[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.
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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 http://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 http://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:
[email protected].
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 http://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: http://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
http://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 http://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 http://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 http://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 http://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 http://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 http://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 http://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 http://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, http://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 http://www.epa.gov/opp00001/science/guidelines.htm.
(24) Available at http://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