Chlorpyrifos; Order Denying PANNA and NRDC's Petition To Revoke Tolerances, 16581-16592 [2017-06777]
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Federal Register / Vol. 82, No. 64 / Wednesday, April 5, 2017 / Notices
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authorizes the Secretary of Energy to
prescribe test procedures that are
reasonably designed to produce results
that measure energy efficiency, energy
use, or estimated operating costs during
a representative average-use cycle, and
that are not unduly burdensome to
conduct. (42 U.S.C. 6293(b)(3)) The test
procedure for battery chargers is
contained in Title 10 of the Code of
Federal Regulations (CFR) part 430,
subpart B, appendix Y, Uniform Test
Method for Measuring the Energy
Consumption of Battery Chargers.
The regulations set forth in 10 CFR
430.27 contain provisions that allow a
person to seek a waiver from the test
procedure requirements for a particular
basic model of a type of covered product
when the petitioner’s basic model for
which the petition for waiver was
submitted contains one or more design
characteristics that: (1) Prevent testing
according to the prescribed test
procedure, or (2) cause the prescribed
test procedures to evaluate the basic
model in a manner so unrepresentative
of its true energy consumption
characteristics as to provide materially
inaccurate comparative data. 10 CFR
430.27(a)(1).DOE may grant the waiver
subject to conditions, including
adherence to alternate test procedures.
10 CFR 430.27(f)(2).
II. Dyson’s Petition for Waiver:
Assertions and Determinations
On April 7, 2016, Dyson filed a
petition for waiver from the DOE test
procedure for battery chargers under 10
CFR 430.27 for the battery charger used
in their robotic vacuum cleaner model
RB01, marketed as the Dyson 360-Eye
(Robot), which is required to be tested
using the DOE battery charger test
procedure at 10 CFR 430.23(aa) and
detailed at 10 CFR part 430, subpart B,
appendix Y. In its petition, Dyson asks
that the requirement contained in the
DOE test procedure for battery chargers
provided in 10 CFR part 430, subpart B,
appendix Y, section 4.4, Limiting Other
Non-Battery-Charger Functions, be
waived with regard to testing of the
Robot battery charger. According to
subsection 4.4.b (and a related provision
at section 5.6.c.1), any function
controlled by the user and not
associated with the battery charging
process must be switched off or be set
to the lowest power-consuming mode.
Dyson asserts that in order to provide
the user with the advanced setting and
management features of the Robot, the
relevant functionalities and circuitry
have to be powered at all times.
Accordingly, Dyson does not believe it
appropriate to make these functions,
which are not associated with the
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battery charging process, user
controllable because they are an integral
part of the Robot itself. Therefore, in
order to ascertain the true energy
consumption characteristics of the
battery charger during the test, Dyson
seeks permission to switch off these
functions by a means that is not
controlled by the user.
Dyson also requested an interim
waiver from the existing DOE test
procedure, which DOE granted. See 81
FR at 62489. After reviewing the
alternate procedure suggested by Dyson,
DOE granted the interim waiver because
DOE determined that Dyson’s petition
for waiver will likely be granted and
decided that it was desirable for public
policy reasons to grant Dyson
immediate relief pending a
determination on the petition for
waiver. Dyson’s petition was published
in the Federal Register on September 9,
2016. 81 FR 62489. DOE received no
comments regarding Dyson’s petition.
On May 20, 2016, DOE published a
test procedure final rule that adopted
amendments to the battery charger test
procedure found in Appendix Y. 81 FR
31827. Subsequently, on December 12,
2016, DOE issued a separate final rule
to add a discrete test method for
uninterruptible power supplies to the
battery charger test procedure. 81 FR
89806. Neither of these final rules
amended the provisions of the battery
charger test procedure from which
Dyson sought a waiver. Since the
amendments in these final rules did not
address the issues presented in the
waiver petition, Dyson’s interim waiver
has remained in effect while DOE has
evaluated the waiver petition. 10 CFR
430.27(h).
III. Consultations With Other Agencies
DOE consulted with the Federal Trade
Commission (FTC) staff concerning the
Dyson petition for waiver. The FTC staff
did not have any objections to granting
a waiver to Dyson.
IV. Order
After careful consideration of all the
material that was submitted by Dyson
and consultation with the FTC staff, in
accordance with 10 CFR 430.27, it is
ordered that:
(1) The petition for waiver submitted
by the Dyson Inc. (Case No. BC–001) is
hereby granted as set forth in the
paragraphs below.
(2) Dyson must test and rate the
Dyson basic models specified in
paragraph (3) on the basis of the current
test procedure contained in 10 CFR part
430, subpart B, appendix Y, except that
Dyson, notwithstanding the instructions
in Appendix Y sections 3.2.4 and 3.3.6,
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16581
may disable power to functions not
associated with the battery charging
process by isolating a terminal of the
battery pack using isolating tape, as
shown in the Appendices to the petition
for waiver.
(3) This order applies only to the
following basic model: RB01, marketed
as the Dyson 360-Eye (‘‘Robot’’), battery
charger.
(4) This waiver shall remain in effect
consistent with the provisions of 10 CFR
430.27.
Issued in Washington, DC, on March 27,
2017.
Steven G. Chalk,
Acting Assistant Secretary, Energy Efficiency
and Renewable Energy
[FR Doc. 2017–06732 Filed 4–4–17; 8:45 am]
BILLING CODE –P
ENVIRONMENTAL PROTECTION
AGENCY
[EPA–HQ–OPP–2007–1005; FRL–9960–77]
Chlorpyrifos; Order Denying PANNA
and NRDC’s Petition To Revoke
Tolerances
Environmental Protection
Agency (EPA).
ACTION: Order.
AGENCY:
In this Order, EPA denies a
petition requesting that EPA revoke all
tolerances for the pesticide chlorpyrifos
under section 408(d) of the Federal
Food, Drug, and Cosmetic Act and
cancel all chlorpyrifos registrations
under the Federal Insecticide, Fungicide
and Rodenticide Act. The petition was
filed in September 2007 by the Pesticide
Action Network North America
(PANNA) and the Natural Resources
Defense Council (NRDC).
DATES: This Order is effective April 5,
2017. Objections and requests for
hearings must be received on or before
June 5, 2017, and must be filed in
accordance with the instructions
provided in 40 CFR part 178 (see also
Unit I. of the SUPPLEMENTARY
INFORMATION.)
SUMMARY:
The docket for this action,
identified by docket identification (ID)
number EPA–HQ–OPP–2007–1005, is
available at https://www.regulations.gov
or at the Office of Pesticide Programs
Regulatory Public Docket (OPP Docket)
in the Environmental Protection Agency
Docket Center (EPA/DC), West William
Jefferson Clinton Bldg., Rm. 3334, 1301
Constitution Ave. NW., Washington, DC
20460–0001. The Public Reading Room
is open from 8:30 a.m. to 4:30 p.m.,
Monday through Friday, excluding legal
ADDRESSES:
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holidays. The telephone number for the
Public Reading Room is (202) 566–1744,
and the telephone number for the OPP
Docket is (703) 305–5805. Please review
the visitor instructions and additional
information about the docket available
at https://www.epa.gov/dockets.
FOR FURTHER INFORMATION CONTACT:
Pesticide Re-Evaluation Division
(7508P), Office of Pesticide Programs,
Environmental Protection Agency, 1200
Pennsylvania Ave. NW., Washington,
DC 20460–0001; telephone number:
(703) 347–0206; email address:
OPPChlorpyrifosInquiries@epa.gov.
SUPPLEMENTARY INFORMATION:
I. General Information
jstallworth on DSK7TPTVN1PROD with NOTICES
A. Does this action apply to me?
In this document EPA denies a
petition by PANNA and the NRDC to
revoke pesticide tolerances and cancel
pesticide registrations. This action may
also be of interest to agricultural
producers, food manufacturers, or
pesticide manufacturers. Potentially
affected entities may include, but are
not limited to those engaged in the
following activities:
• Crop production (North American
Industrial Classification System
(NAICS) code 111), e.g., agricultural
workers; greenhouse, nursery, and
floriculture workers; farmers.
• Animal production (NAICS code
112), e.g., cattle ranchers and farmers,
dairy cattle farmers, livestock farmers.
• Food manufacturing (NAICS code
311), e.g., agricultural workers; farmers;
greenhouse, nursery, and floriculture
workers; ranchers; pesticide applicators.
• Pesticide manufacturing (NAICS
code 32532), e.g., agricultural workers;
commercial applicators; farmers,
greenhouse, nursery, and floriculture
workers; residential users.
This listing is not intended to be
exhaustive, but rather to provide a guide
for readers regarding entities likely to be
affected by this action. Other types of
entities not listed in this unit could also
be affected. The NAICS codes have been
provided to assists you and others in
determining whether this action might
apply to certain entities. If you have any
questions regarding the applicability of
this action to a particular entity, consult
the person listed under FOR FURTHER
INFORMATION CONTACT.
EPA–HQ–OPP–2008–0850 and the
chlorpyrifos tolerance rulemaking
docket under Docket ID No, EPA–HQ–
OPP–2015–0653. To access the
electronic docket, go to https://
www.regulations.gov, select ‘‘Advanced
Search,’’ then ‘‘Docket Search.’’ Insert
the docket ID number where indicated
and select the ‘‘Submit’’ button. Follow
the instructions on the regulations.gov
Web site to view the docket index or
access available documents. All
documents in the docket are listed in
the docket index available in
regulations.gov. Although listed in the
index, some information is not publicly
available, e.g., Confidential Business
Information (CBI) or other information
whose disclosure is restricted by statute.
Certain other material, such as
copyrighted material, is not placed on
the Internet and will be publicly
available only in hard copy form.
Publicly available docket materials are
available in the electronic docket or, if
only available in hard copy, at the OPP
Regulatory Public Docket in Rm. S–
4400, One Potomac Yard (South Bldg.),
2777 S. Crystal Dr., Arlington, VA. The
Docket Facility is open from 8:30 a.m.
to 4 p.m. Monday through Friday,
excluding legal holidays. The Docket
Facility telephone number is (703) 305–
5805.
C. Can I file an objection or hearing
request?
Under section 408(g) of the Federal
Food, Drug and Cosmetic Act (FFDCA)
(21 U.S.C. 346a(g)), any person may file
an objection to any aspect of this order
and may also request a hearing on those
objections. You must file your objection
or request a hearing on this order in
accordance with the instructions
provided in 40 CFR part 178. To ensure
proper receipt by EPA, you must
identify docket ID number EPA–HQ–
OPP–2007–1005 in the subject line on
the first page of your submission. All
objections and requests for a hearing
must be in writing, and must be
received by the Hearing Clerk on or
before June 5, 2017, and may be
submitted by one of the following
methods:
• Mail: U.S. EPA Office of
Administrative Law Judges, Mailcode
1900R, 1200 Pennsylvania Ave. NW.,
Washington, DC 20460
• Hand Delivery: U.S. Environmental
B. How can I get copies of this document Protection Agency Office of
and other related information?
Administrative Law Judges, Ronald
Reagan Building, Rm. M1200, 1300
EPA has established a docket for this
Pennsylvania Ave. NW., Washington,
action under Docket ID No. EPA–HQ–
DC 20004. Deliveries are only accepted
OPP–2007–1005. Additional
during the Office’s normal hours of
information relevant to this action is
operation (8:30 a.m. to 4 p.m., Monday
located in the chlorpyrifos registration
through Friday, excluding legal
review docket under Docket ID No,
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holidays). Special arrangements should
be made for deliveries of boxed
information. The Office’s telephone
number is (202) 564–6255.
In addition to filing an objection or
hearing request with the Hearing Clerk
as described in 40 CFR part 178, please
submit a copy of the filing that does not
contain CBI for inclusion in the public
docket that is described in I.B.1 above.
Information not marked confidential
pursuant to 40 CFR part 2 may be
disclosed publicly by EPA without prior
notice. Submit this copy, identified by
docket ID number EPA–HQ–OPP–2007–
1005, by one of the following methods:
• Federal eRulemaking Portal: https://
www.regulations.gov. Follow the on-line
instructions for submitting comments.
• Mail: U.S. Environmental
Protection Agency Office of Pesticide
Programs (OPP) Public Regulatory
Docket (7502P), 1200 Pennsylvania,
Ave. NW., Washington, DC 20460–0001.
• Delivery: OPP Regulatory Public
Docket (7502P), Environmental
Protection Agency, Rm. S–4400, One
Potomac Yard (South Bldg.), 2777 S.
Crystal Dr., Arlington, VA. Deliveries
are only accepted during the Docket’s
normal hours of operation (8:30 a.m. to
4 p.m., Monday through Friday,
excluding legal holidays). Special
arrangements should be made for
deliveries of boxed information. The
Docket Facility telephone number is
(703) 305–5805.
D. What should be included in
objections?
The objection stage is the second stage
in the petition process under FFDCA
section 408. This multi-stage process is
initiated by a petition requesting
establishment, modification, or
revocation of a tolerance. Once EPA
makes a decision on a petition, and
publishes its decision in the Federal
Register, the second stage of the petition
process is triggered. At this point,
parties who disagree with EPA’s
decision, whether it is a decision to
grant or deny the petition, may file
objections with EPA to the decision
made. The objection stage gives parties
a chance to seek review of EPA’s
decision before the Agency. This is an
opportunity for parties to contest the
conclusions EPA reached and the
determinations underlying those
conclusions. As an administrative
review stage, it is not an opportunity to
raise new issues or arguments or present
facts or information that were available
earlier. On the other hand, parties must
do more than repeat the claims in the
petition. The objection stage is the
opportunity to challenge EPA’s decision
on the petition. An objection fails on its
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face if it does not identify aspects of
EPA’s decision believed to be in error
and explain the reason why EPA’s
decision is incorrect. This two-stage
process insures that issues are fully
aired before the Agency and a
comprehensive record is compiled,
prior to judicial review.
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II. Introduction
A. What action is the Agency taking?
In this document, EPA denies a
petition by PANNA and the NRDC. In a
petition dated September 12, 2007,
PANNA and NRDC (the petitioners)
requested that EPA revoke all tolerances
for the pesticide chlorpyrifos
established under section 408 of the
FFDCA. (Ref. 1) The petition also sought
the cancellation of all chlorpyrifos
pesticide product registrations under
section 6 the Federal Insecticide,
Fungicide and Rodenticide Act (FIFRA),
7 U.S.C. 136d. The PANNA and NRDC
petition (the Petition) raised the
following claims regarding EPA’s
reregistration and active registrations of
chlorpyrifos in support of the request
for tolerance revocation and product
cancellation:
1. EPA has ignored genetic evidence
of vulnerable populations.
2. EPA has needlessly delayed a
decision regarding endocrine disrupting
effects.
3. EPA has ignored data regarding
cancer risks.
4. EPA’s 2006 cumulative risk
assessment (CRA) for the
organophosphates misrepresented risks
and failed to apply FQPA 10X safety
factor. [For convenience’s sake, the legal
requirements regarding the additional
safety margin for infants and children in
section 408(b)(2)(C) of the FFDCA are
referred to throughout this response as
the ‘‘FQPA 10X safety factor’’ or simply
the ‘‘FQPA safety factor.’’ Due to
Congress’ focus on both pre- and postnatal toxicity, EPA has interpreted this
additional safety factor as pertaining to
risks to infants and children that arise
due to pre-natal exposure as well as to
exposure during childhood years.]
5. EPA has over-relied on registrant
data.
6. EPA has failed to properly address
the exporting hazard in foreign
countries from chlorpyrifos.
7. EPA has failed to quantitatively
incorporate data demonstrating longlasting effects from early life exposure to
chlorpyrifos in children.
8. EPA has disregarded data
demonstrating that there is no evidence
of a safe level of exposure during prebirth and early life stages.
9. EPA has failed to cite or
quantitatively incorporate studies and
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clinical reports suggesting potential
adverse effects below 10%
cholinesterase inhibition.
10. EPA has failed to incorporate
inhalation routes of exposure.
In this order EPA is denying the
Petition in full. EPA provided the
petitioners with two interim responses
on July 16, 2012, and July 15, 2014,
respectively. The July 16, 2012,
response denied claim 6 (export hazard)
completely and that portion of the
response was a final agency action. The
remainder of the July 16, 2012, response
and the July 15, 2014, response
expressed EPA’s intention to deny six
other petition claims (1–5 and 10). [In
the 2012 response, EPA did, however,
inform petitioners of its approval of
label mitigation (in the form of rate
reductions and spray drift buffers) to
reduce bystander risks, including risks
from inhalation exposure, which in
effect partially granted petition claim
10.] EPA made clear in both the 2012
and 2014 responses that, absent a
request from petitioners, EPA’s denial of
those six claims would not be made
final until EPA finalized its response to
the entire Petition. Petitioners made no
such request. EPA is finalizing its denial
of those six claims in this order.
The remaining claims (7–9) all related
to same issue: Whether the potential
exists for chlorpyrifos to cause
neurodevelopmental effects in children
at exposure levels below EPA’s existing
regulatory standard (10% cholinesterase
inhibition). While these claims raised
novel, highly complex and unresolved
scientific issues, EPA decided it would
nonetheless expedite the registration
review of chlorpyrifos under FIFRA
section 3(g), and attempt to address
these issues several years in advance of
the October 1, 2022 deadline for
completing that review. Accordingly,
EPA also decided as a policy matter that
it would address the Petition claims
raising these matters on a similar
timeframe. Although EPA had expedited
its registration review to address these
issues, the petitioners were not satisfied
with EPA’s progress in responding to
the Petition and they brought legal
action in the 9th Circuit Court of
Appeals to compel EPA to either issue
an order denying the Petition or to grant
the Petition by initiating the tolerance
revocation process. In August 2015, the
9th Circuit issued a ruling in favor of
the petitioners and ordered EPA to
respond to the Petition by either
denying the Petition or issuing a
proposed or final rule revoking
chlorpyrifos tolerances. In re Pesticide
Action Network of North America v.
EPA, 798 F.3d (9th Cir. 2015).
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On November 6, 2015, pursuant to the
9th Circuit’s order, EPA proposed to
revoke all chlorpyrifos tolerances based
in part on uncertainty surrounding the
potential for chlorpyrifos to cause
neurodevelopmental effects—the issue
raised in petition claims 7–9. Following
publication of the proposal, the 9th
Circuit announced that it would retain
jurisdiction over this matter and on
August 12, 2016, the court further
ordered EPA to complete a final petition
response by March 31, 2017 and made
clear that no further extensions would
be granted. On November 17, 2016, EPA
published a notice of data availability
that released for public comment EPA’s
revised risk assessment that proposed a
new regulatory point of departure based
on the potential for chlorpyrifos to
result in adverse neurodevelopmental
effects.
Following a review of comments on
both the November 2015 proposal and
the November 2016 notice of data
availability, EPA has concluded that,
despite several years of study, the
science addressing neurodevelopmental
effects remains unresolved and that
further evaluation of the science during
the remaining time for completion of
registration review is warranted to
achieve greater certainty as to whether
the potential exists for adverse
neurodevelopmental effects to occur
from current human exposures to
chlorpyrifos. EPA has therefore
concluded that it will not complete the
human health portion of the registration
review or any associated tolerance
revocation of chlorpyrifos without first
attempting to come to a clearer scientific
resolution on those issues. As noted,
Congress has provided that EPA must
complete registration review by October
1, 2022. Because the 9th Circuit’s
August 12, 2016 order has made clear,
however, that further extensions to the
March 31, 2017 deadline for responding
to the Petition would not be granted,
EPA is today also denying all remaining
petition claims.
B. What is the Agency’s authority for
taking this action?
Under section 408(d)(4) of the
FFDCA, EPA is authorized to respond to
a section 408(d) petition to revoke
tolerance either by issuing a final rule
revoking the tolerances, issuing a
proposed rule, or issuing an order
denying the Petition.
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III. Statutory and Regulatory
Background
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A. FFDCA/FIFRA and Applicable
Regulations
1. In general. EPA establishes
maximum residue limits, or
‘‘tolerances,’’ for pesticide residues in
food and feed commodities under
section 408 of the FFDCA. Without such
a tolerance or an exemption from the
requirement of a tolerance, a food
containing a pesticide residue is
‘‘adulterated’’ under section 402 of the
FFDCA and may not be legally moved
in interstate commerce. Section 408 was
substantially rewritten by the Food
Quality Protection Act of 1996 (FQPA)
(Pub. L. 104–170, 110 Stat. 1489 (1996)),
which established a detailed safety
standard for pesticides and integrated
EPA’s regulation of pesticide food
residues under the FFDCA with EPA’s
registration and re-evaluation of
pesticides under FIFRA. The standard
for issuing or maintaining a tolerance
under section 408(b)(2)(A)(i) of the
FFDCA is whether it is ‘‘safe.’’ ‘‘Safe’’ is
defined by section 408(b)(2)(A)(ii) to
mean that ‘‘there is a reasonable
certainty that no harm will result from
aggregate exposure to the pesticide
chemical residue, including all
anticipated dietary exposures and all
other exposures for which there is
reliable information.’’
While the FFDCA authorizes the
establishment of legal limits for
pesticide residues in food, section 3(a)
of FIFRA requires the approval of
pesticides prior to their sale and
distribution, and establishes a
registration regime for regulating the use
of pesticides. FIFRA regulates pesticide
use in conjunction with its registration
scheme by requiring EPA review and
approval of pesticide labels and
specifying that use of a pesticide
inconsistent with its label is a violation
of federal law. In the FQPA, Congress
integrated action under the two statutes
by requiring that the safety standard
under the FFDCA be used as a criterion
in FIFRA registration actions as to
pesticide uses which result in dietary
risk from residues in or on food, (see
FIFRA section 2(bb)), and directing that
EPA coordinate, to the extent
practicable, revocations of tolerances
with pesticide cancellations under
FIFRA. (See FFDCA section 408(l)(1).)
Under section 3(g) of FIFRA, EPA is
required to re-evaluate pesticides under
the FIFRA standard—which includes a
determination regarding the safety of
existing FFDCA tolerances—every 15
years under a program known as
‘‘registration review.’’ The deadline for
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completing the registration review for
chlorpyrifos is October 1, 2022.
2. Procedures for establishing,
amending, or revoking tolerances.
Tolerances are established, amended, or
revoked by rulemaking under the
unique procedural framework set forth
in the FFDCA. Generally, a tolerance
rulemaking is initiated by the party
seeking to establish, amend, or revoke a
tolerance by means of filing a petition
with EPA. (See FFDCA section
408(d)(1).) EPA publishes in the Federal
Register a notice of the petition filing
and requests public comment. After
reviewing the petition, and any
comments received on it, section
408(d)(4) provides that EPA may issue
a final rule establishing, amending, or
revoking the tolerance, issue a proposed
rule to do the same, or deny the
petition.
Once EPA takes final action on the
petition by establishing, amending, or
revoking the tolerance or denying the
petition, section 408(g)(2) allows any
party to file objections with EPA and
seek an evidentiary hearing on those
objections. Objections and hearing
requests must be filed within 60 days.
Section 408(g)(2)(B) provides that EPA
shall ‘‘hold a public evidentiary hearing
if and to the extent the Administrator
determines that such a public hearing is
necessary to receive factual evidence
relevant to material issues of fact raised
by the objections.’’ EPA regulations
make clear that hearings will only be
granted where it is shown that there is
‘‘a genuine and substantial issue of
fact,’’ the requestor has identified
evidence ‘which ‘‘would, if established,
resolve one or more of such issues in
favor of the requestor,’’ and the issue is
‘‘determinative’’ with regard to the relief
requested. (40 CFR 178.32(b).) Further,
a party may not raise issues in
objections unless they were part of the
petition and an objecting party must
state objections to the EPA decision and
not just repeat the allegations in its
petition. Corn Growers v. EPA, 613 F.2d
266 (D.C. Cir. 2010), cert. denied, 131 S.
Ct. 2931 (2011). EPA’s final order on the
objections is subject to judicial review.
(21 U.S.C. 346a(h)(1).)
IV. Chlorpyrifos Regulatory
Background
Chlorpyrifos (0,0-diethyl-0-3,5,6trichloro-2-pyridyl phosphorothioate) is
a broad-spectrum, chlorinated
organophosphate (OP) insecticide that
has been registered for use in the United
States since 1965. By pounds of active
ingredient, it is the most widely used
conventional insecticide in the country.
Currently registered use sites include a
large variety of food crops (including
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tree fruits and nuts, many types of small
fruits and vegetables, including
vegetable seed treatments, grain/oilseed
crops, and cotton, for example), and
non-food use settings (e.g., ornamental
and agricultural seed production, nonresidential turf, industrial sites/rights of
way, greenhouse and nursery
production, sod farms, pulpwood
production, public health and wood
protection). For some of these crops,
chlorpyrifos is currently the only costeffective choice for control of certain
insect pests. In 2000, the chlorpyrifos
registrants reached an agreement with
EPA to voluntarily cancel all residential
use products except those registered for
ant and roach baits in child-resistant
packaging and fire ant mound
treatments.
In 2006, EPA completed FIFRA
section 4 reregistration and FFDCA
tolerance reassessment for chlorpyrifos
and the OP class of pesticides. Having
completed reregistration and tolerance
reassessment, EPA is required to
complete the next re-evaluation of
chlorpyrifos under the FIFRA section
3(g) registration review program by
October 1, 2022. Given ongoing
scientific developments in the study of
the OPs generally, in March 2009 EPA
announced its decision to prioritize the
FIFRA section 3(g) registration review of
chlorpyrifos by opening a public docket
and releasing a preliminary work plan
to complete the chlorpyrifos registration
review by 2015—7 years in advance of
the date required by law.
The registration review of
chlorpyrifos and the OPs has presented
EPA with numerous novel scientific
issues that the agency has taken to
multiple FIFRA Scientific Advisory
Panel (SAP) meetings since the
completion of reregistration. [The SAP
is a federal advisory committee created
by section 25(d) of FIFRA, that serves as
EPA’s primary source of peer review for
significant regulatory and policy matters
involving pesticides.] Many of these
complex scientific issues formed the
basis of the 2007 petition filed by
PANNA and NRDC and EPA therefore
decided to address the Petition on a
similar timeframe to EPA’s expedited
registration review schedule.
Although EPA expedited the
chlorpyrifos registration review in an
attempt to address the novel scientific
issues raised by the Petition in advance
of the statutory deadline, the petitioners
were dissatisfied with the pace of EPA’s
response efforts and have sued EPA in
federal court on three separate occasions
to compel a faster response to the
Petition. As explained in Unit V., EPA
had addressed 7 of the 10 claims
asserted in the Petition by either
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denying the claim, issuing a preliminary
denial or approving label mitigation to
address the claims, but on June 10,
2015, in the PANNA decision, the U.S.
Court of Appeals for the Ninth Circuit
signaled its intent to order EPA to
complete its response to the Petition
and directed EPA to inform the court
how—and by when—EPA intended to
respond. On June 30, 2015, EPA
informed the court that it intended to
propose by April 15, 2016, the
revocation of all chlorpyrifos tolerances
in the absence of pesticide label
mitigation that ensures that exposures
will be safe. On August 10, 2015, the
court rejected EPA’s time line and
issued a mandamus order directing EPA
to ‘‘issue either a proposed or final
revocation rule or a full and final
response to the administrative Petition
by October 31, 2015.’’
On October 30, 2015, EPA issued a
proposed rule to revoke all chlorpyrifos
tolerances which it published in the
Federal Register on November 6, 2015
(80 FR 69080). On December 10, 2015,
the Ninth Circuit issued a further order
requiring EPA to complete any final rule
(or petition denial) and fully respond to
the Petition by December 30, 2016. On
June 30, 2016, EPA sought a 6-month
extension to that deadline in order to
allow EPA to fully consider the most
recent views of the FIFRA SAP with
respect to chlorpyrifos toxicology. The
FIFRA SAP report was finalized and
made available for EPA consideration
on July 20, 2016. (Ref. 2) On August 12,
2016, the court rejected EPA’s request
for a 6-month extension and ordered
EPA to complete its final action by
March 31, 2017 (effectively granting
EPA a three-month extension). On
November 17, 2016, EPA published a
notice of data availability (NODA)
seeking public comment on both EPA’s
revised risk and water assessments and
reopening the comment period on the
proposal to revoke all chlorpyrifos (81
FR 81049). The comment period for the
NODA closed on January 17, 2017.
V. Ruling on Petition
This order denies the Petition on the
nine remaining grounds for which EPA
has not issued a final denial that can be
the subject of objections under section
408(g)(2) of the FFDCA. As noted in
Unit II, on July 16, 2012, EPA denied as
final agency action petitioners’ claim 6
that the registration of chlorpyrifos
created an export hazard for workers in
foreign countries. That response and the
response of July 15, 2014, also included
EPA’s preliminary denial of petition
claims 1–5 and 10 (except to the extent
EPA granted that claim) and EPA’s
responses to those claims are now
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incorporated into this order as set forth
below. This unit also includes EPA’s
basis for denying petition claims 7–9.
Each specific petition claim is
summarized in this Unit V. immediately
prior to EPA’s response to the claim.
1. Genetic Evidence of Vulnerable
Populations
a. Petitioners’ claim. Petitioners claim
that as part of EPA’s reregistration
decision (which was completed in 2006
with the completion of the
organophosphate cumulative risk
assessment) the Agency failed to
calculate an appropriate intra-species
uncertainty factor (i.e., within human
variability) for chlorpyrifos in both its
aggregate and cumulative risk
assessments (CRA). They assert that
certain relevant, robust data, specifically
the Furlong et al. (2006) study (Ref. 3)
that addresses intra-species variability
in the behavior of the detoxifying
enzyme paraoxonase (PON1), indicate
that the Agency should have applied an
intra-species safety factor ‘‘of at least
150X in the aggregate and cumulative
assessments’’ rather than the 10X factor
EPA applied. Petitioners conclude by
noting that applying an intra-species
factor of 100X or higher would require
setting tolerances below the level of
detection, which therefore should
compel EPA to revoke all chlorpyrifos
tolerances.
b. Agency Response. Petitioners are
correct that the Agency, as part of the
2006 OP CRA, evaluated, but did not
rely on Furlong et al. in setting the intraspecies uncertainty factor for that
assessment. The Agency did not rely on
the results of the PON1 data in the OP
CRA because these data do not take into
consideration the complexity of OP
metabolism, which involves multiple
metabolic enzymes, not just PON1. In
addition, EPA believes the methodology
utilized in the Furlong et al. study to
measure intra-species variability—i.e.,
combining values from multiple species
(transgenic mice and human) to
determine the range of sensitivity
within a single species—is not
consistent with well-established
international risk assessment practices.
Further, EPA believes that petitioners’
assertion that the Furlong et al. study
supports an intra-species uncertainty
factor of at least 150X is based on an
analysis of the data that is inconsistent
with EPA policy and widely-accepted
international guidance on the
development of intra-species
uncertainty factors. In addition, the
2008 FIFRA SAP did not support the
use of the Furlong et al (2006) study
alone in deriving an intra-species factor.
For these reasons, and as further
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explained below, EPA believes it is not
appropriate to solely rely on the results
of the Furlong et al. study, or
petitioners’ interpretation of those
results, for purposes of determining the
intra-species uncertainty factor. To
determine that factor, EPA first uses
science tools to quantitatively
characterize human variability in both
exposure and dosimetry, and then
determines the appropriate intra-species
uncertainty factor to protect sensitive
populations. Specifically, for
chlorpyrifos, EPA uses a
physiologically-based pharmacokinetic
(PBPK) model to account for human
variability in the absorption,
distribution, metabolism and excretion
(ADME) of chemicals based on key
physiological, biochemicals, and
physicochemical determinants of these
ADME processes, including the
influence of PON1 variability.
Addressing human variability and
sensitive populations is an important
aspect of the Agency’s risk assessment
process. The Agency is well aware of
the issue of PON1 and has examined the
scientific evidence on this source of
genetic variability. PON1 is one of the
key detoxification enzymes of
chlorpyrifos and is included as part of
the PBPK model used by EPA in the
2014 human health risk assessment
(HHRA) and 2016 revised risk
assessment. Specifically, PON1 is an Aesterase which can metabolize
chlorpyrifos-oxon without inactivating
the enzyme. (Ref. 4) Indeed, as part of
the 2008 SAP, EPA performed a
literature review of PON1 and its
possible use in informing the intraspecies (i.e., within human variability)
uncertainty factor. This literature review
can be found in the draft Appendix E:
Data Derived Extrapolation Factor
Analysis to the draft Science Issue
Paper: Chlorpyrifos Hazard and Dose
Response Characterization. (Ref. 5) In
sum, the Agency considered available
PON1 data from more than 25 studies
from diverse human populations
worldwide.
The Agency focused on the PON1–
192 polymorphism since it has been
linked to chlorpyrifos-oxon sensitivity
in experimental toxicology studies and,
has been evaluated in epidemiology
studies attempting to associate PON1
status with health outcomes following
OP pesticide exposure in adults and
children (Holland et al., 2006; Chen et
al., 2003. (Ref. 6). [Note, Holland et al.
(2006) and Furlong et al. (2006) report
findings from the same cohort. The
Holland reference provides enzymes
activities for specific polymorphisms in
Table 4; the Furlong paper does not
report such values and provides
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information primarily in graphical
form.] However, EPA believes that
focusing on PON1 variability in
isolation from other metabolic action is
not an appropriate approach for
developing a data-driven uncertainty
factor. The Agency solicited feedback
from the SAP on the utility of the PON1
data, by itself, for use in risk
assessment; the SAP was similarly not
supportive of using such data in
isolation. Specifically, the SAP report
states:
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. . . the information on PON1
polymorphisms should not be used as the
sole factor in a data-derived uncertainty
factor for two main reasons: (1) it is only one
enzyme in a complex pathway, and is
subsequent to the bioactivation reaction;
therefore it can only function on the amount
of bioactivation product (i.e., chlorpyrifosoxon) that is delivered to it by CYP450); and
(2) the genotype of PON1 alone is insufficient
to predict vulnerability because the overall
level of enzyme activity is ultimately what
determines detoxification potential from that
pathway; thus, it is better to use PON1 status
because it provides information regarding
PON1 genotype and activity. Some of the
data from laboratory animal studies in PON
knockout animals are using an unrealistic
animal model and frequently very high dose
levels, and do not reflect what might happen
in humans. (Ref. 7)
Based on a detailed review of the
literature and the comments from the
SAP, the Agency has determined that
such data are not appropriate for use
alone in deriving an intra-species
uncertainty factor for use in human
health risk assessment. As indicated by
the SAP report, multiple factors (e.g.,
other enzymes such as P450s,
carboxylesterases,
butyrylcholinesterase) are likely to
impact potential population sensitivity,
rendering the results of the PON1 data,
by themselves, insufficiently reliable to
support a regulatory conclusion about
the potential variation of human
sensitivity to chlorpyrifos.
Since the 2008 SAP, several
epidemiological studies have been
published that considered the
association between PON status/
genotype and health outcome. Hofmann
et al. (2009) recently reported
associations between PON1 status and
inhibition of butyrylcholinesterase
(BuChE) in a group of pesticide handlers
in Washington. The authors note that
this study requires replication with
larger sample size(s) and more blood
samples. (Ref. 8) Given the limitations
of Hofmann et al., the Agency has not
drawn any conclusions from this study.
The Q/R–192 and/or C/T–108
polymorphism at the promoter site have
been evaluated recently as a factor
affecting birth or neurobehavioral
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outcomes following gestational
exposure to OPs. (Refs. 9, 10, 11) These
studies (Eskanazi., et al., 2010 (Ref. 9);
Harley et al., 2011 (Ref. 10); Engel et al.,
2011 (Ref. 11)) were evaluated by EPA
in preparation for the April 2012 SAP
review.
Petitioners further emphasize that the
Furlong et al. study supports an intraspecies uncertainty factor of over 164X
given the range of variability seen in
that study. The 164X value is derived
from sensitivity observed in transgenic
mice expressing human PON1Q–192
compared with mice expressing human
PON1R–192 combined with the range of
plasma arylesterase (AREase) from the
newborn with the lowest PON1 level
compared with the mother with the
highest PON1 level from a group of 130
maternal-newborn pairs from the
CHAMACOS (Center for the Health
Assessment of Mothers and Children of
Salinas) cohort.
EPA believes it is fundamentally at
odds with international risk assessment
practices to combine values from both
mouse and human data to determine the
potential range of variability within a
single species—regardless of whether
the test animals express a human PON1
enzyme. As the 2008 FIFRA SAP
explained, PON1 is but a single enzyme
that should not be considered in
isolation to predict the overall level of
enzyme activity that may affect human
sensitivity to a substance. Using a 164X
intra-species uncertainty factor derived
from the Furlong et al. study would take
this practice one step further by relying
upon combined PON1 values from
different species with differing overall
metabolic activity to derive the intraspecies factor. EPA does not believe this
approach is an appropriate means of
determining the potential range of intraspecies variability.
Finally, petitioners’ assertion that the
Furlong study supports an intra-species
uncertainty factor of at least 150X is
based on an analysis of that study that
is inconsistent with EPA policy and
widely-accepted international guidance
on the development of intra-species
uncertainty factors. In deriving the
intra-species uncertainty factor in its
risk assessments, EPA is guided by the
principles of the 2005 IPCS (Ref. 12)
guidance on chemical specific
adjustment factors (CSAFs) and the
EPA’s 2014 Guidance for Applying
Quantitative Data to Develop DataDerived Extrapolation Factors for
Interspecies and Intraspecies
Extrapolation. (Ref. 13) These guidances
recommend that intra-species factors
should be extrapolated from a measure
of central tendency in the population to
a measure in the sensitive population
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(i.e., to extrapolate from a typical
human to a sensitive human). To base
the factor on the difference between the
single lowest and highest measurements
in a given study, as petitioners suggest
in this instance, would likely greatly
exaggerate potential intra-species
variability. That approach effectively
assumes that the point of departure in
an EPA risk assessment will be derived
from the least sensitive test subject,
thereby necessitating the application of
an intra-species factor that accounts for
the full range of sensitivity across a
species. Since EPA does not develop its
PoDs in this fashion; the approach
suggested by petitioners is not
appropriate.
In summary, the Agency has carefully
considered the issue of PON1 variability
and determined that data addressing
PON1 in isolation are not appropriate
for use alone in deriving an intraspecies uncertainty factor and that the
issue is more appropriately handled
using a PBPK model. Further, the
derivation of the 164X value advocated
by the petitioners is based on combining
values from humanized mice with
human measured values with a range
from highest to lowest; the Furlong et al.
derivation is inappropriate and
inconsistent with international risk
assessment practice. (Ref. 2) The 2008
FIFRA SAP did not support the PON1
data used in isolation. Finally,
petitioners’ statement that the Furlong
et al. study supports an intra-species
uncertainty factor of at least 150X likely
overstates potential variability. EPA
therefore denies this aspect of the
Petition.
2. Endocrine Disrupting Effects
a. Petitioners’ claim. Petitioners
summarize a number of studies
evaluating the effects of chlorpyrifos on
the endocrine system, asserting that,
taken together, the studies ‘‘suggest that
chlorpyrifos may be an endocrine
disrupting chemical, capable of
interfering with multiple hormones
controlling reproduction and
neurodevelopment.’’ The petitioners
then assert that EPA should not have
delayed consideration of endocrine
effects absent finalization of the
Endocrine Disruptor Screening Program
(EDSP) (Ref. 14) and should have
quantitatively incorporated the studies
into the chlorpyrifos IRED.
b. Agency Response. This portion of
the Petition appears largely to be a
complaint about the completeness of
EPA’s reregistration decision and a
request that EPA undertake quantitative
incorporation of endocrine endpoints
into its assessment of chlorpyrifos. The
Petition does not explain whether and
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how endocrine effects should form the
basis of a decision to revoke tolerances.
The basis for seeking revocation of a
tolerance is a showing that the pesticide
is not ‘‘safe.’’ Petitioners have neither
asserted that EPA should revoke
tolerances because effects on the
endocrine system render the tolerances
unsafe, nor have petitioners submitted a
factual analysis demonstrating that
aggregate exposure to chlorpyrifos
presents an unsafe risk to humans based
on effects on the endocrine system.
Rather, the Petition appears to collect a
number of studies suggesting that
chlorpyrifos may have effects on the
endocrine system and that EPA should
have considered those health impacts at
reregistration in a quantitative
assessment.
To the extent that petitioners are
seeking tolerance revocation on these
grounds, the Petition fails to provide a
sufficient basis for revocation because,
in addition to the preceding defects, the
cited data do not provide quantitative
data (i.e., endpoints/points of departure)
that indicate endocrine effects at doses
that are more sensitive than the points
of departure used in the chlorpyrifos
risk assessment that are based on
cholinesterase inhibition. While the
cited studies provide qualitative
information that exposure to
chlorpyrifos may be associated with
effects on the androgen and thyroid
hormonal pathways, these data alone do
not demonstrate that current human
exposures from existing tolerances are
unsafe. The Agency noted similar effects
during its evaluation of information
submitted by People for the Ethical
Treatment of Animals (PETA) and the
Physicians Committee for Responsible
Medicine (PCRM) during its review of
existing information as part of EPA’s
EDSP, as discussed below. Based on the
review of that data, EPA concluded that
the effects seen in those studies do not
call into question EPA’s prior safety
determinations supporting the existing
tolerances; the data do not indicate a
risk warranting regulatory action, and
the petitioners have provided no
specific information to alter this
determination.
Consequently, the Petition does not
support a conclusion that existing
tolerances are unsafe due to potential
endocrine effects. This portion of the
Petition is therefore denied.
As petitioners may be aware, since the
filing of the petition, EPA has
completed the evaluation of
chlorpyrifos under EPA’s EDSP, as
required under FFDCA section 408(p)
that confirms EPA’s conclusions. On
April 15, 2009, a Federal Register notice
was published in which chlorpyrifos
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was included in the initial list of
chemicals (List 1) to receive EDSP Tier
1 test orders. The EDSP program is a
two-tiered screening and testing
program, Tier 1 and Tier 2 tests. Tier 1
includes 11 assays in the battery; these
data are intended to allow EPA to
determine whether certain substances
(including pesticide active and other
ingredients) have the potential to
interact with the endocrine system and
cause an effect in humans or wildlife
similar to an effect produced by a
‘‘naturally occurring estrogen, or other
such endocrine effects as the
Administrator may designate.’’ The
purpose of Tier 2 tests is to identify and
establish a quantitative, dose-response
relationship for any adverse effects that
might result from the interactions with
the endocrine system.
On November 5, 2009, EPA issued
Tier 1 test orders to the registrants of
chlorpyrifos, requiring a battery of 11
screening assays to identify the
potential to interact with the estrogen,
androgen, or thyroid hormonal systems.
(Ref. 15)
The agency received and reviewed all
11 EDSP Tier 1 screening assays for
chlorpyrifos. On June 29, 2015, the
agency completed the EDSP weight of
evidence (WoE) conclusions for the Tier
1 screening assays for List 1 chemicals,
including chlorpyrifos. In addition to
the Tier 1 data, the WoE evaluations
considered other scientifically relevant
information (OSRI), including general
toxicity data and open literature studies
of sufficient quality. In determining
whether chlorpyrifos interacts with the
estrogen, androgen or thyroid pathways,
the agency considered the number and
type of effects induced, the magnitude
and pattern of responses observed
across studies, taxa, and sexes.
Additionally, the agency also
considered the conditions under which
effects occurred, in particular whether
or not endocrine-related responses
occurred at dose(s) that also resulted in
general systemic or overt toxicity. The
agency concluded that, based on weight
of evidence considerations, EDSP Tier 2
testing is not recommended for
chlorpyrifos since there was no
evidence of potential interaction with
the estrogen, androgen and thyroid
pathways. The EDSP Tier 1 WoE
assessment and associated data
evaluation records for chlorpyrifos are
available online. (Ref. 16) This
assessment further supports EPA’s
denial of this portion of the Petition.
3. Cancer Risks
a. Petitioners’ claim. Petitioners claim
that the Agency ‘‘ignored’’ a December
2004 National Institutes of Health
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Agricultural Health Study (AHS) by Lee
et al. (2004) (Ref. 17) that evaluated the
association between chlorpyrifos and
lung cancer incidence. (Ref. 17) The
petition summarizes the results of the
AHS study, stating that the incidence of
lung cancer has a statistically significant
association with chlorpyrifos exposure.
The Petition then asserts that these data
are highly relevant and therefore should
have been referenced in the final
aggregate assessment for chlorpyrifos or
the OP CRA. Petitioners do not
otherwise explain whether and how
these data support the revocation of
tolerances or the cancellation of
pesticide registrations.
b. Agency Response. As explained in
the previous section, the basis for
seeking revocation of a tolerance is a
showing that the pesticide is not ‘‘safe.’’
Claiming that EPA failed to reference
certain data in its risk assessment
regarding carcinogenicity does not
amount to illustrating that the
tolerances are unsafe. To show a lack of
safety, petitioners would have to present
some fact-based argument
demonstrating that aggregate exposure
to chlorpyrifos poses an unsafe
carcinogenic risk. Petitioners have not
presented such an analysis.
Accordingly, EPA is denying the
Petition to revoke chlorpyrifos
tolerances or cancel chlorpyrifos
registrations to the extent the Petition
relies on claims pertaining to
carcinogenicity.
Despite the inadequacy of petitioners’
cancer claims, in the course of the
Agency’s review of chlorpyrifos, EPA
has examined the Lee et al. study cited
by petitioners (Ref. 17) among other
lines of evidence. EPA has concluded
that the Lee et al. investigation does not
alter the Agency’s weight of evidence
determination concerning chlorpyrifos’
carcinogenic potential, and therefore
does not alter the Agency’s current
cancer classification for chlorpyrifos.
Specifically, the Agency does not
believe this evidence raises sufficient
grounds for concern regarding
chlorpyrifos that EPA should consider
initiating action based upon this
information that might lead to
revocation of the chlorpyrifos tolerances
or cancellation of the chlorpyrifos
registrations.
The Agency was aware of the
December 2004 study cited by
petitioners. While Lee et al. observed a
possible association between
chlorpyrifos use and the incidence of
lung cancer, the authors also stressed
that further evaluation was necessary
before concluding the association was
causal in nature. (Ref. 17) Additional
evaluation is necessary because of
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possible alternative explanations for the
Lee et al. study, which include
unmeasured confounding factors or
confounding factors not fully accounted
for in the analysis, and possible false
positive results due to the performance
of multiple statistical tests.
EPA has been a collaborating agency
with the AHS since 1993, and continues
to closely monitor the AHS literature.
The Agency is working closely with the
AHS researchers to clearly understand
the results of their research efforts to
ensure the Agency appropriately
interprets these data as future studies
are published. Between 2003 and 2009
there have been six nested case-control
analyses within the AHS which
evaluated the use of a number of
agricultural pesticides, including
chlorpyrifos, in association with
specific anatomical cancer sites, in
addition to the previously published
cohort study (Ref. 17) cited by the
petitioners. As noted below, both the
Agency and Health Canada have
comprehensively reviewed these data.
In accordance with the Agency’s 2005
Guideline for Cancer Risk Assessment
(Ref. 18), chlorpyrifos is classified as
‘‘Not Likely to be Carcinogenic to
Humans’’ based on the lack of evidence
of carcinogenicity in male or female
mice and male or female rats. In chronic
toxicity/carcinogenicity studies, animals
received chlorpyrifos in their feed every
day of their lives (78 weeks for mice and
104 weeks for rats) at doses thousands
of times greater than any anticipated
exposure to humans from authorized
uses. There was no evidence of cancer
in the experimental animal studies.
Additionally, available evidence from in
vivo and in vitro assays did not support
a mutagenic or genotoxic potential of
chlorpyrifos.
Recently, the Agency conducted its
own review of the six nested casecontrol analyses and one cohort study
within the AHS concerning the
carcinogenic potential of chlorpyrifos.
(Ref. 19) EPA concluded with respect to
the AHS lung cancer results that the
findings are useful for generating
hypotheses, but require confirmation in
future studies. This conclusion is
consistent with that of researchers from
Health Canada. Specifically,
Weichenthal et al. (2010) (Ref. 20)
published a review article in
Environmental Health Perspectives on
pesticide exposure and cancer incidence
in the AHS cohort. Their review of these
same studies concluded that the weight
of experimental toxicological evidence
does not suggest that chlorpyrifos is
carcinogenic, and that epidemiologic
results currently available from the AHS
are inconsistent, lack replication, and
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lack a coherent biologically plausible
carcinogenic mode of action. The
authors did note positive exposureresponse associations for chlorpyrifos
and lung cancer in two separate
evaluations.
In summary, while there is initial
suggestive epidemiological evidence of
an association between chlorpyrifos and
lung cancer to only form a hypothesis as
to a carcinogenic mode of action,
additional research (including follow-up
AHS research) is needed to test the
hypothesis. Consequently, at this time it
is reasonable to conclude chlorpyrifos is
not a carcinogen in view of the lack of
carcinogenicity in the rodent bioassays
and the lack of a genotoxic or mutagenic
potential. The Agency concludes that
existing epidemiological data (including
Lee et al.) do not change the current
weight of the evidence conclusions. The
Agency continues to believe there is not
a sufficient basis to alter its assessment
of chlorpyrifos as not likely to be
carcinogenic to humans when multiple
lines of evidence are considered (e.g.,
epidemiology findings, rodent bioassay,
genotoxicity); therefore, chlorpyrifos
cancer risk would not be a factor in any
potential Agency risk determination to
revoke tolerances for chlorpyrifos.
4. CRA Misrepresents Risks, Failed To
Apply FQPA10X Safety Factor
a. Petitioners’ claim. Petitioners assert
that EPA relied on limited data and
inaccurate interpretations of data to
support its decision to remove the
FQPA safety factor in the 2006 OP CRA.
Specifically, the petitioners challenge
the Agency’s use of data from a paper
by Zheng et al. (2000) (Ref. 21) claiming
that, in contrast to the Agency’s analysis
of the study data, the data does show an
obvious difference between juvenile and
adult responses to chlorpyrifos.
Petitioners conclude by asserting that
the Zheng et al. study supports using a
10X safety factor for chlorpyrifos in the
CRA.
b. Agency Response. Petitioners’
assertions do not provide a sufficient
basis for revoking chlorpyrifos
tolerances. As explained previously, the
ground for seeking revocation of a
tolerance is a showing that the pesticide
is not ‘‘safe.’’ The petitioners’ claim that
the data EPA relied upon support a
different FQPA safety factor for
chlorpyrifos in the CRA does not
amount to a showing that chlorpyrifos
tolerances are unsafe. To show a lack of
safety, petitioners would have to present
a factual analysis demonstrating that the
lack of a 10X safety factor in the CRA
for chlorpyrifos poses unsafe
cumulative exposures to the OPs.
Petitioners have not made such a
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showing. For this reason, EPA is
denying the petitioners’ request to
revoke chlorpyrifos tolerances or cancel
chlorpyrifos registrations to the extent
that request relies on claims pertaining
to EPA’s failure to provide a 10X safety
factor in the 2006 CRA based on the
results of the Zheng et al. study.
Despite the inadequacy of petitioners’
FQPA safety factor claims, EPA
examined the evidence cited by
petitioners for the purpose of evaluating
whether the evidence raises sufficient
grounds for concern regarding
chlorpyrifos that EPA should consider
initiating the actions sought by the
petitioners.
In general, when the Agency conducts
a cumulative assessment, the scope of
cumulative risk is limited to the
common mechanism endpoint—which
in this case of the 2006 OP CRA, was
cholinesterase inhibition, the primary
toxicity mode of action for the OPs. As
such, for the OP CRA, experimental
toxicology data on AChE inhibition
were used for developing relative
potency estimates, points of departure,
and informing the FQPA safety factor
used in the OP CRA. EPA relied on
brain AChE data from adult female rats
dosed for 21 days or longer for
estimating relative potency and points
of departure. At approximately three
weeks of oral exposure to OPs, AChE
inhibition reaches steady state in the
adult rat such that continued dosing
does not result in increased inhibition.
This timeframe of toxicity (21-days and
longer) was selected as there was high
confidence in the potency estimates
derived from the steady state toxicology
studies due to the stability of the AChE
inhibition.
The Agency’s 2006 OP CRA contained
EPA’s complete FQPA safety factor
analysis, (Ref. 22) which involved
consideration of pre-natal and post-natal
experimental toxicology studies, in
addition to exposure information. In the
OP CRA, pre-natal exposure AChE
studies in rats show that the fetus is no
more sensitive than the dam to AChE
inhibition and the fetus is often less
sensitive than the dam. Thus, evaluating
the potential for increased toxicity of
juveniles from post-natal exposure was
a key component in determining the
magnitude of the FQPA safety factors in
the OP CRA. Furthermore, because
characteristics of children are directly
accounted for in the cumulative
exposure assessment, the Agency’s
methods did not underestimate
exposure to OPs.
In the 2006 OP CRA, each OP was
assigned a 10X FQPA safety factor
unless chemical-specific AChE data on
young animals were available to
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generate a data derived safety factor. To
best match the relative potency factor
(RPF)s and PODs based on repeated
dosing, the Agency used repeated
dosing data in juveniles for developing
the FQPA safety factors. For
chlorpyrifos, at the time of the 2006 OP
CRA, the only such data available were
from the Zheng et al. literature study.
The petitioners are correct that Dr.
Carey Pope of Oklahoma State
University provided the Agency with
the raw data from the Zheng et al. study.
These raw data were used to develop
the plot in the 2006 OP CRA which was
reproduced in the Petition. Petitioners
accurately note that for other OPs a
benchmark dose modeling approach
was used and that no BMD values were
reported for chlorpyrifos. In
determining the FQPA safety factor,
petitioners claim that the Agency
misinterpreted the brain AChE data
from Zheng et al.
As shown in the plot reproduced on
page 15 of the Petition, the doseresponse data in the Zheng et al. study
are variable and lack a monotonic shape
at the low dose end of the dose response
curve. The Agency acknowledges that at
the high dose, the pups appear to be
more sensitive. However, at the low
dose end of the response curve, relevant
for human exposures and, thus, the
cumulative risk assessment (i.e., at or
near the 10% inhibition level), little to
no difference is observed. Therefore,
despite the lack of BMD estimates for
the Zheng et al. study, the Agency is
confident in the value used to address
the common mechanism endpoint
(AChE inhibition) addressed in the 2006
CRA. Since that time, the Agency
attempted BMD modeling of the Zheng
et al. data as part of the 2011
preliminary chlorpyrifos HHRA (Ref.
23) which yielded low confidence
results due to the variability in the data.
Dow AgroSciences submitted a
comparative cholinesterase study (CCA)
for chlorpyrifos. CCA studies are
specially designed studies to compare
the dose-response relationship in
juvenile and adult rats. This CCA study
includes two components: (1) Acute,
single dosing in post-natal day 11 and
young adult rats and (2) 11-days of
repeating dosing in rat pups from
PND11–21 and 11-days of repeated
dosing in adult rats. The CCA study for
chlorpyrifos is considered by EPA to be
high quality and well-designed. The
preliminary risk assessment for
chlorpyrifos’ reports BMD estimates
from this CCA study. Specifically, for
the repeated dosing portion of the study,
the BMD10s of 0.80 (0.69 BMDL10) and
1.0 (0.95 BMDL10) mg/kg/day
respectively for female pups and adults
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support the FQPA safety factor of 1X for
the AChE inhibition endpoint used in
the 2006 OP CRA. As such, petitioners’
claims regarding the CRA and FQPA
safety factor is denied.
5. Over-Reliance on Registrant Data
a. Petitioners’ claims. Petitioners
assert that in reregistering chlorpyrifos
EPA ‘‘cherry picked’’ data, ‘‘ignoring
robust, peer-reviewed data in favor of
weak, industry-sponsored data to
determine that chlorpyrifos could be reregistered and food tolerances be
retained.’’ As such, the Agency’s
reassessment decision is not
scientifically defensible.
b. Agency response. This portion of
the Petition does not purport to be an
independent basis for revoking
chlorpyrifos tolerances or cancelling
chlorpyrifos registrations. Rather, this
claim appears to underlie petitioners’
arguments in other sections of the
Petition. While petitioners claim that
EPA ignored robust, peer-reviewed data
in favor of weak, industry-sponsored
data for the reregistration of
chlorpyrifos, petitioners do not cite to
any studies other than those used to
support their other claims. In general,
petitioners did not provide any studies
in the Petition that EPA failed to
evaluate. Since the specific studies cited
by petitioners are not associated with
this claim, but rather their other claims,
EPA’s response to the specific studies
are, therefore, addressed in its responses
to petitioners’ other claims. However,
EPA explains below why, as a general
matter, the Agency does not believe it
‘‘over-relied’’ on registrant data in
evaluating the risks of chlorpyrifos in its
2006 reregistration decision.
In spite of petitioners’ claim, the
Agency does not ignore robust, peerreviewed data in favor of industrysponsored data. Further, EPA has a very
public and well-documented set of
procedures that it applies to the use and
significance accorded all data utilized to
inform risk management decisions.
Registrant generated data, in response to
FIFRA and FFDCA requirements, are
conducted and evaluated in accordance
with a series of internationally
harmonized and scientifically peerreviewed study protocols designed to
maintain a high standard of scientific
quality and reproducibility. (Refs. 23
and 24.)
Additionally, to further inform the
Agency’s risk assessment, EPA is
committed to the consideration of other
sources of information such as data
identified in the open, peer-reviewed
literature and information submitted by
the public as part of the regulatory
evaluation of a pesticide. An important
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issue, when evaluating any study, is its
scientific soundness and quality, and
thus, the level of confidence in the
study findings to contribute to the risk
assessment.
The literature was searched, fully
considered, and provided additional
information on, chlorpyrifos mode of
action, pharmacokinetics, epidemiology,
neurobehavioral effects in laboratory
animals, and age dependent sensitivity
to cholinesterase inhibition.
Therefore, by evaluating registrant
data in accordance with internationally
harmonized and scientifically peerreviewed study protocols, undertaking
thorough open literature searches, and
considering information provided by the
public, the Agency is confident that its
assessment for chlorpyrifos in 2006 was
reasonably based upon the best
available science at the time of the
assessment. Previous sections of this
response to petitioners’ claims regarding
the Agency’s inadequate use of various
data only further highlights and
supports the scientifically defensible
results of the Agency’s assessment.
Petitioners’ claim that the Agency
overly relies on registrant data is
therefore denied.
6. EPA Has Failed To Properly Address
the Exporting Hazard in Foreign
Countries From Chlorpyrifos
As noted in Unit II., in EPA’s July 16,
2012 interim petition response EPA
issued a final denial of this claim. That
denial constituted final agency action
and EPA is not reopening consideration
of that claim.
7.–9. EPA Failed To Quantitatively
Incorporate Data Demonstrating LongLasting Effects From Early Life Exposure
to Chlorpyrifos in Children; EPA
Disregarded Data Demonstrating That
There Is No Evidence of a Safe Level of
Exposure During Pre-Birth and Early
Life Stages; EPA Failed To Cite or
Quantitatively Incorporate Studies and
Clinical Reports Suggesting Potential
Adverse Effects Below 10%
Cholinesterase Inhibition
a. Petitioners’ claims. The petitioners
assert that human epidemiology and
rodent developmental neurotoxicity
data suggest that pre-natal and early life
exposure to chlorpyrifos can result in
long-lasting, possibly permanent
damage to the nervous system and that
these effects are likely occurring at
exposure levels below 10%
cholinesterase inhibition, EPA’s existing
regulatory standard for chlorpyrifos and
other OPs. They assert that EPA has
therefore used the wrong endpoint as a
basis for regulation and that, taking into
account the full spectrum of toxicity,
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chlorpyrifos does not meet the FFDCA
safety standard or the FIFRA standard
for registration.
b. Agency response. EPA has grouped
claims 7–9 together because they
fundamentally all raise the same issue:
Whether the potential exists for
chlorpyrifos to cause
neurodevelopmental effects in infants
and children from exposures (either to
mothers during pregnancy or directly to
infants and children) that are lower than
those resulting in 10% cholinesterase
inhibition—the basis for EPA’s longstanding point of departure in regulating
chlorpyrifos and other OPs. While
petitioners may perhaps disagree, unlike
the claims addressed above, these
claims were not truly challenges to
EPA’s 2006 reregistration decision for
chlorpyrifos, but rather, challenges to
EPA’s ongoing approval of chlorpyrifos
under FIFRA and the FFDCA that rely
in large measure on data published after
EPA completed both its 2001
chlorpyrifos Interim Reregistration
Decision and the 2006 OP CRA that
concluded the reregistration process for
chlorpyrifos and all other OPs. As
matters that largely came to light after
the completion of reregistration, these
petition issues are issues to be
addressed as part of the registration
review of chlorpyrifos—the next round
of re-evaluation under section 3(g) of
FIFRA. As petitioners are aware, past
EPA administrations prioritized the
registration review of the OPs in no
small measure to begin to focus on the
question of OP neurodevelopmental
toxicity, which was, and remains, an
issue at the cutting edge of science,
involving significant uncertainties. EPA
has three times presented approaches
and proposals to the FIFRA SAP for
evaluating recent epidemiologic data
(some of which is cited in the Petition)
exploring the possible connection
between in utero and early childhood
exposure to chlorpyrifos and adverse
neurodevelopmental effects. The SAP’s
reports have rendered numerous
recommendations for additional study
and sometimes conflicting advice for
how EPA should consider (or not
consider) the epidemiology data in
conducting EPA’s registration review
human health risk assessment for
chlorpyrifos. While industry and public
interest groups on both sides of this
issue can debate what the
recommendations mean and which
recommendations should be followed,
one thing should be clear to all persons
following this issue: the science on this
question is not resolved and would
likely benefit from additional inquiry.
EPA has, however, been unable to
persuade the 9th Circuit Court of
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Appeals that further inquiry into this
area of unsettled science should delay
EPA’s response to the Petition. Faced
with an order requiring EPA to respond
to the Petition, in October 2015, EPA
chose to issue a proposed rule to revoke
all chlorpyrifos tolerances based in part
on the uncertain science surrounding
neurodevelopmental toxicity suggested
by certain epidemiology studies. The
comments EPA has received on that
proposal and on EPA’s November 17,
2016 NODA suggest that there continue
to be considerable areas of uncertainty
with regard to what the epidemiology
data show and deep disagreement over
how those data should be considered in
EPA’s risk assessment.
Although not a legal consideration, it
is important to recognize that for many
decades chlorpyrifos has been and
remains one of the most widely used
pesticides in the United States, making
any decision to retain or remove this
pesticide from the market an extremely
significant policy choice. In light of the
significance of this decision and in light
of the significant uncertainty that exists
regarding the potential for chlorpyrifos
to cause adverse neurodevelopmental
effects, EPA’s preference is to fully
explore approaches raised by the SAP
and commenters on the proposed rule,
and possibly seek additional
authoritative peer review of EPA’s risk
assessment prior to finalizing any
regulatory action in the course of
registration review. As the 9th Circuit
has made clear in its August 12, 2016
order in PANNA v. EPA, EPA must
provide a final response to the Petition
by March 31, 2017, regardless of
whether the science remains unsettled
and irrespective of whatever options
may exist for more a complete
resolution of these issues during the
registration review process.
While EPA acknowledges its
obligation to respond to the Petition as
required by the court, the court’s order
does not and cannot compel EPA to
complete the registration review of
chlorpyrifos in advance of the October
1, 2022 deadline provided in section
3(g) of FIFRA, 7 U.S.C. 136a(g).
Although past EPA administrations had
chosen to attempt to complete that
review several years in advance of the
statutory deadline (and respond to the
Petition on the same time frame), it has
turned out that it is not possible to fully
address these issues early in the
registration review period. As a result,
EPA has concluded that it should alter
its priorities and adjust the schedule for
chlorpyrifos so that it can complete its
review of the science addressing
neurodevelopmental effects prior to
making a final registration review
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decision whether to retain, limit or
remove chlorpyrifos from the market.
Accordingly, EPA is denying these
Petition claims and intends to complete
a full and appropriate review of the
neurodevelopmental data before either
finalizing the proposed rule of October
30, 2015, or taking an alternative
regulatory path.
EPA’s denial of the Petition on the
grounds provided above is wholly
consistent with governing law. The
petition provision in FFDCA section
408(d) does not address the timing for
responding to this petition nor does it
limit the extent to which EPA may
coordinate its petition responses with
the registration review provisions of
FIFRA section 3(g). Further, provided
EPA completes registration review by
October 1, 2022, Congress otherwise
gave the EPA Administrator the
discretion to determine the schedule
and timing for completing the review of
the approximately over 1000 pesticide
active ingredients currently subject to
evaluation under section 3(g). EPA may
lawfully re-prioritize the registration
review schedule developed by earlier
administrations provided that decision
is consistent with law and an
appropriate exercise of discretion. See
Federal Communications Commission v.
Fox Television Stations, 129 S.Ct. 1800
(2009) (Administrative Procedure Act
does not require that a policy change be
justified by reasons more substantial
than those required to adopt a policy in
the first instance). Nothing in FIFRA
section 3(g) precludes EPA from altering
a previously established registration
review schedule. Given the absence of a
clear statutory directive, FIFRA and the
FFDCA provide EPA with discretion to
take into account EPA’s registration
review of a pesticide in determining
how and when the Agency responds to
FFDCA petitions to revoke tolerances.
As outlined above, given the importance
of this matter and the fact that critical
questions remain regarding the
significance of the data addressing
neurodevelopmental effects, EPA
believes there is good reason to extend
the registration review of chlorpyrifos
and therefore to deny the Petition. To
find otherwise would effectively give
petitioners under the FFDCA the
authority to re-order scheduling
decisions regarding the FIFRA
registration review process that
Congress has vested in the
Administrator.
10. Inhalation Exposure From
Volatilization
a. Petitioners’ claim. Petitioners assert
that when EPA completed its 2006 OP
CRA, EPA failed to consider and
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incorporate significant exposures to
chlorpyrifos-contaminated air that exist
for some populations in communities
where chlorpyrifos is applied.
Petitioners assert that these exposures
exceeded safe levels when considering
cholinesterase inhibition as a point of
departure and that developmental
neurotoxicity may occur at even lower
exposure levels than those resulting in
cholinesterase inhibition.
b. Agency response. To the extent
petitioners are asserting that human
exposure to chlorpyrifos spray drift and
volatilized chlorpyrifos present
neurodevelopmental risks for infants
and children, EPA is denying this claim
for the reasons stated above in our
response to claims 7–9. As noted, EPA
believes that, given the uncertainties
associated with this identified risk
concern, the appropriate course of
action is for EPA to deny the Petition
and work to further resolve this area of
unsettled science in the time remaining
for the completion of registration review
under section 3(g) of FIFRA.
With respect to petitioners’ claim that
exposures to spray drift and volatilized
chlorpyrifos present a risk from
cholinesterase inhibition, EPA is
denying the Petition for the reasons
previously identified in EPA’s Spray
Drift Mitigation Decision of July 16,
2012 [EPA–HQ–OPP–2008–0850] and
EPA’s interim response of July 15, 2014
[EPA–HQ–OPP–2007–1005] addressing
chlorpyrifos volatilization. In the Spray
Drift Mitigation Decision, EPA
determined that the chlorpyrifos
registrants’ adoption of label mitigation
(in the form of label use rate reductions
and no spray buffer zones) eliminated
risk from cholinesterase inhibition as a
result of spray drift. As for risks
presented by volatilized chlorpyrifos
that may occur following application,
EPA’s July 15, 2014 interim response to
the Petition explained that recent vapor
phase inhalation studies for both
chlorpyrifos and chlorpyrifos-oxon
made clear that neither vapor phase
chlorpyrifos nor chlorpyrifos-oxon
presents a risk of cholinesterase
inhibition. Specifically, those studies, as
indicated in EPA’s memorandum,
Chlorpyrifos: Reevaluation of the
Potential Risks from Volatilization in
Consideration of Chlorpyrifos Parent
and Oxon Vapor Inhalation Toxicity
Studies (Ref. 25), revealed that levels of
chlorpyrifos and chlorpyrifos-oxon in
vapor form are much lower than the
levels seen in earlier aerosol studies that
are better suited for evaluating spray
drift. Indeed, no cholinesterase
inhibition was observed in either
volatility study. What is clear from these
data is that the air cannot hold levels of
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volatilized chlorpyrifos or its oxon that
are capable of causing adverse effects
from cholinesterase inhibition.
VI. Regulatory Assessment
Requirements
As indicated previously, this action
announces the Agency’s order denying
a petition filed, in part, under section
408(d) of FFDCA. As such, this action
is an adjudication and not a rule. The
regulatory assessment requirements
applicable to rulemaking do not,
therefore, apply to this action.
VII. Submission to Congress and the
Comptroller General
The Congressional Review Act, 5
U.S.C. 801 et seq., does not apply
because this action is not a rule for
purposes of 5 U.S.C. 804(3).
IX. References
The following is a listing of the
documents that are specifically
referenced in this document. The docket
includes these documents and other
information considered by EPA,
including documents that are referenced
within the documents that are included
in the docket, even if the referenced
document is not physically located in
the docket. For assistance in locating
these other documents, please consult
the technical person listed under FOR
FURTHER INFORMATION CONTACT.
1. The Petition from NRDC and PANNA and
EPA’s various responses to it are
available in docket number EPA–HQ–
OPP–2007–1005 available at https://
www.regulations.gov.
2. FIFRA Scientific Advisory Panel (2016).
‘‘Chlorpyrifos: Analysis of Biomonitoring
Data’’. Available at: https://
www.epa.gov/sap/meeting-materialsapril-19-21-2016-scientific-advisorypanel.
3. Furlong CE, Holland N, Richter RJ,
Bradman A, Ho A, Eskenazi B (2006).
PON1status of farmworker mothers and
children as a predictor of
organophosphate sensitivity.
Pharmacogenet Genomics. 2006 Mar;
16(3):183–90.
4. Sultatos LG; Murphy SD, (1983). Kinetic
Analysis Of The Microsomal
Biotransformation Of The
Phosphorothioate Insecticides
Chlorpyrifos And Parathion.
Fundemental and Applied Toxicology.
3:16–21.
5. U.S. EPA (2008). Draft Appendix E
available at https://www.epa.gov/scipoly/
sap/meetings/2008/september/
appendixe.pdf. Draft Science Issue
Paper: Chlorpyrifos Hazard and Dose
Response Characterization. August 21,
2008. Available at https://www.epa.gov/
scipoly/sap/meetings/2008/september/
chlorpyrifoscharacter.pdf.
6. Holland, N., Furlong, C., Bastaki, M.,
Richter, R., Bradman, A., Huen, K.,
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Beckman, K., and Eskenazi, B. (2006).
Paraoxonase polymorphisms,
haplotypes, and enzyme activity in
Latino mothers and newborns. Environ.
Health Perspect. 114(7), 985–991; Chen,
J., Kumar, M., Chan, W., Berkowitz, G.,
and Wetmur, J. (2003). Increased
Influence of Genetic Variation on PON1
Activity in Neonates. Environmental
Health Perspective 111, 11:1403–9.
7. U.S. EPA (2008). Transmittal of Meeting
Minutes of the FIFRA Scientific
Advisory Panel Meeting Held September
16–18, 2008 on the Agency’s Evaluation
of the Toxicity Profile of Chlorpyrifos.
Available at https://www.epa.gov/scipoly/
sap/meetings/2008/september/
sap0908report.pdf at 61.
8. Engel, S.M., Wetmur, J., Chen, J., Zhu, C.,
Boyd Barr, D., Canfield, R.L., Wolff,
M.S., (2011) Prenatal Exposure to
Organophosphates, Paraoxonase 1, and
Cognitive Development in Childhood
Environ Health Perspect 119:1182–1188
(2011). doi:10.1289/ehp.1003183 [Online
21 April 2011].
9. Hofmann, J.N., Keifer, M.C., Furlong, C.E.,
De Roos, A.J., Farin., F.M., Fenske, R.A.,
van Belle, G., Checkoway, H. (2009)
Serum Cholinesterase Inhibition in
Relation to Paraoxonase-1 (PON1) Status
among Organophosphate-Exposed
Agricultural Pesticide Handlers./Environ
Health Perspect 117:1402–1408 (2009).
doi:10.1289/ehp.0900682. Available at
https://dx.doi.org/ [Online 9 June 2009].
10. Eskenazi, B; Huen, K., Marks, A., Harley,
K.G., Bradman, A., Boyd Barr, D.,
Holland, N. (2010) PON1 and
Neurodevelopment in Children from the
CHAMACOS Study Exposed to
Organophosphate Pesticides in Utero.
Environmental Health Perspectives. Vol.
118 (12): 1775–1781).
11. Harley KG, Huen K, Schall RA, Holland
NT, Bradman A, et al.,(2011) Association
of Organophosphate Pesticide Exposure
and Paraoxonase with Birth Outcome in
Mexican-American Women. PLoS ONE
6(8): e23923. doi:10.1371/
journal.pone.0023923.
12. IPCS (International Programme on
Chemical Safety) 2005. ChemicalSpecific Adjustment Factors for
Interspecies Differences and Human
Variability: Guidance Document for Use
of Data in Dose/Concentration-Response
Assessment. Harmonization Project
Document No. 2. World Health
Organization, International Programme
on Chemical Safety, Geneva,
Switzerland.
13. U.S. EPA (2014). Guidance for Applying
Quantitative Data to Develop DataDerived Extrapolation Factors for
Interspecies and Intraspecies
Extrapolation. Available at https://
www.epa.gov/risk/guidance-applyingquantitative-data-develop-data-derivedextrapolation-factors-interspecies-and.
14. For additional information on the
Endocrine Disruptor Screening program
see https://www.epa.gov/endo/.
15. For information related to the status of
EDSP test orders/DCIs, status of EDSP
OSRI: order recipient submissions and
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EPA responses, and other EDSP assay
information see https://www.epa.gov/
endo/pubs/toresources/index.htm.
16. For available Data Evaluation Records
(DERs) for EDSP Tier 1, see https://
www.epa.gov/endocrine-disruption/
endocrine-disruptor-screening-programtier-1-screening-determinations-and.
17. Hoppin JA, Lubin JH, Rusiecki JA,
Sandler DP, Dosemeci M, Alavanja MC.
(2004) Cancer incidence among pesticide
applicators exposed to chlorpyrifos in
the Agricultural Health Study. J Natl
Cancer Inst, 96(23), 1781–1789.
(hereinafter Lee et al., 2004).
18. U.S. EPA (2005). Guidelines for
Carcinogen Risk Assessment. Available
at https://www.epa.gov/raf/publications/
pdfs/CANCER_GUIDELINES_FINAL_325-05.PDF.
19. Christenson, C. (2011). D388167,
Chlorpyrifos Carcinogenicity: Review of
Evidence from the U.S. Agricultural
Health Study (AHS) Epidemiologic
Evaluations 2003–2009.
20. Weichenthal S, Moase C, Chan P (2010).
A review of pesticide exposure and
cancer incidence in the agricultural
health study cohort. Cien Saude Colet.
2012 Jan;17(1):255–70. PubMed PMID:
22218559.
21. Zheng Q, Olivier K, Won YK, Pope CN.
(2000). Comparative cholinergic
neurotoxicity of oral chlorpyrifos
exposures in pre-weaning and adult rats.
Toxicological Sciences, 55(1): 124–132.
22. For additional information on the
organophosphate cumulative risk
assessment, see https://epa.gov/
pesticides/cumulative/2006-op/op_cra_
main.pdf.
23. U.S. EPA (2011). Chlorpyrifos:
Preliminary Human Health Risk
Assessment for Registration. Available in
docket number EPA–HQ–OPP–2008–
0850, https://www.regulations.gov/
#!documentDetail;D=EPA-HQ-OPP-20080850-0025.
(23) For additional information on EPA’s
Harmonized Test Guidelines and
international efforts at harmonization,
see https://www.epa.gov/opp00001/
science/guidelines.htm.
(24) Available at https://www.regulations.gov
in docket EPA–HQ–OPP–2008–0850.
Authority: 7 U.S.C. 136 et seq. and 21
U.S.C. 346a.
Dated: March 29, 2017.
E. Scott Pruitt,
Administrator.
[FR Doc. 2017–06777 Filed 4–4–17; 8:45 am]
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the Federal Register. Copies of the
agreements are available through the
Commission’s Web site (www.fmc.gov)
or by contacting the Office of
Agreements at (202)-523–5793 or
tradeanalysis@fmc.gov.
Agreement No.: 010071–045.
Title: Cruise Lines International
Association Agreement.
Parties: A-Rosa Flussschiff GmbH;
Acromas Shipping, Ltd./Saga Shipping;
Aida Cruises; AMA Waterways;
American Cruise Lines, Inc.; Aqua
Expeditions Pte. Ltd.; Australian Pacific
Touring Pty Ltd.; Avalon Waterways;
Azamara Cruises; Carnival Cruise Lines;
Celebrity Cruises, Inc.; Celestyal
Cruises; Costa Cruise Lines; Compagnie
Du Ponant; Croisieurope; Crystal
Cruises; Cunard Line; Disney Cruise
Line; Dream Cruises Management Ltd.;
Emerald Waterways; French America
Line; Hapag-Lloyd Kreuzfahrten Gmbh;
Heritage River Journeys Pvt Ltd.;
Holland America Line; Luftner Cruises;
MSC Cruises; NCL Corporation; Oceania
Cruises; P & O Cruises; P & O Cruises
Australia; PandaW River Expeditions;
Paul Gauguin Cruises; Pearl Seas
Cruises; Princess Cruises; Pullmantur
Cruises Ship Management Ltd.; Regent
Seven Seas Cruises; Riviera Tours Ltd.;
Royal Caribbean International; Scenic
Luxury Cruises & Tours Ltd.; Seabourn
Cruise Line; SeaDream Yacht Club;
Shearings Holidays Ltd.; Silversea
Cruises, Ltd.; Star Cruises (HK) Limited;
St. Helena Line/Andrew Weir Shipping
Ltd.; Tauck River Cruising; Thomson
Cruises; Travelmarvel; Tui Cruises
Gmbh; Uniworld River Cruises, Inc.;
Venice Simplon-Orient-Express Ltd./
Belmond; and Windstar Cruises.
Filing Party: Andre Picciurro, Esq.
Kaye, Rose & Partners, LLP; Emerald
Plaza, 402 West Broadway, Suite 1300;
San Diego, CA 92101–3542.
Synopsis: The Amendment would
update the Agreement membership and
revise language in the Agreement
regarding the election of the Chair and
Vice Chair of the Agreement.
Agreement No.: 012476.
Title: HSDG/HLAG/CMA CGM Slot
Charter Agreement.
Parties: Hamburg Sud; Hapag-Lloyd
AG; and CMA CGM S.A.
Filing Party: Wayne Rohde; Cozen
O’Connor; 1200 19th Street NW.,
Washington, DC 20036.
Synopsis: The Agreement authorizes
HSDG and HLAG to charter space to
CMA CGM in the trade between the U.S.
East Coast on the one hand, and
Colombia, Ecuador, Peru and Chile on
the other hand. The Parties have
requested expedited review.
PO 00000
Frm 00023
Fmt 4703
Sfmt 4703
Agreement No.: 012477.
Title: CMA CGM/HLAG U.S.-West
Med Slot Charter Agreement.
Parties: CMA CGM, S.A.; and Hapag
Lloyd AG.
Filing Party: Draughn B. Arbona, Esq;
CMA CGM (America) LLC; 5701 Lake
Wright Drive; Norfolk, VA 23502.
Synopsis: This Agreement authorizes
CMA CGM to charter space to HLAG in
the trade between Italy and Spain on the
one hand, and the U.S. East Coast on the
other hand.
Agreement No.: 012478.
Title: NYK/OOCL Space Charter
Agreement.
Parties: Nippon Yusen Kaisha and
Orient Overseas Container Line Limited.
Filing Party: Joshua P. Stein; Cozen
O’Connor; 1200 Nineteenth Street NW.,
Washington, DC 20036.
Synopsis: The Agreement authorizes
NYK to charter space to OOCL on the
service referred to as the PS1 and
operated under THE Alliance
Agreement (FMC Agreement No.
012439) and to enter into arrangements
related to the chartering of such space.
By Order of the Federal Maritime
Commission.
Dated: March 31, 2017.
Rachel E. Dickon,
Assistant Secretary.
[FR Doc. 2017–06734 Filed 4–4–17; 8:45 am]
BILLING CODE 6731–AA–P
FEDERAL RESERVE SYSTEM
Change in Bank Control Notices;
Acquisitions of Shares of a Bank or
Bank Holding Company
The notificants listed below have
applied under the Change in Bank
Control Act (12 U.S.C. 1817(j)) and
225.41 of the Board’s Regulation Y (12
CFR 225.41) to acquire shares of a bank
or bank holding company. The factors
that are considered in acting on the
notices are set forth in paragraph 7 of
the Act (12 U.S.C. 1817(j)(7)).
The notices are available for
immediate inspection at the Federal
Reserve Bank indicated. The notices
also will be available for inspection at
the offices of the Board of Governors.
Interested persons may express their
views in writing to the Reserve Bank
indicated for that notice or to the offices
of the Board of Governors. Comments
must be received not later than April 21,
2017.
A. Federal Reserve Bank of
Minneapolis (Jacquelyn K. Brunmeier,
Assistant Vice President) 90 Hennepin
Avenue, Minneapolis, Minnesota
55480–0291:
E:\FR\FM\05APN1.SGM
05APN1
Agencies
[Federal Register Volume 82, Number 64 (Wednesday, April 5, 2017)]
[Notices]
[Pages 16581-16592]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2017-06777]
=======================================================================
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ENVIRONMENTAL PROTECTION AGENCY
[EPA-HQ-OPP-2007-1005; FRL-9960-77]
Chlorpyrifos; Order Denying PANNA and NRDC's Petition To Revoke
Tolerances
AGENCY: Environmental Protection Agency (EPA).
ACTION: Order.
-----------------------------------------------------------------------
SUMMARY: In this Order, EPA denies a petition requesting that EPA
revoke all tolerances for the pesticide chlorpyrifos under section
408(d) of the Federal Food, Drug, and Cosmetic Act and cancel all
chlorpyrifos registrations under the Federal Insecticide, Fungicide and
Rodenticide Act. The petition was filed in September 2007 by the
Pesticide Action Network North America (PANNA) and the Natural
Resources Defense Council (NRDC).
DATES: This Order is effective April 5, 2017. Objections and requests
for hearings must be received on or before June 5, 2017, and must be
filed in accordance with the instructions provided in 40 CFR part 178
(see also Unit I. of the SUPPLEMENTARY INFORMATION.)
ADDRESSES: The docket for this action, identified by docket
identification (ID) number EPA-HQ-OPP-2007-1005, is available at https://www.regulations.gov or at the Office of Pesticide Programs Regulatory
Public Docket (OPP Docket) in the Environmental Protection Agency
Docket Center (EPA/DC), West William Jefferson Clinton Bldg., Rm. 3334,
1301 Constitution Ave. NW., Washington, DC 20460-0001. The Public
Reading Room is open from 8:30 a.m. to 4:30 p.m., Monday through
Friday, excluding legal
[[Page 16582]]
holidays. The telephone number for the Public Reading Room is (202)
566-1744, and the telephone number for the OPP Docket is (703) 305-
5805. Please review the visitor instructions and additional information
about the docket available at https://www.epa.gov/dockets.
FOR FURTHER INFORMATION CONTACT: Pesticide Re-Evaluation Division
(7508P), Office of Pesticide Programs, Environmental Protection Agency,
1200 Pennsylvania Ave. NW., Washington, DC 20460-0001; telephone
number: (703) 347-0206; email address:
OPPChlorpyrifosInquiries@epa.gov.
SUPPLEMENTARY INFORMATION:
I. General Information
A. Does this action apply to me?
In this document EPA denies a petition by PANNA and the NRDC to
revoke pesticide tolerances and cancel pesticide registrations. This
action may also be of interest to agricultural producers, food
manufacturers, or pesticide manufacturers. Potentially affected
entities may include, but are not limited to those engaged in the
following activities:
Crop production (North American Industrial Classification
System (NAICS) code 111), e.g., agricultural workers; greenhouse,
nursery, and floriculture workers; farmers.
Animal production (NAICS code 112), e.g., cattle ranchers
and farmers, dairy cattle farmers, livestock farmers.
Food manufacturing (NAICS code 311), e.g., agricultural
workers; farmers; greenhouse, nursery, and floriculture workers;
ranchers; pesticide applicators.
Pesticide manufacturing (NAICS code 32532), e.g.,
agricultural workers; commercial applicators; farmers, greenhouse,
nursery, and floriculture workers; residential users.
This listing is not intended to be exhaustive, but rather to
provide a guide for readers regarding entities likely to be affected by
this action. Other types of entities not listed in this unit could also
be affected. The NAICS codes have been provided to assists you and
others in determining whether this action might apply to certain
entities. If you have any questions regarding the applicability of this
action to a particular entity, consult the person listed under FOR
FURTHER INFORMATION CONTACT.
B. How can I get copies of this document and other related information?
EPA has established a docket for this action under Docket ID No.
EPA-HQ-OPP-2007-1005. Additional information relevant to this action is
located in the chlorpyrifos registration review docket under Docket ID
No, EPA-HQ-OPP-2008-0850 and the chlorpyrifos tolerance rulemaking
docket under Docket ID No, EPA-HQ-OPP-2015-0653. To access the
electronic docket, go to https://www.regulations.gov, select ``Advanced
Search,'' then ``Docket Search.'' Insert the docket ID number where
indicated and select the ``Submit'' button. Follow the instructions on
the regulations.gov Web site to view the docket index or access
available documents. All documents in the docket are listed in the
docket index available in regulations.gov. Although listed in the
index, some information is not publicly available, e.g., Confidential
Business Information (CBI) or other information whose disclosure is
restricted by statute. Certain other material, such as copyrighted
material, is not placed on the Internet and will be publicly available
only in hard copy form. Publicly available docket materials are
available in the electronic docket or, if only available in hard copy,
at the OPP Regulatory Public Docket in Rm. S-4400, One Potomac Yard
(South Bldg.), 2777 S. Crystal Dr., Arlington, VA. The Docket Facility
is open from 8:30 a.m. to 4 p.m. Monday through Friday, excluding legal
holidays. The Docket Facility telephone number is (703) 305-5805.
C. Can I file an objection or hearing request?
Under section 408(g) of the Federal Food, Drug and Cosmetic Act
(FFDCA) (21 U.S.C. 346a(g)), any person may file an objection to any
aspect of this order and may also request a hearing on those
objections. You must file your objection or request a hearing on this
order in accordance with the instructions provided in 40 CFR part 178.
To ensure proper receipt by EPA, you must identify docket ID number
EPA-HQ-OPP-2007-1005 in the subject line on the first page of your
submission. All objections and requests for a hearing must be in
writing, and must be received by the Hearing Clerk on or before June 5,
2017, and may be submitted by one of the following methods:
Mail: U.S. EPA Office of Administrative Law Judges,
Mailcode 1900R, 1200 Pennsylvania Ave. NW., Washington, DC 20460
Hand Delivery: U.S. Environmental Protection Agency Office
of Administrative Law Judges, Ronald Reagan Building, Rm. M1200, 1300
Pennsylvania Ave. NW., Washington, DC 20004. Deliveries are only
accepted during the Office's normal hours of operation (8:30 a.m. to 4
p.m., Monday through Friday, excluding legal holidays). Special
arrangements should be made for deliveries of boxed information. The
Office's telephone number is (202) 564-6255.
In addition to filing an objection or hearing request with the
Hearing Clerk as described in 40 CFR part 178, please submit a copy of
the filing that does not contain CBI for inclusion in the public docket
that is described in I.B.1 above. Information not marked confidential
pursuant to 40 CFR part 2 may be disclosed publicly by EPA without
prior notice. Submit this copy, identified by docket ID number EPA-HQ-
OPP-2007-1005, by one of the following methods:
Federal eRulemaking Portal: https://www.regulations.gov.
Follow the on-line instructions for submitting comments.
Mail: U.S. Environmental Protection Agency Office of
Pesticide Programs (OPP) Public Regulatory Docket (7502P), 1200
Pennsylvania, Ave. NW., Washington, DC 20460-0001.
Delivery: OPP Regulatory Public Docket (7502P),
Environmental Protection Agency, Rm. S-4400, One Potomac Yard (South
Bldg.), 2777 S. Crystal Dr., Arlington, VA. Deliveries are only
accepted during the Docket's normal hours of operation (8:30 a.m. to 4
p.m., Monday through Friday, excluding legal holidays). Special
arrangements should be made for deliveries of boxed information. The
Docket Facility telephone number is (703) 305-5805.
D. What should be included in objections?
The objection stage is the second stage in the petition process
under FFDCA section 408. This multi-stage process is initiated by a
petition requesting establishment, modification, or revocation of a
tolerance. Once EPA makes a decision on a petition, and publishes its
decision in the Federal Register, the second stage of the petition
process is triggered. At this point, parties who disagree with EPA's
decision, whether it is a decision to grant or deny the petition, may
file objections with EPA to the decision made. The objection stage
gives parties a chance to seek review of EPA's decision before the
Agency. This is an opportunity for parties to contest the conclusions
EPA reached and the determinations underlying those conclusions. As an
administrative review stage, it is not an opportunity to raise new
issues or arguments or present facts or information that were available
earlier. On the other hand, parties must do more than repeat the claims
in the petition. The objection stage is the opportunity to challenge
EPA's decision on the petition. An objection fails on its
[[Page 16583]]
face if it does not identify aspects of EPA's decision believed to be
in error and explain the reason why EPA's decision is incorrect. This
two-stage process insures that issues are fully aired before the Agency
and a comprehensive record is compiled, prior to judicial review.
II. Introduction
A. What action is the Agency taking?
In this document, EPA denies a petition by PANNA and the NRDC. In a
petition dated September 12, 2007, PANNA and NRDC (the petitioners)
requested that EPA revoke all tolerances for the pesticide chlorpyrifos
established under section 408 of the FFDCA. (Ref. 1) The petition also
sought the cancellation of all chlorpyrifos pesticide product
registrations under section 6 the Federal Insecticide, Fungicide and
Rodenticide Act (FIFRA), 7 U.S.C. 136d. The PANNA and NRDC petition
(the Petition) raised the following claims regarding EPA's
reregistration and active registrations of chlorpyrifos in support of
the request for tolerance revocation and product cancellation:
1. EPA has ignored genetic evidence of vulnerable populations.
2. EPA has needlessly delayed a decision regarding endocrine
disrupting effects.
3. EPA has ignored data regarding cancer risks.
4. EPA's 2006 cumulative risk assessment (CRA) for the
organophosphates misrepresented risks and failed to apply FQPA 10X
safety factor. [For convenience's sake, the legal requirements
regarding the additional safety margin for infants and children in
section 408(b)(2)(C) of the FFDCA are referred to throughout this
response as the ``FQPA 10X safety factor'' or simply the ``FQPA safety
factor.'' Due to Congress' focus on both pre- and post-natal toxicity,
EPA has interpreted this additional safety factor as pertaining to
risks to infants and children that arise due to pre-natal exposure as
well as to exposure during childhood years.]
5. EPA has over-relied on registrant data.
6. EPA has failed to properly address the exporting hazard in
foreign countries from chlorpyrifos.
7. EPA has failed to quantitatively incorporate data demonstrating
long-lasting effects from early life exposure to chlorpyrifos in
children.
8. EPA has disregarded data demonstrating that there is no evidence
of a safe level of exposure during pre-birth and early life stages.
9. EPA has failed to cite or quantitatively incorporate studies and
clinical reports suggesting potential adverse effects below 10%
cholinesterase inhibition.
10. EPA has failed to incorporate inhalation routes of exposure.
In this order EPA is denying the Petition in full. EPA provided the
petitioners with two interim responses on July 16, 2012, and July 15,
2014, respectively. The July 16, 2012, response denied claim 6 (export
hazard) completely and that portion of the response was a final agency
action. The remainder of the July 16, 2012, response and the July 15,
2014, response expressed EPA's intention to deny six other petition
claims (1-5 and 10). [In the 2012 response, EPA did, however, inform
petitioners of its approval of label mitigation (in the form of rate
reductions and spray drift buffers) to reduce bystander risks,
including risks from inhalation exposure, which in effect partially
granted petition claim 10.] EPA made clear in both the 2012 and 2014
responses that, absent a request from petitioners, EPA's denial of
those six claims would not be made final until EPA finalized its
response to the entire Petition. Petitioners made no such request. EPA
is finalizing its denial of those six claims in this order.
The remaining claims (7-9) all related to same issue: Whether the
potential exists for chlorpyrifos to cause neurodevelopmental effects
in children at exposure levels below EPA's existing regulatory standard
(10% cholinesterase inhibition). While these claims raised novel,
highly complex and unresolved scientific issues, EPA decided it would
nonetheless expedite the registration review of chlorpyrifos under
FIFRA section 3(g), and attempt to address these issues several years
in advance of the October 1, 2022 deadline for completing that review.
Accordingly, EPA also decided as a policy matter that it would address
the Petition claims raising these matters on a similar timeframe.
Although EPA had expedited its registration review to address these
issues, the petitioners were not satisfied with EPA's progress in
responding to the Petition and they brought legal action in the 9th
Circuit Court of Appeals to compel EPA to either issue an order denying
the Petition or to grant the Petition by initiating the tolerance
revocation process. In August 2015, the 9th Circuit issued a ruling in
favor of the petitioners and ordered EPA to respond to the Petition by
either denying the Petition or issuing a proposed or final rule
revoking chlorpyrifos tolerances. In re Pesticide Action Network of
North America v. EPA, 798 F.3d (9th Cir. 2015).
On November 6, 2015, pursuant to the 9th Circuit's order, EPA
proposed to revoke all chlorpyrifos tolerances based in part on
uncertainty surrounding the potential for chlorpyrifos to cause
neurodevelopmental effects--the issue raised in petition claims 7-9.
Following publication of the proposal, the 9th Circuit announced that
it would retain jurisdiction over this matter and on August 12, 2016,
the court further ordered EPA to complete a final petition response by
March 31, 2017 and made clear that no further extensions would be
granted. On November 17, 2016, EPA published a notice of data
availability that released for public comment EPA's revised risk
assessment that proposed a new regulatory point of departure based on
the potential for chlorpyrifos to result in adverse neurodevelopmental
effects.
Following a review of comments on both the November 2015 proposal
and the November 2016 notice of data availability, EPA has concluded
that, despite several years of study, the science addressing
neurodevelopmental effects remains unresolved and that further
evaluation of the science during the remaining time for completion of
registration review is warranted to achieve greater certainty as to
whether the potential exists for adverse neurodevelopmental effects to
occur from current human exposures to chlorpyrifos. EPA has therefore
concluded that it will not complete the human health portion of the
registration review or any associated tolerance revocation of
chlorpyrifos without first attempting to come to a clearer scientific
resolution on those issues. As noted, Congress has provided that EPA
must complete registration review by October 1, 2022. Because the 9th
Circuit's August 12, 2016 order has made clear, however, that further
extensions to the March 31, 2017 deadline for responding to the
Petition would not be granted, EPA is today also denying all remaining
petition claims.
B. What is the Agency's authority for taking this action?
Under section 408(d)(4) of the FFDCA, EPA is authorized to respond
to a section 408(d) petition to revoke tolerance either by issuing a
final rule revoking the tolerances, issuing a proposed rule, or issuing
an order denying the Petition.
[[Page 16584]]
III. Statutory and Regulatory Background
A. FFDCA/FIFRA and Applicable Regulations
1. In general. EPA establishes maximum residue limits, or
``tolerances,'' for pesticide residues in food and feed commodities
under section 408 of the FFDCA. Without such a tolerance or an
exemption from the requirement of a tolerance, a food containing a
pesticide residue is ``adulterated'' under section 402 of the FFDCA and
may not be legally moved in interstate commerce. Section 408 was
substantially rewritten by the Food Quality Protection Act of 1996
(FQPA) (Pub. L. 104-170, 110 Stat. 1489 (1996)), which established a
detailed safety standard for pesticides and integrated EPA's regulation
of pesticide food residues under the FFDCA with EPA's registration and
re-evaluation of pesticides under FIFRA. The standard for issuing or
maintaining a tolerance under section 408(b)(2)(A)(i) of the FFDCA is
whether it is ``safe.'' ``Safe'' is defined by section 408(b)(2)(A)(ii)
to mean that ``there is a reasonable certainty that no harm will result
from aggregate exposure to the pesticide chemical residue, including
all anticipated dietary exposures and all other exposures for which
there is reliable information.''
While the FFDCA authorizes the establishment of legal limits for
pesticide residues in food, section 3(a) of FIFRA requires the approval
of pesticides prior to their sale and distribution, and establishes a
registration regime for regulating the use of pesticides. FIFRA
regulates pesticide use in conjunction with its registration scheme by
requiring EPA review and approval of pesticide labels and specifying
that use of a pesticide inconsistent with its label is a violation of
federal law. In the FQPA, Congress integrated action under the two
statutes by requiring that the safety standard under the FFDCA be used
as a criterion in FIFRA registration actions as to pesticide uses which
result in dietary risk from residues in or on food, (see FIFRA section
2(bb)), and directing that EPA coordinate, to the extent practicable,
revocations of tolerances with pesticide cancellations under FIFRA.
(See FFDCA section 408(l)(1).) Under section 3(g) of FIFRA, EPA is
required to re-evaluate pesticides under the FIFRA standard--which
includes a determination regarding the safety of existing FFDCA
tolerances--every 15 years under a program known as ``registration
review.'' The deadline for completing the registration review for
chlorpyrifos is October 1, 2022.
2. Procedures for establishing, amending, or revoking tolerances.
Tolerances are established, amended, or revoked by rulemaking under the
unique procedural framework set forth in the FFDCA. Generally, a
tolerance rulemaking is initiated by the party seeking to establish,
amend, or revoke a tolerance by means of filing a petition with EPA.
(See FFDCA section 408(d)(1).) EPA publishes in the Federal Register a
notice of the petition filing and requests public comment. After
reviewing the petition, and any comments received on it, section
408(d)(4) provides that EPA may issue a final rule establishing,
amending, or revoking the tolerance, issue a proposed rule to do the
same, or deny the petition.
Once EPA takes final action on the petition by establishing,
amending, or revoking the tolerance or denying the petition, section
408(g)(2) allows any party to file objections with EPA and seek an
evidentiary hearing on those objections. Objections and hearing
requests must be filed within 60 days. Section 408(g)(2)(B) provides
that EPA shall ``hold a public evidentiary hearing if and to the extent
the Administrator determines that such a public hearing is necessary to
receive factual evidence relevant to material issues of fact raised by
the objections.'' EPA regulations make clear that hearings will only be
granted where it is shown that there is ``a genuine and substantial
issue of fact,'' the requestor has identified evidence `which ``would,
if established, resolve one or more of such issues in favor of the
requestor,'' and the issue is ``determinative'' with regard to the
relief requested. (40 CFR 178.32(b).) Further, a party may not raise
issues in objections unless they were part of the petition and an
objecting party must state objections to the EPA decision and not just
repeat the allegations in its petition. Corn Growers v. EPA, 613 F.2d
266 (D.C. Cir. 2010), cert. denied, 131 S. Ct. 2931 (2011). EPA's final
order on the objections is subject to judicial review. (21 U.S.C.
346a(h)(1).)
IV. Chlorpyrifos Regulatory Background
Chlorpyrifos (0,0-diethyl-0-3,5,6-trichloro-2-pyridyl
phosphorothioate) is a broad-spectrum, chlorinated organophosphate (OP)
insecticide that has been registered for use in the United States since
1965. By pounds of active ingredient, it is the most widely used
conventional insecticide in the country. Currently registered use sites
include a large variety of food crops (including tree fruits and nuts,
many types of small fruits and vegetables, including vegetable seed
treatments, grain/oilseed crops, and cotton, for example), and non-food
use settings (e.g., ornamental and agricultural seed production, non-
residential turf, industrial sites/rights of way, greenhouse and
nursery production, sod farms, pulpwood production, public health and
wood protection). For some of these crops, chlorpyrifos is currently
the only cost-effective choice for control of certain insect pests. In
2000, the chlorpyrifos registrants reached an agreement with EPA to
voluntarily cancel all residential use products except those registered
for ant and roach baits in child-resistant packaging and fire ant mound
treatments.
In 2006, EPA completed FIFRA section 4 reregistration and FFDCA
tolerance reassessment for chlorpyrifos and the OP class of pesticides.
Having completed reregistration and tolerance reassessment, EPA is
required to complete the next re-evaluation of chlorpyrifos under the
FIFRA section 3(g) registration review program by October 1, 2022.
Given ongoing scientific developments in the study of the OPs
generally, in March 2009 EPA announced its decision to prioritize the
FIFRA section 3(g) registration review of chlorpyrifos by opening a
public docket and releasing a preliminary work plan to complete the
chlorpyrifos registration review by 2015--7 years in advance of the
date required by law.
The registration review of chlorpyrifos and the OPs has presented
EPA with numerous novel scientific issues that the agency has taken to
multiple FIFRA Scientific Advisory Panel (SAP) meetings since the
completion of reregistration. [The SAP is a federal advisory committee
created by section 25(d) of FIFRA, that serves as EPA's primary source
of peer review for significant regulatory and policy matters involving
pesticides.] Many of these complex scientific issues formed the basis
of the 2007 petition filed by PANNA and NRDC and EPA therefore decided
to address the Petition on a similar timeframe to EPA's expedited
registration review schedule.
Although EPA expedited the chlorpyrifos registration review in an
attempt to address the novel scientific issues raised by the Petition
in advance of the statutory deadline, the petitioners were dissatisfied
with the pace of EPA's response efforts and have sued EPA in federal
court on three separate occasions to compel a faster response to the
Petition. As explained in Unit V., EPA had addressed 7 of the 10 claims
asserted in the Petition by either
[[Page 16585]]
denying the claim, issuing a preliminary denial or approving label
mitigation to address the claims, but on June 10, 2015, in the PANNA
decision, the U.S. Court of Appeals for the Ninth Circuit signaled its
intent to order EPA to complete its response to the Petition and
directed EPA to inform the court how--and by when--EPA intended to
respond. On June 30, 2015, EPA informed the court that it intended to
propose by April 15, 2016, the revocation of all chlorpyrifos
tolerances in the absence of pesticide label mitigation that ensures
that exposures will be safe. On August 10, 2015, the court rejected
EPA's time line and issued a mandamus order directing EPA to ``issue
either a proposed or final revocation rule or a full and final response
to the administrative Petition by October 31, 2015.''
On October 30, 2015, EPA issued a proposed rule to revoke all
chlorpyrifos tolerances which it published in the Federal Register on
November 6, 2015 (80 FR 69080). On December 10, 2015, the Ninth Circuit
issued a further order requiring EPA to complete any final rule (or
petition denial) and fully respond to the Petition by December 30,
2016. On June 30, 2016, EPA sought a 6-month extension to that deadline
in order to allow EPA to fully consider the most recent views of the
FIFRA SAP with respect to chlorpyrifos toxicology. The FIFRA SAP report
was finalized and made available for EPA consideration on July 20,
2016. (Ref. 2) On August 12, 2016, the court rejected EPA's request for
a 6-month extension and ordered EPA to complete its final action by
March 31, 2017 (effectively granting EPA a three-month extension). On
November 17, 2016, EPA published a notice of data availability (NODA)
seeking public comment on both EPA's revised risk and water assessments
and reopening the comment period on the proposal to revoke all
chlorpyrifos (81 FR 81049). The comment period for the NODA closed on
January 17, 2017.
V. Ruling on Petition
This order denies the Petition on the nine remaining grounds for
which EPA has not issued a final denial that can be the subject of
objections under section 408(g)(2) of the FFDCA. As noted in Unit II,
on July 16, 2012, EPA denied as final agency action petitioners' claim
6 that the registration of chlorpyrifos created an export hazard for
workers in foreign countries. That response and the response of July
15, 2014, also included EPA's preliminary denial of petition claims 1-5
and 10 (except to the extent EPA granted that claim) and EPA's
responses to those claims are now incorporated into this order as set
forth below. This unit also includes EPA's basis for denying petition
claims 7-9. Each specific petition claim is summarized in this Unit V.
immediately prior to EPA's response to the claim.
1. Genetic Evidence of Vulnerable Populations
a. Petitioners' claim. Petitioners claim that as part of EPA's
reregistration decision (which was completed in 2006 with the
completion of the organophosphate cumulative risk assessment) the
Agency failed to calculate an appropriate intra-species uncertainty
factor (i.e., within human variability) for chlorpyrifos in both its
aggregate and cumulative risk assessments (CRA). They assert that
certain relevant, robust data, specifically the Furlong et al. (2006)
study (Ref. 3) that addresses intra-species variability in the behavior
of the detoxifying enzyme paraoxonase (PON1), indicate that the Agency
should have applied an intra-species safety factor ``of at least 150X
in the aggregate and cumulative assessments'' rather than the 10X
factor EPA applied. Petitioners conclude by noting that applying an
intra-species factor of 100X or higher would require setting tolerances
below the level of detection, which therefore should compel EPA to
revoke all chlorpyrifos tolerances.
b. Agency Response. Petitioners are correct that the Agency, as
part of the 2006 OP CRA, evaluated, but did not rely on Furlong et al.
in setting the intra-species uncertainty factor for that assessment.
The Agency did not rely on the results of the PON1 data in the OP CRA
because these data do not take into consideration the complexity of OP
metabolism, which involves multiple metabolic enzymes, not just PON1.
In addition, EPA believes the methodology utilized in the Furlong et
al. study to measure intra-species variability--i.e., combining values
from multiple species (transgenic mice and human) to determine the
range of sensitivity within a single species--is not consistent with
well-established international risk assessment practices. Further, EPA
believes that petitioners' assertion that the Furlong et al. study
supports an intra-species uncertainty factor of at least 150X is based
on an analysis of the data that is inconsistent with EPA policy and
widely-accepted international guidance on the development of intra-
species uncertainty factors. In addition, the 2008 FIFRA SAP did not
support the use of the Furlong et al (2006) study alone in deriving an
intra-species factor. For these reasons, and as further explained
below, EPA believes it is not appropriate to solely rely on the results
of the Furlong et al. study, or petitioners' interpretation of those
results, for purposes of determining the intra-species uncertainty
factor. To determine that factor, EPA first uses science tools to
quantitatively characterize human variability in both exposure and
dosimetry, and then determines the appropriate intra-species
uncertainty factor to protect sensitive populations. Specifically, for
chlorpyrifos, EPA uses a physiologically-based pharmacokinetic (PBPK)
model to account for human variability in the absorption, distribution,
metabolism and excretion (ADME) of chemicals based on key
physiological, biochemicals, and physicochemical determinants of these
ADME processes, including the influence of PON1 variability.
Addressing human variability and sensitive populations is an
important aspect of the Agency's risk assessment process. The Agency is
well aware of the issue of PON1 and has examined the scientific
evidence on this source of genetic variability. PON1 is one of the key
detoxification enzymes of chlorpyrifos and is included as part of the
PBPK model used by EPA in the 2014 human health risk assessment (HHRA)
and 2016 revised risk assessment. Specifically, PON1 is an A-esterase
which can metabolize chlorpyrifos-oxon without inactivating the enzyme.
(Ref. 4) Indeed, as part of the 2008 SAP, EPA performed a literature
review of PON1 and its possible use in informing the intra-species
(i.e., within human variability) uncertainty factor. This literature
review can be found in the draft Appendix E: Data Derived Extrapolation
Factor Analysis to the draft Science Issue Paper: Chlorpyrifos Hazard
and Dose Response Characterization. (Ref. 5) In sum, the Agency
considered available PON1 data from more than 25 studies from diverse
human populations worldwide.
The Agency focused on the PON1-192 polymorphism since it has been
linked to chlorpyrifos-oxon sensitivity in experimental toxicology
studies and, has been evaluated in epidemiology studies attempting to
associate PON1 status with health outcomes following OP pesticide
exposure in adults and children (Holland et al., 2006; Chen et al.,
2003. (Ref. 6). [Note, Holland et al. (2006) and Furlong et al. (2006)
report findings from the same cohort. The Holland reference provides
enzymes activities for specific polymorphisms in Table 4; the Furlong
paper does not report such values and provides
[[Page 16586]]
information primarily in graphical form.] However, EPA believes that
focusing on PON1 variability in isolation from other metabolic action
is not an appropriate approach for developing a data-driven uncertainty
factor. The Agency solicited feedback from the SAP on the utility of
the PON1 data, by itself, for use in risk assessment; the SAP was
similarly not supportive of using such data in isolation. Specifically,
the SAP report states:
. . . the information on PON1 polymorphisms should not be used
as the sole factor in a data-derived uncertainty factor for two main
reasons: (1) it is only one enzyme in a complex pathway, and is
subsequent to the bioactivation reaction; therefore it can only
function on the amount of bioactivation product (i.e., chlorpyrifos-
oxon) that is delivered to it by CYP450); and (2) the genotype of
PON1 alone is insufficient to predict vulnerability because the
overall level of enzyme activity is ultimately what determines
detoxification potential from that pathway; thus, it is better to
use PON1 status because it provides information regarding PON1
genotype and activity. Some of the data from laboratory animal
studies in PON knockout animals are using an unrealistic animal
model and frequently very high dose levels, and do not reflect what
might happen in humans. (Ref. 7)
Based on a detailed review of the literature and the comments from
the SAP, the Agency has determined that such data are not appropriate
for use alone in deriving an intra-species uncertainty factor for use
in human health risk assessment. As indicated by the SAP report,
multiple factors (e.g., other enzymes such as P450s, carboxylesterases,
butyrylcholinesterase) are likely to impact potential population
sensitivity, rendering the results of the PON1 data, by themselves,
insufficiently reliable to support a regulatory conclusion about the
potential variation of human sensitivity to chlorpyrifos.
Since the 2008 SAP, several epidemiological studies have been
published that considered the association between PON status/genotype
and health outcome. Hofmann et al. (2009) recently reported
associations between PON1 status and inhibition of
butyrylcholinesterase (BuChE) in a group of pesticide handlers in
Washington. The authors note that this study requires replication with
larger sample size(s) and more blood samples. (Ref. 8) Given the
limitations of Hofmann et al., the Agency has not drawn any conclusions
from this study. The Q/R-192 and/or C/T-108 polymorphism at the
promoter site have been evaluated recently as a factor affecting birth
or neurobehavioral outcomes following gestational exposure to OPs.
(Refs. 9, 10, 11) These studies (Eskanazi., et al., 2010 (Ref. 9);
Harley et al., 2011 (Ref. 10); Engel et al., 2011 (Ref. 11)) were
evaluated by EPA in preparation for the April 2012 SAP review.
Petitioners further emphasize that the Furlong et al. study
supports an intra-species uncertainty factor of over 164X given the
range of variability seen in that study. The 164X value is derived from
sensitivity observed in transgenic mice expressing human PON1Q-192
compared with mice expressing human PON1R-192 combined with the range
of plasma arylesterase (AREase) from the newborn with the lowest PON1
level compared with the mother with the highest PON1 level from a group
of 130 maternal-newborn pairs from the CHAMACOS (Center for the Health
Assessment of Mothers and Children of Salinas) cohort.
EPA believes it is fundamentally at odds with international risk
assessment practices to combine values from both mouse and human data
to determine the potential range of variability within a single
species--regardless of whether the test animals express a human PON1
enzyme. As the 2008 FIFRA SAP explained, PON1 is but a single enzyme
that should not be considered in isolation to predict the overall level
of enzyme activity that may affect human sensitivity to a substance.
Using a 164X intra-species uncertainty factor derived from the Furlong
et al. study would take this practice one step further by relying upon
combined PON1 values from different species with differing overall
metabolic activity to derive the intra-species factor. EPA does not
believe this approach is an appropriate means of determining the
potential range of intra-species variability.
Finally, petitioners' assertion that the Furlong study supports an
intra-species uncertainty factor of at least 150X is based on an
analysis of that study that is inconsistent with EPA policy and widely-
accepted international guidance on the development of intra-species
uncertainty factors. In deriving the intra-species uncertainty factor
in its risk assessments, EPA is guided by the principles of the 2005
IPCS (Ref. 12) guidance on chemical specific adjustment factors (CSAFs)
and the EPA's 2014 Guidance for Applying Quantitative Data to Develop
Data-Derived Extrapolation Factors for Interspecies and Intraspecies
Extrapolation. (Ref. 13) These guidances recommend that intra-species
factors should be extrapolated from a measure of central tendency in
the population to a measure in the sensitive population (i.e., to
extrapolate from a typical human to a sensitive human). To base the
factor on the difference between the single lowest and highest
measurements in a given study, as petitioners suggest in this instance,
would likely greatly exaggerate potential intra-species variability.
That approach effectively assumes that the point of departure in an EPA
risk assessment will be derived from the least sensitive test subject,
thereby necessitating the application of an intra-species factor that
accounts for the full range of sensitivity across a species. Since EPA
does not develop its PoDs in this fashion; the approach suggested by
petitioners is not appropriate.
In summary, the Agency has carefully considered the issue of PON1
variability and determined that data addressing PON1 in isolation are
not appropriate for use alone in deriving an intra-species uncertainty
factor and that the issue is more appropriately handled using a PBPK
model. Further, the derivation of the 164X value advocated by the
petitioners is based on combining values from humanized mice with human
measured values with a range from highest to lowest; the Furlong et al.
derivation is inappropriate and inconsistent with international risk
assessment practice. (Ref. 2) The 2008 FIFRA SAP did not support the
PON1 data used in isolation. Finally, petitioners' statement that the
Furlong et al. study supports an intra-species uncertainty factor of at
least 150X likely overstates potential variability. EPA therefore
denies this aspect of the Petition.
2. Endocrine Disrupting Effects
a. Petitioners' claim. Petitioners summarize a number of studies
evaluating the effects of chlorpyrifos on the endocrine system,
asserting that, taken together, the studies ``suggest that chlorpyrifos
may be an endocrine disrupting chemical, capable of interfering with
multiple hormones controlling reproduction and neurodevelopment.'' The
petitioners then assert that EPA should not have delayed consideration
of endocrine effects absent finalization of the Endocrine Disruptor
Screening Program (EDSP) (Ref. 14) and should have quantitatively
incorporated the studies into the chlorpyrifos IRED.
b. Agency Response. This portion of the Petition appears largely to
be a complaint about the completeness of EPA's reregistration decision
and a request that EPA undertake quantitative incorporation of
endocrine endpoints into its assessment of chlorpyrifos. The Petition
does not explain whether and
[[Page 16587]]
how endocrine effects should form the basis of a decision to revoke
tolerances. The basis for seeking revocation of a tolerance is a
showing that the pesticide is not ``safe.'' Petitioners have neither
asserted that EPA should revoke tolerances because effects on the
endocrine system render the tolerances unsafe, nor have petitioners
submitted a factual analysis demonstrating that aggregate exposure to
chlorpyrifos presents an unsafe risk to humans based on effects on the
endocrine system. Rather, the Petition appears to collect a number of
studies suggesting that chlorpyrifos may have effects on the endocrine
system and that EPA should have considered those health impacts at
reregistration in a quantitative assessment.
To the extent that petitioners are seeking tolerance revocation on
these grounds, the Petition fails to provide a sufficient basis for
revocation because, in addition to the preceding defects, the cited
data do not provide quantitative data (i.e., endpoints/points of
departure) that indicate endocrine effects at doses that are more
sensitive than the points of departure used in the chlorpyrifos risk
assessment that are based on cholinesterase inhibition. While the cited
studies provide qualitative information that exposure to chlorpyrifos
may be associated with effects on the androgen and thyroid hormonal
pathways, these data alone do not demonstrate that current human
exposures from existing tolerances are unsafe. The Agency noted similar
effects during its evaluation of information submitted by People for
the Ethical Treatment of Animals (PETA) and the Physicians Committee
for Responsible Medicine (PCRM) during its review of existing
information as part of EPA's EDSP, as discussed below. Based on the
review of that data, EPA concluded that the effects seen in those
studies do not call into question EPA's prior safety determinations
supporting the existing tolerances; the data do not indicate a risk
warranting regulatory action, and the petitioners have provided no
specific information to alter this determination.
Consequently, the Petition does not support a conclusion that
existing tolerances are unsafe due to potential endocrine effects. This
portion of the Petition is therefore denied.
As petitioners may be aware, since the filing of the petition, EPA
has completed the evaluation of chlorpyrifos under EPA's EDSP, as
required under FFDCA section 408(p) that confirms EPA's conclusions. On
April 15, 2009, a Federal Register notice was published in which
chlorpyrifos was included in the initial list of chemicals (List 1) to
receive EDSP Tier 1 test orders. The EDSP program is a two-tiered
screening and testing program, Tier 1 and Tier 2 tests. Tier 1 includes
11 assays in the battery; these data are intended to allow EPA to
determine whether certain substances (including pesticide active and
other ingredients) have the potential to interact with the endocrine
system and cause an effect in humans or wildlife similar to an effect
produced by a ``naturally occurring estrogen, or other such endocrine
effects as the Administrator may designate.'' The purpose of Tier 2
tests is to identify and establish a quantitative, dose-response
relationship for any adverse effects that might result from the
interactions with the endocrine system.
On November 5, 2009, EPA issued Tier 1 test orders to the
registrants of chlorpyrifos, requiring a battery of 11 screening assays
to identify the potential to interact with the estrogen, androgen, or
thyroid hormonal systems. (Ref. 15)
The agency received and reviewed all 11 EDSP Tier 1 screening
assays for chlorpyrifos. On June 29, 2015, the agency completed the
EDSP weight of evidence (WoE) conclusions for the Tier 1 screening
assays for List 1 chemicals, including chlorpyrifos. In addition to the
Tier 1 data, the WoE evaluations considered other scientifically
relevant information (OSRI), including general toxicity data and open
literature studies of sufficient quality. In determining whether
chlorpyrifos interacts with the estrogen, androgen or thyroid pathways,
the agency considered the number and type of effects induced, the
magnitude and pattern of responses observed across studies, taxa, and
sexes. Additionally, the agency also considered the conditions under
which effects occurred, in particular whether or not endocrine-related
responses occurred at dose(s) that also resulted in general systemic or
overt toxicity. The agency concluded that, based on weight of evidence
considerations, EDSP Tier 2 testing is not recommended for chlorpyrifos
since there was no evidence of potential interaction with the estrogen,
androgen and thyroid pathways. The EDSP Tier 1 WoE assessment and
associated data evaluation records for chlorpyrifos are available
online. (Ref. 16) This assessment further supports EPA's denial of this
portion of the Petition.
3. Cancer Risks
a. Petitioners' claim. Petitioners claim that the Agency
``ignored'' a December 2004 National Institutes of Health Agricultural
Health Study (AHS) by Lee et al. (2004) (Ref. 17) that evaluated the
association between chlorpyrifos and lung cancer incidence. (Ref. 17)
The petition summarizes the results of the AHS study, stating that the
incidence of lung cancer has a statistically significant association
with chlorpyrifos exposure. The Petition then asserts that these data
are highly relevant and therefore should have been referenced in the
final aggregate assessment for chlorpyrifos or the OP CRA. Petitioners
do not otherwise explain whether and how these data support the
revocation of tolerances or the cancellation of pesticide
registrations.
b. Agency Response. As explained in the previous section, the basis
for seeking revocation of a tolerance is a showing that the pesticide
is not ``safe.'' Claiming that EPA failed to reference certain data in
its risk assessment regarding carcinogenicity does not amount to
illustrating that the tolerances are unsafe. To show a lack of safety,
petitioners would have to present some fact-based argument
demonstrating that aggregate exposure to chlorpyrifos poses an unsafe
carcinogenic risk. Petitioners have not presented such an analysis.
Accordingly, EPA is denying the Petition to revoke chlorpyrifos
tolerances or cancel chlorpyrifos registrations to the extent the
Petition relies on claims pertaining to carcinogenicity.
Despite the inadequacy of petitioners' cancer claims, in the course
of the Agency's review of chlorpyrifos, EPA has examined the Lee et al.
study cited by petitioners (Ref. 17) among other lines of evidence. EPA
has concluded that the Lee et al. investigation does not alter the
Agency's weight of evidence determination concerning chlorpyrifos'
carcinogenic potential, and therefore does not alter the Agency's
current cancer classification for chlorpyrifos. Specifically, the
Agency does not believe this evidence raises sufficient grounds for
concern regarding chlorpyrifos that EPA should consider initiating
action based upon this information that might lead to revocation of the
chlorpyrifos tolerances or cancellation of the chlorpyrifos
registrations.
The Agency was aware of the December 2004 study cited by
petitioners. While Lee et al. observed a possible association between
chlorpyrifos use and the incidence of lung cancer, the authors also
stressed that further evaluation was necessary before concluding the
association was causal in nature. (Ref. 17) Additional evaluation is
necessary because of
[[Page 16588]]
possible alternative explanations for the Lee et al. study, which
include unmeasured confounding factors or confounding factors not fully
accounted for in the analysis, and possible false positive results due
to the performance of multiple statistical tests.
EPA has been a collaborating agency with the AHS since 1993, and
continues to closely monitor the AHS literature. The Agency is working
closely with the AHS researchers to clearly understand the results of
their research efforts to ensure the Agency appropriately interprets
these data as future studies are published. Between 2003 and 2009 there
have been six nested case-control analyses within the AHS which
evaluated the use of a number of agricultural pesticides, including
chlorpyrifos, in association with specific anatomical cancer sites, in
addition to the previously published cohort study (Ref. 17) cited by
the petitioners. As noted below, both the Agency and Health Canada have
comprehensively reviewed these data.
In accordance with the Agency's 2005 Guideline for Cancer Risk
Assessment (Ref. 18), chlorpyrifos is classified as ``Not Likely to be
Carcinogenic to Humans'' based on the lack of evidence of
carcinogenicity in male or female mice and male or female rats. In
chronic toxicity/carcinogenicity studies, animals received chlorpyrifos
in their feed every day of their lives (78 weeks for mice and 104 weeks
for rats) at doses thousands of times greater than any anticipated
exposure to humans from authorized uses. There was no evidence of
cancer in the experimental animal studies. Additionally, available
evidence from in vivo and in vitro assays did not support a mutagenic
or genotoxic potential of chlorpyrifos.
Recently, the Agency conducted its own review of the six nested
case-control analyses and one cohort study within the AHS concerning
the carcinogenic potential of chlorpyrifos. (Ref. 19) EPA concluded
with respect to the AHS lung cancer results that the findings are
useful for generating hypotheses, but require confirmation in future
studies. This conclusion is consistent with that of researchers from
Health Canada. Specifically, Weichenthal et al. (2010) (Ref. 20)
published a review article in Environmental Health Perspectives on
pesticide exposure and cancer incidence in the AHS cohort. Their review
of these same studies concluded that the weight of experimental
toxicological evidence does not suggest that chlorpyrifos is
carcinogenic, and that epidemiologic results currently available from
the AHS are inconsistent, lack replication, and lack a coherent
biologically plausible carcinogenic mode of action. The authors did
note positive exposure-response associations for chlorpyrifos and lung
cancer in two separate evaluations.
In summary, while there is initial suggestive epidemiological
evidence of an association between chlorpyrifos and lung cancer to only
form a hypothesis as to a carcinogenic mode of action, additional
research (including follow-up AHS research) is needed to test the
hypothesis. Consequently, at this time it is reasonable to conclude
chlorpyrifos is not a carcinogen in view of the lack of carcinogenicity
in the rodent bioassays and the lack of a genotoxic or mutagenic
potential. The Agency concludes that existing epidemiological data
(including Lee et al.) do not change the current weight of the evidence
conclusions. The Agency continues to believe there is not a sufficient
basis to alter its assessment of chlorpyrifos as not likely to be
carcinogenic to humans when multiple lines of evidence are considered
(e.g., epidemiology findings, rodent bioassay, genotoxicity);
therefore, chlorpyrifos cancer risk would not be a factor in any
potential Agency risk determination to revoke tolerances for
chlorpyrifos.
4. CRA Misrepresents Risks, Failed To Apply FQPA10X Safety Factor
a. Petitioners' claim. Petitioners assert that EPA relied on
limited data and inaccurate interpretations of data to support its
decision to remove the FQPA safety factor in the 2006 OP CRA.
Specifically, the petitioners challenge the Agency's use of data from a
paper by Zheng et al. (2000) (Ref. 21) claiming that, in contrast to
the Agency's analysis of the study data, the data does show an obvious
difference between juvenile and adult responses to chlorpyrifos.
Petitioners conclude by asserting that the Zheng et al. study supports
using a 10X safety factor for chlorpyrifos in the CRA.
b. Agency Response. Petitioners' assertions do not provide a
sufficient basis for revoking chlorpyrifos tolerances. As explained
previously, the ground for seeking revocation of a tolerance is a
showing that the pesticide is not ``safe.'' The petitioners' claim that
the data EPA relied upon support a different FQPA safety factor for
chlorpyrifos in the CRA does not amount to a showing that chlorpyrifos
tolerances are unsafe. To show a lack of safety, petitioners would have
to present a factual analysis demonstrating that the lack of a 10X
safety factor in the CRA for chlorpyrifos poses unsafe cumulative
exposures to the OPs. Petitioners have not made such a showing. For
this reason, EPA is denying the petitioners' request to revoke
chlorpyrifos tolerances or cancel chlorpyrifos registrations to the
extent that request relies on claims pertaining to EPA's failure to
provide a 10X safety factor in the 2006 CRA based on the results of the
Zheng et al. study.
Despite the inadequacy of petitioners' FQPA safety factor claims,
EPA examined the evidence cited by petitioners for the purpose of
evaluating whether the evidence raises sufficient grounds for concern
regarding chlorpyrifos that EPA should consider initiating the actions
sought by the petitioners.
In general, when the Agency conducts a cumulative assessment, the
scope of cumulative risk is limited to the common mechanism endpoint--
which in this case of the 2006 OP CRA, was cholinesterase inhibition,
the primary toxicity mode of action for the OPs. As such, for the OP
CRA, experimental toxicology data on AChE inhibition were used for
developing relative potency estimates, points of departure, and
informing the FQPA safety factor used in the OP CRA. EPA relied on
brain AChE data from adult female rats dosed for 21 days or longer for
estimating relative potency and points of departure. At approximately
three weeks of oral exposure to OPs, AChE inhibition reaches steady
state in the adult rat such that continued dosing does not result in
increased inhibition. This timeframe of toxicity (21-days and longer)
was selected as there was high confidence in the potency estimates
derived from the steady state toxicology studies due to the stability
of the AChE inhibition.
The Agency's 2006 OP CRA contained EPA's complete FQPA safety
factor analysis, (Ref. 22) which involved consideration of pre-natal
and post-natal experimental toxicology studies, in addition to exposure
information. In the OP CRA, pre-natal exposure AChE studies in rats
show that the fetus is no more sensitive than the dam to AChE
inhibition and the fetus is often less sensitive than the dam. Thus,
evaluating the potential for increased toxicity of juveniles from post-
natal exposure was a key component in determining the magnitude of the
FQPA safety factors in the OP CRA. Furthermore, because characteristics
of children are directly accounted for in the cumulative exposure
assessment, the Agency's methods did not underestimate exposure to OPs.
In the 2006 OP CRA, each OP was assigned a 10X FQPA safety factor
unless chemical-specific AChE data on young animals were available to
[[Page 16589]]
generate a data derived safety factor. To best match the relative
potency factor (RPF)s and PODs based on repeated dosing, the Agency
used repeated dosing data in juveniles for developing the FQPA safety
factors. For chlorpyrifos, at the time of the 2006 OP CRA, the only
such data available were from the Zheng et al. literature study.
The petitioners are correct that Dr. Carey Pope of Oklahoma State
University provided the Agency with the raw data from the Zheng et al.
study. These raw data were used to develop the plot in the 2006 OP CRA
which was reproduced in the Petition. Petitioners accurately note that
for other OPs a benchmark dose modeling approach was used and that no
BMD values were reported for chlorpyrifos. In determining the FQPA
safety factor, petitioners claim that the Agency misinterpreted the
brain AChE data from Zheng et al.
As shown in the plot reproduced on page 15 of the Petition, the
dose-response data in the Zheng et al. study are variable and lack a
monotonic shape at the low dose end of the dose response curve. The
Agency acknowledges that at the high dose, the pups appear to be more
sensitive. However, at the low dose end of the response curve, relevant
for human exposures and, thus, the cumulative risk assessment (i.e., at
or near the 10% inhibition level), little to no difference is observed.
Therefore, despite the lack of BMD estimates for the Zheng et al.
study, the Agency is confident in the value used to address the common
mechanism endpoint (AChE inhibition) addressed in the 2006 CRA. Since
that time, the Agency attempted BMD modeling of the Zheng et al. data
as part of the 2011 preliminary chlorpyrifos HHRA (Ref. 23) which
yielded low confidence results due to the variability in the data.
Dow AgroSciences submitted a comparative cholinesterase study (CCA)
for chlorpyrifos. CCA studies are specially designed studies to compare
the dose-response relationship in juvenile and adult rats. This CCA
study includes two components: (1) Acute, single dosing in post-natal
day 11 and young adult rats and (2) 11-days of repeating dosing in rat
pups from PND11-21 and 11-days of repeated dosing in adult rats. The
CCA study for chlorpyrifos is considered by EPA to be high quality and
well-designed. The preliminary risk assessment for chlorpyrifos'
reports BMD estimates from this CCA study. Specifically, for the
repeated dosing portion of the study, the BMD10s of 0.80
(0.69 BMDL10) and 1.0 (0.95 BMDL10) mg/kg/day
respectively for female pups and adults support the FQPA safety factor
of 1X for the AChE inhibition endpoint used in the 2006 OP CRA. As
such, petitioners' claims regarding the CRA and FQPA safety factor is
denied.
5. Over-Reliance on Registrant Data
a. Petitioners' claims. Petitioners assert that in reregistering
chlorpyrifos EPA ``cherry picked'' data, ``ignoring robust, peer-
reviewed data in favor of weak, industry-sponsored data to determine
that chlorpyrifos could be re-registered and food tolerances be
retained.'' As such, the Agency's reassessment decision is not
scientifically defensible.
b. Agency response. This portion of the Petition does not purport
to be an independent basis for revoking chlorpyrifos tolerances or
cancelling chlorpyrifos registrations. Rather, this claim appears to
underlie petitioners' arguments in other sections of the Petition.
While petitioners claim that EPA ignored robust, peer-reviewed data in
favor of weak, industry-sponsored data for the reregistration of
chlorpyrifos, petitioners do not cite to any studies other than those
used to support their other claims. In general, petitioners did not
provide any studies in the Petition that EPA failed to evaluate. Since
the specific studies cited by petitioners are not associated with this
claim, but rather their other claims, EPA's response to the specific
studies are, therefore, addressed in its responses to petitioners'
other claims. However, EPA explains below why, as a general matter, the
Agency does not believe it ``over-relied'' on registrant data in
evaluating the risks of chlorpyrifos in its 2006 reregistration
decision.
In spite of petitioners' claim, the Agency does not ignore robust,
peer-reviewed data in favor of industry-sponsored data. Further, EPA
has a very public and well-documented set of procedures that it applies
to the use and significance accorded all data utilized to inform risk
management decisions. Registrant generated data, in response to FIFRA
and FFDCA requirements, are conducted and evaluated in accordance with
a series of internationally harmonized and scientifically peer-reviewed
study protocols designed to maintain a high standard of scientific
quality and reproducibility. (Refs. 23 and 24.)
Additionally, to further inform the Agency's risk assessment, EPA
is committed to the consideration of other sources of information such
as data identified in the open, peer-reviewed literature and
information submitted by the public as part of the regulatory
evaluation of a pesticide. An important issue, when evaluating any
study, is its scientific soundness and quality, and thus, the level of
confidence in the study findings to contribute to the risk assessment.
The literature was searched, fully considered, and provided
additional information on, chlorpyrifos mode of action,
pharmacokinetics, epidemiology, neurobehavioral effects in laboratory
animals, and age dependent sensitivity to cholinesterase inhibition.
Therefore, by evaluating registrant data in accordance with
internationally harmonized and scientifically peer-reviewed study
protocols, undertaking thorough open literature searches, and
considering information provided by the public, the Agency is confident
that its assessment for chlorpyrifos in 2006 was reasonably based upon
the best available science at the time of the assessment. Previous
sections of this response to petitioners' claims regarding the Agency's
inadequate use of various data only further highlights and supports the
scientifically defensible results of the Agency's assessment.
Petitioners' claim that the Agency overly relies on registrant data is
therefore denied.
6. EPA Has Failed To Properly Address the Exporting Hazard in Foreign
Countries From Chlorpyrifos
As noted in Unit II., in EPA's July 16, 2012 interim petition
response EPA issued a final denial of this claim. That denial
constituted final agency action and EPA is not reopening consideration
of that claim.
7.-9. EPA Failed To Quantitatively Incorporate Data Demonstrating Long-
Lasting Effects From Early Life Exposure to Chlorpyrifos in Children;
EPA Disregarded Data Demonstrating That There Is No Evidence of a Safe
Level of Exposure During Pre-Birth and Early Life Stages; EPA Failed To
Cite or Quantitatively Incorporate Studies and Clinical Reports
Suggesting Potential Adverse Effects Below 10% Cholinesterase
Inhibition
a. Petitioners' claims. The petitioners assert that human
epidemiology and rodent developmental neurotoxicity data suggest that
pre-natal and early life exposure to chlorpyrifos can result in long-
lasting, possibly permanent damage to the nervous system and that these
effects are likely occurring at exposure levels below 10%
cholinesterase inhibition, EPA's existing regulatory standard for
chlorpyrifos and other OPs. They assert that EPA has therefore used the
wrong endpoint as a basis for regulation and that, taking into account
the full spectrum of toxicity,
[[Page 16590]]
chlorpyrifos does not meet the FFDCA safety standard or the FIFRA
standard for registration.
b. Agency response. EPA has grouped claims 7-9 together because
they fundamentally all raise the same issue: Whether the potential
exists for chlorpyrifos to cause neurodevelopmental effects in infants
and children from exposures (either to mothers during pregnancy or
directly to infants and children) that are lower than those resulting
in 10% cholinesterase inhibition--the basis for EPA's long-standing
point of departure in regulating chlorpyrifos and other OPs. While
petitioners may perhaps disagree, unlike the claims addressed above,
these claims were not truly challenges to EPA's 2006 reregistration
decision for chlorpyrifos, but rather, challenges to EPA's ongoing
approval of chlorpyrifos under FIFRA and the FFDCA that rely in large
measure on data published after EPA completed both its 2001
chlorpyrifos Interim Reregistration Decision and the 2006 OP CRA that
concluded the reregistration process for chlorpyrifos and all other
OPs. As matters that largely came to light after the completion of
reregistration, these petition issues are issues to be addressed as
part of the registration review of chlorpyrifos--the next round of re-
evaluation under section 3(g) of FIFRA. As petitioners are aware, past
EPA administrations prioritized the registration review of the OPs in
no small measure to begin to focus on the question of OP
neurodevelopmental toxicity, which was, and remains, an issue at the
cutting edge of science, involving significant uncertainties. EPA has
three times presented approaches and proposals to the FIFRA SAP for
evaluating recent epidemiologic data (some of which is cited in the
Petition) exploring the possible connection between in utero and early
childhood exposure to chlorpyrifos and adverse neurodevelopmental
effects. The SAP's reports have rendered numerous recommendations for
additional study and sometimes conflicting advice for how EPA should
consider (or not consider) the epidemiology data in conducting EPA's
registration review human health risk assessment for chlorpyrifos.
While industry and public interest groups on both sides of this issue
can debate what the recommendations mean and which recommendations
should be followed, one thing should be clear to all persons following
this issue: the science on this question is not resolved and would
likely benefit from additional inquiry.
EPA has, however, been unable to persuade the 9th Circuit Court of
Appeals that further inquiry into this area of unsettled science should
delay EPA's response to the Petition. Faced with an order requiring EPA
to respond to the Petition, in October 2015, EPA chose to issue a
proposed rule to revoke all chlorpyrifos tolerances based in part on
the uncertain science surrounding neurodevelopmental toxicity suggested
by certain epidemiology studies. The comments EPA has received on that
proposal and on EPA's November 17, 2016 NODA suggest that there
continue to be considerable areas of uncertainty with regard to what
the epidemiology data show and deep disagreement over how those data
should be considered in EPA's risk assessment.
Although not a legal consideration, it is important to recognize
that for many decades chlorpyrifos has been and remains one of the most
widely used pesticides in the United States, making any decision to
retain or remove this pesticide from the market an extremely
significant policy choice. In light of the significance of this
decision and in light of the significant uncertainty that exists
regarding the potential for chlorpyrifos to cause adverse
neurodevelopmental effects, EPA's preference is to fully explore
approaches raised by the SAP and commenters on the proposed rule, and
possibly seek additional authoritative peer review of EPA's risk
assessment prior to finalizing any regulatory action in the course of
registration review. As the 9th Circuit has made clear in its August
12, 2016 order in PANNA v. EPA, EPA must provide a final response to
the Petition by March 31, 2017, regardless of whether the science
remains unsettled and irrespective of whatever options may exist for
more a complete resolution of these issues during the registration
review process.
While EPA acknowledges its obligation to respond to the Petition as
required by the court, the court's order does not and cannot compel EPA
to complete the registration review of chlorpyrifos in advance of the
October 1, 2022 deadline provided in section 3(g) of FIFRA, 7 U.S.C.
136a(g). Although past EPA administrations had chosen to attempt to
complete that review several years in advance of the statutory deadline
(and respond to the Petition on the same time frame), it has turned out
that it is not possible to fully address these issues early in the
registration review period. As a result, EPA has concluded that it
should alter its priorities and adjust the schedule for chlorpyrifos so
that it can complete its review of the science addressing
neurodevelopmental effects prior to making a final registration review
decision whether to retain, limit or remove chlorpyrifos from the
market. Accordingly, EPA is denying these Petition claims and intends
to complete a full and appropriate review of the neurodevelopmental
data before either finalizing the proposed rule of October 30, 2015, or
taking an alternative regulatory path.
EPA's denial of the Petition on the grounds provided above is
wholly consistent with governing law. The petition provision in FFDCA
section 408(d) does not address the timing for responding to this
petition nor does it limit the extent to which EPA may coordinate its
petition responses with the registration review provisions of FIFRA
section 3(g). Further, provided EPA completes registration review by
October 1, 2022, Congress otherwise gave the EPA Administrator the
discretion to determine the schedule and timing for completing the
review of the approximately over 1000 pesticide active ingredients
currently subject to evaluation under section 3(g). EPA may lawfully
re-prioritize the registration review schedule developed by earlier
administrations provided that decision is consistent with law and an
appropriate exercise of discretion. See Federal Communications
Commission v. Fox Television Stations, 129 S.Ct. 1800 (2009)
(Administrative Procedure Act does not require that a policy change be
justified by reasons more substantial than those required to adopt a
policy in the first instance). Nothing in FIFRA section 3(g) precludes
EPA from altering a previously established registration review
schedule. Given the absence of a clear statutory directive, FIFRA and
the FFDCA provide EPA with discretion to take into account EPA's
registration review of a pesticide in determining how and when the
Agency responds to FFDCA petitions to revoke tolerances. As outlined
above, given the importance of this matter and the fact that critical
questions remain regarding the significance of the data addressing
neurodevelopmental effects, EPA believes there is good reason to extend
the registration review of chlorpyrifos and therefore to deny the
Petition. To find otherwise would effectively give petitioners under
the FFDCA the authority to re-order scheduling decisions regarding the
FIFRA registration review process that Congress has vested in the
Administrator.
10. Inhalation Exposure From Volatilization
a. Petitioners' claim. Petitioners assert that when EPA completed
its 2006 OP CRA, EPA failed to consider and
[[Page 16591]]
incorporate significant exposures to chlorpyrifos-contaminated air that
exist for some populations in communities where chlorpyrifos is
applied. Petitioners assert that these exposures exceeded safe levels
when considering cholinesterase inhibition as a point of departure and
that developmental neurotoxicity may occur at even lower exposure
levels than those resulting in cholinesterase inhibition.
b. Agency response. To the extent petitioners are asserting that
human exposure to chlorpyrifos spray drift and volatilized chlorpyrifos
present neurodevelopmental risks for infants and children, EPA is
denying this claim for the reasons stated above in our response to
claims 7-9. As noted, EPA believes that, given the uncertainties
associated with this identified risk concern, the appropriate course of
action is for EPA to deny the Petition and work to further resolve this
area of unsettled science in the time remaining for the completion of
registration review under section 3(g) of FIFRA.
With respect to petitioners' claim that exposures to spray drift
and volatilized chlorpyrifos present a risk from cholinesterase
inhibition, EPA is denying the Petition for the reasons previously
identified in EPA's Spray Drift Mitigation Decision of July 16, 2012
[EPA-HQ-OPP-2008-0850] and EPA's interim response of July 15, 2014
[EPA-HQ-OPP-2007-1005] addressing chlorpyrifos volatilization. In the
Spray Drift Mitigation Decision, EPA determined that the chlorpyrifos
registrants' adoption of label mitigation (in the form of label use
rate reductions and no spray buffer zones) eliminated risk from
cholinesterase inhibition as a result of spray drift. As for risks
presented by volatilized chlorpyrifos that may occur following
application, EPA's July 15, 2014 interim response to the Petition
explained that recent vapor phase inhalation studies for both
chlorpyrifos and chlorpyrifos-oxon made clear that neither vapor phase
chlorpyrifos nor chlorpyrifos-oxon presents a risk of cholinesterase
inhibition. Specifically, those studies, as indicated in EPA's
memorandum, Chlorpyrifos: Reevaluation of the Potential Risks from
Volatilization in Consideration of Chlorpyrifos Parent and Oxon Vapor
Inhalation Toxicity Studies (Ref. 25), revealed that levels of
chlorpyrifos and chlorpyrifos-oxon in vapor form are much lower than
the levels seen in earlier aerosol studies that are better suited for
evaluating spray drift. Indeed, no cholinesterase inhibition was
observed in either volatility study. What is clear from these data is
that the air cannot hold levels of volatilized chlorpyrifos or its oxon
that are capable of causing adverse effects from cholinesterase
inhibition.
VI. Regulatory Assessment Requirements
As indicated previously, this action announces the Agency's order
denying a petition filed, in part, under section 408(d) of FFDCA. As
such, this action is an adjudication and not a rule. The regulatory
assessment requirements applicable to rulemaking do not, therefore,
apply to this action.
VII. Submission to Congress and the Comptroller General
The Congressional Review Act, 5 U.S.C. 801 et seq., does not apply
because this action is not a rule for purposes of 5 U.S.C. 804(3).
IX. References
The following is a listing of the documents that are specifically
referenced in this document. The docket includes these documents and
other information considered by EPA, including documents that are
referenced within the documents that are included in the docket, even
if the referenced document is not physically located in the docket. For
assistance in locating these other documents, please consult the
technical person listed under FOR FURTHER INFORMATION CONTACT.
1. The Petition from NRDC and PANNA and EPA's various responses to
it are available in docket number EPA-HQ-OPP-2007-1005 available at
https://www.regulations.gov.
2. FIFRA Scientific Advisory Panel (2016). ``Chlorpyrifos: Analysis
of Biomonitoring Data''. Available at: https://www.epa.gov/sap/meeting-materials-april-19-21-2016-scientific-advisory-panel.
3. Furlong CE, Holland N, Richter RJ, Bradman A, Ho A, Eskenazi B
(2006). PON1status of farmworker mothers and children as a predictor
of organophosphate sensitivity. Pharmacogenet Genomics. 2006 Mar;
16(3):183-90.
4. Sultatos LG; Murphy SD, (1983). Kinetic Analysis Of The
Microsomal Biotransformation Of The Phosphorothioate Insecticides
Chlorpyrifos And Parathion. Fundemental and Applied Toxicology.
3:16-21.
5. U.S. EPA (2008). Draft Appendix E available at https://www.epa.gov/scipoly/sap/meetings/2008/september/appendixe.pdf. Draft
Science Issue Paper: Chlorpyrifos Hazard and Dose Response
Characterization. August 21, 2008. Available at https://www.epa.gov/scipoly/sap/meetings/2008/september/chlorpyrifoscharacter.pdf.
6. Holland, N., Furlong, C., Bastaki, M., Richter, R., Bradman, A.,
Huen, K., Beckman, K., and Eskenazi, B. (2006). Paraoxonase
polymorphisms, haplotypes, and enzyme activity in Latino mothers and
newborns. Environ. Health Perspect. 114(7), 985-991; Chen, J.,
Kumar, M., Chan, W., Berkowitz, G., and Wetmur, J. (2003). Increased
Influence of Genetic Variation on PON1 Activity in Neonates.
Environmental Health Perspective 111, 11:1403-9.
7. U.S. EPA (2008). Transmittal of Meeting Minutes of the FIFRA
Scientific Advisory Panel Meeting Held September 16-18, 2008 on the
Agency's Evaluation of the Toxicity Profile of Chlorpyrifos.
Available at https://www.epa.gov/scipoly/sap/meetings/2008/september/sap0908report.pdf at 61.
8. Engel, S.M., Wetmur, J., Chen, J., Zhu, C., Boyd Barr, D.,
Canfield, R.L., Wolff, M.S., (2011) Prenatal Exposure to
Organophosphates, Paraoxonase 1, and Cognitive Development in
Childhood Environ Health Perspect 119:1182-1188 (2011). doi:10.1289/
ehp.1003183 [Online 21 April 2011].
9. Hofmann, J.N., Keifer, M.C., Furlong, C.E., De Roos, A.J.,
Farin., F.M., Fenske, R.A., van Belle, G., Checkoway, H. (2009)
Serum Cholinesterase Inhibition in Relation to Paraoxonase-1 (PON1)
Status among Organophosphate-Exposed Agricultural Pesticide
Handlers./Environ Health Perspect 117:1402-1408 (2009). doi:10.1289/
ehp.0900682. Available at https://dx.doi.org/ [Online 9 June 2009].
10. Eskenazi, B; Huen, K., Marks, A., Harley, K.G., Bradman, A.,
Boyd Barr, D., Holland, N. (2010) PON1 and Neurodevelopment in
Children from the CHAMACOS Study Exposed to Organophosphate
Pesticides in Utero. Environmental Health Perspectives. Vol. 118
(12): 1775-1781).
11. Harley KG, Huen K, Schall RA, Holland NT, Bradman A, et
al.,(2011) Association of Organophosphate Pesticide Exposure and
Paraoxonase with Birth Outcome in Mexican-American Women. PLoS ONE
6(8): e23923. doi:10.1371/journal.pone.0023923.
12. IPCS (International Programme on Chemical Safety) 2005.
Chemical-Specific Adjustment Factors for Interspecies Differences
and Human Variability: Guidance Document for Use of Data in Dose/
Concentration-Response Assessment. Harmonization Project Document
No. 2. World Health Organization, International Programme on
Chemical Safety, Geneva, Switzerland.
13. U.S. EPA (2014). Guidance for Applying Quantitative Data to
Develop Data-Derived Extrapolation Factors for Interspecies and
Intraspecies Extrapolation. Available at https://www.epa.gov/risk/guidance-applying-quantitative-data-develop-data-derived-extrapolation-factors-interspecies-and.
14. For additional information on the Endocrine Disruptor Screening
program see https://www.epa.gov/endo/.
15. For information related to the status of EDSP test orders/DCIs,
status of EDSP OSRI: order recipient submissions and
[[Page 16592]]
EPA responses, and other EDSP assay information see https://www.epa.gov/endo/pubs/toresources/index.htm.
16. For available Data Evaluation Records (DERs) for EDSP Tier 1,
see https://www.epa.gov/endocrine-disruption/endocrine-disruptor-screening-program-tier-1-screening-determinations-and.
17. Hoppin JA, Lubin JH, Rusiecki JA, Sandler DP, Dosemeci M,
Alavanja MC. (2004) Cancer incidence among pesticide applicators
exposed to chlorpyrifos in the Agricultural Health Study. J Natl
Cancer Inst, 96(23), 1781-1789. (hereinafter Lee et al., 2004).
18. U.S. EPA (2005). Guidelines for Carcinogen Risk Assessment.
Available at https://www.epa.gov/raf/publications/pdfs/CANCER_GUIDELINES_FINAL_3-25-05.PDF.
19. Christenson, C. (2011). D388167, Chlorpyrifos Carcinogenicity:
Review of Evidence from the U.S. Agricultural Health Study (AHS)
Epidemiologic Evaluations 2003-2009.
20. Weichenthal S, Moase C, Chan P (2010). A review of pesticide
exposure and cancer incidence in the agricultural health study
cohort. Cien Saude Colet. 2012 Jan;17(1):255-70. PubMed PMID:
22218559.
21. Zheng Q, Olivier K, Won YK, Pope CN. (2000). Comparative
cholinergic neurotoxicity of oral chlorpyrifos exposures in pre-
weaning and adult rats. Toxicological Sciences, 55(1): 124-132.
22. For additional information on the organophosphate cumulative
risk assessment, see https://epa.gov/pesticides/cumulative/2006-op/op_cra_main.pdf.
23. U.S. EPA (2011). Chlorpyrifos: Preliminary Human Health Risk
Assessment for Registration. Available in docket number EPA-HQ-OPP-
2008-0850, https://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPP-
2008-0850-0025.
(23) For additional information on EPA's Harmonized Test Guidelines
and international efforts at harmonization, see https://www.epa.gov/opp00001/science/guidelines.htm.
(24) Available at https://www.regulations.gov in docket EPA-HQ-OPP-
2008-0850.
Authority: 7 U.S.C. 136 et seq. and 21 U.S.C. 346a.
Dated: March 29, 2017.
E. Scott Pruitt,
Administrator.
[FR Doc. 2017-06777 Filed 4-4-17; 8:45 am]
BILLING CODE 6560-50-P