Drinking Water: Preliminary Regulatory Determination on Perchlorate, 60262-60282 [E8-24042]
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FERC Online service, please e-mail
FERCOnlineSupport@ferc.gov or call
(866) 208–3676 (toll free). For TTY, call
(202) 502–8659.
Kimberly D. Bose,
Secretary.
[FR Doc. E8–24157 Filed 10–9–08; 8:45 am]
BILLING CODE 6717–01–P
DEPARTMENT OF ENERGY
Federal Energy Regulatory
Commission
[Docket No. ER08–1522–000]
WG Energy LLC; Supplemental Notice
That Initial Market-Based Rate Filing
Includes Request for Blanket Section
204 Authorization
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October 6, 2008.
This is a supplemental notice in the
above-referenced proceeding of WG
Energy LLC’s application for marketbased rate authority, with an
accompanying rate tariff, noting that
such application includes a request for
blanket authorization, under 18 CFR
Part 34, of future issuances of securities
and assumptions of liability.
Any person desiring to intervene or to
protest should file with the Federal
Energy Regulatory Commission, 888
First Street, NE., Washington, DC 20426,
in accordance with Rules 211 and 214
of the Commission’s Rules of Practice
and Procedure (18 CFR 385.211 and
385.214). Anyone filing a motion to
intervene or protest must serve a copy
of that document on the Applicant.
Notice is hereby given that the
deadline for filing protests with regard
to the applicant’s request for blanket
authorization, under 18 CFR Part 34, of
future issuances of securities and
assumptions of liability, is October 27,
2008.
The Commission encourages
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The filings in the above-referenced
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clicking on the appropriate link in the
above list. They are also available for
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There is an eSubscription link on the
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FERC Online service, please e-mail
FERCOnlineSupport@ferc.gov or call
(866) 208–3676 (toll free). For TTY, call
(202) 502–8659.
Kimberly D. Bose,
Secretary.
[FR Doc. E8–24160 Filed 10–9–08; 8:45 am]
BILLING CODE 6717–01–P
DEPARTMENT OF ENERGY
Federal Energy Regulatory
Commission
interventions in lieu of paper using the
‘‘eFiling’’ link at https://www.ferc.gov.
Persons unable to file electronically
should submit an original and 14 copies
of the protest or intervention to the
Federal Energy Regulatory Commission,
888 First Street, NE., Washington, DC
20426.
This filing is accessible on-line at
https://www.ferc.gov, using the
‘‘eLibrary’’ link and is available for
review in the Commission’s Public
Reference Room in Washington, DC.
There is an ‘‘eSubscription’’ link on the
Web site that enables subscribers to
receive e-mail notification when a
document is added to a subscribed
docket(s). For assistance with any FERC
Online service, please e-mail
FERCOnlineSupport@ferc.gov or call
(866) 208–3676 (toll free). For TTY, call
(202) 502–8659.
Comment Date: 5 p.m. Eastern Time
Friday October 17, 2008.
Kimberly D. Bose,
Secretary.
[FR Doc. E8–24152 Filed 10–9–08; 8:45 am]
[Docket No. PR08–30–000]
BILLING CODE 6717–01–P
Enterprise Texas Pipeline LLC; Notice
of Petition for Rate Approval
October 6, 2008.
Take notice that on September 30,
2008, Enterprise Texas Pipeline LLC
(Enterprise Texas) filed a petition for
rate approval pursuant to section
284.123(b)(2) of the Commission’s
regulations. Enterprise Texas requests
that the Commission approve an
incremental rate of $0.6370 per MMBtu
for service on the Sherman Extension
commencing on September 30, 2008.
Any person desiring to participate in
this rate proceeding must file a motion
to intervene or to protest this filing must
file in accordance with Rules 211 and
214 of the Commission’s Rules of
Practice and Procedure (18 CFR 385.211
and 385.214). Protests will be
considered by the Commission in
determining the appropriate action to be
taken, but will not serve to make
protestants parties to the proceeding.
Any person wishing to become a party
must file a notice of intervention or
motion to intervene, as appropriate.
Such notices, motions, or protests must
be filed on or before the date as
indicated below. Anyone filing an
intervention or protest must serve a
copy of that document on the Applicant.
Anyone filing an intervention or protest
on or before the intervention or protest
date need not serve motions to intervene
or protests on persons other than the
Applicant.
The Commission encourages
electronic submission of protests and
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ENVIRONMENTAL PROTECTION
AGENCY
[EPA–HQ–OW–2008–0068; FRL–8727–6]
RIN 2040–ZA02
Drinking Water: Preliminary Regulatory
Determination on Perchlorate
Environmental Protection
Agency (EPA).
ACTION: Notice.
AGENCY:
SUMMARY: This action presents EPA’s
preliminary regulatory determination
for perchlorate in accordance with the
Safe Drinking Water Act (SDWA). The
Agency has determined that a national
primary drinking water regulation
(NPDWR) for perchlorate would not
present ‘‘a meaningful opportunity for
health risk reduction for persons served
by public water systems.’’ The SDWA
requires EPA to make determinations
every five years of whether to regulate
at least five contaminants on the
Contaminant Candidate List (CCL). EPA
included perchlorate on the first and
second CCLs that were published in the
Federal Register on March 2, 1998 and
February 24, 2005. Most recently, EPA
presented final regulatory
determinations regarding 11
contaminants on the second CCL in a
notice published in the Federal Register
on July 30, 2008. In today’s action, EPA
presents supporting rationale and
requests public comment on its
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preliminary regulatory determination
for perchlorate. EPA will make a final
regulatory determination for perchlorate
after considering comments and
information provided in the 30-day
comment period following this notice.
EPA plans to publish a health advisory
for perchlorate at the time the Agency
publishes its final regulatory
determination to provide State and local
public health officials with technical
information that they may use in
addressing local contamination.
DATES: Comments must be received on
or before November 10, 2008.
ADDRESSES: Submit your comments,
identified by Docket ID No. EPA–HQ–
OW–2008–0068, by one of the following
methods:
• www.regulations.gov: Follow the
on-line instructions for submitting
comments.
• Mail: Water Docket, Environmental
Protection Agency, Mailcode: 2822T,
1200 Pennsylvania Ave., NW.,
Washington, DC 20460.
• Hand Delivery: Water Docket, EPA
Docket Center (EPA/DC) EPA West,
Room 3334, 1301 Constitution Ave.,
NW., Washington, DC. Such deliveries
are only accepted during the Docket’s
normal hours of operation, and special
arrangements should be made for
deliveries of boxed information.
Instructions: Direct your comments to
Docket ID No. EPA–HQ–OW–2008–
0068. EPA’s policy is that all comments
received will be included in the public
docket without change and may be
made available online at
www.regulations.gov, including any
personal information provided, unless
the comment includes information
claimed to be Confidential Business
Information (CBI) or other information
whose disclosure is restricted by statute.
Do not submit information that you
consider to be CBI or otherwise
protected through www.regulations.gov
or e-mail. The www.regulations.gov Web
site is an ‘‘anonymous access’’ system,
which means EPA will not know your
identity or contact information unless
you provide it in the body of your
comment. If you send an e-mail
comment directly to EPA without going
through www.regulations.gov your email address will be automatically
captured and included as part of the
comment that is placed in the public
docket and made available on the
Internet. If you submit an electronic
comment, EPA recommends that you
include your name and other contact
information in the body of your
comment and with any disk or CD–ROM
you submit. If EPA cannot read your
comment due to technical difficulties
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and cannot contact you for clarification,
EPA may not be able to consider your
comment. Electronic files should avoid
the use of special characters, any form
of encryption, and be free of any defects
or viruses. For additional instructions
on submitting comments, go to Unit I.B
of the SUPPLEMENTARY INFORMATION
section of this document.
Docket: All documents in the docket
are listed in the www.regulations.gov
index. Although listed in the index,
some information is not publicly
available, e.g., CBI or other information
whose disclosure is restricted by statute.
Certain other material, such as
copyrighted material, will be publicly
available only in hard copy. Publicly
available docket materials are available
either electronically in
www.regulations.gov or in hard copy at
the Water Docket, EPA/DC, EPA West,
Room 3334, 1301 Constitution Ave.,
NW., Washington, DC. The Public
Reading Room is open from 8:30 a.m. to
4:30 p.m., Monday through Friday,
excluding legal holidays. The telephone
number for the Public Reading Room is
(202) 566–1744, and the telephone
number for the EPA Docket Center is
(202) 566–2426.
FOR FURTHER INFORMATION CONTACT: Eric
Burneson, Office of Ground Water and
Drinking Water, Standards and Risk
Management Division, at (202) 564–
5250 or e-mail burneson.eric@epa.gov.
For general information contact the EPA
Safe Drinking Water Hotline at (800)
426–4791 or e-mail: hotlinesdwa@epa.gov.
Abbreviations and Acronyms
a. i.—active ingredient
<—less than
≤—less than or equal to
>—greater than
≥—greater than or equal to
µ—microgram, one-millionth of a gram
µg/g—micrograms per gram
µg/kg—micrograms per kilogram
µg/L—micrograms per liter
ATSDR—Agency for Toxic Substances and
Disease Registry
AWWARF—American Water Works
Association Research Foundation
BMD—bench mark dose
BMDL—bench mark dose level
BW—body weight for an adult, assumed to be
70 kilograms (kg)
CASRN—Chemical Abstract Services
Registry Number
CBI—confidential business information
ChE—cholinesterase
CCL—Contaminant Candidate List
CCL 1—EPA’s First Contaminant Candidate
List
CCL 2—EPA’s Second Contaminant
Candidate List
CDC—Centers for Disease Control and
Prevention
CDPH—-California Department of Public
Health
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CFR—Code of Federal Regulations
CMR—Chemical Monitoring Reform
CWS—community water system
DW—dry weight
DWEL—drinking water equivalent level
DWI—drinking water intake
EPA—United States Environmental
Protection Agency
EPCRA—Emergency Planning and
Community Right-to-Know Act
FDA—United States Food and Drug
Administration
FQPA—Food Quality Protection Act
FR—Federal Register
FW—fresh weight
g—gram
g/day—grams per day
HRL—health reference level
IOC—inorganic compound
IRIS—Integrated Risk Information System
kg—kilogram
L—liter
LD50 —an estimate of a single dose that is
expected to cause the death of 50 percent
of the exposed animals; it is derived from
experimental data.
LOAEL—lowest-observed-adverse-effect level
MA DEP—Massachusetts Department of
Environmental Protection
MCL—maximum contaminant level
MCLG—maximum contaminant level goal
mg—milligram, one-thousandth of a gram
mg/kg—milligrams per kilogram body weight
mg/kg/day—milligrams per kilogram body
weight per day
mg/L—milligrams per liter
mg/m3—milligrams per cubic meter
MRL—minimum or method reporting limit
(depending on the study or survey cited)
N—number of samples
NAS—National Academy of Sciences
NCEH—National Center for Environmental
Health (CDC)
NCFAP—National Center for Food and
Agricultural Policy
NCI—National Cancer Institute
NCWS—non-community water system
ND—not detected (or non-detect)
NDWAC—National Drinking Water Advisory
Council
NHANES—National Health and Nutrition
Examination Survey (CDC)
NIS—sodium iodide symporter
NOEL—no-observed-effect-level
NPDWR—national primary drinking water
regulation
NPS—National Pesticide Survey
NQ—not quantifiable (or non-quantifiable)
NRC—National Research Council
NTP—National Toxicology Program
OA—oxanilic acid
OW—Office of Water
OPP—Office of Pesticide Programs
PBPK—physiologically based
pharmacokinetic
PCR—polymerase chain reaction
PGWDB—pesticides in ground water data
base
PWS—public water system
RAIU—radioactive iodide uptake
RED—Reregistration Eligibility Decision
RfC—reference concentration
RfD—reference dose
RSC—relative source contribution
SAB—Science Advisory Board
SDWA—Safe Drinking Water Act
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SOC—synthetic organic compound
SVOC—semi-volatile organic compound
T3—triiodothyronine
T4—thyroxine
TDS—Total Diet Study (FDA)
TRI—Toxics Release Inventory
TSH—thyroid stimulating hormone
TT—treatment technique
UCMR 1—First Unregulated Contaminant
Monitoring Regulation
UF—uncertainty factor
US—United States of America
USDA—United States Department of
Agriculture
USGS—United States Geological Survey
UST—underground storage tanks
VOC—volatile organic compound
WHO—World Health Organization
comment, EPA will issue a final
regulatory determination.
B. What Should I Consider as I Prepare
My Comments for EPA?
SUPPLEMENTARY INFORMATION:
I. General Information
A. Does This Action Impose Any
Requirements on My Public Water
System?
B. What Should I Consider as I Prepare My
Comments for EPA?
II. Purpose, Background and Summary of
This Action
A. What is the Purpose of This Action?
B. Background on the CCL and Regulatory
Determinations
C. What Comments and Information Did
EPA Receive Regarding Perchlorate in
Response to the May 1, FR Notice?
D. What is EPA’s Preliminary
Determination on Perchlorate and What
Happens Next?
III. What Scientific Data and Analyses Did
EPA Evaluate in Making a Preliminary
Regulatory Determination for
Perchlorate?
A. Evaluation of Adverse Health Effects
B. Evaluation of Perchlorate Occurrence in
Drinking Water
C. Evaluation of Perchlorate Exposure from
Sources Other Than Drinking Water
IV. Preliminary Regulatory Determination on
Perchlorate
A. May Perchlorate Have an Adverse Effect
on the Health of Persons?
B. Is Perchlorate Known to Occur or is
There a Substantial Likelihood That
Perchlorate Occurs at a Frequency and
Level of Public Health Concern in Public
Water Systems?
C. Is There a Meaningful Opportunity for
the Reduction of Health Risks From
Perchlorate for Persons Served by Public
Water Systems?
V. EPA’s Next Steps
VI. References
SUPPLEMENTARY INFORMATION:
I. General Information
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A. Does This Action Impose Any
Requirements on My Public Water
System?
Today’s action seeks public comment
on EPA’s preliminary determination
that a national primary drinking water
regulation is not necessary for
perchlorate, and thus imposes no
requirements on public water systems.
After review and consideration of public
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You may find the following
suggestions helpful for preparing your
comments:
1. Explain your views as clearly as
possible.
2. Describe any assumptions that you
used.
3. Provide any technical information
and/or data you used that support your
views.
4. If you estimate potential burden or
costs, explain how you arrived at your
estimate.
5. Provide specific examples to
illustrate your concerns.
6. Offer alternatives.
7. Make sure to submit your
comments by the comment period
deadline.
8. To ensure proper receipt by EPA,
identify the appropriate docket
identification number in the subject line
on the first page of your response. It
would also be helpful if you provided
the name, date, and Federal Register
citation related to your comments.
II. Purpose, Background and Summary
of This Action
This section briefly summarizes the
purpose of this action, the statutory
requirements, previous activities related
to the Contaminant Candidate List and
regulatory determinations, and the
approach used and outcome of this
preliminary regulatory determination.
A. What is the Purpose of This Action?
The purpose of today’s action is to
present EPA’s preliminary regulatory
determination on perchlorate, the
process and the rationale used to make
this determination, a brief summary of
the supporting documentation, and a
request for public comment.
B. Background on the CCL and
Regulatory Determinations
1. Statutory Requirements for CCL
and Regulatory Determinations. The
specific statutory requirements for the
Contaminant Candidate List (CCL) and
regulatory determinations can be found
in section 1412(b)(1) of the Safe
Drinking Water Act (SDWA). The CCL is
a list of contaminants that are not
subject to any proposed or promulgated
national primary drinking water
regulations (NPDWRs), are known or
anticipated to occur in public water
systems (PWSs), and may require
regulation under the SDWA. The 1996
SDWA Amendments also direct EPA to
determine, every five years, whether to
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regulate at least five contaminants from
the CCL. The SDWA requires EPA to
publish a Maximum Contaminant Level
Goal1 (MCLG) and promulgate an
NPDWR 2 for a contaminant if the
Administrator determines that:
(a) The contaminant may have an
adverse effect on the health of persons;
(b) The contaminant is known to
occur or there is a substantial likelihood
that the contaminant will occur in
public water systems with a frequency
and at levels of public health concern;
and
(c) In the sole judgment of the
Administrator, regulation of such
contaminant presents a meaningful
opportunity for health risk reduction for
persons served by public water systems.
While carrying out the process to
make a determination, the law requires
EPA to take into consideration the effect
contaminants have on subgroups that
comprise a meaningful portion of the
general population (such as infants,
children, pregnant women, the elderly,
individuals with a history of serious
illness or other subpopulations) that are
identifiable as being at greater risk of
adverse health effects than the general
population.
If EPA makes a final determination
that a national primary drinking water
regulation is needed, the Agency has 24
months to publish a proposed MCLG
and NPDWR. After the proposal, the
Agency has 18 months to publish and
promulgate a final MCLG and NPDWR
(SDWA section 1412(b) (1) (E)).3
EPA published preliminary regulatory
determinations for nine CCL 1
contaminants on June 3, 2002, (67 FR
38222 (USEPA, 2002a)), and final
regulatory determinations on July 18,
2003 (68 FR 42898 (USEPA, 2003a)).
EPA published preliminary regulatory
determinations for eleven CCL 2
contaminants on May 1, 2007, (72 FR
24016 (USEPA, 2007)) and finalized
these regulatory determinations on July
30, 2008 (73 FR 44251 (USEPA, 2008c)).
As part of its May 1, 2007, FR notice of
preliminary regulatory determinations
for 11 contaminants, EPA also presented
information on several contaminants
1 The MCLG is the ‘‘maximum level of a
contaminant in drinking water at which no known
off anticipated adverse effect on the health of
persons would occur, and which allows an
adequate margin of safety. Maximum contaminant
level goals are non-enforceable heath goals’’ (CFR
141.2).
2 An NPDWR is a legally enforceable standard
that applies to public water systems. An NPDWR
sets a legal limit (called a maximum contaminant
level or MCL) or specifies a certain treatment
technique (TT) for public water systems for a
specific contaminant or group of contaminants.
3 The statute authorizes a nine month extension
of this promulgation date.
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from the second CCL for which the
Agency was not yet making a
preliminary regulatory determination,
including perchlorate. Specifically, EPA
indicated that additional information
was needed to more fully characterize
perchlorate exposure and determine
whether it is appropriate to regulate
perchlorate in drinking water (i.e.,
whether setting a national primary
drinking water standard would provide
a meaningful opportunity to reduce risk
for people served by public water
systems). The May 1, 2007, FR notice
describes how the Agency was
considering additional information
including FDA food data and CDC
human exposure data to determine
whether to regulate perchlorate. (See the
May 1, 2007, FR notice at 24038 for a
discussion regarding the information
that EPA had on perchlorate as well as
the additional information that was
needed before the Agency could make a
preliminary regulatory determination
for perchlorate).
C. What Comments and Information Did
EPA Receive Regarding Perchlorate in
Response to the May 1, FR Notice?
Eight commenters on the Regulatory
Determinations 2 Preliminary FR notice
addressed perchlorate. EPA received
comments that supported and
comments that opposed regulating
perchlorate. One of the commenters
who encouraged regulation stated that
perchlorate is known to occur in public
water supplies in a number of States
and ‘‘while occurrence data does [sic]
not suggest that perchlorate occurs at
levels of public health concern in the
vast majority of public drinking water
supplies, and the population at risk
appears to be small, that group does
include a sensitive subpopulation
(pregnant women and developing
fetuses) of significant concern.’’ Another
commenter wrote ‘‘the contamination of
water supplies by perchlorate is ongoing’’ and ‘‘perchlorate that has
entered the soil and contaminated
aquifers will likely lead to additional
impacted sites.’’ A commenter wrote
that ‘‘a number of States are moving to
regulate perchlorate and a patchwork of
different regulations will confuse the
public and the regulated water
community.’’
The commenters opposed to
regulating perchlorate also cited the
available information to support their
recommendation. One commenter wrote
that ‘‘the extensive scientific record
indicates that establishing a drinking
water standard for perchlorate would
not yield a meaningful opportunity to
reduce risk to human health.’’ Another
commenter stated that perchlorate ‘‘does
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not appear, at this stage, to be a
nationwide problem.’’
Several commenters also addressed
EPA’s assessment that additional
investigation is necessary to ascertain
total human exposure before a
preliminary regulatory determination
could be made. Commenters wrote that
the principal study on which EPA’s
Reference Dose (RfD) is based already
accounts for background sources of
perchlorate and therefore EPA should
not adjust the RfD to account for other
non-drinking-water exposures.
EPA has considered the perchlorate
comments submitted in connection with
the May 1, 2007, notice in the
development of today’s action. EPA will
consider these and any further
comments submitted in response to this
notice before preparing a final
regulatory determination for
perchlorate.
D. What is EPA’s Preliminary Regulatory
Determination on Perchlorate and What
Happens Next?
EPA is making a preliminary
regulatory determination in this notice
that a national primary drinking water
rule is not necessary for perchlorate
because a national primary drinking
water regulation would not provide a
meaningful opportunity to reduce
health risk. EPA will make a final
regulatory determination for perchlorate
after considering comments and
information provided in the 30-day
comment period following this notice.
One of the analyses that EPA considered
for this preliminary determination is a
physiologically-based pharmacokinetic
(PBPK) model that predicts radioactive
iodide uptake (RAIU) inhibition in the
thyroid for various sub-populations and
drinking water concentrations. The
model, which is described in section
IV.B.5, has already been published in
peer-reviewed articles (Clewell et al.,
2007 and Merrill et al., 2005), but EPA
subjected the model to intensive
internal review prior to considering it
for this regulatory determination and
made several adjustments as a result.
EPA believes it is appropriate to have
these adjustments peer-reviewed. While
the application of the model to nonadult subpopulations was part of the
previously peer-reviewed articles, EPA
will also ask the peer reviewers to
comment on this issue to help EPA
ensure that the model is appropriate for
use in assessing health outcomes
associated with perchlorate exposure for
these populations. EPA intends to
complete this review before publishing
its final determination and will consider
any comments from the reviewers.
Additionally, EPA plans to publish a
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health advisory for perchlorate at the
time the Agency publishes its final
regulatory determination to provide
State and local public health officials
with information that they may use in
addressing local contamination.
Additionally, at the same time that
EPA publishes a health advisory for
perchlorate, the Agency will withdraw
its existing January 2006 guidance
regarding perchlorate and potential
cleanup levels under the National Oil
and Hazardous Substances Contingency
Plan (National Contingency Plan, NCP)
and will replace it with revised
guidance. (See memorandum dated
January 26, 2006, from Susan Parker
Bodine to EPA Regional Administrators
(US EPA, 2006).) Specifically, the
January 2006 guidance, in part,
addresses the use of preliminary
remediation goals (PRGs) for perchlorate
contaminated water at National Priority
List (NPL) sites. The January 2006
guidance recommends a PRG of 24.5
ppb, assuming that all exposure comes
from ground water at the site. The
recommended PRG is based on the
assumption that all exposure comes
from ground water, because at the time
the January 2006 guidance was issued
there was insufficient information
available on the levels of perchlorate in
food to calculate a national relative
source contribution (RSC). In the
absence of such national data on the
levels of perchlorate found in foods, the
approach outlined in the January 2006
guidance was considered by the Agency
to be the most scientifically defensible.
In addition, because the recommended
PRG generally is the starting point for
determining appropriate site-specific
cleanup levels, the guidance also
indicates that the cleanup level at any
site should be evaluated on a case-bycase basis, and modified accordingly,
based on site-specific information,
including exposure to non-water
sources, such as foods. EPA now has
sufficient data to calculate a national
RSC and has used this RSC to calculate
a health reference level (HRL) for
drinking water as part of the basis for
today’s preliminary determination.
When EPA issues the final regulatory
determination for perchlorate, the final
HRL will be the basis for the health
advisory value in the health advisory
document the Agency expects to issue at
that time. Thereafter, it may be
appropriate to use the health advisory
value as a ‘‘to be considered’’ (TBC)
value in developing potential cleanup
levels for perchlorate at Superfund sites.
In addition, some State regulations may
be applicable or relevant and
appropriate requirements (ARARs)
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when establishing cleanup levels for
perchlorate at Superfund sites.
III. What Scientific Data and Analyses
Did EPA Evaluate in Making a
Preliminary Regulatory Determination
for Perchlorate?
This section summarizes the health
effects, occurrence, and population
exposure evaluation information EPA
used to support the preliminary
regulatory determination for
perchlorate. EPA’s conclusions with
respect to these data are discussed in
Section IV.
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A. Evaluation of Precursor and Adverse
Health Effects
Section 1412(b)(1)(A)(i) of the SDWA
requires EPA to determine whether a
candidate contaminant may have an
adverse effect on public health. EPA
described the overall process the
Agency used to evaluate health effects
information in the May 1, 2007, Federal
Register Notice (72 FR 24016 (USEPA,
2007)). This section presents specific
information about the potential for
precursor and adverse health effects
from perchlorate, including a discussion
of an extensive report completed by the
National Academy of Sciences (NAS) on
the issue and other research published
after that report.
1. NAS Review of Perchlorate Health
Implications and EPA’s Reference Dose
In 2003, the National Research
Council (NRC) of the NAS was asked to
assess the current state of the science
regarding potential adverse effects of
disruption of thyroid function by
perchlorate in humans and laboratory
animals at various stages of life and,
based on this review, to determine
whether EPA’s findings in its 2002 draft
risk assessment were consistent with the
current scientific evidence.
In January 2005, the NRC published
‘‘Health Implications of Perchlorate
Ingestion,’’ a review of the state of the
science regarding potential adverse
health effects of perchlorate exposure
and mode-of-action for perchlorate
toxicity (NRC, 2005).
Perchlorate can interfere with the
normal functioning of the thyroid gland
by competitively inhibiting the
transport of iodide into the thyroid.
Iodide is an important component of
two thyroid hormones, T4 and T3, and
the transfer of iodide from the blood
into the thyroid is an essential step in
the synthesis of these two hormones.
Iodide transport into the thyroid is
mediated by a protein molecule known
as the sodium (Na∂)-iodide (I¥)
symporter (NIS). NIS molecules bind
iodide with very high affinity, but they
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also bind other ions that have a similar
shape and electric charge, such as
perchlorate. The binding of these other
ions to the NIS inhibits iodide transport
into the thyroid, which can result in
intrathyroidal iodide deficiency and
consequently decreased synthesis of T4
and T3. There is compensation for lowlevels of iodide deficiency, however,
such that the body maintains blood
serum concentrations of thyroid
hormones within narrow limits through
feedback control mechanisms. The
compensation for decreased thyroid
hormone is accomplished by increased
secretion of the thyroid stimulating
hormone (TSH) from the pituitary gland
triggered by the reduced hormone
levels, which has among its effects the
increased production of T4 and T3
(USEPA, 2005b). The thyroid’s ability to
compensate in this way is limited,
though, such that sufficiently high
levels of perchlorate exposure result in
a reduction of T4 and T3 blood levels
(after thyroid iodine stores are
depleted). Sustained changes in thyroid
hormone and TSH secretion can result
in thyroid hypertrophy and hyperplasia
(i.e., abnormal growth or enlargement of
the thyroid) (USEPA, 2005b).
Children born with congenital
hypothyroidism may suffer from mild
cognitive deficits despite hormone
remediation (Rovet, 2002; Zoeller and
Rovet, 2004), and subclinical
hypothyroidism and reductions in T4
(i.e., hypothyroxinemia) in pregnant
women have been associated with
neurodevelopmental delays and IQ
deficits in their children (Pop et al.,
1999, 2003; Haddow et al., 1999;
Kooistra et al., 2006; Morreale de
Escobar, 2000, 2004). Animal studies
support these observations, and recent
findings indicate that
neurodevelopmental deficits are evident
under conditions of hypothyroxinemia
and occur in the absence of growth
retardation (Auso et al., 2004; Gilbert
and Sui, 2008; Sharlin et al., 2008;
Goldey et al., 1995).
Results from studies of the effects of
perchlorate exposure on hormone levels
have been mixed. One recent study did
not identify any effects of perchlorate on
blood serum hormones (Amitai et al.,
2007), while another study (Blount et
al., 2006b) did identify such effects. The
results of the Blount study are discussed
further in Section III.A.2.
The data from epidemiological studies
of the general population provide some
information on possible effects of
perchlorate exposure. Based upon
analysis of the data available at the time
NRC (2005) acknowledged that ecologic
epidemiological data alone are not
sufficient to demonstrate whether or not
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an association is causal, and that these
studies can provide evidence bearing on
possible associations. Noting the
limitations of specific studies, the NRC
(2005; chapter 3) committee concluded
that the available epidemiological
evidence is not consistent with a causal
association between perchlorate and
congenital hypothyroidism, changes in
thyroid function in normal birthweight,
full-term newborns, or hypothyroidism
or other thyroid disorders in adults. The
committee considered the evidence to
be inadequate to determine whether or
not there is a causal association between
perchlorate exposure and adverse
neurodevelopmental outcomes in
children. The committee noted that no
studies have investigated the
relationship between perchlorate
exposure and adverse outcomes among
especially vulnerable groups, such as
the offspring of mothers who had low
dietary iodide intake, or lowbirthweight or preterm infants (US EPA,
2005b).
The NRC recommended data from the
Greer et al. (2002) human clinical study
as the basis for deriving a reference dose
(RfD) for perchlorate (NRC, 2005). Greer
et al., (2002) report the results of a study
that measured thyroid iodide uptake,
hormone levels, and urinary iodide
excretion in a group of 37 healthy adults
who were administered perchlorate
doses orally over a period of 14 days.
Dose levels ranged from 7 to 500 µg/kg/
day in the different experimental
groups. The investigators found that the
24-hour inhibition of iodide intake
ranged from 1.8 percent in the lowest
dose group to 67.1 percent in the
highest dose group. However, no
significant differences were seen in
measured blood serum thyroid hormone
levels (T3, T4, total and free) in any
dose group. The statistical no observed
effect level (NOEL) for the perchlorateinduced inhibition of thyroid iodide
uptake was determined to be 7 µg/kg/
day, corresponding to an iodide uptake
inhibition of 1.8 percent. Although the
NRC committee concluded that
hypothyroidism is the first adverse
effect in the continuum of effects of
perchlorate exposure, NRC
recommended that ‘‘the most healthprotective and scientifically valid
approach’’ was to base the perchlorate
RfD on the inhibition of iodide uptake
by the thyroid (NRC, 2005). NRC
concluded that iodide uptake inhibition,
although not adverse, is the most
appropriate precursor event in the
continuum of possible effects of
perchlorate exposure and would
precede any adverse health effects of
perchlorate exposure. The lowest dose
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(7 µg/kg/day) administered in the Greer
et al., (2002) study was considered a
NOEL (rather than a no-observedadverse-effect level or NOAEL) because
iodide uptake inhibition is not an
adverse effect, but a biochemical
precursor. The NRC further determined
that, ‘‘the very small decrease (1.8
percent) in thyroid radioiodide uptake
in the lowest dose group was well
within the variation of repeated
measurements in normal subjects.’’ A
summary of the data considered and the
NRC deliberations can be found in the
NRC report (2005).
The NRC recommended that EPA
apply an intraspecies uncertainty factor
of 10 to the NOEL to account for
differences in sensitivity between the
healthy adults in the Greer et al., (2002)
study and the most sensitive
population, fetuses of pregnant women
who might have hypothyroidism or
iodide deficiency. Because the fetus
depends on an adequate supply of
maternal thyroid hormone for its central
nervous system development during the
first trimester of pregnancy, iodide
uptake inhibition from low-level
perchlorate exposure has been
identified as a concern in connection
with increasing the risk of
neurodevelopmental impairment in
fetuses of high-risk mothers (NRC,
2005). The NRC (2005) viewed the
uncertainty factor of 10 as conservative
and protective of health given that the
point of departure (the NOEL) is based
on a non-adverse effect (iodide uptake
inhibition), which precedes the adverse
effect in a continuum of possible effects
of perchlorate exposure. The NRC panel
concluded that no additional
uncertainty factor was needed for the
use of a less-than-chronic study, for
deficiencies in the database, or for
interspecies variability. EPA’s Integrated
Risk Information System (IRIS) adopted
the NRC’s recommendations resulting in
an RfD of 0.7 µg/kg/day, derived by
applying a ten-fold total uncertainty
factor to the NOEL of 7 µg/kg/day
(USEPA, 2005b).
The NRC emphasized that its
recommendation ‘‘differs from the
traditional approach to deriving the
RfD.’’ The NRC recommended ‘‘using a
nonadverse effect rather than an adverse
effect as the point of departure for the
perchlorate risk asessement. Using a
nonadverse effect that is upstream of the
adverse effect is a more conservative,
health-protective approach to the
perchlorate risk assessment.’’ The NRC
also noted that the purpose of the 10fold uncertainty factor is to protect
sensitive subpopulations in the face of
uncertainty regarding their relative
sensitivity to perchlorate exposure. The
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NRC recognized that additional
information on these relative
sensitivities could be used to reduce
this uncertainty factor in the future
(NRC, 2005).4
2. Biomonitoring Studies
After the NRC report was released,
several papers were published that
investigated whether biomonitoring data
associated with the National Health and
Nutrition Examination Survey
(NHANES) could be used to discern if
there was a relationship between
perchlorate levels in the body and
thyroid function. These papers also help
to evaluate populations that might be
considered to be more sensitive to
perchlorate exposure.
Blount et al., (2006b) published a
study examining the relationship
between urinary levels of perchlorate
and blood serum levels of TSH and total
T4 in 2,299 men and women (ages 12
years and older) who participated in
CDC’s 2001–2002 NHANES.5 Blount et
al., (2006b) evaluated perchlorate along
with a number of covariates known or
likely to be associated with T4 or TSH
levels to assess the relationship between
perchlorate and these hormones, and
the influence of other factors on this
relationship. These covariates included
gender, age, race/ethnicity, body mass
index, serum albumin, serum cotinine (a
marker of nicotine exposure), estimated
total caloric intake, pregnancy status,
post-menopausal status, premenarche
status, serum C-reactive protein, hours
fasting before sample collection, urinary
thiocyanate, urinary nitrate, and use of
selected medications. The study found
that perchlorate was a statistically
significant predictor of thyroid
hormones in women, but not in men.
After finding evidence of gender
differences, the researchers focused on
further analyzing the NHANES data for
the 1,111 women participants. They
divided these 1,111 women into two
categories, higher-iodide and loweriodide urinary content, using a cut point
of 100 µg/L of urinary iodide based on
the median level the World Health
Organization (WHO) considers
4 ‘‘There can be variability in responses among
humans. The intraspecies uncertainty factor
accounts for that variability and is intended to
protect populations more sensitive than the
population tested. In the absence of data on the
range of sensitivity among humans, a default
uncertainty factor of 10 is typically applied. The
factor could be set at 1 if data indicate that sensitive
populations do not vary substantially from those
tested.’’ (NRC 2005, p 173)
5 While CDC researchers measured urinary
perchlorate concentration for 2,820 NHANES
participants, TSH and total T4 serum levels were
only available for 2,299 of these participants.
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indicative of sufficient iodide intake 6
for a population. Hypothyroid women
were excluded from the analysis.
According to the study’s authors, about
36 percent of women living in the
United States have urinary iodide levels
less than 100 µg/L (Caldwell et al.,
2005). For women with urinary iodide
levels less than 100 µg/L, the study
found that urinary perchlorate is
associated with a decrease in (a negative
predictor for) T4 levels and an increase
in (a positive predictor for) TSH levels.
For women with urinary iodide levels
greater than or equal to 100 µg/L, the
researchers found that perchlorate is a
significant positive predictor of TSH,
but not a predictor of T4. The
researchers state that perchlorate could
be a surrogate for another unrecognized
determinant of thyroid function.
Also, the study reports that while
large doses of perchlorate are known to
decrease thyroid function, this is the
first time an association of decreased
thyroid function has been observed at
these low levels of perchlorate
exposure. The clinical significance of
the variations in T4/TSH levels, which
were generally within normal limits, has
not been determined. The researchers
noted several limitations of the study
(e.g., assumption that urinary
perchlorate correlates with perchlorate
levels in the stroma and tissue and
measurement of total T4 rather than free
T4) and recommended that these
findings be affirmed in at least one more
large study focusing on women with
low urine iodide levels. It is also not
known whether the association between
perchlorate and thyroid hormone levels
is causal or mediated by some other
correlate of both, although the
relationship between urine perchlorate
and total TSH and T4 levels persisted
after statistical adjustments for some
additional covariates known to predict
thyroid hormone levels (e.g., total
kilocalorie intake, estrogen use, and
serum C-reactive protein levels). A
planned follow-up study will include
additional measures of thyroid health
and function (e.g., TPO-antibodies, free
T4). An additional paper by Blount et
al., (2006c), discussed further in Section
III. C. 2. a., found that almost all
participants in the NHANES survey,
including the participants in this group,
had urinary levels of perchlorate
corresponding to estimated dose levels
that are below the RfD of 0.7 µg/kg/day.
The Blount study suggested that
perchlorate could be a surrogate for
another unrecognized determinant of
6 WHO notes that the prevalence of goiter begins
to increase in populations with a median urinary
iodide level below 100 µg/L (WHO, 1994).
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thyroid function. There are other
chemicals, including nitrate and
thiocyanate, which can affect thyroid
function. Steinmaus et al., (2007)
further analyzed the data from NHANES
2001–2002 to assess the impact of
smoking, cotinine and thiocyanate on
the relationship between urinary
perchlorate and blood serum T4 and
TSH. Thiocyanate is a metabolite of
cyanide found in tobacco smoke and is
naturally occurring in some foods,
including cabbage, broccoli, and
cassava. Increased serum thiocyanate
levels are associated with increasing
levels of smoking. Thiocyanate affects
the thyroid by the same mechanism as
perchlorate (competitive inhibition of
iodide uptake). Steinmaus et al.
analyzed the data to determine whether
smoking status (smoker or nonsmoker),
serum thiocyanate, or serum cotinine
were better predictors of T4 and TSH
changes than perchlorate, or if the
effects reflected the combined effects of
perchlorate and thiocyanate
Of female subjects 12 years of age and
older in NHANES 2001–2002, 1,203
subjects had data on blood serum T4,
serum TSH, urinary perchlorate, iodine
and creatinine. Subjects with extreme
T4 or TSH (3 individuals) or with a
reported history of thyroid disease (91)
were excluded from further analyses. Of
the remaining women, 385 (35 percent)
had urinary iodine levels below 100
µg/l. Steinmaus, et al. evaluated serum
cotinine as an indicator of nicotine
exposure, with levels greater than 10 ng/
ml classified as high and levels less than
0.015 ng/ml classified as low.
The authors found no association
between either perchlorate or T4 and
smoking, cotinine or thiocyanate in men
or in women with urinary iodine levels
greater than 100 µg/l. In addition, they
found no association between cotinine
and T4 or TSH in women with iodine
levels lower than 100 µg/l. However, in
women with urinary iodine levels lower
than 100 µg/l, an association between
urinary perchlorate and decreased
serum T4 was stronger in smokers than
in non-smokers, and stronger in those
with high urinary thiocyanate levels
than in those with low urinary
thiocyanate levels. Although noting that
their findings need to be confirmed with
further research, the authors concluded
that for these low-iodine women the
results suggest that at commonlyoccurring perchlorate exposure levels,
thiocyanate in tobacco smoke and
perchlorate interact in affecting thyroid
function, and that agents other than
tobacco smoke might cause similar
interactions (Steimaus et al., 2007).
EPA also evaluated whether health
information is available regarding
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children, pregnant women and lactating
mothers. The NRC report discussed a
number of epidemiological studies that
looked at thyroid hormone levels in
infants. A more recent study by Amitai
et al., (2007) assessed T4 values in
newborns in Israel whose mothers
resided in areas where drinking water
contained perchlorate at ‘‘very high’’
(340 µg/L), ‘‘high’’ (12.94 µg/L), or
‘‘low’’ (<3 µg/L) perchlorate
concentrations. The mean (± standard
deviation) T4 value of the newborns in
the very high, high, and low exposure
groups was 13.8 ± 3.8, 13.9 ± 3.4, and
14.0 ± 3.5 µg/dL, respectively, showing
no significant difference in T4 levels
between the perchlorate exposure
groups. This is consistent with the
conclusions drawn by the NRC review
of other epidemiological studies of
newborns. The NRC (2005) also noted
‘‘no epidemiologic studies are available
on the association between perchlorate
exposure and thyroid dysfunction
among low-birthweight or preterm
newborns, offspring of mothers who had
iodide deficiency during gestation, or
offspring of hypothyroid mothers.’’
3. Physiologically-based
Pharmacokinetic (PBPK) Models
PBPK models represent an important
class of dosimetry models that can be
used to predict internal doses to target
organs, as well as some effects of those
doses (e.g., radioactive iodide uptake
inhibition in the thyroid). To predict
internal dose level, PBPK models use
physiological, biochemical, and
physicochemical data to construct
mathematical representations of
processes associated with the
absorption, distribution, metabolism,
and elimination of compounds. With
the appropriate data, these models can
be used to extrapolate across and within
species and for different exposure
scenarios, and to address various
sources of uncertainty in health
assessments, including uncertainty
regarding the relative sensitivities of
various subpopulations.
Clewell et al., (2007) developed multicompartment PBPK models describing
the absorption and distribution of
perchlorate for the pregnant woman and
fetus, the lactating woman and neonate,
and the young child. This work built
upon Merrill et al.’s, (2005) model for
the average adult. Related research that
served as the basis for the more recent
PBPK modeling efforts was discussed by
the NRC in their January 2005 report on
perchlorate.
The models estimated the levels of
perchlorate absorbed through the
gastrointestinal tract and its subsequent
distribution within the body. Clewell et
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al., (2007) provided estimates of internal
dose and resulting iodide uptake
inhibition across all life stages, and for
pregnant and lactating women. The
paper reported iodide uptake inhibition
levels for external doses of 1, 10, 100,
and 1000 µg/kg/day. Results at the lower
two doses indicated that the highest
perchlorate blood concentrations in
response to an external dose would
occur in the fetus, followed by the
lactating woman and the neonate.
Predicted blood levels for all three
groups (i.e., fetus, lactating women and
neonates) were four- to five-fold higher
than for non-pregnant adults. Smaller
relative differences were predicted at
external doses of 100 and 1000 µg/kg/
day. The authors attributed this change
to saturation of uptake mechanisms. The
model predicted minimal effect of
perchlorate on iodide uptake inhibition
in all groups at the 1 µg/kg/day external
dose (about one and one half times the
RfD), estimating 1.1 percent inhibition
or less across all groups. Inhibition was
predicted to be 10 percent or less in all
groups at an external dose of 10 µg/kg/
day (about 14 times the RfD).
The results of the model
extrapolations were evaluated against
data developed in two epidemiologic
studies performed in Chile, one
studying school children (Tellez et al.,
2005) and another following women
through pregnancy and lactation (Gibbs
et al., 2004). The model predicted
average blood serum concentrations of
perchlorate in the women from the
Gibbs et al., (2004) study which were
nearly identical to their measured
perchlorate blood serum concentrations.
The blood serum perchlorate
concentrations predicted from the
Tellez et al., (2005) study were within
the range of the measured
concentrations, and the concentrations
of perchlorate in breast milk predicted
from the model were within two
standard deviations of the measured
concentrations. The authors concluded
that the model predictions were
consistent with empirical results and
that the predicted extent of iodide
inhibition in the most sensitive
population (the fetus) is not significant
at EPA’s RfD of 0.7 µg/kg-day.
The NRC recommended that
inhibition of iodide uptake by the
thyroid, which is a precursor event and
not an adverse effect, should be used as
the basis for the perchlorate risk
assessment (NRC, 2005). Consistent
with this recommendation, iodide
uptake inhibition was used by EPA as
the critical effect in determining the
reference dose (RfD) for perchlorate.
Therefore, PBPK models of perchlorate
and radioiodide, which were developed
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to describe thyroidal radioactive iodide
uptake (RAIU) inhibition by perchlorate
for the average adult (Merrill et al.,
2005), pregnant woman and fetus,
lactating woman and neonate, and the
young child (Clewell et al., 2007) were
evaluated by EPA based on their ability
to provide additional information
surrounding this critical effect for
potentially sensitive subgroups and
reduce some of the uncertainty
regarding the relative sensitivities of
these subgroups.
EPA evaluated the PBPK model code
provided by the model authors and
found minor errors in mathematical
equations and computer code, as well as
some inconsistencies between model
code files. EPA made several changes to
the code in order to harmonize the
models and more adequately reflect the
biology (see USEPA, 2008b) for more
information.
Model parameters describing urinary
excretion of perchlorate and iodide were
determined to be particularly important
in the prediction of RAIU inhibition in
all subgroups; therefore, a range of
biologically plausible values available
in the peer-reviewed literature was
evaluated in depth using the PBPK
models. Exposure rates were also
determined to be critical for the
estimation of RAIU inhibition by the
models and were also further evaluated.
Overall, detailed examination of
Clewell et al., (2007) and Merrill et al.,
(2005) confirmed that the model
structures were appropriate for
predicting percent inhibition of RAIU
by perchlorate in most lifestages.
Unfortunately, the lack of biological
information during early fetal
development limits the applicability of
the PBPK modeling of the fetus to a late
gestational timeframe (i.e., near full
term pregnancy, ∼GW 40), so EPA did
not make use of model predictions
regarding early fetal RAIU inhibition.
Although quantitative outputs of EPA’s
revised PBPK models differ somewhat
from the published values, the EPA
evaluation confirmed that, with
modifications (as described in USEPA,
2008b), the Clewell et al., (2007) and
Merrill et al., (2005) models provide an
appropriate basis for calculating the
lifestage differences in the degree of
thyroidal RAIU inhibition at a given
level of perchlorate exposure. The
results of EPA’s model application are
discussed in Section IV.B.5.
B. Evaluation of Perchlorate Occurrence
in Drinking Water
The primary source of drinking water
occurrence data used to support this
preliminary regulatory determination is
the data provided by public water
systems in accordance with the first
Unregulated Contaminant Monitoring
Regulation (UCMR 1). The Agency also
evaluated supplemental sources of
occurrence information.
1. The Unregulated Contaminant
Monitoring Regulation. In 1999, EPA
developed the UCMR program in
coordination with the CCL and the
National Drinking Water Contaminant
Occurrence Database (NCOD) to provide
national occurrence information on
unregulated contaminants (September
17, 1999, 64 FR 50556 (USEPA, 1999b);
March 2, 2000, 65 FR 11372 (USEPA,
2000b); and January 11, 2001, 66 FR
2273 (USEPA, 2001b)).
EPA designed the UCMR 1 data
collection with three parts (or tiers).
Occurrence data for perchlorate are from
the first tier of UCMR (also known as
UCMR 1 List 1 Assessment Monitoring).
EPA required all large 7 PWSs, plus a
statistically representative national
sample of 800 small 8 PWSs, to conduct
Assessment Monitoring.9
Approximately one-third of the
participating small systems were
scheduled to monitor for these
contaminants during each calendar year
from 2001 through 2003. Large systems
could conduct one year of monitoring
anytime during the 2001–2003 UCMR 1
period. EPA specified a quarterly
monitoring schedule for 1,896 surface
water systems and a twice-a-year, six-
month interval monitoring schedule for
1,969 ground water systems. The
objective of the UCMR 1 sampling
approach for small systems was to
collect contaminant occurrence data
from a statistically selected, nationally
representative sample of small systems.
The small system sample was stratified
and population-weighted, and included
some other sampling adjustments, such
as including at least 2 systems from
each State. With contaminant
monitoring data from all large PWSs and
a statistical, nationally representative
sample of small PWSs, the UCMR 1 List
1 Assessment Monitoring program
provides a contaminant occurrence data
set suitable for national drinking water
estimates.
EPA collected and analyzed drinking
water occurrence data for perchlorate
from 3,865 PWSs between 2001 and
2005 under the UCMR 1. EPA found
that 160 (approximately 4.1 percent) of
the 3,865 PWSs that sampled and
reported had at least 1 analytical
detection of perchlorate (in at least 1
sampling point) at levels greater than or
equal to the method reporting limit
(MRL) of 4 µg/L. These 160 systems are
located in 26 States and 2 territories. Of
these 160 PWSs, 8 are small systems
(serving 10,000 or fewer people) and
152 are large systems (serving more than
10,000 people). These 160 systems
reported 637 detections of perchlorate at
levels greater than or equal to 4 µg/L,
which is approximately 11.3 percent of
the 5,629 samples collected by these 160
systems and approximately 1.9 percent
of the 34,331 samples collected by all
3,865 systems. The maximum reported
concentration of perchlorate was 420
µg/L, from a single surface water sample
from a PWS in Puerto Rico. The average
concentration of perchlorate for those
samples with positive detections for
perchlorate was 9.85 µg/L and the
median concentration was 6.40 µg/L. A
summary of the perchlorate occurrence
statistics in UCMR 1 is shown in Table
1.
TABLE 1—UCMR 1 OCCURRENCE OF PERCHLORATE AT CONCENTRATIONS >= 4 µG/L 10
Number of
samples
System size
Samples
w/detects
Sampling
points
tested
Sampling
points
w/detects
Sampled
systems
Systems
w/detects
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Small Systems .................................................................
Large Systems .................................................................
3,295
31,036
15
622
1,454
13,533
8
379
797
3,068
8
152
Total Systems ...........................................................
34,331
637
14,987
387
3,865
160
Notes:
7 Systems
8 Systems
serving more than 10,000 people.
serving 10,000 people or fewer.
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9 Large and small systems that purchase 100
percent of their water supply were not required to
participate in the UCMR 1 Assessment Monitoring
or the UCMR 1 Screening Survey.
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10 Table 1 shows perchlorate detection sat levels
greater than and equal to the MRL of 4 µg/L.
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1. For both large and small systems, at 3,865 systems with data, there were 34,331 samples taken at 14,987 (entry) points resulting in 637
(1.86%) sample detects representing 387 (2.58%) of the entry/sample points in 160 (4.14%) of the systems.
2. For 3,068 large systems with data, there were 31,036 samples taken at 13,533 entry points resulting in 622 (2.00%) detections representing
379 (2.80%) entry/sample points in 152 (4.95%) of the systems.
3. For 797 small systems with data, there were 3,295 samples taken at 1,454 entry points, resulting in a total of 15 (0.455%) detections representing 8 (0.55%) entry/sample points at 8 (1%) of the systems.
Table 2 presents EPA’s estimates of
the population served by water systems
for which the highest reported
perchlorate concentration was greater
than various threshold concentrations
ranging from 4 µg/L (MRL) to 25 µg/L.
The fourth column of Table 2 presents
a high end estimate of the population
served drinking water above a
threshold. This column presents the
total population served by systems in
which at least one sample was found to
contain perchlorate above the threshold
concentration. EPA considers this a high
end estimate because it is based upon
the assumption that the entire system
population is served water from the
entry point that had the highest reported
perchlorate concentration. In fact, many
water systems have multiple entry
points into which treated water is
pumped for distribution to their
consumers. For the systems with
multiple entry points, it is unlikely that
the entire service population receives
water from the one entry point with the
highest single concentration. Therefore,
EPA included a less conservative
estimate of the population served water
above a threshold in the fifth column in
Table 2. EPA developed this estimate by
assuming the population was equally
distributed among all entry points. For
example, if a system with 10 entry
points serving 200,000 people had a
sample from a single entry point with a
concentration at or above a given
threshold, EPA assumed that the entry
point served one-tenth of the system
population, and added 20,000 people to
the total when estimating the
population in the last column of Table
2. This approach may provide either an
overestimate or an underestimate of the
population served by the affected entry
point. In contrast, in the example above,
EPA added the entire system population
of 200,000 to the more conservative
population served estimate in column 4,
which is likely an overestimate.
TABLE 2—UCMR 1 OCCURRENCE AND POPULATION ESTIMATES FOR PERCHLORATE ABOVE VARIOUS THRESHOLDS
PWSs with at
least 1
detection >
threshold of
interest
PWS entry or
sample points
with at least 1
detection >
threshold of
interest b
4.01% ......................
(155 of 3,865) .........
3.16% ......................
(122 of 3,865) .........
2.12% ......................
(82 of 3,865) ...........
1.35% ......................
(52 of 3,865) ...........
1.09% ......................
(42 of 3,865) ...........
0.80% ......................
(31 of 3,865) ...........
0.70% ......................
(27 of 3,865) ...........
0.49% ......................
(19 of 3,865) ...........
0.36% ......................
(14 of 3,865) ...........
2.48% ......................
(371 of 14,987) .......
1.88% ......................
(281 of 14,987) .......
1.14% ......................
(171 of 14,987) .......
0.65% ......................
(97 of 14,987) .........
0.42% ......................
(63 of 14,984) .........
0.29% ......................
(44 of 14,987) .........
0.24% ......................
(36 of 14,987) .........
0.16% ......................
(24 of 14,987) .........
0.12% ......................
(18 of 14,987) .........
Thresholds a
4 µg/L ...................................................................................................
5 µg/L ...................................................................................................
7 µg/L ...................................................................................................
10 µg/L .................................................................................................
12 µg/L .................................................................................................
15 µg/L .................................................................................................
17 µg/L .................................................................................................
20 µg/L .................................................................................................
25 µg/L .................................................................................................
Population
served by
PWSs with
at least 1
detection >
threshold of
interest c
e 16.6
Population
estimate for
entry
or sample
points
having at
least 1
detection >
threshold of
interest d
M
5.1 M
14.6 M
4.0 M
7.2 M
2.2 M
5.0 M
1.5 M
3.6 M
1.2 M
2.0 M
0.9 M
1.9 M
0.8 M
1.5 M
0.7 M
1.0 M
0.4 M
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Footnotes:
a All occurrence measures in this table were conducted on a basis reflecting values greater than the listed thresholds.
b The entry/sample-point-level population served estimate is based on the system entry/sample points that had at least 1 analytical detection
for perchlorate greater than the threshold of interest. The UCMR 1 small system survey was designed to be representative of the nation’s small
systems, not necessarily to be representative of small system entry points.
c The system-level population served estimate is based on the systems that had at least 1 analytical detection for perchlorate greater than the
threshold of interest.
d Because the population served by each entry/sample point is not known, EPA assumed that the total population served by a particular system is equally distributed across all entry/sample points. To derive the entry/sample point-level population estimate, EPA summed the population
values for the entry/sample points that had at least 1 analytical detection greater than the threshold of interest.
e This value does not include the population associated with 5 systems serving 200,000 people that measured perchlorate at 4 µg/L in at least
one sample.
2. Supplemental Occurrence Data.
The Agency also evaluated drinking
water monitoring data for perchlorate in
California and Massachusetts. EPA
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considers these State data to be
supplemental for purposes of this
regulatory determination, because they
are not nationally representative. EPA
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believes these State’s monitoring results
are generally consistent with the results
collected by EPA under UCMR 1. The
California Department of Public Health
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(CDPH) last updated its perchlorate
monitoring results on July 10, 2008
(CDPH, 2008). The Massachusetts’s
Department of Environmental Protection
(MA DEP) last updated its draft report
on The Occurrence and Sources of
Perchlorate in Massachusetts in April,
2006 (MA DEP, 2005).
C. Evaluation of Perchlorate Exposure
From Sources Other Than Drinking
Water
An important element of EPA’s
regulatory determination process is to
consider the contaminant exposure that
individuals are likely to receive from
sources other than drinking water. An
individual’s total exposure to a
contaminant is more relevant to his or
her risk for adverse health effects than
is exposure to the contaminant from
drinking water alone.
Because there are significant sources
of perchlorate exposure other than
through the drinking water route, EPA
determined that data on exposure to
perchlorate from these sources is critical
to the evaluation of whether or not there
is a meaningful opportunity for health
risk reduction through a national
primary drinking water rule for
perchlorate. Dietary studies pose a
particular challenge because there is
great variety in the American diet and
many foods must be analyzed to enable
a comprehensive dietary exposure
estimate. However, EPA believes that
two recent studies provide a sound basis
for evaluating total perchlorate
exposure. These are the Food and Drug
Administration (FDA) Total Diet Study
and an analysis of NHANES/UCMR data
conducted by EPA and CDC.
FDA’s Total Diet Study (TDS)
combines nationwide sampling and
analysis of hundreds of food items along
with national surveys of food intake to
develop comprehensive dietary
exposure estimates for a variety of
demographic groups in the U.S. CDC’s
NHANES data base measured
perchlorate in the urine of a
representative sample of Americans.
EPA and CDC used data from the
NHANES data base and UCMR
monitoring to estimate perchlorate
exposure from food and water together,
and food alone, for different subpopulations. This section of the notice
provides details on the results of these
studies. Because the sources of exposure
encompassed by each of these studies
overlap, EPA has considered them both
in making a regulatory determination in
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an effort to provide the most
comprehensive basis for the preliminary
determination.
In this section, EPA also provides a
brief review of other dietary and
biomonitoring studies that, while not
directly incorporated into our
determination, tend to reinforce the
results of the primary exposure studies.
1. Food Studies. The FDA, the United
States Department of Agriculture
(USDA), and other researchers have
studied perchlorate in foods. The most
recent and most comprehensive
information available on the occurrence
of perchlorate in the diet has been
published by FDA. This section
describes two perchlorate studies
released by FDA.—the Total Diet Study
and FDA’s Exploratory Survey Data on
Perchlorate in Food.
a. FDA Total Diet Study, 2005 and
2006. Since 1961, FDA has periodically
conducted a broad-based food
monitoring study known as the Total
Diet Study (TDS). The purpose of the
TDS is to measure substances in foods
representative of the total diet of the
U.S. population, and to make estimates
of the average dietary intake of those
substances for selected age-gender
groups. A detailed history of the TDS
can be found at the following Web site:
https://www.cfsan.fda.gov/∼comm/tdstoc.html.
Murray et al., (2008) briefly describe
the design of the current TDS. Dietary
intakes of perchlorate were estimated by
combining analytical results from the
TDS with food consumption estimates
developed specifically for estimating
dietary exposure from TDS results.
While the perchlorate data for TDS
foods were collected in 2005–2006, the
food consumption data in the current
TDS food list is based on results (Egan
et al., 2007) from the USDA’s 1994–96,
1998 Continuing Survey of Food Intakes
by Individuals (94–98 CSFII), which
includes data for all age groups
collected in 1994–96, and for children
from birth through age 9 collected in
1998. Although over 6,000 different
foods and beverages were included in
the food consumption surveys, these
foods and beverages were collapsed into
a set of 285 representative foods and
beverages by aggregating the foods
according to the similarity of their
primary ingredients and then selecting
the specific food consumed in greatest
quantity from each group as the
representative TDS food for that group.
The consumption amounts of all the
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foods in a group were aggregated and
assigned to the representative food for
that group. It is these 285 representative
foods and beverages that are on the
current TDS food list. This approach to
estimating dietary intakes assumes that
the analytical profiles (e.g., perchlorate
concentrations) of the representative
foods are similar to those of the larger
group of foods from the original
consumption survey to which they
correspond. This approach provides a
reasonable estimate of total dietary
exposure to the analytes from all foods
in the diet, not from the representative
TDS foods alone. The sampled TDS
foods are purchased at retail from
grocery stores and fast-food restaurants.
The foods are prepared table-ready prior
to analyses, using distilled water when
water is called for in the recipe. The
analytical method developed and used
by FDA to measure perchlorate in food
samples has a nominal limit of detection
(LOD) of 1.00 ppb and a limit of
quantitation (LOQ) of 3.00 ppb
(Krynitsky et al., 2006).
Murray et al., (2008) reports that FDA
included perchlorate as an analyte in
TDS baby foods in 2005 and in all other
TDS foods in 2006. Iodine was analyzed
in all TDS foods from five market
baskets surveyed in late 2003 through
2004. Using these data collectively, FDA
developed estimates of average dietary
perchlorate and iodine intake for 14 agegender groups. To account for
uncertainties associated with samples
with no detectable concentrations of
perchlorate or iodine (non-detects or
NDs), FDA calculated a lower-bound
and upper-bound for each estimate of
average dietary exposure, assuming that
NDs equal to zero and the LOD,
respectively. Specifically, FDA
multiplied these upper- and lowerbound concentrations by the average
daily consumption amount of the
representative food for the given
subpopulation group to provide a range
of average intakes for each TDS food.
Table 3 summarizes the FDA
estimated upper- and lower-bound
average dietary perchlorate intakes
(from food) for 14 age-gender groups on
a per kilogram of body weight per day
basis to enable direct comparison to the
perchlorate RfD. Murray et al., (2008)
reports that average body weights for
each population group were based on
self-reported body weights from
respondents in the 94–98 CSFII.
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TABLE 3—LOWER- AND UPPER-BOUND (ND = 0 AND LOD) PERCHLORATE INTAKES FROM FDA’S TDS RESULTS FOR
2005–2006
Average perchlorate intake
from food
(µg/kg/day)
Population group
Lower-bound
Infants—6–11 mo ....................................................................................................................................................
Children—2 yr ..........................................................................................................................................................
Children—6 yr ..........................................................................................................................................................
Children—10 yr ........................................................................................................................................................
Teenage Girls—14–16 yr ........................................................................................................................................
Teenage Boys—14–16 yr ........................................................................................................................................
Women—25–30 yr ...................................................................................................................................................
Men—25–30 yr ........................................................................................................................................................
Women—40–45 yr ...................................................................................................................................................
Men—40–45 yr ........................................................................................................................................................
Women—60–65 yr ...................................................................................................................................................
Men—60–65 yr ........................................................................................................................................................
Women—70+ yr .......................................................................................................................................................
Men—70+ yr ............................................................................................................................................................
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Based on their analysis of TDS data,
FDA reports that detectable levels of
perchlorate were found in at least one
sample in 74 percent (211 of 286) of
TDS foods (Murray et al., 2008). The
average estimated perchlorate intakes
for the 14 age-gender groups range from
0.08 to 0.39 µg/kg/day, compared with
the RfD of 0.7 µg/kg/day. Though not
shown here, Murray et al., (2008)
reports that average estimated iodine
intakes for the 14 age-gender groups
range from 138 to 353 µg/person/day,
and for all groups exceed the relevant
U.S. dietary reference values used for
assessing the nutritional status of
populations.11
The results of the TDS dietary intake
assessment provide an estimate of the
average dietary perchlorate intakes by
specific age-gender groups in the U.S.
However, Murray et al. note that the
current TDS design ‘‘does not allow for
estimates of intakes at the extremes
(i.e., upper or lower percentiles of food
consumption) or for population
subgroups within the 14 age/sex groups
that may have specific nutritional needs
(e.g., the subgroups of pregnant and
lactating women within the groups of
women of child bearing age).’’
Nevertheless, Murray et al. stated that:
‘‘These TDS results increase
substantially the available data for
characterizing dietary exposure to
perchlorate and provide a useful basis
for beginning to evaluate overall
11 Murray et al., (2008) compared estimated
average iodine intakes with U.S. Dietary Reference
Intakes for iodine (NAS, 2000). The reference values
cited by Murray et al., (2008) are as follows: 130
µg/person/day for infants, 65 µg/person/day for
children 1–8 years, 73 µg/person/day for children
9–13 years, and 95 µg/person/day for the remainder
of population.
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perchlorate and iodine estimated dietary
intakes in the U.S. population.’’
b. FDA Exploratory Survey Data on
Perchlorate in Food, 2003–2005. Prior to
including perchlorate in the TDS, FDA
conducted exploratory surveys from
October 2003 to September 2005 to
determine the occurrence of perchlorate
in a variety of foods. In May 2007, FDA
provided an estimate of perchlorate
exposure from these surveys (https://
www.cfsan.fda.gov/∼dms/clo4ee.html).
Using the data from these exploratory
studies and food and beverage
consumption values from USDA’s 94–98
CSFII, FDA estimated mean perchlorate
exposures of 0.053 µg/kg/day for all ages
(2+ years), 0.17 µg/kg/day for children
(2–5 years), and 0.037 µg/kg/day for
females (15–45 years). There are
uncertainties associated with the
preliminary exposure assessment
because the 27 foods and beverages
selected represent only about 32 to 42
percent of the total diet depending on
the population group. Additionally, the
overall goal of the sampling plan was to
gather initial information on occurrence
of perchlorate in foods from various
locations with a high likelihood of
perchlorate contamination. With the
preceding caveats in mind, the results of
these exploratory studies are generally
consistent with the more complete
results of the 2005–2006 TDS. For the
purpose of developing a national
estimate of dietary perchlorate
exposure, the results of FDA’s
exploratory studies are superseded by
the results of the TDS.
c. Other Published Food Studies.
Since publication of EPA’s May 2007
notice, Pearce et al., (2007) published an
analysis of perchlorate concentrations in
17 brands of prepared ready to eat and
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0.26
0.35
0.25
0.17
0.09
0.12
0.09
0.08
0.09
0.09
0.09
0.09
0.09
0.11
Upper-bound
0.29
0.39
0.28
0.20
0.11
0.14
0.11
0.11
0.11
0.11
0.10
0.11
0.11
0.12
concentrated liquid infant formula.
Perchlorate concentrations in the 17
samples ranged from 0.22 to 4.1 µg/L,
with a median concentration of 1.5 µg/
L. The researchers did not estimate the
dose infants would consume at the
concentrations observed in the study.
FDA also included sampling and
analysis of infant formula in their 2008
TDS analysis, discussed above.
Studies, such as those published by
Kirk et al., (2003, 2005) and Sanchez et
al., (2005a, 2005b) have examined
perchlorate in milk and produce. These
studies and others were summarized in
EPA’s May 2007 notice describing the
status of EPA’s evaluation of perchlorate
(72 FR 24016 (USEPA, 2007)).
2. Biomonitoring Studies. Researchers
have also begun to investigate
perchlorate occurrence in humans by
analyzing for perchlorate in urine and
breast milk. For example, CDC has
included perchlorate in its National
Biomonitoring Program, which develops
methods to measure environmental
chemicals in humans. With this
information, the CDC can obtain data on
levels and trends of exposure to
environmental chemicals in the U.S.
population.
a. Urinary Biomonitoring. In the
largest study of its kind, Blount et al.,
(2006c) measured perchlorate in urine
samples collected from a nationally
representative sample of 2,820 U.S.
residents as part of the 2001–2002
NHANES. Blount et al., (2006c) detected
perchlorate at concentrations greater
than 0.05 µg/L in all 2,820 urine
samples tested, with a median
concentration of 3.6 µg/L and a 95th
percentile of 14 µg/L. Women of
reproductive age (15–44 years) had a
median urinary perchlorate
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concentration of 2.9 µg/L and a 95th
percentile of 13 µg/L. The demographic
with the highest concentration of
urinary perchlorate was children (6–11
years), who had a median urinary
perchlorate concentration of 5.2 µg/L.
Blount et al., (2006c) estimated a total
daily perchlorate dose for the NHANES
participants aged 20 and older (for
whom a creatinine correction method
was available) and found a median dose
of 0.066 µg/kg/day (about one tenth of
the RfD) and a 95th percentile dose of
0.234 µg/kg/day (about one third of the
RfD). Eleven adults (0.7 percent) had
estimated perchlorate exposure greater
than perchlorate’s RfD of 0.7 µg/kg/day
(the highest calculated exposure was
3.78 µg/kg/day). Because of daily
variability in diet and perchlorate
exposure, and the short residence time
of perchlorate in the body, these single
sample measurements may overestimate
long-term average exposure for
individuals at the upper end of the
distribution and may underestimate the
long-term average exposure for
individuals at the lower end of the
distribution. Blount et al. did not
estimate daily perchlorate dose for
children and adolescents due to the
limited validation of estimation
methods for these age groups at that
time (Blount et al., 2006c).
In a recent unpublished, but peer
reviewed, study, EPA and CDC
investigators merged the data sets from
NHANES and UCMR 1 to identify the
NHANES participants from counties
which had a perchlorate detection
during the UCMR survey (USEPA,
2008a). The study assumes, based on
previous analyses of perchlorate
pharmacokinetics, that urine is the sole
excretion pathway other than in
lactating women. Since all NHANES
participants’ urine contained
perchlorate, separating out those who
had a higher potential for additional
exposure via drinking water from those
who had a lower potential for drinking
water exposure left the remainder of
participants whose exposure was
expected to be primarily from food.
The advantage of a urinary
biomonitoring study is that it analyzes
the perchlorate actually ingested in the
diets of a large number of individuals
rather than using estimators of
perchlorate ingestion from a variety of
foods for a diverse population. The
methodology provides a novel
opportunity to use public water system
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occurrence and human biomonitoring
data to directly inform EPA’s decision.
The approach is reasonable for
estimating perchlorate intake at various
percentiles from food and to gain an
understanding of the relative
contribution from water. A limitation is
in the use of NHANES’s spot urine
testing, and creatinine corrections for a
population with diverse physiological
characteristics, to calculate the daily
perchlorate dose. The cross sectional
study attempts to capture a
representative exposure, but was limited
by the need to match up drinking water
occurrence data with biomonitoring
data on a county-wide basis, even
though county and public water system
service area boundaries often do not
coincide. There also may have been
some temporal mismatch between the
occurrence and biomonitoring data.
As noted, the primary goal of the
study was to derive the dose of
perchlorate coming from food alone by
eliminating possible sources of water
contribution. Individuals’ data were
placed into one of three bins based on
likelihood of perchlorate being in their
tap water. The bins were further sorted
by age and sex. Bin I was comprised of
NHANES 2001–2002 data for
individuals residing in the same
counties as public water systems that
had at least one positive measurement
of perchlorate during the sample period,
as measured in UCMR 1. Therefore, this
bin represented those who were more
likely to be exposed to perchlorate in
both food and water. For the most part,
the average perchlorate level in urine for
all age groups was the highest in this
bin, and the creatinine-corrected
average dose for all individuals in this
group was 0.101 µg/kg/day, with a
geometric mean of 0.080 µg/kg/day.
In contrast, Bin III was comprised of
data for individuals considered less
likely to have exposure to perchlorate
via drinking water, as defined in one of
three ways: (1) They resided in counties
where there were no quantified
detections of perchlorate in public
drinking water systems sampled as part
of UCMR (i.e., UCMR 1 results were
below the minimum reporting limit of 4
µg/L); or (2) they self-reported that they
had not consumed tap water in the
previous 24 hours regardless of where
they resided (i.e., they may have resided
in a county with a positive UCMR
finding, but did not drink tap water); or
(3) again, not considering the UCMR
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60273
status of the county, their response to
NHANES indicated they used a reverse
osmosis filter which may be effective for
removing perchlorate. Bin III thus
represents results of urinary perchlorate
from individuals who were less likely to
experience perchlorate exposure via tap
water, and were thus more likely to
have their perchlorate exposure caused
solely by intake from food. The average
creatinine-corrected perchlorate dose for
these individuals was 0.090 µg/kg/day,
with a geometric mean of 0.062 µg/kg/
day.
Finally, Bin II included individuals
residing in counties which had not been
sampled in UCMR. As such, there is no
information on potential perchlorate in
their public drinking water. The average
creatinine-corrected perchlorate dose for
these individuals was 0.072 µg/kg/day,
with a geometric mean of 0.053 µg/kg/
day. The results for Bin II are somewhat
anomalous, and may suggest either that
drinking water concentrations are even
lower in these non-monitored counties
than in the Bin III counties or that food
exposure for these counties was lower
than for the counties in either Bin I or
III. In any case, EPA’s analysis to
determine the RSC did not focus on Bin
II, as discussed below.
A summary of selected results for
individuals in Bins I and III is shown in
Table 4. The estimates of daily
perchlorate intake presented in Table 4
from the NHANES–UCMR analysis are
somewhat higher than those of Blount et
al., (2006). The Blount et al., (2006)
estimates were limited to adults 20
years of age and older because
application of the set of creatinine
excretion equations used by Blount et
al. to estimate perchlorate dose was
limited to adults. Mage et al., (2007)
provides an expanded set of equations
that allows for estimating daily
creatinine excretion rates for children,
as well as for adults. Since children
tend to have higher exposure on a per
body weight basis than adults, it is not
surprising that the estimates based on
both adults and children are somewhat
higher than the Blount estimates based
on adults alone. The mean total
exposure for people that are more likely
to be exposed to perchlorate in food and
water (Bin I) was calculated to be 0.101
µg/kg/day. The average exposure for
people more likely to be exposed to
perchlorate from food alone (Bin III) was
0.090 µg/kg/day.
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TABLE 4—ESTIMATED DAILY PERCHLORATE INTAKES (µG/KG/DAY) FOR TWO BINS BASED ON UCMR 1 OCCURRENCE
DATA
Number of
people
Average
(mean)
Geometric
mean
50th
percentile
90th
percentile
Group
Bin*
Total .................................................................................
I
III
320
2,063
0.101
0.090
0.080
0.062
0.075
0.058
0.193
0.167
Age: 6–11 .........................................................................
I
III
52
270
0.152
0.150
0.132
0.118
0.131
0.124
0.237
0.280
Age: 12–19 .......................................................................
I
III
100
608
0.109
0.080
0.078
0.061
0.070
0.060
0.286
0.158
Age: 20 or more ...............................................................
I
III
168
1,185
0.091
0.085
0.074
0.057
0.071
0.055
0.186
0.143
Females: 15–44 ...............................................................
I
III
57
505
0.081
0.093
0.062
0.055
0.071
0.052
0.141
0.143
Pregnant Females ............................................................
I
III
8
98
0.097
0.123
0.086
0.064
0.060
0.056
0.121
0.263
mstockstill on PROD1PC66 with NOTICES
* Bin I was comprised of individuals residing in counties which had at least one positive measurement of perchlorate somewhere in the public
drinking water supply. Bin III was comprised of individuals considered less likely to have exposure to perchlorate via drinking water based on a
three-part test (see text).
Using Bin III as the dose most closely
representing only dietary perchlorate
exposure, one can compare results from
the FDA TDS, shown previously in
Table 3. For example, for females 14–16,
women 25–30, and women 40–45 years
old, the FDA mean food dose was 0.09–
0.1 µg/kg/day. In the EPA–CDC
biomonitoring study of NHANES–
UCMR, the mean food dose for women
of child-bearing age (15–44 years old)
was 0.093 µg/kg/day. The results from
calculating likely food intakes (TDS
study) and from urinalysis from actual
intakes (NHANES/UCMR) are in close
agreement where comparisons can be
made.
b. Breast Milk. A number of studies
have investigated perchlorate in human
breast milk. The most recent study
included measurements from 49 healthy
Boston-area volunteers (10–250 days
postpartum, median 48 days; Pearce et
al., 2007). Perchlorate was found in all
samples, ranging from 1.3–411 µg/L,
with a median concentration of 9.1
µg/L and a mean concentration of 33
µg/L. No correlation was found between
perchlorate and iodine concentrations
in breast milk. EPA notes that the
Boston-area public water systems did
not detect perchlorate in drinking water
samples collected for the U.S. EPA’s
Unregulated Contaminant Monitoring
Rule from 2001 to 2003, nor did Boston
area systems detect perchlorate in
samples collected in response to the
Massachusetts DEP 2004 emergency
regulations for perchlorate (see Section
III.B of this notice).
Kirk et al., (2005) analyzed 36 breast
milk samples from 18 States (CA, CT,
FL, GA, HI, MD, ME, MI, MO, NC, NE,
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NJ, NM, NY, TX, VA, WA, WV) and
found perchlorate concentrations in all
samples ranging from 1.4 to 92.2 µg/L,
with a mean concentration of 10.5 µg/
L. Kirk et al., (2007) later did a smaller
study involving 10 women, which
included 6 samples on each of 3 days
in a temporal study. Half the women
were from Texas, but the others were
from CO, FL, MO, NM, and NC. They
found significant variation in all
samples (n=147), with a range, mean,
and median perchlorate concentration
of 0.5–39.5 µg/L, 5.8 µg/L, and 4.0
µg/L, respectively.
´
Tellez et al., (2005) reported maternal
parameters for participants from a study
conducted in Chile. Breast milk samples
indicated that a significant amount of
perchlorate leaves the body of the
nursing mother through breast milk, in
addition to urine. However, the breast
milk perchlorate levels were highly
variable and no significant correlations
could be established between breast
milk perchlorate and either urine
perchlorate or breast milk iodide
concentrations for the individuals
´
evaluated in these Chilean cities (Tellez
et al., 2005).
Blount et al., (2007) also suggests
breast milk as an excretion pathway and
the NHANES–UCMR study authors
observed a difference between the
urinary perchlorate concentration of
breast feeding women versus pregnant
women with an overall mean
concentration of 0.130 µg/kg/day for 117
pregnant women compared to a
concentration of 0.073 µg/kg/day for the
24 breast-feeding women (USEPA,
2008a).
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Dasgupta et al., (2008) analyzed breast
milk samples and 24 hour urine samples
from 13 lactating women from Texas for
perchlorate and iodine. For breast milk,
they found perchlorate concentrations
ranging from 0.01 to 48 µg/L, with a
median concentration of 7.3 µg/L and a
mean concentration of 9.3 µg/L (457
total samples). For iodine,
concentrations ranged from 1 to 1,200
µg/L, with a median concentration of 43
µg/L and a mean concentration of 120
µg/L (447 total samples). For urine they
found perchlorate concentrations
ranging from 0.6 to 80 µg/L, with a
median concentration of 3.2 µg/L and a
mean concentration of 4.0 µg/L (110
total samples). For iodine,
concentrations ranged from 26 to 630
µg/L, with a median concentration of
110 µg/L and a mean concentration of
140 µg/L (117 total samples)
IV. Preliminary Regulatory
Determination for Perchlorate
In making preliminary regulatory
determinations, EPA uses the criteria
mandated by the 1996 SDWA
Amendments. EPA has found that
perchlorate, at sufficiently high doses,
may have an adverse effect on the health
of persons, and that perchlorate is found
in a small percentage of public water
supply systems. However, EPA has
determined that regulation of
perchlorate in drinking water systems
does not present a meaningful
opportunity to reduce health risk for
persons served by public water systems.
This section describes how EPA has
evaluated these three criteria in light of
the data presented in Section III to make
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a preliminary regulatory determination
for perchlorate.
A. May Perchlorate Have an Adverse
Effect on the Health of Persons?
Yes. Perchlorate interacts with the
sodium iodide symporter, reducing
iodine uptake into the thyroid gland
and, at sufficiently high doses, the
amount of T4 produced and available
for release into circulation. Sustained
changes in thyroid hormone secretion
can result in hypothyroidism. Thyroid
hormones stimulate diverse metabolic
activities in most tissues and
individuals suffering from
hypothyroidism experience a general
slowing of metabolism of a number of
organ systems. In adults, these effects
are reversed once normal hormone
levels are restored (NRC, 2005).
In fetuses, infants, and young
children, thyroid hormones are critical
for normal growth and development.
Irreversible changes, particularly in the
brain, are associated with hormone
insufficiencies during development in
humans (Chan and Kilby, 2000 and
Glinoer, 2007). Disruption of iodide
uptake presents particular risks for
fetuses and infants (Glinoer, 2007 and
Delange, 2004). Because the fetus
depends on an adequate supply of
maternal thyroid hormone for its central
nervous system development during the
first trimester of pregnancy, iodide
uptake inhibition from perchlorate
exposure has been identified as a
concern in connection with increasing
the risk of neurodevelopmental
impairment in fetuses of high-risk
mothers (NRC, 2005). Poor iodide
uptake and subsequent impairment of
thyroid function in pregnant and
lactating women have been linked to
delayed development and decreased
learning capability in infants and
children with fetal and neonatal
exposure (NRC, 2005)
The NRC recommended basing the
RfD on a precursor to an adverse effect
rather than an adverse effect per se. The
precursor event precedes a downstream
adverse effect in the dose response
continuum. In this case, NRC used
prevention of iodide uptake inhibition,
a precursor to adverse thyroid effects, to
establish a level at which no adverse
effects would be anticipated in exposed
populations. This approach is consistent
with the Agency’s policy on the use of
precursor events when appropriate in
establishing the critical effect upon
which an RfD is based (U.S. EPA,
2002c).
Based on the information above, EPA
finds that perchlorate, at sufficiently
high doses, may have an adverse effect
on the health of persons.
B. Is Perchlorate Known To Occur or Is
There a Substantial Likelihood That
Perchlorate Occurs at a Frequency and
at a Level of Public Health Concern in
Public Water Systems?
No. EPA has found that perchlorate
occurs infrequently at levels of health
concern in public water systems.
Specifically, EPA established a Health
Reference Level (HRL) as the level of
concern and evaluated the information
on the occurrence of perchlorate in
public water systems presented in
Section III.B in relation to this HRL. The
HRL is a benchmark against which EPA
compares the concentrations of a
contaminant found in public water
systems to determine if it is at a level
of public health concern. For past
regulatory determinations for noncarcinogens, EPA has calculated an HRL
using the Agency’s reference dose (RfD)
as follows:
HRL = [(RfD × BW)/DWI] × RSC
Where:
RfD = Reference Dose
BW = Body Weight for an adult assumed to
be 70 kilograms (kg)
DWI = Drinking Water Intake for an adult,
assumed to be 2 L/day
RSC = Relative Source Contribution, or the
remaining portion of the reference dose
available for drinking water after other
sources of exposure have been
considered (e.g., food, ambient air)
In addition, EPA has used a RSC
default value of 20 percent for screening
purposes to estimate the HRL for past
regulatory determinations because it has
lacked adequate data to develop an
empirical RSC. In the absence of such
60275
data, EPA has determined that it is
appropriate to use a conservative value
that is more likely to understate than to
overstate the amount of contaminant
that can be safely ingested through
drinking water. For its two previous sets
of regulatory determinations, EPA did
not find contaminants at frequencies
and levels of concern in comparison to
the conservative screening-level HRL.
Therefore, it was not necessary for the
Agency to further evaluate the RSC in
making regulatory determinations for
these contaminants.
However, the Agency believes that
sufficient exposure data are available for
perchlorate to enable EPA to estimate a
better informed RSC and HRL that is
more appropriate for fetuses of pregnant
women (the most sensitive
subpopulations identified by the NRC).
These exposure data include the further
analysis by EPA of the UCMR data and
the CDC’s NHANES biomonitoring data,
as well as the FDA’s Total Diet Study.
The following sections describe EPA’s
analyses of each of these data sources to
estimate RSCs and HRLs for this
sensitive subpopulation.
1. Total Diet Study for Estimation of
an RSC. The results of FDA’s recent
evaluation of perchlorate under the TDS
were presented in Section III.C.1 of this
notice. The TDS estimates are
representative of average, national,
dietary perchlorate exposure, for the
age-gender groups that were selected.
EPA used FDA’s dietary exposure
estimates to calculate RSC values by
subtracting the dietary estimates from
the RfD (0.7 µg/kg/day), dividing this
difference by the RfD, and multiplying
the result by 100 (to convert it to a
percentage). Because EPA believes that
dietary ingestion is the only significant
pathway for non-drinking-water
perchlorate exposure, the resulting RSCs
represent the amount of perchlorate
exposure (as a percentage of the RfD)
that the average individual within a
subgroup would have to ingest via
drinking water in order to reach a level
of total perchlorate exposure that equals
the RfD. These RSCs, displayed as
percentages, are presented in Table 5.
TABLE 5—RELATIVE SOURCE CONTRIBUTIONS REMAINING FOR WATER BASED ON TDS FOR VARIOUS SUBGROUPS
Total perchlorate intake
from food
(µg/kg/day)
mstockstill on PROD1PC66 with NOTICES
Population group
Infants, 6–11 mo ..........................................................................................................................
Children, 2 yr ...............................................................................................................................
Children, 6 yr ...............................................................................................................................
Children, 10 yr .............................................................................................................................
Teenage Girls, 14–16 yr ..............................................................................................................
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0.26–0.29
0.35–0.39
0.25–0.28
0.17–0.20
0.09–0.11
E:\FR\FM\10OCN1.SGM
10OCN1
RfD that
remains
(µg/kg/day)
0.41–0.44
0.31–0.35
0.42–0.45
0.50–0.53
0.59–0.61
RSC remaining for drinking
water
(as a percentage of the
RfD)
59–63
44–50
60–64
71–76
84–87
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Federal Register / Vol. 73, No. 198 / Friday, October 10, 2008 / Notices
TABLE 5—RELATIVE SOURCE CONTRIBUTIONS REMAINING FOR WATER BASED ON TDS FOR VARIOUS SUBGROUPS—
Continued
Total perchlorate intake
from food
(µg/kg/day)
Population group
Teenage Boys, 14–16 yr .............................................................................................................
Women, 25–30 yr ........................................................................................................................
Men, 25–30 yr ..............................................................................................................................
Women, 40–45 yr ........................................................................................................................
Men, 40–45 yr ..............................................................................................................................
Women, 60–65 yr ........................................................................................................................
Men, 60–65 yr ..............................................................................................................................
Women, 70+ yr ............................................................................................................................
Men, 70+ yr ..................................................................................................................................
The subpopulation that is the most
sensitive to perchlorate exposure is the
fetus of an iodine-deficient pregnant
woman. The FDA TDS does not estimate
the dietary intake of perchlorate
specifically for pregnant women (nor
can it specifically address iodinedeficient women); but it does present
dietary estimates for three groups of
women of childbearing age (Teenage
girls 14–16, Women 25–30 and Women
40–45). The calculated RSCs range from
84 to 87 percent for women of
childbearing age. Murray et al. (2008)
suggested that perchlorate intake rates
for pregnant and lactating women are
‘‘likely to be somewhat higher than
those of women of childbearing age as
a whole.’’ If this is true, an RSC derived
based upon the TDS mean dietary intake
for women of childbearing age may
underestimate the relative source
contribution from food for pregnant
women.
2. Urinary Data for Estimation of an
RSC. As described in Section III.C.2 of
this notice, EPA and CDC researchers
analyzed NHANES urinary data in
conjunction with UCMR occurrence
data at the CDC’s National Center for
Environmental Health (NCEH) to
evaluate exposure to perchlorate. These
data were partitioned to provide an
estimate of what portion of the overall
RfD that
remains
(µg/kg/day)
0.12–0.14
0.09–0.11
0.08–0.11
0.09–0.11
0.09–0.11
0.09–0.10
0.09–0.11
0.09–0.11
0.11–0.12
RSC remaining for drinking
water
(as a percentage of the
RfD)
0.56–0.58
0.59–0.61
0.69–0.62
0.59–0.61
0.59–0.61
0.60–0.61
0.59–0.61
0.59–0.61
0.58–0.59
80–83
84–87
84–89
84–87
84–87
86–87
84–87
84–87
83–84
exposure likely came from food alone.
In this analysis, EPA and CDC
researchers were able to characterize the
distribution of actual perchlorate
exposure as seen in their urine for
pregnant women. This means that the
analysis could determine not only the
mean exposure, but also the exposure of
highly exposed individuals. Results of
this analysis, presented in Table 6,
indicate that for pregnant women,
exposure to perchlorate from food is
0.263 µg/kg/day at the 90th percentile,
representing nearly 38 percent of the
RfD, and thus leaving an RSC for water
of 62 percent.
TABLE 6—DOSE REMAINING FOR WATER, AND FRACTION OF RFD (RSC) BASED ON NHANES–UCMR ANALYSIS
CALCULATIONS OF PERCHLORATE IN FOOD
Mean food
dose
(µg/kg/day)
Group
RfD that
remains
(µg/kg/day)
RSC as %
of RfD
Median
food dose
(µg/kg/day)
RfD that
remains
(µg/kg/day)
RSC as %
of RfD
90th
percentile
food dose
(µg/kg/day)
RfD that
remains
(µg/kg/day)
RSC as %
of RfD
0.090
0.150
0.080
0.085
0.093
0.123
0.61
0.55
0.62
0.615
0.607
0.58
87
79
89
88
87
82
0.075
0.124
0.060
0.055
0.052
0.056
0.625
0.58
0.64
0.645
0.65
0.64
89
83
91
92
93
91
0.167
0.280
0.158
0.143
0.143
0.263
0.533
0.42
0.542
0.557
0.557
0.437
76
60
77
80
80
62
mstockstill on PROD1PC66 with NOTICES
Total population .....................................
Ages 6–11 .............................................
Ages 12–19 ...........................................
Ages 20 + ..............................................
Female 15–44 .......................................
Pregnant ................................................
3. HRL Derivation. EPA believes the
NHANES–UCMR analysis is the best
available information to characterize
non-drinking water exposures to
perchlorate for the most sensitive
subpopulation. The FDA Total Diet
Study provides a nationally
representative estimate of the mean
dietary exposure to perchlorate for 14
age and gender groups, including
women of childbearing age. However,
this study does not provide specific
estimates for the most sensitive
subpopulation, the iodine-deficient
pregnant woman and her fetus. Also,
this study estimates only mean
exposures, so it does not account for the
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perchlorate exposure of highly exposed
individuals. The NHANES–UCMR
analysis provides a distribution of
exposure (not just a mean) specific to
almost 100 pregnant women who are
not likely to have been exposed to
perchlorate from their drinking water,
although it also does not separate out
iodine-deficient pregnant women
because of data limitations. Table 7
presents the HRLs developed for the
most sensitive subpopulation using the
TDS data and the NHANES–UCMR data.
EPA notes that the mean RSC for
pregnant women estimated from the
NHANES–UCMR data is very close to,
but slightly lower than, the mean for
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women of childbearing age estimated
from the TDS data. This shows close
agreement between the two data sets
and is consistent with the suggestion in
Murray et al. that food exposures for
pregnant women are likely to be
somewhat higher than for women of
childbearing age as a whole. (Note that
higher food exposure equates to a lower
RSC because a smaller fraction of the
RfD is left to be allocated to drinking
water.) While the means are available
(and in close agreement) from both data
sets, EPA believes it is more protective
to estimate the HRL for drinking water
by subtracting the 90th percentile
exposure in food from the reference
E:\FR\FM\10OCN1.SGM
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Federal Register / Vol. 73, No. 198 / Friday, October 10, 2008 / Notices
dose to assure that the highly exposed
individuals from this most sensitive
subpopulation are considered in the
evaluation of whether perchlorate is
found at levels of health concern. The
NHANES–UCMR data allow for the
calculation of the 90th percentile food
exposure, which results in an HRL of 15
µg/L for the pregnant woman.
TABLE 7—HEALTH REFERENCE LEVELS FOR PREGNANT WOMEN USING TDS DATA AND NHANES–UCMR DATA
Subpopulation
Body
weight a
Drinking
water consumption a
Source of RSC derivation
Women of Childbearing Age .......................
Pregnant Women .........................................
Pregnant Women .........................................
70 kg ........
70 kg ........
70 kg ........
2 liters ......
2 liters ......
2 liters ......
TDS mean (Table 5) ....................................
NHANES–UCMR mean (Table 6) ...............
NHANES–UCMR 90th percentile (Table 6)
RSC
(percent)
84–87
82
62
HRL
21 µg/L
20 µg/L
15 µg/L
mstockstill on PROD1PC66 with NOTICES
Footnotes:
a Default values used by EPA in the derivation of HRLs.
4. Frequency of Exposure at Health
Reference Level. The number of
pregnant women potentially exposed to
perchlorate in public drinking water
above these HRLs can be estimated from
the UCMR data. Using the data
presented in Table 2, approximately 0.8
percent of the systems had one or more
detections of perchlorate at or above 15
µg/L, the HRL determined for pregnant
women in this analysis. These systems
serve a total of 2.0 million persons in
their entire service area, of which 1.0
million are females, and thus might
become pregnant at some point during
their lives. However, not all water
system customers are living in
households that are served water from
the entry point(s) that tested positive.
Table 2 also provides a more refined
estimate of the potentially exposed
population by factoring in an estimate of
the portion of the system population
served by each entry point (as described
in Section III.B.1. of this notice). Using
this second approach, which is likely to
be more accurate, the number of people
served by entry points which exceed the
HRL is 0.9 million, of which 0.45
million are females. EPA estimates that
at any one time, 1.4 percent of the
population from Table 2 served by water
systems (or entry points) that detected
perchlorate at levels greater than 15
µg/L (Table 7) are pregnant women. This
estimate is based on the number of live
births (4,059,000, Ventura et al., 2004)
as a percentage of the total U.S.
population in 2000 (281,421,906, U.S.
Census Bureau, 2002). Therefore, a best
estimate of about 16,000 pregnant
women (with a high end estimate of
28,000) could be exposed at levels
exceeding the HRL at any given time.
Based on this analysis, EPA concludes
that perchlorate occurs infrequently at
levels of health concern in public water
systems. There are a small percentage of
public water systems (0.8 percent)
where drinking water above the HRL, in
combination with perchlorate from
food, may result in exposures to
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pregnant women at levels that exceed
the EPA reference dose for perchlorate.
However, as explained in section IV.C,
these exposures to perchlorate in
drinking water at concentrations above
the HRL do not rise to the level of a
meaningful opportunity for public
health risk reduction through a national
primary drinking water regulation.
5. Consideration of Sensitive
Subpopulations
In making a regulatory determination,
the SDWA requires EPA to take into
consideration the effect of contaminants
on subgroups that comprise a
meaningful portion of the general
population that are identifiable as being
at greater risk of adverse health effects
due to exposure to contaminants in
drinking water than the general
population.
As noted above, in past regulatory
determinations, EPA has calculated a
screening level HRL based on drinking
water consumption and body weight
information for adults in general,
combined with default assumptions
about RSC, in the absence of robust
empirical data. For this preliminary
perchlorate determination, EPA has
improved on this approach by using
body weight, drinking water and food
exposure data for pregnant women, in
order to protect the most sensitive
subpopulation identified by the NRC
(i.e., the fetuses of these women). In
addition, EPA has used 90th percentile
rather than mean food exposure data to
ensure that the HRL protects highly
exposed pregnant women and their
fetuses. However, infants, developing
children, and people with iodine
deficiency or thyroid disorders were
also identified as sensitive
subpopulations by the NRC. Because
infants and children eat and drink more
on a per body weight basis than adults,
eating a normal diet and drinking water
with 15 µg/L of perchlorate may result
in exposure that is greater than the
reference dose in these groups. To
address this concern, the potential effect
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of this intake on inhibition of iodide
uptake in these subgroups (i.e., relative
sensitivity) was evaluated using PBPK
modeling, as discussed in Section
III.A.3. Because the NRC (NRC, 2005)
found that the inhibition of iodide
uptake by the thyroid, which is a nonadverse precursor to any adverse effect,
should be used as the basis for
perchlorate risk assessment, evaluating
iodide uptake inhibition is important for
determining whether the HRL of 15
µg/L (derived for pregnant women) is
also an appropriate health reference
level for the other sensitive
subpopulations. Reducing some of the
uncertainty regarding the relative
sensitivities of these subpopulations
will help to address the concerns that
some groups may be exposed above the
reference dose (calculated using groupspecific body weight and intake
information), particularly if PBPK
modeling predicts that at the HRL, these
groups do not experience precursor
effects (RAIU inhibition) that exceed the
no effect level from which the reference
dose was derived.
a. Published PBPK Models. The
Clewell et al. (2007) and Merrill et al.
(2005) PBPK models predict the
distribution and elimination of
perchlorate after it is ingested. The
models also predict the level of RAIU
inhibition that would result from
different levels of perchlorate exposure
for different subpopulations, including
children and infants.
Clewell et al. (2007) predicted that at
a perchlorate dose of 0.001 mg/kg/day (1
µg/kg/day), approximately one and one
half times the RfD, iodide uptake
inhibition in the most sensitive
populations, i.e., fetuses and infants,
was no greater than 1.1 percent. This is
below the level (1.8 percent) of
inhibition at the NRC identified noeffect level (NOEL) in healthy adults
and recommended as the point of
departure for calculating the RfD,
applying a 10-fold intraspecies
uncertainty factor. The fact that for all
subpopulations the predicted RAIU at a
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level slightly above the RfD is still
below the RAIU at the NOEL is
consistent with the NRC’s conclusion
that the RfD would protect even the
most sensitive sub-populations.
However, because the Clewell model
does not account for reduced urinary
clearance that occurs in young infants,
EPA modified the model as discussed in
Section III.A.3 to address this and other
limitations.
b. Results of EPA’s Application of the
Published Models. EPA evaluated the
published models (Clewell et al., 2007,
and Merrill et al., 2005) and used them
to further explore the relationship
between water concentrations and
iodide uptake inhibition in different
subpopulations. As noted in Section
III.A.3 and discussed in more detail in
EPA’s description of the model (USEPA,
2008b), EPA determined that it was
appropriate to make several changes to
the models’ computer codes in order to
harmonize them and more adequately
reflect the biology. EPA considered in
detail the data currently available for
parameters determined to be
particularly important to the models’
predictions, and modified the model
parameters describing exposure as well
as urinary excretion of perchlorate and
iodide. These modifications resulted in
predicted RAIU inhibition rates that
were up to 1.5 times the predicted
inhibition rates in the earlier versions of
the model. EPA believes its revisions
have improved the predictive power of
the model and has used its results as the
basis for the following discussion.
Consistent with both the unmodified
Clewell model and the NRC’s
conclusions, EPA’s analysis identified
the near-term fetus (gestation week 40
fetus) as the most sensitive subgroup,
with a percent RAIU inhibition that was
5-fold higher than the percent inhibition
of the average adult at a dose equal to
the point of departure (7 µg/kg/day).
After correcting the model for reduced
urinary clearance in infants, the same
analysis shows that the predicted
percent RAIU inhibition is
approximately 1-to 2-fold higher for the
breast-fed and bottle-fed infant (7–60
days) than for the average adult, and is
slightly lower for the 1–2 year old child
than for the average adult. While
uncertainty remains regarding the
model’s predictions, EPA believes that it
is a useful tool, in conjunction with
appropriate exposure information, for
evaluating the relative sensitivity of
particular subpopulations (infants and
children) that can inform our
assessment of whether the HRL is an
appropriate health reference level for all
subpopulations (not just pregnant
women).
EPA thus applied the adjusted model
to the HRL of 15 µg/L to determine the
predicted percent RAIU inhibition
(Table 8). Iodide uptake inhibition
levels for all other subpopulations,
including infants and children, were
estimated to be not greater than 2.0
percent at the 15 µg/L drinking water
concentration and not greater than 2.2
percent when also considering
perchlorate in food. The highest iodide
update inhibition level (2.2 percent) was
seen for the 7 day bottle fed infant; all
other subpopulations, including the 60
day bottle fed infant as well as the 7 and
60 day breast fed infant had inhibition
levels below 1.4 percent when also
considering perchlorate in food. The 2.2
percent inhibition level for 7-day old
bottle fed infants is comparable to the
1.8 percent inhibition level that the NRC
identified as a no effect level in healthy
adults and recommended as the point of
departure for calculating the RfD.12
Table 8 also shows the exposure to
each subpopulation in µg/kg of body
weight. EPA notes that for some
subgroups, the modeled exposure
exceeds the RfD, though not for the most
sensitive subgroup (i.e., pregnant
women and their fetuses) from which
the HRL was derived. EPA has used
these exposure estimates as one input
into the PBPK model to reduce the
uncertainty associated with the relative
sensitivities of other subgroups,
particularly infants and children. EPA
believes use of the model enhances its
assessment beyond considering
exposure alone by predicting the
resulting iodide uptake inhibition that
may result from that exposure. As noted
above, the NRC concluded that the
‘‘most health protective and
scientifically valid approach’’ was to
base the point of departure for the RfD
on the inhibition of iodide uptake by the
thyroid (NRC, 2005), a non-adverse
precursor effect. The predicted RAIU
inhibition for all subgroups is
comparable to or less than the RAIU at
the NOEL selected by the NRC.
Therefore EPA believes the HRL of 15
µg/L, derived for pregnant women, is
also an appropriate health reference
level for other sub-populations, against
which to evaluate monitored levels of
perchlorate occurrence in drinking
water systems.
TABLE 8—PREDICTED PERCENT RADIOACTIVE IODIDE UPTAKE (RAIU) INHIBITION AND CORRESPONDING PERCHLORATE
INTAKE FROM WATER AT 15 µG/L WITH AND WITHOUT FOOD INTAKE
90th
Percentile
water intake
(L/day) b
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Percent RAIU
inhibition
from only
water at 15
µg/L
TDS estimated perchlorate intake from
food (µg/kgday) c
Perchlorate
intake from
food and
water at 15
µg/L (µg/kgday)
Percent RAIU
inhibition
from food
and water at
15 µg/L
2.24
2.11
Body weight
(kg) a
Perchlorate
intake from
only water
at 15 µg/L
(µg/kg-day)
0.48
0.48
0.15
0.21
0.10
0.10
0.58
0.58
0.18
0.26
2.18
2.34
2.57
....................
0.50
0.50
0.50
....................
0.49
0.49
0.47
0.90
0.10
0.10
0.10
....................
0.60
0.60
0.60
....................
0.59
0.59
0.57
1.1
2.96
0.60
1.36
0.61
1.27
0.18
1.1
0.17
0.73
0.10
0.70
1.59
0.71
1.48
0.21
1.3
0.20
0.84
Average adult .....................................
Non-pregnant woman ........................
Pregnant woman:
Mom—GW 13 .............................
Mom—GW 20 .............................
Mom—GW 40 .............................
Fetus—GW 40 g ..........................
Breast-fed infant:
Mom—7 d ...................................
Infant—7 d ..................................
Mom—60 d .................................
Infant—60 d ................................
74
3.6
72
5
12 The model does not exactly match the average
measured inhibition at each exposure
concentration. At the point of departure (7 µg/kg/
day), the model predicts a value of 2.1 percent for
adults, rather than the 1.8 percent from the Greer
et al. (2002) study. Thus, the model slightly overpredicts the level of inhibition for this group at this
exposure level, though this relationship may not
hold true for other sub-groups and exposure levels.
In any event, the difference between the average
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(d)
0.10
(d)
measured value of 1.8 percent and the modelpredicted value of 2.1 percent is well within the
statistical uncertainty in the data.
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TABLE 8—PREDICTED PERCENT RADIOACTIVE IODIDE UPTAKE (RAIU) INHIBITION AND CORRESPONDING PERCHLORATE
INTAKE FROM WATER AT 15 µG/L WITH AND WITHOUT FOOD INTAKE—Continued
90th
Percentile
water intake
(L/day) b
Body weight
(kg) a
Bottle-fed infant:
Infant—7 d ..................................
Infant—60 d ................................
Child:
6–12 mo f ....................................
1–2 yr f ........................................
Perchlorate
intake from
only water
at 15 µg/L
(µg/kg-day)
3.6
5
e 0.84
e 1.14
3.53
3.42
1.03
0.64
1.68
0.84
Perchlorate
intake from
food and
water at 15
µg/L (µg/kgday)
3.87
3.74
2.2
1.4
0.275
0.370
1.96
1.21
0.53
0.33
2.0
1.3
9.2
11.4
TDS estimated perchlorate intake from
food (µg/kgday) c
1.42 µg/L
1.42 µg/L
Percent RAIU
inhibition
from only
water at 15
µg/L
0.46
0.23
Percent RAIU
inhibition
from food
and water at
15 µg/L
a Calculations for a 70 kg ‘‘average’’ adult are shown, while the body weight (BW) for the non-pregnant woman is from U.S. EPA 2004 (based
on CSFII 94–96, 98) and BWs for the child are mean values from Kahn and Stralka (2008). BWs for pregnant and breast feeding moms, fetuses,
bottle and breast fed infants are predicted weights (functions of age or gestation week) using growth equations from Gentry et al. (2002) as implemented in the PBPK models (Clewell et al. 2007; non-pregnant value is BW at day 0 of gestation).
b Water intake levels for adults other than the lactating mother are based on normalized 90th percentile values for total water intake (direct and
indirect) multiplied by the age- or gestation-week-dependent BW, as follows: 0.032 L/kg-day for average adult and non-pregnant woman; 0.033 L/
kg-day for the pregnant woman. A fixed ingestion rate was used for the lactating mother because, while her BW is expected to drop during the
weeks following the end of pregnancy, the demands of breast-feeding will be increasing. Values are from Kahn and Stralka (2008), except values
for women are from U.S. EPA (2004).
c The dietary values used correspond to the midpoint of the range of lower- and upper-bound average perchlorate levels for each subgroup, as
identified from the FDA TDS in Murray et al. (2008), except for the bottle-fed infant. EPA used 1.42 µg/L as the concentration of perchlorate in
infant formula. This is based on an average of available FDA TDS data, with 1⁄2 LOD included in the average for the samples in which perchlorate was not detected.
d The breast-fed infants are assumed to have no direct exposure via food or water. The prediction for breast-fed infants in this table results
from the dose from both food and water to the mother providing breast milk to the infant. Breast-fed infant ‘‘water intake’’ is the breast milk ingestion rate obtained by fitting an age-dependent function to the breast-milk ingestion data (L/kg-day) from Arcus-Arth et al. (2005). Urinary clearance rates for the lactating woman equal to that of the average adult were used, consistent with data presented in Delange (2004).
e For the bottle-fed infant, normalized total water intake (direct and indirect, L/kg-day) was described as a smooth function of infant age fit to
the results from Kahn and Stralka (2008), and multiplied by BW(age). For the 7-day-old infant, the data used to fit the function included the 90th
percentile community water-consumers only intake (0.235 L/kg-day, N=40) for the <1 month old infant. For the 60-day-old infant, the 90th percentile community water-consumers only intake (0.228 L/kg-day, N=114) for the 1- to <3 months-old infant was used.
f For the 6- to 12-month and 1- to 2-year-old children, EPA set the water ingestion based on published exposure tables and selected the age at
which the model-predicted BW (from growth equations) matched the exposure-table mean. This approach resulted in model predictions for a 9.6month-old child (to represent 6- to 12-month-old children) and a 1.3-year old (to represent 1- to 2-year-old children).
g Due to data limitations, RAIU inhibition is calculated only for fetuses at GW 40.
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c. Modeling Uncertainties
EPA recognizes that there are
uncertainties associated with this
modeling, as there are for any modeling
effort. For example, this analysis does
not take into account within-group
variability in pharmacokinetics,
uncertainty in model parameters and
predictions, or population differences in
pharmacodynamics (PD) of receptor
binding and upregulation. Also, the
NRC identified fetuses of pregnant
women that are hypothyroid or iodine
deficient as the most sensitive
subpopulation. The model predictions
of RAIU inhibition in the various
subgroups are average inhibition for
typical, healthy individuals, not for
hypothyroid or iodine deficient
individuals. However, EPA did not rely
on this analysis for determining the
HRL. Rather, the HRL of 15 µg/L was
calculated directly from the RfD to
protect the most sensitive
subpopulation, the fetuses of pregnant
women, using high end exposure
assumptions (e.g., estimated 90th
percentile drinking water consumption
and estimated 90th percentile
perchlorate dietary (food) exposure).
The PBPK modeling was used to
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provide information on the potential
effects of exposure at the HRL for other
subgroups, such as infants and children.
In addition, the predicted inhibitions
are averages for the subgroup as a
whole, given the exposure assumptions
used in the model. Thus, some members
of a group would be expected to have
RAIU inhibition greater than indicated
in Table 8 for a particular perchlorate
concentration, while others would have
lesser inhibition. EPA was able to
partially address this variability by
using 90th percentile water
consumption rates and mean body
weights in the analysis to consider the
highly exposed portions of the various
subgroups. Most members of the
subgroups would be expected to have
exposures less than those indicated in
Table 8.
There is also some uncertainty
regarding the water intake rates,
particularly for infants. EPA described
water intake by infants as a smooth
function fit to the 90th percentile
community water-consumers intake-rate
data (intake per unit BW) of Kahn and
Stralka (2008), which is then multiplied
by the age-dependent BW to account for
the changes occurring over the first
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weeks of life. This resulted in an
estimated 90th percentile water intake
rate of 0.84 L/day for the 7-day bottle
fed infant and used by EPA in PBPK
model simulations. General information
on water and formula intake for 7-day
old infants is also available in
guidelines for healthy growth and
nutrition of the American Academy of
Pediatrics (AAP, 2008). The values
estimated using the guidelines from the
AAP (0.126 L/kg-day assuming 80% is
the percent water used in preparation of
formula) for 7-day-old infants are close
to the mean consumers-only intake rate
for the 1–30 day-old infants from Kahn
and Stralka (2008; 0.137 L/kg-day
N=40).
However, FDA has suggested an
alternate approach, using the caloric
intake requirement of a 7-day old infant
as the basis for calculating consumption
(FDA, 2008). This would likely yield a
lower estimate of intake than the 0.84 L/
day EPA has used in the model. If intake
is lower, this would yield a lower
prediction of RAIU inhibition, as can be
seen from the value predicted for the 7day old breast fed infant (1.4 percent).
EPA plans to ask specifically for
feedback on the consumption estimates
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for 7-day old bottle-fed infants when the
model revisions are peer reviewed.
There is also uncertainty regarding
the appropriate duration of exposure
(i.e., days, weeks, months) to compare to
the perchlorate RfD, which EPA defines
as ‘‘an estimate (with uncertainty
spanning perhaps an order of
magnitude) of a daily exposure to the
human population (including sensitive
subgroups) that is likely to be without
an appreciable risk of deleterious effects
during a lifetime.’’ Reference values,
like the RfD, are derived based on an
assumption of continuous exposure
throughout the duration specified, while
intake levels may rapidly change day to
day or during certain life stages. For
comparability with the RfD, continuous
perchlorate exposure was assumed in
EPA’s modeling analysis. Using
perchlorate levels predicted for a
continuous exposure (constant rate of
introduction to the stomach), rather
than incorporating changes in exposure
and other input parameters over time
(i.e., simulating the timing and quantity
of specific ingestion events during the
day), substantially reduced the effects of
parameter uncertainty in the modeling.
RAIU inhibition, on the other hand, is
evaluated as the change in thyroid
uptake of a pulse of iodide
(radiolabeled, from an IV injection) at a
time 24 hours after the pulse is
administered. Thus, it represents the
inhibition on a given day. This was true
in the Greer study on which the RfD is
based, and it is also true in the model.
For all lifestages except the developing
infant, the day-to-day variation in RAIU
inhibition at the levels under
consideration will have little or no
effect. However, the effects of short-term
inhibition in the infant (and fetus) may
be of greater consequence than in the
adult, although infants may also have
less short-term variability in their diet
and intake levels than adults. To
address this concern, we present the
results for the infant at both 7 days and
60 days after birth. The model predicts
a fairly smooth variation in effect
between these two ages.
d. Summary of Modeling Analysis
In deciding whether to regulate
perchlorate, EPA focused attention on
the most sensitive subpopulation, a
pregnant woman and her fetus. EPA
calculated an HRL of 15 µg/L for
pregnant women using RSC information
derived from an analysis of NHANES
and UCMR data. EPA also conducted
PBPK modeling to evaluate predicted
biological outcomes associated with
drinking water concentrations at the
health reference level for different
sensitive subpopulations. For pregnant
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women, EPA assumed a 90th percentile
water ingestion rate of 0.033 L/kg-day,
a food intake rate that represented the
midpoint of the range of average
perchlorate dietary exposures reported
in Murray et al. (2008), and used the
Clewell et al. (2007) PBPK model-fitted
body weight. EPA believes that the
model-fitted body weight provides a
more realistic weight for the pregnant
woman than EPA’s 70 kg default
assumption for adults. In addition,
rather than using the default assumption
of 2L/day water ingestion, EPA used a
90th percentile water ingestion rate
normalized for body weight and based
on data specifically for pregnant women
(USEPA 2004b). Using these
assumptions, the model predicted that
the pregnant woman’s dose of
perchlorate would not exceed the
reference dose if she consumed drinking
water with a concentration of 15 µg/L or
less, which is consistent with the
derivation of the HRL from the reference
dose, based on average body weight,
90th percentile water consumption, and
90th percentile food exposure for
pregnant women. The model further
predicted that the percent inhibition in
the fetus of a pregnant woman
consuming drinking water with 15 µg/
L perchlorate (in combination with a
normal diet) is 1.1 percent, below the
1.8 percent that the NRC determined to
be a no-effect level in healthy adults.
EPA evaluated other subpopulations to
estimate iodide uptake inhibition and
determined that 7-day old bottle-fed
infants were predicted to have a 2.2
percent inhibition level, after also
accounting for food exposure, and all
other subpopulations, including 60-day
old bottle-fed infants, 7 and 60 day old
breast-fed infants, and children, were
predicted to have levels of inhibition of
1.4 percent or less, after accounting for
food. All of these levels are comparable
to or below the 1.8 percent no effect
inhibition level from the Greer study.
Based on the health protective
approach for deriving the RfD (i.e., use
of a NOEL rather than a NOAEL as the
point of departure), the conservative
assumptions used in deriving the RSC
and corresponding HRL (use of 90th
percentile food exposure data
specifically from pregnant women), and
the PBPK modeling analysis of RAIU
inhibition in potentially sensitive
subpopulations, EPA believes drinking
water with perchlorate concentrations at
or below the HRL of 15 µg/L is
protective of all subpopulations. Based
upon the HRL and the analysis of
drinking water occurrence, EPA
concludes that perchlorate does not
occur at a frequency and level of health
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concern to warrant a national drinking
water regulation.
C. Is There a Meaningful Opportunity
for the Reduction of Health Risks From
Perchlorate for Persons Served by Public
Water Systems?
The Agency does not believe that a
national primary drinking water
regulation for perchlorate presents a
meaningful opportunity for health risk
reduction for persons served by public
water systems. EPA has found that
perchlorate occurs infrequently above
levels of health concern. Only 31 out of
3,865 systems (0.8 percent) detected
perchlorate in drinking water above the
HRL of 15 µg/L. EPA’s best estimate is
that 0.9 million people (with an upper
bound estimate of 2 million people) may
be consuming water containing
perchlorate at levels that could exceed
the HRL for perchlorate and the Agency
estimates that fewer than 30,000 of them
are pregnant women at any given time.
EPA’s RfD was derived by applying a
10 fold uncertainty factor to the dose
corresponding to a non-statistically
significant mean 1.8 percent decline in
RAIU in healthy adults following two
weeks of daily exposure to perchlorate
(Greer et al., 2002). Because iodide
uptake inhibition is not an adverse
effect but a precursor biochemical
change, this point of departure (7 ug/kg/
day) is a NOEL which provides for a
more conservative and health-protective
approach to perchlorate hazard
assessment. After taking perchlorate in
the diet into consideration, at the HRL
of 15 µg/L for perchlorate in drinking
water, the models predicted that the
percent RAIU inhibition in fetuses
would be 1.1 percent, while the
inhibition in all other subgroups except
the 7-day-old bottle fed infant would be
no greater than 1.4 percent. For the 7day-old bottle fed infant, the predicted
inhibition is 2.2 percent. All of these
values are comparable to or below the
percent inhibition at the NOEL in the
Greer study.
Based on these analyses, EPA has
determined that a national primary
drinking water regulation for
perchlorate would not present a
meaningful opportunity for health risk
reduction for persons served by public
water systems.
V. EPA’s Next Steps
EPA requests comment on this
preliminary determination that a
national primary drinking water
regulation for perchlorate would not
present a meaningful opportunity for
health risk reduction for persons served
by public water systems. EPA also
requests comment upon the scientific
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data and supporting analyses for this
determination. In past regulatory
determinations, EPA has qualitatively
but not quantitatively evaluated the
health effects of exposure at the HRL on
infants and children. Because the
evaluation of the potential impacts of
exposure at the HRL of 15 µg/L on
infants and children is a novel
approach, EPA specifically requests
comment on its use of the revised PBPK
model to evaluate these potential
impacts.
EPA will respond to the public
comments it receives on the preliminary
determination and will review the
comments from the peer review of its
model application. After considering
comments, EPA plans to issue a final
regulatory determination for perchlorate
by December 2008. EPA also plans to
publish a health advisory for
perchlorate at the time of the final
determination to provide information to
Federal, Regional, State, and local
public health officials regarding
potential health risks from perchloratecontaminated drinking water.
mstockstill on PROD1PC66 with NOTICES
VI. References
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Bright futures guidelines for health
supervision of infants, children, and
adolescents (2008) https://
brightfutures.aap.org/pdfs/
Guidelines_PDF/6–
Promoting_Healthy_Nutrition.pdf.
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M, Blount BC, Valentin-Blasini L, Fisher
N, Israeli A, and Leventhal A. (2007).
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Arcus-Arth, A., G. Krowech, and L. Zeise.
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Auso E., R. Lavado-Autric, E. Cuevas, F.E.
Del Rey, G, Morreale De Escobar, and P.
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Blount, B.C., L. Valentın-Blasini, D.L. Ashley.
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Dasgupta, P.K., A.B. Kirk, J.V. Dyke, and S.I.
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Gibbs et al., 2004. J.P. Gibbs, L. Narayanan
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water in Taltal, J. Occup. Environ. Med
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Greer, M.A., G. Goodman, R.C. Pleuss, and
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Health Perspect Vol. 110. pp. 927–937.
Haddow, J.E., G.E. Palomaki, et al. 1999.
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neuropsychological development of the
child. New England Journal of Medicine
341(8): 549–55.
Kahn, H., and K. Stralka. 2008. Estimated
daily average per capita water ingestion
by child and adult age categories based
on USDA’s 1994–96 and 1998 continuing
survey of food intakes by individuals.
Journal of Exposure Analysis and
Environmental Epidemiology (accepted
for publication).
Kirk, A.B., E.E. Smith, K. Tian, T.A.
Anderson, and P.K. Dasgupta. 2003.
Perchlorate in Milk. Environmental
Science and Technology. Vol. 37, No. 21.
pp. 4979–4981.
Kirk, A.B., P.K. Martinelango, K. Tian, A.
Dutta, E.E. Smith, and P.K. Dasgupta.
2005. Perchlorate and iodide in dairy
and breast milk. Environmental Science
and Technology. Vol. 39, No. 7. pp.
2011–2017.
Kirk, A.B., J.V. Dyke, C.F. Martin, and P.K.
Dasgupta. 2007. Temporal patterns in
perchlorate, thiocyanate and iodide
excretion in human milk. Environ Health
Perspect Online Vol. 115, No. 2. pp. 182–
186.
Kooistra, L., S. Crawford, A.L. van Baar, E.P.
Brouwers, and V.J. Pop. 2006. Neonatal
effects of maternal hypothyroxinemia
during early pregnancy. Pediatrics; 117;
161–167.
Krynitsky, A.J., R.A. Niemann, A.D.
Williams, M.L. Hopper. 2006.
Streamlined sample preparation
procedure for determination of
perchlorate anion in foods by ion
chromatography-tandem mass
spectrometry. Analytica Chimica Acta
Vol 567. pp. 94–99. (As cited in Murray
et al., 2007)
Mage, D.T., R.H. Allen, A. Kodali. 2007.
Creatinine corrections for estimating
children’s and adults’ pesticide intake
doses in equilibrium with urinary
pesticide and creatinine concentrations.
J. Expos Sci Enviro Epidem. 18, pp. 360–
368.
Massachusetts Department of Environmental
Protection (MA DEP). 2005. The
occurrence and sources of perchlorate in
Massachusetts. Draft Report. Available
on the Internet at: https://www.mass.gov/
dep/cleanup/sites/percsour.pdf. Updated
April 2006.
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Merrill, E.A., R.A. Clewell, P.J. Robinson,
A.M. Jarabek, T.R. Sterner, and J.W.
Fisher. 2005. PBPK model for radioactive
iodide and perchlorate kinetics and
perchlorate-induced inhibition of iodide
uptake in humans. Toxicological
Sciences 83: 25–43.
Morreale de Escobar, G., M.J. Obregon, and
F. Escobar del Rey. 2004. Is
neuropsychological development related
to material hypothyroidism or to
maternal hypothyroxinemia? The Journal
of Clinical Endocrinology & Metabolism
Vol. 85. No. 11.
Morreale de Escobar, G., M.J. Obregon, and
F. Escobar del Rey. 2004. Role of thyroid
hormone during early brain
development. European Journal of
Endocrinology 151: U25–U37.
Murray, C.W III, S.K. Egan, H. Kim, N. Beru,
P.M. Bolger. 2008. U.S. Food and Drug
Administration’s Total Diet Study:
Dietary Intake of Perchlorate and Iodine.
Journal of Exposure Science and
Environmental Epidemiology, advance
online publication, January 2, 2008.
National Research Council (NRC). 2005.
Health Implications of Perchlorate
Ingestion. National Academies Press,
Board on Environmental Studies and
Toxicology. January 2005. 276 p.
Pearce, E.N., A.M. Leung, B.C. Blount, H.R.
Bazrafshan, X. He, S. Pino, L. ValentinBlasini, L.E. Braverman. 2007. Breast
milk iodine and perchlorate
concentrations in lactating Boston-area
women. J Clin Endocrin Metab Vol. 92,
No. 5, pp. 1673–1677.
Pop, V.J., J.L. Kuijpens, A.L. van Baar, G.
Verkerk, M.M. van Son, J.J. de Vijlder, T.
Vulsma, W.M. Wiersinga. H.A. Drexhage,
and H.L. Vader. 1999. Low maternal free
thyroxine concentrations during early
pregnancy are associated with impaired
psychomotor development in infancy.
Clin Endocrinol (Oxf). Feb;50(2):149–55.
Pop, V.J., E.P. Brouwers, H.L. Vader, T.
Vulsma, A.L. van Baar, and J.J. de Vijlder
JJ. 2003. Maternal hypothyroxinaemia
during early pregnancy and subsequent
child development: A 3-year follow-up
study. Clin Endocrinol (Oxf).
Sep;59(3):282–8.
Rovet, J.F., 2002. Congenital hypothyroidism:
An analysis of persisting deficits and
associated factors. Child
Neuropsychology Vol. 8, No. 3. pp. 150–
162.
Sanchez, C., Blount, B., L Valentin-Blasini,
L., Krieger, R. Perchlorate, thiocyanate,
and nitrate in edible cole crops (Brassica
sp.) produced in the lower Colorado
River region. Bull Environ Contam
Toxicol. 2007 Oct 26.
Sanchez, C.A., R.I Krieger, N. Khandaker,
R.C. Moore, K.C. Holts, and L.L. Neidel.
2005a. Accumulation and perchlorate
exposure potential of lettuce produced in
the lower Colorado River region. Journal
of Agricultural and Food Chemistry Vol.
53. pp. 5479–5486.
Sanchez C.A., K.S. Crump, R.I. Krieger, N.R.
Khandaker, and J.P. Gibbs. 2005b.
Perchlorate and nitrate in leafy
vegetables of North America.
Environmental Science and Technology
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Sharlin, D.S., D. Tighe, et al. 2008. The
balance between oligodendrocyte and
astrocyte production in major white
matter tracts is linearly related to serum
total thyroxine. Endocrinology 149(5):
2527–36.
Steinmaus, C., M.D. Miller, R. Howd. 2007.
Impact of smoking and thiocyanate on
perchlorate and thyroid hormone
associations in the 2001–2002 National
Health and Nutrition Examination
Survey. Environ Health Perspect
115(9):1333–8.
´
´
Tellez, R.T., P.M. Chacon, C.R. Abraca, B.C.
Blount, C.B. Van Landingham, K.S.
Crump, and J.P. Gibbs. 2005. Chronic
environmental exposure to perchlorate
through drinking water and thyroid
function during pregnancy and the
neonatal period. Thyroid Vol. 15, No. 9.
pp. 963–975.
U.S. Census Bureau, 2002. U.S. Summary:
2000. U.S. Department of Commerce,
Economics and Statistics
Administration, U.S. Census Bureau.
C2KPROF/00–US. July 2002.
USEPA. 1997a. Announcement of the Draft
Drinking Water Contaminant Candidate
List; Notice. Federal Register. Vol. 62,
No. 193. p. 52193, October 6, 1997.
USEPA. 1998a. Announcement of the Draft
Drinking Water Contaminant Candidate
List; Notice. Federal Register. Vol. 63,
No. 40. p. 10273, March 2, 1998.
USEPA. 1999b. Revisions to the Unregulated
Contaminant Monitoring Regulation for
Public Water Systems. Federal Register.
Vol. 64, No. 180. p. 50556, September 17,
1999.
USEPA. 2000b. Unregulated Contaminant
Monitoring Regulation for Public Water
Systems: Analytical Methods for
Perchlorate and Acetochlor;
Announcement of Laboratory Approval
and Performance Testing (PT) Program
for the Analysis of Perchlorate; Final
Rule and Proposed Rule. Federal
Register. Vol. 65, No. 42. p. 11372,
March 2, 2000.
USEPA. 2001b. Unregulated Contaminant
Monitoring Regulation for Public Water
Systems; Analytical Methods for List 2
Contaminants; Clarifications to the
Unregulated Contaminant Monitoring
Regulation. Federal Register. Vol. 66,
No. 8. p. 2273, January 11, 2001.
USEPA. 2002a. Announcement of
Preliminary Regulatory Determinations
for Priority Contaminants on the
Drinking Water Contaminant Candidate
List. Federal Register. Vol. 67, No. 106.
p. 38222, June 3, 2002.
USEPA. 2002b. Perchlorate Environmental
Contamination: Toxicological Review
and Risk Characterization. EPA/635/R–
02/003. National Center for
Environmental Assessment, Office of
Research and Development, U.S. EPA.
USEPA. 2002c. A review of the reference
dose and reference concentration
processes. Risk Assessment Forum,
Washington, DC; EPA/630/P–02/0002F.
Available from: https://www.epa.gov/iris/
backgr-d.htm.
USEPA. 2003a. Announcement of Regulatory
PO 00000
Frm 00055
Fmt 4703
Sfmt 4703
Determinations for Priority
Contaminants on the Drinking Water
Contaminant Candidate List. Federal
Register. Vol. 68, No. 138. p. 42897, July
18, 2003.
USEPA. 2004a. Drinking Water Contaminant
Candidate List 2; Notice. Federal
Register. Vol. 69, No. 64. p. 17406, April
2, 2004.
USEPA. 2004b. Estimated Per Capita Water
Ingestion and Body Weight in the United
States—An Update Based on Data
Collected by the United States
Department of Agriculture’s 1994–1996
and 1998 Continuing Survey of Food
Intakes by Individuals. EPA–822–R–00–
001. Office of Science and Technology,
Office of Water, U.S. EPA.
USEPA. 2005a. Notice—Drinking Water
Contaminant Candidate List 2; Final
Notice. Federal Register. Vol. 70, No. 36.
p. 9071, February 24, 2005.
USEPA. 2005b. ‘‘Integrated Risk Information
System (IRIS), Perchlorate and
Perchlorate Salts.’’ February 2005.
Available on the Internet at: https://
www.epa.gov/iris/subst/1007.htm.
Accessed February 2, 2005.
USEPA 2006. Assessment Guidance for
Perchlorate. Memorandum from Susan
Bodine, Assistant Administrator of the
Office of Solid Waste and Emergency
Response, to EPA Regional
Administrators. Available on the Internet
at: https://www.epa.gov/fedfac/pdf/
perchlorate_guidance.pdf. Accessed
August 20, 2008
USEPA. 2007. Drinking Water: Regulatory
Determinations Regarding Contaminants
on the Second Drinking Water
Contaminant Candidate List—
Preliminary Determinations. Federal
Register. 72 FR 24016. May 1, 2007.
USEPA, 2008a Evaluation of Perchlorate
Exposure from Food and Drinking Water:
Results of NHANES Biomonitoring Data
and UCMR 1 Occurrence Data Merge.
USEPA. 2008b. Inhibition of the SodiumIodide Symporter by Perchlorate:
Evaluation of Lifestage Sensitivity Using
Physiologically-Based Pharmacokinetic
Modeling. {NOTE: Final title/reference
info for the document will be provided
before publication.}
USEPA. 2008c. Drinking Water: Regulatory
Determinations Regarding Contaminants
on the Second Drinking Water
Contaminant Candidate List—Final
Determinations. Federal Register. 73 FR
44251. July 30, 2008.
Ventura SJ, Abma JC, Mosher WD, Henshaw
S. Estimated pregnancy rates for the
United States, 1990–2000: an update.
National vital statistics reports; vol 52 no
23. Hyattsville, Maryland: National
Center for Health Statistics. 2004.
Zoeller, R.T., and J. Rovet. 2004. Timing of
thyroid hormone action in the
developing brain: clinical observations
and experimental findings. J
Neuroendocrinology 16: 809–18.
Dated: October 3, 2008.
Stephen L. Johnson,
Administrator.
[FR Doc. E8–24042 Filed 10–9–08; 8:45 am]
BILLING CODE 6560–50–P
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[Federal Register Volume 73, Number 198 (Friday, October 10, 2008)]
[Notices]
[Pages 60262-60282]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: E8-24042]
=======================================================================
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ENVIRONMENTAL PROTECTION AGENCY
[EPA-HQ-OW-2008-0068; FRL-8727-6]
RIN 2040-ZA02
Drinking Water: Preliminary Regulatory Determination on
Perchlorate
AGENCY: Environmental Protection Agency (EPA).
ACTION: Notice.
-----------------------------------------------------------------------
SUMMARY: This action presents EPA's preliminary regulatory
determination for perchlorate in accordance with the Safe Drinking
Water Act (SDWA). The Agency has determined that a national primary
drinking water regulation (NPDWR) for perchlorate would not present ``a
meaningful opportunity for health risk reduction for persons served by
public water systems.'' The SDWA requires EPA to make determinations
every five years of whether to regulate at least five contaminants on
the Contaminant Candidate List (CCL). EPA included perchlorate on the
first and second CCLs that were published in the Federal Register on
March 2, 1998 and February 24, 2005. Most recently, EPA presented final
regulatory determinations regarding 11 contaminants on the second CCL
in a notice published in the Federal Register on July 30, 2008. In
today's action, EPA presents supporting rationale and requests public
comment on its
[[Page 60263]]
preliminary regulatory determination for perchlorate. EPA will make a
final regulatory determination for perchlorate after considering
comments and information provided in the 30-day comment period
following this notice. EPA plans to publish a health advisory for
perchlorate at the time the Agency publishes its final regulatory
determination to provide State and local public health officials with
technical information that they may use in addressing local
contamination.
DATES: Comments must be received on or before November 10, 2008.
ADDRESSES: Submit your comments, identified by Docket ID No. EPA-HQ-OW-
2008-0068, by one of the following methods:
www.regulations.gov: Follow the on-line instructions for
submitting comments.
Mail: Water Docket, Environmental Protection Agency,
Mailcode: 2822T, 1200 Pennsylvania Ave., NW., Washington, DC 20460.
Hand Delivery: Water Docket, EPA Docket Center (EPA/DC)
EPA West, Room 3334, 1301 Constitution Ave., NW., Washington, DC. Such
deliveries are only accepted during the Docket's normal hours of
operation, and special arrangements should be made for deliveries of
boxed information.
Instructions: Direct your comments to Docket ID No. EPA-HQ-OW-2008-
0068. EPA's policy is that all comments received will be included in
the public docket without change and may be made available online at
www.regulations.gov, including any personal information provided,
unless the comment includes information claimed to be Confidential
Business Information (CBI) or other information whose disclosure is
restricted by statute. Do not submit information that you consider to
be CBI or otherwise protected through www.regulations.gov or e-mail.
The www.regulations.gov Web site is an ``anonymous access'' system,
which means EPA will not know your identity or contact information
unless you provide it in the body of your comment. If you send an e-
mail comment directly to EPA without going through www.regulations.gov
your e-mail address will be automatically captured and included as part
of the comment that is placed in the public docket and made available
on the Internet. If you submit an electronic comment, EPA recommends
that you include your name and other contact information in the body of
your comment and with any disk or CD-ROM you submit. If EPA cannot read
your comment due to technical difficulties and cannot contact you for
clarification, EPA may not be able to consider your comment. Electronic
files should avoid the use of special characters, any form of
encryption, and be free of any defects or viruses. For additional
instructions on submitting comments, go to Unit I.B of the
SUPPLEMENTARY INFORMATION section of this document.
Docket: All documents in the docket are listed in the
www.regulations.gov index. Although listed in the index, some
information is not publicly available, e.g., CBI or other information
whose disclosure is restricted by statute. Certain other material, such
as copyrighted material, will be publicly available only in hard copy.
Publicly available docket materials are available either electronically
in www.regulations.gov or in hard copy at the Water Docket, EPA/DC, EPA
West, Room 3334, 1301 Constitution Ave., NW., Washington, DC. The
Public Reading Room is open from 8:30 a.m. to 4:30 p.m., Monday through
Friday, excluding legal holidays. The telephone number for the Public
Reading Room is (202) 566-1744, and the telephone number for the EPA
Docket Center is (202) 566-2426.
FOR FURTHER INFORMATION CONTACT: Eric Burneson, Office of Ground Water
and Drinking Water, Standards and Risk Management Division, at (202)
564-5250 or e-mail burneson.eric@epa.gov. For general information
contact the EPA Safe Drinking Water Hotline at (800) 426-4791 or e-
mail: hotline-sdwa@epa.gov.
Abbreviations and Acronyms
a. i.--active ingredient
<--less than
<=--less than or equal to
>--greater than
>=--greater than or equal to
[mu]--microgram, one-millionth of a gram
[mu]g/g--micrograms per gram
[mu]g/kg--micrograms per kilogram
[mu]g/L--micrograms per liter
ATSDR--Agency for Toxic Substances and Disease Registry
AWWARF--American Water Works Association Research Foundation
BMD--bench mark dose
BMDL--bench mark dose level
BW--body weight for an adult, assumed to be 70 kilograms (kg)
CASRN--Chemical Abstract Services Registry Number
CBI--confidential business information
ChE--cholinesterase
CCL--Contaminant Candidate List
CCL 1--EPA's First Contaminant Candidate List
CCL 2--EPA's Second Contaminant Candidate List
CDC--Centers for Disease Control and Prevention
CDPH---California Department of Public Health
CFR--Code of Federal Regulations
CMR--Chemical Monitoring Reform
CWS--community water system
DW--dry weight
DWEL--drinking water equivalent level
DWI--drinking water intake
EPA--United States Environmental Protection Agency
EPCRA--Emergency Planning and Community Right-to-Know Act
FDA--United States Food and Drug Administration
FQPA--Food Quality Protection Act
FR--Federal Register
FW--fresh weight
g--gram
g/day--grams per day
HRL--health reference level
IOC--inorganic compound
IRIS--Integrated Risk Information System
kg--kilogram
L--liter
LD50 --an estimate of a single dose that is expected to
cause the death of 50 percent of the exposed animals; it is derived
from experimental data.
LOAEL--lowest-observed-adverse-effect level
MA DEP--Massachusetts Department of Environmental Protection
MCL--maximum contaminant level
MCLG--maximum contaminant level goal
mg--milligram, one-thousandth of a gram
mg/kg--milligrams per kilogram body weight
mg/kg/day--milligrams per kilogram body weight per day
mg/L--milligrams per liter
mg/m\3\--milligrams per cubic meter
MRL--minimum or method reporting limit (depending on the study or
survey cited)
N--number of samples
NAS--National Academy of Sciences
NCEH--National Center for Environmental Health (CDC)
NCFAP--National Center for Food and Agricultural Policy
NCI--National Cancer Institute
NCWS--non-community water system
ND--not detected (or non-detect)
NDWAC--National Drinking Water Advisory Council
NHANES--National Health and Nutrition Examination Survey (CDC)
NIS--sodium iodide symporter
NOEL--no-observed-effect-level
NPDWR--national primary drinking water regulation
NPS--National Pesticide Survey
NQ--not quantifiable (or non-quantifiable)
NRC--National Research Council
NTP--National Toxicology Program
OA--oxanilic acid
OW--Office of Water
OPP--Office of Pesticide Programs
PBPK--physiologically based pharmacokinetic
PCR--polymerase chain reaction
PGWDB--pesticides in ground water data base
PWS--public water system
RAIU--radioactive iodide uptake
RED--Reregistration Eligibility Decision
RfC--reference concentration
RfD--reference dose
RSC--relative source contribution
SAB--Science Advisory Board
SDWA--Safe Drinking Water Act
[[Page 60264]]
SOC--synthetic organic compound
SVOC--semi-volatile organic compound
T3--triiodothyronine
T4--thyroxine
TDS--Total Diet Study (FDA)
TRI--Toxics Release Inventory
TSH--thyroid stimulating hormone
TT--treatment technique
UCMR 1--First Unregulated Contaminant Monitoring Regulation
UF--uncertainty factor
US--United States of America
USDA--United States Department of Agriculture
USGS--United States Geological Survey
UST--underground storage tanks
VOC--volatile organic compound
WHO--World Health Organization
Supplementary Information:
I. General Information
A. Does This Action Impose Any Requirements on My Public Water
System?
B. What Should I Consider as I Prepare My Comments for EPA?
II. Purpose, Background and Summary of This Action
A. What is the Purpose of This Action?
B. Background on the CCL and Regulatory Determinations
C. What Comments and Information Did EPA Receive Regarding
Perchlorate in Response to the May 1, FR Notice?
D. What is EPA's Preliminary Determination on Perchlorate and
What Happens Next?
III. What Scientific Data and Analyses Did EPA Evaluate in Making a
Preliminary Regulatory Determination for Perchlorate?
A. Evaluation of Adverse Health Effects
B. Evaluation of Perchlorate Occurrence in Drinking Water
C. Evaluation of Perchlorate Exposure from Sources Other Than
Drinking Water
IV. Preliminary Regulatory Determination on Perchlorate
A. May Perchlorate Have an Adverse Effect on the Health of
Persons?
B. Is Perchlorate Known to Occur or is There a Substantial
Likelihood That Perchlorate Occurs at a Frequency and Level of
Public Health Concern in Public Water Systems?
C. Is There a Meaningful Opportunity for the Reduction of Health
Risks From Perchlorate for Persons Served by Public Water Systems?
V. EPA's Next Steps
VI. References
SUPPLEMENTARY INFORMATION:
I. General Information
A. Does This Action Impose Any Requirements on My Public Water System?
Today's action seeks public comment on EPA's preliminary
determination that a national primary drinking water regulation is not
necessary for perchlorate, and thus imposes no requirements on public
water systems. After review and consideration of public comment, EPA
will issue a final regulatory determination.
B. What Should I Consider as I Prepare My Comments for EPA?
You may find the following suggestions helpful for preparing your
comments:
1. Explain your views as clearly as possible.
2. Describe any assumptions that you used.
3. Provide any technical information and/or data you used that
support your views.
4. If you estimate potential burden or costs, explain how you
arrived at your estimate.
5. Provide specific examples to illustrate your concerns.
6. Offer alternatives.
7. Make sure to submit your comments by the comment period
deadline.
8. To ensure proper receipt by EPA, identify the appropriate docket
identification number in the subject line on the first page of your
response. It would also be helpful if you provided the name, date, and
Federal Register citation related to your comments.
II. Purpose, Background and Summary of This Action
This section briefly summarizes the purpose of this action, the
statutory requirements, previous activities related to the Contaminant
Candidate List and regulatory determinations, and the approach used and
outcome of this preliminary regulatory determination.
A. What is the Purpose of This Action?
The purpose of today's action is to present EPA's preliminary
regulatory determination on perchlorate, the process and the rationale
used to make this determination, a brief summary of the supporting
documentation, and a request for public comment.
B. Background on the CCL and Regulatory Determinations
1. Statutory Requirements for CCL and Regulatory Determinations.
The specific statutory requirements for the Contaminant Candidate List
(CCL) and regulatory determinations can be found in section 1412(b)(1)
of the Safe Drinking Water Act (SDWA). The CCL is a list of
contaminants that are not subject to any proposed or promulgated
national primary drinking water regulations (NPDWRs), are known or
anticipated to occur in public water systems (PWSs), and may require
regulation under the SDWA. The 1996 SDWA Amendments also direct EPA to
determine, every five years, whether to regulate at least five
contaminants from the CCL. The SDWA requires EPA to publish a Maximum
Contaminant Level Goal\1\ (MCLG) and promulgate an NPDWR \2\ for a
contaminant if the Administrator determines that:
---------------------------------------------------------------------------
\1\ The MCLG is the ``maximum level of a contaminant in drinking
water at which no known off anticipated adverse effect on the health
of persons would occur, and which allows an adequate margin of
safety. Maximum contaminant level goals are non-enforceable heath
goals'' (CFR 141.2).
\2\ An NPDWR is a legally enforceable standard that applies to
public water systems. An NPDWR sets a legal limit (called a maximum
contaminant level or MCL) or specifies a certain treatment technique
(TT) for public water systems for a specific contaminant or group of
contaminants.
---------------------------------------------------------------------------
(a) The contaminant may have an adverse effect on the health of
persons;
(b) The contaminant is known to occur or there is a substantial
likelihood that the contaminant will occur in public water systems with
a frequency and at levels of public health concern; and
(c) In the sole judgment of the Administrator, regulation of such
contaminant presents a meaningful opportunity for health risk reduction
for persons served by public water systems.
While carrying out the process to make a determination, the law
requires EPA to take into consideration the effect contaminants have on
subgroups that comprise a meaningful portion of the general population
(such as infants, children, pregnant women, the elderly, individuals
with a history of serious illness or other subpopulations) that are
identifiable as being at greater risk of adverse health effects than
the general population.
If EPA makes a final determination that a national primary drinking
water regulation is needed, the Agency has 24 months to publish a
proposed MCLG and NPDWR. After the proposal, the Agency has 18 months
to publish and promulgate a final MCLG and NPDWR (SDWA section 1412(b)
(1) (E)).\3\
---------------------------------------------------------------------------
\3\ The statute authorizes a nine month extension of this
promulgation date.
---------------------------------------------------------------------------
EPA published preliminary regulatory determinations for nine CCL 1
contaminants on June 3, 2002, (67 FR 38222 (USEPA, 2002a)), and final
regulatory determinations on July 18, 2003 (68 FR 42898 (USEPA,
2003a)). EPA published preliminary regulatory determinations for eleven
CCL 2 contaminants on May 1, 2007, (72 FR 24016 (USEPA, 2007)) and
finalized these regulatory determinations on July 30, 2008 (73 FR 44251
(USEPA, 2008c)). As part of its May 1, 2007, FR notice of preliminary
regulatory determinations for 11 contaminants, EPA also presented
information on several contaminants
[[Page 60265]]
from the second CCL for which the Agency was not yet making a
preliminary regulatory determination, including perchlorate.
Specifically, EPA indicated that additional information was needed to
more fully characterize perchlorate exposure and determine whether it
is appropriate to regulate perchlorate in drinking water (i.e., whether
setting a national primary drinking water standard would provide a
meaningful opportunity to reduce risk for people served by public water
systems). The May 1, 2007, FR notice describes how the Agency was
considering additional information including FDA food data and CDC
human exposure data to determine whether to regulate perchlorate. (See
the May 1, 2007, FR notice at 24038 for a discussion regarding the
information that EPA had on perchlorate as well as the additional
information that was needed before the Agency could make a preliminary
regulatory determination for perchlorate).
C. What Comments and Information Did EPA Receive Regarding Perchlorate
in Response to the May 1, FR Notice?
Eight commenters on the Regulatory Determinations 2 Preliminary FR
notice addressed perchlorate. EPA received comments that supported and
comments that opposed regulating perchlorate. One of the commenters who
encouraged regulation stated that perchlorate is known to occur in
public water supplies in a number of States and ``while occurrence data
does [sic] not suggest that perchlorate occurs at levels of public
health concern in the vast majority of public drinking water supplies,
and the population at risk appears to be small, that group does include
a sensitive subpopulation (pregnant women and developing fetuses) of
significant concern.'' Another commenter wrote ``the contamination of
water supplies by perchlorate is on-going'' and ``perchlorate that has
entered the soil and contaminated aquifers will likely lead to
additional impacted sites.'' A commenter wrote that ``a number of
States are moving to regulate perchlorate and a patchwork of different
regulations will confuse the public and the regulated water
community.''
The commenters opposed to regulating perchlorate also cited the
available information to support their recommendation. One commenter
wrote that ``the extensive scientific record indicates that
establishing a drinking water standard for perchlorate would not yield
a meaningful opportunity to reduce risk to human health.'' Another
commenter stated that perchlorate ``does not appear, at this stage, to
be a nationwide problem.''
Several commenters also addressed EPA's assessment that additional
investigation is necessary to ascertain total human exposure before a
preliminary regulatory determination could be made. Commenters wrote
that the principal study on which EPA's Reference Dose (RfD) is based
already accounts for background sources of perchlorate and therefore
EPA should not adjust the RfD to account for other non-drinking-water
exposures.
EPA has considered the perchlorate comments submitted in connection
with the May 1, 2007, notice in the development of today's action. EPA
will consider these and any further comments submitted in response to
this notice before preparing a final regulatory determination for
perchlorate.
D. What is EPA's Preliminary Regulatory Determination on Perchlorate
and What Happens Next?
EPA is making a preliminary regulatory determination in this notice
that a national primary drinking water rule is not necessary for
perchlorate because a national primary drinking water regulation would
not provide a meaningful opportunity to reduce health risk. EPA will
make a final regulatory determination for perchlorate after considering
comments and information provided in the 30-day comment period
following this notice. One of the analyses that EPA considered for this
preliminary determination is a physiologically-based pharmacokinetic
(PBPK) model that predicts radioactive iodide uptake (RAIU) inhibition
in the thyroid for various sub-populations and drinking water
concentrations. The model, which is described in section IV.B.5, has
already been published in peer-reviewed articles (Clewell et al., 2007
and Merrill et al., 2005), but EPA subjected the model to intensive
internal review prior to considering it for this regulatory
determination and made several adjustments as a result. EPA believes it
is appropriate to have these adjustments peer-reviewed. While the
application of the model to non-adult subpopulations was part of the
previously peer-reviewed articles, EPA will also ask the peer reviewers
to comment on this issue to help EPA ensure that the model is
appropriate for use in assessing health outcomes associated with
perchlorate exposure for these populations. EPA intends to complete
this review before publishing its final determination and will consider
any comments from the reviewers. Additionally, EPA plans to publish a
health advisory for perchlorate at the time the Agency publishes its
final regulatory determination to provide State and local public health
officials with information that they may use in addressing local
contamination.
Additionally, at the same time that EPA publishes a health advisory
for perchlorate, the Agency will withdraw its existing January 2006
guidance regarding perchlorate and potential cleanup levels under the
National Oil and Hazardous Substances Contingency Plan (National
Contingency Plan, NCP) and will replace it with revised guidance. (See
memorandum dated January 26, 2006, from Susan Parker Bodine to EPA
Regional Administrators (US EPA, 2006).) Specifically, the January 2006
guidance, in part, addresses the use of preliminary remediation goals
(PRGs) for perchlorate contaminated water at National Priority List
(NPL) sites. The January 2006 guidance recommends a PRG of 24.5 ppb,
assuming that all exposure comes from ground water at the site. The
recommended PRG is based on the assumption that all exposure comes from
ground water, because at the time the January 2006 guidance was issued
there was insufficient information available on the levels of
perchlorate in food to calculate a national relative source
contribution (RSC). In the absence of such national data on the levels
of perchlorate found in foods, the approach outlined in the January
2006 guidance was considered by the Agency to be the most
scientifically defensible. In addition, because the recommended PRG
generally is the starting point for determining appropriate site-
specific cleanup levels, the guidance also indicates that the cleanup
level at any site should be evaluated on a case-by-case basis, and
modified accordingly, based on site-specific information, including
exposure to non-water sources, such as foods. EPA now has sufficient
data to calculate a national RSC and has used this RSC to calculate a
health reference level (HRL) for drinking water as part of the basis
for today's preliminary determination. When EPA issues the final
regulatory determination for perchlorate, the final HRL will be the
basis for the health advisory value in the health advisory document the
Agency expects to issue at that time. Thereafter, it may be appropriate
to use the health advisory value as a ``to be considered'' (TBC) value
in developing potential cleanup levels for perchlorate at Superfund
sites. In addition, some State regulations may be applicable or
relevant and appropriate requirements (ARARs)
[[Page 60266]]
when establishing cleanup levels for perchlorate at Superfund sites.
III. What Scientific Data and Analyses Did EPA Evaluate in Making a
Preliminary Regulatory Determination for Perchlorate?
This section summarizes the health effects, occurrence, and
population exposure evaluation information EPA used to support the
preliminary regulatory determination for perchlorate. EPA's conclusions
with respect to these data are discussed in Section IV.
A. Evaluation of Precursor and Adverse Health Effects
Section 1412(b)(1)(A)(i) of the SDWA requires EPA to determine
whether a candidate contaminant may have an adverse effect on public
health. EPA described the overall process the Agency used to evaluate
health effects information in the May 1, 2007, Federal Register Notice
(72 FR 24016 (USEPA, 2007)). This section presents specific information
about the potential for precursor and adverse health effects from
perchlorate, including a discussion of an extensive report completed by
the National Academy of Sciences (NAS) on the issue and other research
published after that report.
1. NAS Review of Perchlorate Health Implications and EPA's Reference
Dose
In 2003, the National Research Council (NRC) of the NAS was asked
to assess the current state of the science regarding potential adverse
effects of disruption of thyroid function by perchlorate in humans and
laboratory animals at various stages of life and, based on this review,
to determine whether EPA's findings in its 2002 draft risk assessment
were consistent with the current scientific evidence.
In January 2005, the NRC published ``Health Implications of
Perchlorate Ingestion,'' a review of the state of the science regarding
potential adverse health effects of perchlorate exposure and mode-of-
action for perchlorate toxicity (NRC, 2005).
Perchlorate can interfere with the normal functioning of the
thyroid gland by competitively inhibiting the transport of iodide into
the thyroid. Iodide is an important component of two thyroid hormones,
T4 and T3, and the transfer of iodide from the blood into the thyroid
is an essential step in the synthesis of these two hormones. Iodide
transport into the thyroid is mediated by a protein molecule known as
the sodium (Na+)-iodide (I-) symporter (NIS). NIS
molecules bind iodide with very high affinity, but they also bind other
ions that have a similar shape and electric charge, such as
perchlorate. The binding of these other ions to the NIS inhibits iodide
transport into the thyroid, which can result in intrathyroidal iodide
deficiency and consequently decreased synthesis of T4 and T3. There is
compensation for low-levels of iodide deficiency, however, such that
the body maintains blood serum concentrations of thyroid hormones
within narrow limits through feedback control mechanisms. The
compensation for decreased thyroid hormone is accomplished by increased
secretion of the thyroid stimulating hormone (TSH) from the pituitary
gland triggered by the reduced hormone levels, which has among its
effects the increased production of T4 and T3 (USEPA, 2005b). The
thyroid's ability to compensate in this way is limited, though, such
that sufficiently high levels of perchlorate exposure result in a
reduction of T4 and T3 blood levels (after thyroid iodine stores are
depleted). Sustained changes in thyroid hormone and TSH secretion can
result in thyroid hypertrophy and hyperplasia (i.e., abnormal growth or
enlargement of the thyroid) (USEPA, 2005b).
Children born with congenital hypothyroidism may suffer from mild
cognitive deficits despite hormone remediation (Rovet, 2002; Zoeller
and Rovet, 2004), and subclinical hypothyroidism and reductions in T4
(i.e., hypothyroxinemia) in pregnant women have been associated with
neurodevelopmental delays and IQ deficits in their children (Pop et
al., 1999, 2003; Haddow et al., 1999; Kooistra et al., 2006; Morreale
de Escobar, 2000, 2004). Animal studies support these observations, and
recent findings indicate that neurodevelopmental deficits are evident
under conditions of hypothyroxinemia and occur in the absence of growth
retardation (Auso et al., 2004; Gilbert and Sui, 2008; Sharlin et al.,
2008; Goldey et al., 1995).
Results from studies of the effects of perchlorate exposure on
hormone levels have been mixed. One recent study did not identify any
effects of perchlorate on blood serum hormones (Amitai et al., 2007),
while another study (Blount et al., 2006b) did identify such effects.
The results of the Blount study are discussed further in Section
III.A.2.
The data from epidemiological studies of the general population
provide some information on possible effects of perchlorate exposure.
Based upon analysis of the data available at the time NRC (2005)
acknowledged that ecologic epidemiological data alone are not
sufficient to demonstrate whether or not an association is causal, and
that these studies can provide evidence bearing on possible
associations. Noting the limitations of specific studies, the NRC
(2005; chapter 3) committee concluded that the available
epidemiological evidence is not consistent with a causal association
between perchlorate and congenital hypothyroidism, changes in thyroid
function in normal birthweight, full-term newborns, or hypothyroidism
or other thyroid disorders in adults. The committee considered the
evidence to be inadequate to determine whether or not there is a causal
association between perchlorate exposure and adverse neurodevelopmental
outcomes in children. The committee noted that no studies have
investigated the relationship between perchlorate exposure and adverse
outcomes among especially vulnerable groups, such as the offspring of
mothers who had low dietary iodide intake, or low-birthweight or
preterm infants (US EPA, 2005b).
The NRC recommended data from the Greer et al. (2002) human
clinical study as the basis for deriving a reference dose (RfD) for
perchlorate (NRC, 2005). Greer et al., (2002) report the results of a
study that measured thyroid iodide uptake, hormone levels, and urinary
iodide excretion in a group of 37 healthy adults who were administered
perchlorate doses orally over a period of 14 days. Dose levels ranged
from 7 to 500 [mu]g/kg/day in the different experimental groups. The
investigators found that the 24-hour inhibition of iodide intake ranged
from 1.8 percent in the lowest dose group to 67.1 percent in the
highest dose group. However, no significant differences were seen in
measured blood serum thyroid hormone levels (T3, T4, total and free) in
any dose group. The statistical no observed effect level (NOEL) for the
perchlorate-induced inhibition of thyroid iodide uptake was determined
to be 7 [mu]g/kg/day, corresponding to an iodide uptake inhibition of
1.8 percent. Although the NRC committee concluded that hypothyroidism
is the first adverse effect in the continuum of effects of perchlorate
exposure, NRC recommended that ``the most health-protective and
scientifically valid approach'' was to base the perchlorate RfD on the
inhibition of iodide uptake by the thyroid (NRC, 2005). NRC concluded
that iodide uptake inhibition, although not adverse, is the most
appropriate precursor event in the continuum of possible effects of
perchlorate exposure and would precede any adverse health effects of
perchlorate exposure. The lowest dose
[[Page 60267]]
(7 [mu]g/kg/day) administered in the Greer et al., (2002) study was
considered a NOEL (rather than a no-observed-adverse-effect level or
NOAEL) because iodide uptake inhibition is not an adverse effect, but a
biochemical precursor. The NRC further determined that, ``the very
small decrease (1.8 percent) in thyroid radioiodide uptake in the
lowest dose group was well within the variation of repeated
measurements in normal subjects.'' A summary of the data considered and
the NRC deliberations can be found in the NRC report (2005).
The NRC recommended that EPA apply an intraspecies uncertainty
factor of 10 to the NOEL to account for differences in sensitivity
between the healthy adults in the Greer et al., (2002) study and the
most sensitive population, fetuses of pregnant women who might have
hypothyroidism or iodide deficiency. Because the fetus depends on an
adequate supply of maternal thyroid hormone for its central nervous
system development during the first trimester of pregnancy, iodide
uptake inhibition from low-level perchlorate exposure has been
identified as a concern in connection with increasing the risk of
neurodevelopmental impairment in fetuses of high-risk mothers (NRC,
2005). The NRC (2005) viewed the uncertainty factor of 10 as
conservative and protective of health given that the point of departure
(the NOEL) is based on a non-adverse effect (iodide uptake inhibition),
which precedes the adverse effect in a continuum of possible effects of
perchlorate exposure. The NRC panel concluded that no additional
uncertainty factor was needed for the use of a less-than-chronic study,
for deficiencies in the database, or for interspecies variability.
EPA's Integrated Risk Information System (IRIS) adopted the NRC's
recommendations resulting in an RfD of 0.7 [mu]g/kg/day, derived by
applying a ten-fold total uncertainty factor to the NOEL of 7 [mu]g/kg/
day (USEPA, 2005b).
The NRC emphasized that its recommendation ``differs from the
traditional approach to deriving the RfD.'' The NRC recommended ``using
a nonadverse effect rather than an adverse effect as the point of
departure for the perchlorate risk asessement. Using a nonadverse
effect that is upstream of the adverse effect is a more conservative,
health-protective approach to the perchlorate risk assessment.'' The
NRC also noted that the purpose of the 10-fold uncertainty factor is to
protect sensitive subpopulations in the face of uncertainty regarding
their relative sensitivity to perchlorate exposure. The NRC recognized
that additional information on these relative sensitivities could be
used to reduce this uncertainty factor in the future (NRC, 2005).\4\
---------------------------------------------------------------------------
\4\ ``There can be variability in responses among humans. The
intraspecies uncertainty factor accounts for that variability and is
intended to protect populations more sensitive than the population
tested. In the absence of data on the range of sensitivity among
humans, a default uncertainty factor of 10 is typically applied. The
factor could be set at 1 if data indicate that sensitive populations
do not vary substantially from those tested.'' (NRC 2005, p 173)
---------------------------------------------------------------------------
2. Biomonitoring Studies
After the NRC report was released, several papers were published
that investigated whether biomonitoring data associated with the
National Health and Nutrition Examination Survey (NHANES) could be used
to discern if there was a relationship between perchlorate levels in
the body and thyroid function. These papers also help to evaluate
populations that might be considered to be more sensitive to
perchlorate exposure.
Blount et al., (2006b) published a study examining the relationship
between urinary levels of perchlorate and blood serum levels of TSH and
total T4 in 2,299 men and women (ages 12 years and older) who
participated in CDC's 2001-2002 NHANES.\5\ Blount et al., (2006b)
evaluated perchlorate along with a number of covariates known or likely
to be associated with T4 or TSH levels to assess the relationship
between perchlorate and these hormones, and the influence of other
factors on this relationship. These covariates included gender, age,
race/ethnicity, body mass index, serum albumin, serum cotinine (a
marker of nicotine exposure), estimated total caloric intake, pregnancy
status, post-menopausal status, premenarche status, serum C-reactive
protein, hours fasting before sample collection, urinary thiocyanate,
urinary nitrate, and use of selected medications. The study found that
perchlorate was a statistically significant predictor of thyroid
hormones in women, but not in men.
---------------------------------------------------------------------------
\5\ While CDC researchers measured urinary perchlorate
concentration for 2,820 NHANES participants, TSH and total T4 serum
levels were only available for 2,299 of these participants.
---------------------------------------------------------------------------
After finding evidence of gender differences, the researchers
focused on further analyzing the NHANES data for the 1,111 women
participants. They divided these 1,111 women into two categories,
higher-iodide and lower-iodide urinary content, using a cut point of
100 [mu]g/L of urinary iodide based on the median level the World
Health Organization (WHO) considers indicative of sufficient iodide
intake \6\ for a population. Hypothyroid women were excluded from the
analysis. According to the study's authors, about 36 percent of women
living in the United States have urinary iodide levels less than 100
[mu]g/L (Caldwell et al., 2005). For women with urinary iodide levels
less than 100 [mu]g/L, the study found that urinary perchlorate is
associated with a decrease in (a negative predictor for) T4 levels and
an increase in (a positive predictor for) TSH levels. For women with
urinary iodide levels greater than or equal to 100 [mu]g/L, the
researchers found that perchlorate is a significant positive predictor
of TSH, but not a predictor of T4. The researchers state that
perchlorate could be a surrogate for another unrecognized determinant
of thyroid function.
---------------------------------------------------------------------------
\6\ WHO notes that the prevalence of goiter begins to increase
in populations with a median urinary iodide level below 100 [mu]g/L
(WHO, 1994).
---------------------------------------------------------------------------
Also, the study reports that while large doses of perchlorate are
known to decrease thyroid function, this is the first time an
association of decreased thyroid function has been observed at these
low levels of perchlorate exposure. The clinical significance of the
variations in T4/TSH levels, which were generally within normal limits,
has not been determined. The researchers noted several limitations of
the study (e.g., assumption that urinary perchlorate correlates with
perchlorate levels in the stroma and tissue and measurement of total T4
rather than free T4) and recommended that these findings be affirmed in
at least one more large study focusing on women with low urine iodide
levels. It is also not known whether the association between
perchlorate and thyroid hormone levels is causal or mediated by some
other correlate of both, although the relationship between urine
perchlorate and total TSH and T4 levels persisted after statistical
adjustments for some additional covariates known to predict thyroid
hormone levels (e.g., total kilocalorie intake, estrogen use, and serum
C-reactive protein levels). A planned follow-up study will include
additional measures of thyroid health and function (e.g., TPO-
antibodies, free T4). An additional paper by Blount et al., (2006c),
discussed further in Section III. C. 2. a., found that almost all
participants in the NHANES survey, including the participants in this
group, had urinary levels of perchlorate corresponding to estimated
dose levels that are below the RfD of 0.7 [mu]g/kg/day.
The Blount study suggested that perchlorate could be a surrogate
for another unrecognized determinant of
[[Page 60268]]
thyroid function. There are other chemicals, including nitrate and
thiocyanate, which can affect thyroid function. Steinmaus et al.,
(2007) further analyzed the data from NHANES 2001-2002 to assess the
impact of smoking, cotinine and thiocyanate on the relationship between
urinary perchlorate and blood serum T4 and TSH. Thiocyanate is a
metabolite of cyanide found in tobacco smoke and is naturally occurring
in some foods, including cabbage, broccoli, and cassava. Increased
serum thiocyanate levels are associated with increasing levels of
smoking. Thiocyanate affects the thyroid by the same mechanism as
perchlorate (competitive inhibition of iodide uptake). Steinmaus et al.
analyzed the data to determine whether smoking status (smoker or
nonsmoker), serum thiocyanate, or serum cotinine were better predictors
of T4 and TSH changes than perchlorate, or if the effects reflected the
combined effects of perchlorate and thiocyanate
Of female subjects 12 years of age and older in NHANES 2001-2002,
1,203 subjects had data on blood serum T4, serum TSH, urinary
perchlorate, iodine and creatinine. Subjects with extreme T4 or TSH (3
individuals) or with a reported history of thyroid disease (91) were
excluded from further analyses. Of the remaining women, 385 (35
percent) had urinary iodine levels below 100 [mu]g/l. Steinmaus, et al.
evaluated serum cotinine as an indicator of nicotine exposure, with
levels greater than 10 ng/ml classified as high and levels less than
0.015 ng/ml classified as low.
The authors found no association between either perchlorate or T4
and smoking, cotinine or thiocyanate in men or in women with urinary
iodine levels greater than 100 [mu]g/l. In addition, they found no
association between cotinine and T4 or TSH in women with iodine levels
lower than 100 [mu]g/l. However, in women with urinary iodine levels
lower than 100 [mu]g/l, an association between urinary perchlorate and
decreased serum T4 was stronger in smokers than in non-smokers, and
stronger in those with high urinary thiocyanate levels than in those
with low urinary thiocyanate levels. Although noting that their
findings need to be confirmed with further research, the authors
concluded that for these low-iodine women the results suggest that at
commonly-occurring perchlorate exposure levels, thiocyanate in tobacco
smoke and perchlorate interact in affecting thyroid function, and that
agents other than tobacco smoke might cause similar interactions
(Steimaus et al., 2007).
EPA also evaluated whether health information is available
regarding children, pregnant women and lactating mothers. The NRC
report discussed a number of epidemiological studies that looked at
thyroid hormone levels in infants. A more recent study by Amitai et
al., (2007) assessed T4 values in newborns in Israel whose mothers
resided in areas where drinking water contained perchlorate at ``very
high'' (340 [mu]g/L), ``high'' (12.94 [mu]g/L), or ``low'' (<3 [mu]g/L)
perchlorate concentrations. The mean ( standard deviation)
T4 value of the newborns in the very high, high, and low exposure
groups was 13.8 3.8, 13.9 3.4, and 14.0
3.5 [mu]g/dL, respectively, showing no significant
difference in T4 levels between the perchlorate exposure groups. This
is consistent with the conclusions drawn by the NRC review of other
epidemiological studies of newborns. The NRC (2005) also noted ``no
epidemiologic studies are available on the association between
perchlorate exposure and thyroid dysfunction among low-birthweight or
preterm newborns, offspring of mothers who had iodide deficiency during
gestation, or offspring of hypothyroid mothers.''
3. Physiologically-based Pharmacokinetic (PBPK) Models
PBPK models represent an important class of dosimetry models that
can be used to predict internal doses to target organs, as well as some
effects of those doses (e.g., radioactive iodide uptake inhibition in
the thyroid). To predict internal dose level, PBPK models use
physiological, biochemical, and physicochemical data to construct
mathematical representations of processes associated with the
absorption, distribution, metabolism, and elimination of compounds.
With the appropriate data, these models can be used to extrapolate
across and within species and for different exposure scenarios, and to
address various sources of uncertainty in health assessments, including
uncertainty regarding the relative sensitivities of various
subpopulations.
Clewell et al., (2007) developed multi-compartment PBPK models
describing the absorption and distribution of perchlorate for the
pregnant woman and fetus, the lactating woman and neonate, and the
young child. This work built upon Merrill et al.'s, (2005) model for
the average adult. Related research that served as the basis for the
more recent PBPK modeling efforts was discussed by the NRC in their
January 2005 report on perchlorate.
The models estimated the levels of perchlorate absorbed through the
gastrointestinal tract and its subsequent distribution within the body.
Clewell et al., (2007) provided estimates of internal dose and
resulting iodide uptake inhibition across all life stages, and for
pregnant and lactating women. The paper reported iodide uptake
inhibition levels for external doses of 1, 10, 100, and 1000 [mu]g/kg/
day. Results at the lower two doses indicated that the highest
perchlorate blood concentrations in response to an external dose would
occur in the fetus, followed by the lactating woman and the neonate.
Predicted blood levels for all three groups (i.e., fetus, lactating
women and neonates) were four- to five-fold higher than for non-
pregnant adults. Smaller relative differences were predicted at
external doses of 100 and 1000 [mu]g/kg/day. The authors attributed
this change to saturation of uptake mechanisms. The model predicted
minimal effect of perchlorate on iodide uptake inhibition in all groups
at the 1 [mu]g/kg/day external dose (about one and one half times the
RfD), estimating 1.1 percent inhibition or less across all groups.
Inhibition was predicted to be 10 percent or less in all groups at an
external dose of 10 [mu]g/kg/day (about 14 times the RfD).
The results of the model extrapolations were evaluated against data
developed in two epidemiologic studies performed in Chile, one studying
school children (Tellez et al., 2005) and another following women
through pregnancy and lactation (Gibbs et al., 2004). The model
predicted average blood serum concentrations of perchlorate in the
women from the Gibbs et al., (2004) study which were nearly identical
to their measured perchlorate blood serum concentrations. The blood
serum perchlorate concentrations predicted from the Tellez et al.,
(2005) study were within the range of the measured concentrations, and
the concentrations of perchlorate in breast milk predicted from the
model were within two standard deviations of the measured
concentrations. The authors concluded that the model predictions were
consistent with empirical results and that the predicted extent of
iodide inhibition in the most sensitive population (the fetus) is not
significant at EPA's RfD of 0.7 [mu]g/kg-day.
The NRC recommended that inhibition of iodide uptake by the
thyroid, which is a precursor event and not an adverse effect, should
be used as the basis for the perchlorate risk assessment (NRC, 2005).
Consistent with this recommendation, iodide uptake inhibition was used
by EPA as the critical effect in determining the reference dose (RfD)
for perchlorate. Therefore, PBPK models of perchlorate and radioiodide,
which were developed
[[Page 60269]]
to describe thyroidal radioactive iodide uptake (RAIU) inhibition by
perchlorate for the average adult (Merrill et al., 2005), pregnant
woman and fetus, lactating woman and neonate, and the young child
(Clewell et al., 2007) were evaluated by EPA based on their ability to
provide additional information surrounding this critical effect for
potentially sensitive subgroups and reduce some of the uncertainty
regarding the relative sensitivities of these subgroups.
EPA evaluated the PBPK model code provided by the model authors and
found minor errors in mathematical equations and computer code, as well
as some inconsistencies between model code files. EPA made several
changes to the code in order to harmonize the models and more
adequately reflect the biology (see USEPA, 2008b) for more information.
Model parameters describing urinary excretion of perchlorate and
iodide were determined to be particularly important in the prediction
of RAIU inhibition in all subgroups; therefore, a range of biologically
plausible values available in the peer-reviewed literature was
evaluated in depth using the PBPK models. Exposure rates were also
determined to be critical for the estimation of RAIU inhibition by the
models and were also further evaluated.
Overall, detailed examination of Clewell et al., (2007) and Merrill
et al., (2005) confirmed that the model structures were appropriate for
predicting percent inhibition of RAIU by perchlorate in most
lifestages. Unfortunately, the lack of biological information during
early fetal development limits the applicability of the PBPK modeling
of the fetus to a late gestational timeframe (i.e., near full term
pregnancy, ~GW 40), so EPA did not make use of model predictions
regarding early fetal RAIU inhibition. Although quantitative outputs of
EPA's revised PBPK models differ somewhat from the published values,
the EPA evaluation confirmed that, with modifications (as described in
USEPA, 2008b), the Clewell et al., (2007) and Merrill et al., (2005)
models provide an appropriate basis for calculating the lifestage
differences in the degree of thyroidal RAIU inhibition at a given level
of perchlorate exposure. The results of EPA's model application are
discussed in Section IV.B.5.
B. Evaluation of Perchlorate Occurrence in Drinking Water
The primary source of drinking water occurrence data used to
support this preliminary regulatory determination is the data provided
by public water systems in accordance with the first Unregulated
Contaminant Monitoring Regulation (UCMR 1). The Agency also evaluated
supplemental sources of occurrence information.
1. The Unregulated Contaminant Monitoring Regulation. In 1999, EPA
developed the UCMR program in coordination with the CCL and the
National Drinking Water Contaminant Occurrence Database (NCOD) to
provide national occurrence information on unregulated contaminants
(September 17, 1999, 64 FR 50556 (USEPA, 1999b); March 2, 2000, 65 FR
11372 (USEPA, 2000b); and January 11, 2001, 66 FR 2273 (USEPA, 2001b)).
EPA designed the UCMR 1 data collection with three parts (or
tiers). Occurrence data for perchlorate are from the first tier of UCMR
(also known as UCMR 1 List 1 Assessment Monitoring). EPA required all
large \7\ PWSs, plus a statistically representative national sample of
800 small \8\ PWSs, to conduct Assessment Monitoring.\9\ Approximately
one-third of the participating small systems were scheduled to monitor
for these contaminants during each calendar year from 2001 through
2003. Large systems could conduct one year of monitoring anytime during
the 2001-2003 UCMR 1 period. EPA specified a quarterly monitoring
schedule for 1,896 surface water systems and a twice-a-year, six-month
interval monitoring schedule for 1,969 ground water systems. The
objective of the UCMR 1 sampling approach for small systems was to
collect contaminant occurrence data from a statistically selected,
nationally representative sample of small systems. The small system
sample was stratified and population-weighted, and included some other
sampling adjustments, such as including at least 2 systems from each
State. With contaminant monitoring data from all large PWSs and a
statistical, nationally representative sample of small PWSs, the UCMR 1
List 1 Assessment Monitoring program provides a contaminant occurrence
data set suitable for national drinking water estimates.
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\7\ Systems serving more than 10,000 people.
\8\ Systems serving 10,000 people or fewer.
\9\ Large and small systems that purchase 100 percent of their
water supply were not required to participate in the UCMR 1
Assessment Monitoring or the UCMR 1 Screening Survey.
---------------------------------------------------------------------------
EPA collected and analyzed drinking water occurrence data for
perchlorate from 3,865 PWSs between 2001 and 2005 under the UCMR 1. EPA
found that 160 (approximately 4.1 percent) of the 3,865 PWSs that
sampled and reported had at least 1 analytical detection of perchlorate
(in at least 1 sampling point) at levels greater than or equal to the
method reporting limit (MRL) of 4 [mu]g/L. These 160 systems are
located in 26 States and 2 territories. Of these 160 PWSs, 8 are small
systems (serving 10,000 or fewer people) and 152 are large systems
(serving more than 10,000 people). These 160 systems reported 637
detections of perchlorate at levels greater than or equal to 4 [mu]g/L,
which is approximately 11.3 percent of the 5,629 samples collected by
these 160 systems and approximately 1.9 percent of the 34,331 samples
collected by all 3,865 systems. The maximum reported concentration of
perchlorate was 420 [mu]g/L, from a single surface water sample from a
PWS in Puerto Rico. The average concentration of perchlorate for those
samples with positive detections for perchlorate was 9.85 [mu]g/L and
the median concentration was 6.40 [mu]g/L. A summary of the perchlorate
occurrence statistics in UCMR 1 is shown in Table 1.
---------------------------------------------------------------------------
\10\ Table 1 shows perchlorate detection sat levels greater than
and equal to the MRL of 4 [mu]g/L.
Table 1--UCMR 1 Occurrence of Perchlorate at Concentrations >= 4 [mu]g/L \10\
----------------------------------------------------------------------------------------------------------------
Sampling Sampling
System size Number of Samples w/ points points w/ Sampled Systems w/
samples detects tested detects systems detects
----------------------------------------------------------------------------------------------------------------
Small Systems..................... 3,295 15 1,454 8 797 8
Large Systems..................... 31,036 622 13,533 379 3,068 152
�����������������������������������
Total Systems................. 34,331 637 14,987 387 3,865 160
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Notes:
[[Page 60270]]
1. For both large and small systems, at 3,865 systems with data, there were 34,331 samples taken at 14,987
(entry) points resulting in 637 (1.86%) sample detects representing 387 (2.58%) of the entry/sample points in
160 (4.14%) of the systems.
2. For 3,068 large systems with data, there were 31,036 samples taken at 13,533 entry points resulting in 622
(2.00%) detections representing 379 (2.80%) entry/sample points in 152 (4.95%) of the systems.
3. For 797 small systems with data, there were 3,295 samples taken at 1,454 entry points, resulting in a total
of 15 (0.455%) detections representing 8 (0.55%) entry/sample points at 8 (1%) of the systems.
Table 2 presents EPA's estimates of the population served by water
systems for which the highest reported perchlorate concentration was
greater than various threshold concentrations ranging from 4 [mu]g/L
(MRL) to 25 [mu]g/L. The fourth column of Table 2 presents a high end
estimate of the population served drinking water above a threshold.
This column presents the total population served by systems in which at
least one sample was found to contain perchlorate above the threshold
concentration. EPA considers this a high end estimate because it is
based upon the assumption that the entire system population is served
water from the entry point that had the highest reported perchlorate
concentration. In fact, many water systems have multiple entry points
into which treated water is pumped for distribution to their consumers.
For the systems with multiple entry points, it is unlikely that the
entire service population receives water from the one entry point with
the highest single concentration. Therefore, EPA included a less
conservative estimate of the population served water above a threshold
in the fifth column in Table 2. EPA developed this estimate by assuming
the population was equally distributed among all entry points. For
example, if a system with 10 entry points serving 200,000 people had a
sample from a single entry point with a concentration at or above a
given threshold, EPA assumed that the entry point served one-tenth of
the system population, and added 20,000 people to the total when
estimating the population in the last column of Table 2. This approach
may provide either an overestimate or an underestimate of the
population served by the affected entry point. In contrast, in the
example above, EPA added the entire system population of 200,000 to the
more conservative population served estimate in column 4, which is
likely an overestimate.
Table 2--UCMR 1 Occurrence and Population Estimates for Perchlorate Above Various Thresholds
----------------------------------------------------------------------------------------------------------------
Population
estimate
Population for entry
served by or sample
PWS entry or sample PWSs with points
PWSs with at least 1 points with at least 1 at least 1 having at
Thresholds \a\ detection > threshold of detection > threshold of detection > least 1
interest interest \b\ threshold detection >
of threshold
interest of
\c\ interest
\d\
----------------------------------------------------------------------------------------------------------------
4 [mu]g/L..................... 4.01%..................... 2.48%..................... \e\ 16.6 M 5.1 M
(155 of 3,865)............ (371 of 14,987)...........
5 [mu]g/L..................... 3.16%..................... 1.88%..................... 14.6 M 4.0 M
(122 of 3,865)............ (281 of 14,987)...........
7 [mu]g/L..................... 2.12%..................... 1.14%..................... 7.2 M 2.2 M
(82 of 3,865)............. (171 of 14,987)...........
10 [mu]g/L.................... 1.35%..................... 0.65%..................... 5.0 M 1.5 M
(52 of 3,865)............. (97 of 14,987)............
12 [mu]g/L.................... 1.09%..................... 0.42%..................... 3.6 M 1.2 M
(42 of 3,865)............. (63 of 14,984)............
15 [mu]g/L.................... 0.80%..................... 0.29%..................... 2.0 M 0.9 M
(31 of 3,865)............. (44 of 14,987)............
17 [mu]g/L.................... 0.70%..................... 0.24%..................... 1.9 M 0.8 M
(27 of 3,865)............. (36 of 14,987)............
20 [mu]g/L.................... 0.49%..................... 0.16%..................... 1.5 M 0.7 M
(19 of 3,865)............. (24 of 14,987)............
25 [mu]g/L.................... 0.36%..................... 0.12%..................... 1.0 M 0.4 M
(14 of 3,865)............. (18 of 14,987)............
----------------------------------------------------------------------------------------------------------------
Footnotes:
\a\ All occurrence measures in this table were conducted on a basis reflecting values greater than the listed
thresholds.
\b\ The entry/sample-point-level population served estimate is based on the system entry/sample points that had
at least 1 analytical detection for perchlorate greater than the threshold of interest. The UCMR 1 small
system survey was designed to be representative of the nation's small systems, not necessarily to be
representative of small system entry points.
\c\ The system-level population served estimate is based on the systems that had at least 1 analytical detection
for perchlorate greater than the threshold of interest.
\d\ Because the population served by each entry/sample point is not known, EPA assumed that the total population
served by a particular system is equally distributed across all entry/sample points. To derive the entry/
sample point-level population estimate, EPA summed the population values for the entry/sample points that had
at least 1 analytical detection greater than the threshold of interest.
\e\ This value does not include the population associated with 5 systems serving 200,000 people that measured
perchlorate at 4 [mu]g/L in at least one sample.
2. Supplemental Occurrence Data. The Agency also evaluated drinking
water monitoring data for perchlorate in California and Massachusetts.
EPA considers these State data to be supplemental for purposes of this
regulatory determination, because they are not nationally
representative. EPA believes these State's monitoring results are
generally consistent with the results collected by EPA under UCMR 1.
The California Department of Public Health
[[Page 60271]]
(CDPH) last updated its perchlorate monitoring results on July 10, 2008
(CDPH, 2008). The Massachusetts's Department of Environmental
Protection (MA DEP) last updated its draft report on The Occurrence and
Sources of Perchlorate in Massachusetts in April, 2006 (MA DEP, 2005).
C. Evaluation of Perchlorate Exposure From Sources Other Than Drinking
Water
An important element of EPA's regulatory determination process is
to consider the contaminant exposure that individuals are likely to
receive from sources other than drinking water. An individual's total
exposure to a contaminant is more relevant to his or her risk for
adverse health effects than is exposure to the contaminant from
drinking water alone.
Because there are significant sources of perchlorate exposure other
than through the drinking water route, EPA determined that data on
exposure to perchlorate from these sources is critical to the
evaluation of whether or not there is a meaningful opportunity for
health risk reduction through a national primary drinking water rule
for perchlorate. Dietary studies pose a particular challenge because
there is great variety in the American diet and many foods must be
analyzed to enable a comprehensive dietary exposure estimate. However,
EPA believes that two recent studies provide a sound basis for
evaluating total perchlorate exposure. These are the Food and Drug
Administration (FDA) Total Diet Study and an analysis of NHANES/UCMR
data conducted by EPA and CDC.
FDA's Total Diet Study (TDS) combines nationwide sampling and
analysis of hundreds of food items along with national surveys of food
intake to develop comprehensive dietary exposure estimates for a
variety of demographic groups in the U.S. CDC's NHANES data base
measured perchlorate in the urine of a representative sample of
Americans. EPA and CDC used data from the NHANES data base and UCMR
monitoring to estimate perchlorate exposure from food and water
together, and food alone, for different sub-populations. This section
of the notice provides details on the results of these studies. Because
the sources of exposure encompassed by each of these studies overlap,
EPA has considered them both in making a regulatory determination in an
effort to provide the most comprehensive basis for the preliminary
determination.
In this s