
[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]


=======================================================================
-----------------------------------------------------------------------

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 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: 
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 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


