1926.57). The Ventilation
standard includes an abrasive blasting
subsection (29 CFR 1926.57(f)), which
requires that abrasive blasting
respirators be worn by all abrasive
blasting operators when working inside
blast-cleaning rooms (29 CFR
1926.57(f)(5)(ii)(A)), or when using
silica sand in manual blasting
operations where the nozzle and blast
are not physically separated from the
operator in an exhaust-ventilated
enclosure (29 CFR 1926.57(f)(5)(ii)(B)),
or when needed to protect workers from
exposures to hazardous substances in
excess of the limits set in § 1926.55 (29
CFR 1926.57(f)(5)(ii)(C); ACGIH, 1971).
For maritime, standard 29 CFR
1915.34(c) covers similar requirements
for respiratory protection needed in
blasting operations. Due to these
requirements, OSHA believes that
abrasive blasters already have controls
in place and wear respiratory protection
during blasting operations. Thus, in
estimating costs for Regulatory
Alternatives #2a and #2b, OSHA judged
that the reduction of the TWA PEL
would not impose costs for additional
engineering controls or respiratory
protection in abrasive blasting (see
Appendix VIII–C of Chapter VIII in the
PEA for details). OSHA requests
comment on this issue—in particular,
whether abrasive blasters using blast
material that may contain beryllium as
a trace contaminant are already using all
feasible engineering and work practice
controls, respiratory protection, and PPE
that would be required by Regulatory
Alternatives #2a and #2b.
In the estimation of benefits for
Regulatory Alternative #2a, OSHA has
estimated a range to account for
significant uncertainty in the benefits to
this population from some of the
ancillary provisions of the proposed
beryllium standard. It is unclear how
many of the workers associated with
abrasive blasting work would benefit
from dermal protection, as
comprehensive dermal protection may
already be used by most blasting
operators. It is also unclear whether the
housekeeping requirements of the
proposed standard would be feasible to
implement in the context of abra