Chlorpyrifos; Tolerance Revocations, 48315-48336 [2021-18091]

Agencies

• ENVIRONMENTAL PROTECTION AGENCY

[Federal Register Volume 86, Number 165 (Monday, August 30, 2021)]
[Rules and Regulations]
[Pages 48315-48336]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2021-18091]


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ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 180

[EPA-HQ-OPP-2021-0523; FRL-5993-04-OCSPP]


Chlorpyrifos; Tolerance Revocations

AGENCY: Environmental Protection Agency (EPA).

ACTION: Final rule.

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SUMMARY: On April 29, 2021, the United States Court of Appeals for the 
Ninth Circuit ordered EPA to issue a final rule concerning the 
chlorpyrifos tolerances by August 20, 2021. Based on the currently 
available data and taking into consideration the currently registered 
uses for chlorpyrifos, EPA is unable to conclude that the risk from 
aggregate exposure from the use of chlorpyrifos meets the safety 
standard of the Federal Food, Drug, and Cosmetic Act (FFDCA). 
Accordingly, EPA is revoking all tolerances for chlorpyrifos.

DATES: This final rule is effective October 29, 2021. The tolerances 
for all commodities expire on February 28, 2022.
    Written objections, requests for hearings, or requests for a stay 
identified by the docket identification (ID) number EPA-HQ-OPP-2021-
0523 must be received on or before October 29, 2021, and must be filed 
in accordance with the instructions provided in 40 CFR part 178 (see 
also Unit I.C. of the SUPPLEMENTARY INFORMATION unit in this document).

ADDRESSES: The docket for this action, identified by docket 
identification (ID) number EPA-HQ-OPP-2021-0523, is available at https://www.regulations.gov or at the Office of Pesticide Programs Regulatory 
Public Docket (OPP Docket) in the Environmental Protection Agency 
Docket Center (EPA/DC), West William Jefferson Clinton Bldg., Rm. 3334, 
1301 Constitution Ave. NW, Washington, DC 20460-0001.
    Due to public health concerns related to COVID-19, the EPA/DC and 
Reading Room are closed to visitors with limited exceptions. The staff 
continues to provide remote customer service via email, phone, and 
webform. For the latest status information on EPA/DC services and 
docket access, visit https://www.epa.gov/dockets.

FOR FURTHER INFORMATION CONTACT: Elissa Reaves, 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?

    You may be potentially affected by this action if you are an 
agricultural producer, food manufacturer, or pesticide manufacturer. 
The following list of North American Industrial Classification System 
(NAICS) codes is not intended to be exhaustive, but rather provides a 
guide to help readers determine whether this document applies to them. 
Potentially affected entities may include:
     Crop production (NAICS code 111).
     Animal production (NAICS code 112).
     Food manufacturing (NAICS code 311).
     Pesticide manufacturing (NAICS code 32532).
    Other types of entities not listed in this unit could also be 
affected. The NAICS codes have been provided to assist you and others 
in determining whether this action might apply to certain entities. To 
determine whether you or your business may be affected by this action, 
you should carefully examine the applicability provisions in Unit II. 
If you have any questions regarding the applicability of this action to 
a particular entity, consult the contact listed under FOR FURTHER 
INFORMATION CONTACT.

B. How can I get electronic access to other related information?

    You may access a frequently updated electronic version of 40 CFR 
part 180 through the Government Printing Office's e-CFR site at https://www.ecfr.gov/cgi-bin/text-idx?&c=ecfr&tpl=/ecfrbrowse/Title40/40tab_02.tpl.

C. How can I file an objection or hearing request?

    Under FFDCA section 408(g), 21 U.S.C. 346a, any person may file an 
objection to any aspect of this regulation and may also request a 
hearing on those objections. You must file your objection or request a 
hearing on this regulation 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-2021-0523 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 
October 29, 2021. Addresses for mail and hand delivery of objections 
and hearing requests are provided in 40 CFR 178.25(b), although at this 
time, EPA strongly encourages those interested in submitting objections 
or a hearing request, to submit objections and hearing requests 
electronically. See Order Urging Electronic Service and Filing (April 
10, 2020), https://www.epa.gov/sites/production/files/2020-05/documents/2020-04-10_-_order_urging_electronic_service_and_filing.pdf. 
At this time, because of the COVID-19 pandemic, the judges and staff of 
the Office of Administrative Law Judges (OALJ) are working remotely and 
not able to accept filings or correspondence by courier, personal 
deliver, or commercial delivery, and the ability to receive filings or 
correspondence by U.S. Mail is similarly limited. When submitting 
documents to the U.S. EPA OALJ, a person should utilize the OALJ e-
filing system, at https://yosemite.epa.gov/OA/EAB/EAB-ALJ_upload.nsf.
    Although EPA's regulations require submission via U.S. Mail or hand 
delivery, EPA intends to treat submissions filed via electronic means 
as properly filed submissions during this time that the Agency 
continues to maximize telework due to the pandemic; therefore, EPA 
believes the preference for submission via electronic means will not be 
prejudicial. If it is

[[Page 48316]]

impossible for a person to submit documents electronically or receive 
service electronically, e.g., the person does not have any access to a 
computer, the person shall so advise OALJ by contacting the Hearing 
Clerk at (202) 564-6281. If a person is without access to a computer 
and must file documents by U.S. Mail, the person shall notify the 
Hearing Clerk every time it files a document in such a manner. The 
address for mailing documents is U.S. Environmental Protection Agency, 
Office of Administrative Law Judges, Mail Code 1900R, 1200 Pennsylvania 
Ave. NW, Washington, DC 20460.
    In addition to filing an objection or hearing request with the 
Hearing Clerk as described in 40 CFR part 178 and above, please submit 
a copy of the filing (excluding any Confidential Business Information 
(CBI)) for inclusion in the public docket. Information not marked 
confidential pursuant to 40 CFR part 2 may be disclosed publicly by EPA 
without prior notice. Submit the non-CBI copy of your objection or 
hearing request, identified by docket ID number EPA-HQ-OPP-2021-0523, 
using the Federal eRulemaking Portal at https://www.regulations.gov. 
Follow the online instructions for submitting comments. Do not submit 
electronically any information you consider to be CBI or other 
information whose disclosure is restricted by statute.
    If you would like to submit CBI with your hearing request, please 
first contact the Pesticide Re-Evaluation Division by telephone, 703-
347-0206, or by email address: [email protected]. Do not 
submit CBI to EPA through the Federal eRulemaking Portal or email.

D. What can I do if I want the Agency to maintain a tolerance that the 
Agency has revoked?

    Any affected party has 60 days from the date of publication of this 
order to file objections to any aspect of this order with EPA and to 
request an evidentiary hearing on those objections (21 U.S.C. 
346a(g)(2)). A person may raise objections without requesting a 
hearing.
    The objections submitted must specify the provisions of the 
regulation deemed objectionable and the grounds for the objection (40 
CFR 178.25). While 40 CFR 180.33(i) indicates a fee is due with each 
objection, EPA currently cannot collect such fees per 21 U.S.C. 
346a(m)(3). If a hearing is requested, the objections must include a 
statement of the factual issue(s) on which a hearing is requested, the 
requestor's contentions on such issues, and a summary of any evidence 
relied upon by the objector (40 CFR 178.27).
    Although any person may file an objection, EPA will not consider 
any legal or factual issue presented in objections, if that issue could 
reasonably have been raised earlier in the Agency's review of 
chlorpyrifos relative to this petition. Similarly, if you fail to file 
an objection to an issue resolved in the final rule within the time 
period specified, you will have waived the right to challenge the final 
rule's resolution of that issue (40 CFR 178.30(a)). After the specified 
time, issues resolved in the final rule cannot be raised again in any 
subsequent proceedings on this rule. See Nader v EPA, 859 F.2d 747 (9th 
Cir. 1988), cert denied 490 U.S. 1931 (1989).
    EPA will review any objections and hearing requests in accordance 
with 40 CFR 178.30, and will publish its determination with respect to 
each in the Federal Register. A request for a hearing will be granted 
only to resolve factual disputes; objections of a purely policy or 
legal nature will be resolved in the Agency's final order, and will 
only be subject to judicial review pursuant to 21 U.S.C. 346a(h)(1), 
(40 CFR 178.20(c) and 178.32(b)(1)). A hearing will only be held if the 
Administrator determines that the material submitted shows the 
following: (1) There is a genuine and substantial issue of fact; (2) 
There is a reasonable probability that available evidence identified by 
the requestor would, if established, resolve one or more of such issues 
in favor of the requestor, taking into account uncontested claims to 
the contrary; and (3) Resolution of the issue(s) in the manner sought 
by the requestor would be adequate to justify the action requested (40 
CFR 178.30).
    You must file your objection or request a hearing on this 
regulation 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-2021-0523 in the subject line on the first page of 
your submission. All requests must be in writing and must be received 
by the Hearing Clerk as required by 40 CFR part 178 on or before 
October 29, 2021.

II. Background

A. What action is the Agency taking?

    EPA is revoking all tolerances for residues of chlorpyrifos. In 
2007, the Pesticide Action Network North America (PANNA) and the 
Natural Resources Defense Council (NRDC) filed a petition with EPA 
under section 408(d) of the Federal Food, Drug, and Cosmetic Act 
(FFDCA), 21 U.S.C. 346a(d), requesting that EPA revoke all chlorpyrifos 
tolerances. (Ref. 1). In an April 29, 2021 decision concerning the 
Agency's orders denying that 2007 Petition and the subsequent 
objections to that denial, the Ninth Circuit ordered EPA to ``(1) grant 
the 2007 Petition; (2) issue a final regulation within 60 days 
following issuance of the mandate that either (a) revokes all 
chlorpyrifos tolerances or (b) modifies chlorpyrifos tolerances and 
simultaneously certifies that, with the tolerances so modified, the EPA 
`has determined 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,' including for `infants and 
children'; and (3) modify or cancel related FIFRA registrations for 
food use in a timely fashion consistent with the requirements of 21 
U.S.C. 346a(a)(1).'' League of United Latin Am. Citizens v. Regan, 996 
F.3d 673 (9th Cir. 2021) (the LULAC decision).
    In today's action, EPA is granting the 2007 Petition, which 
requested revocation of the tolerances. While EPA previously responded 
to and denied the individual claims in the original petition, the Court 
found EPA's denial, at least with regard to the issues raised in the 
litigation, to be unsupported by the record before the Court and 
ordered EPA to grant the 2007 Petition and issue a final rule revoking 
or modifying tolerances. EPA is granting the petition by granting the 
relief sought by the petition, i.e., the revocation of the chlorpyrifos 
tolerances, for the reasons stated in this rulemaking. Moreover, the 
Court expressly ordered EPA to respond to the petition by issuing a 
final rule under FFDCA section 408(d)(4)(A)(i). 996 F.3d at 702. That 
provision of the statute involves the issuance of a final rule 
``without further notice and without further period for public 
comment.'' 21 U.S.C. 346a(d)(4)(A)(i). While the FFDCA provides an 
option for EPA to respond to a petition with the issuance of a proposed 
rule under FFDCA section 408(d)(4)(A)(ii) and thereafter to finalize 
the proposal, the Court did not direct EPA to exercise its authority to 
finalize its 2015 proposal to revoke tolerances pursuant to 
subparagraph (d)(4)(A)(ii). Nothing in the Ninth Circuit's opinion 
reflects an expectation that, in complying with the Court's order, EPA 
would or should finalize the 2015 proposed rule. As such, EPA is 
viewing this action as independent from the 2015 proposal, and this 
final rule is based on the Agency's current assessment of the available 
scientific information, rather

[[Page 48317]]

than a continuation of and finalization of the Agency's proposal in 
2015 to revoke chlorpyrifos tolerances.
    In this final rule, EPA is revoking all tolerances for residues of 
chlorpyrifos contained in 40 CFR 180.342. This includes tolerances for 
residues of chlorpyrifos on specific food and feed commodities 
(180.342(a)(1)); on all food commodities treated in food handling and 
food service establishments in accordance with prescribed conditions 
(180.342(a)(2) and (a)(3)); and on specific commodities when used under 
regional registrations (180.342(c)).
    EPA finds that, taking into consideration the currently available 
information and the currently registered uses of chlorpyrifos, EPA 
cannot make a safety finding to support leaving the current tolerances 
for residues of chlorpyrifos in place, as required under the FFDCA 
section 408(b)(2). 21 U.S.C. 346a(b)(2). As described in greater detail 
below, the Agency's analysis indicates that aggregate exposures (i.e., 
exposures from food, drinking water, and residential exposures), which 
stem from currently registered uses, exceed safe levels, when relying 
on the well-established 10% red blood cell acetylcholinesterase (RBC 
AChE) inhibition as an endpoint for risk assessment and including the 
statutory tenfold (10X) margin of safety to account for uncertainties 
related to the potential for neurodevelopmental effects to infants, 
children, and pregnant women. Accordingly, the Agency is therefore 
revoking all tolerances because given the currently registered uses of 
chlorpyrifos, EPA cannot determine that there is a reasonable certainty 
that no harm will result from aggregate exposure to residues, including 
all anticipated dietary (food and drinking water) exposures and all 
other exposures for which there is reliable information.

B. What is the Agency's authority for taking this action?

    EPA is taking this action pursuant to the authority in FFDCA 
sections 408(b)(1)(A), 408(b)(2)(A), and 408(d)(4)(A)(i). 21 U.S.C. 
346a(b)(1)(A), (b)(2)(A), (d)(4)(A)(i).

C. Overview of Final Rule

    When assessing pesticides, EPA performs a number of analyses to 
determine the risks from aggregate exposure to pesticide residues. For 
further discussion of the regulatory requirements of section 408 of the 
FFDCA, see https://www.epa.gov/laws-regulations/summary-federal-food-drug-and-cosmetic-act, and for a complete description of the risk 
assessment process, see https://www.epa.gov/pesticide-science-and-assessing-pesticide-risks/overview-risk-assessment-pesticide-program 
and https://www.epa.gov/pesticide-science-and-assessing-pesticide-risks/epas-risk-assessment-process-tolerance-reassessment.
    In general, to assess the risk of a pesticide tolerance, EPA 
combines information on pesticide toxicity with information regarding 
the route, magnitude, and duration of exposure to the pesticide. The 
risk assessment process involves four distinct steps: (1) 
Identification of the toxicological hazards posed by a pesticide; (2) 
Determination of the exposure ``level of concern'' for humans, which 
includes choosing a point of departure (PoD) that reflects the adverse 
health endpoint that is most sensitive to the pesticide, as well as 
uncertainty factors; (3) Estimation of human exposure to the pesticide 
through all applicable routes; and (4) Characterization of human risk 
based on comparison of the estimated human exposure to the level of 
concern. For tolerances, if aggregate exposure to humans is greater 
than the Agency's determined level of concern, the Agency's 
determination is the tolerances are not safe.
    The following provides a brief roadmap of the Units in this rule.
     Unit III. contains an overview of the statutory 
background, including the safety standard in FFDCA, and the 
registration standard under FIFRA. FFDCA provides the statutory basis 
for evaluating tolerances and directs the Agency to revoke tolerances 
that are not safe.
     Unit IV. provides an overview of the FFDCA petition that 
requested that EPA revoke chlorpyrifos tolerances on the grounds that 
those tolerances were not safe under the FFDCA. While that petition 
raised numerous issues, the primary scientific challenge to the 
chlorpyrifos tolerances that was before the Ninth Circuit related to 
whether EPA had selected the correct PoD for assessing risk. While 
EPA's PoD was based on inhibition of the enzyme acetylcholinesterase 
(AChE), petitioners asserted that the most sensitive health endpoint 
was neurodevelopmental outcomes from exposure to chlorpyrifos. A 
summary of that petition, EPA's response to that petition, and the 
subsequent litigation and Ninth Circuit's order directing EPA to revoke 
or modify the chlorpyrifos tolerances is included in this section.
     Unit V. provides an overview of the regulatory background 
for chlorpyrifos, including the numerous human health risk assessments 
EPA has conducted and FIFRA Scientific Advisory Panels (SAPs) that were 
convened to discuss the complex scientific issues associated with 
chlorpyrifos.
     Units VI. through VIII. summarizes EPA's risk assessment, 
which reflect the four-step process described above.
     Unit VI, which focuses on the hazard assessment of 
chlorpyrifos, combines the first two steps to provide a full picture of 
how EPA conducts its hazard assessment. After describing the process 
generally, this unit discusses EPA's analysis of the hazards posed by 
chlorpyrifos, including a discussion of the available data on AChE 
inhibition and the potential for neurodevelopmental outcomes in the 
young. Unit VI. also discusses the Agency's process for determining the 
endpoint on which to regulate chlorpyrifos exposure and the rationale 
for basing the PoD analysis on 10% AChE inhibition. Finally, this Unit 
includes a discussion of the FQPA safety factor and the Agency's 
reasons for retaining the default 10X value.
     Unit VII. describes EPA's exposure assessment for 
chlorpyrifos. The unit includes a description of the general approach 
for estimating exposures to pesticide residues in or on food and in 
drinking water, as well as exposures that come from non-occupational 
and non-dietary sources, also referred to as residential exposures. The 
unit walks through how EPA conducted those exposure assessments for 
chlorpyrifos, including a detailed discussion of the recent refinements 
to the drinking water analysis conducted by EPA for chlorpyrifos.
     Unit VIII. describes the Agency's process for assessing 
aggregate risk based on the hazard discussed in Unit VI. and the 
exposure discussed in Unit VII. and provides the Agency's rationale and 
conclusions concerning the overall risks posed by chlorpyrifos based on 
the currently registered uses. Unit VIII. concludes that the aggregate 
risks exceed the level of concern and therefore the chlorpyrifos 
tolerances must be revoked.
    Units IX. and X. address procedural matters, international 
obligations, statutory and executive order review requirements, and the 
specific revisions that will be made to the Code of Federal Regulations 
with this final rule.

III. Statutory Background

A. Federal Food, Drug, and Cosmetic Act (FFDCA) Tolerances

    A ``tolerance'' represents the maximum level for residues of 
pesticide chemicals legally allowed in or on raw agricultural 
commodities and processed

[[Page 48318]]

foods. Section 408 of FFDCA, 21 U.S.C. 346a, authorizes the 
establishment of tolerances, exemptions from tolerance requirements, 
modifications of tolerances, and revocation of tolerances for residues 
of pesticide chemicals in or on raw agricultural commodities and 
processed foods. Without a tolerance or exemption, pesticide residues 
in or on food is considered unsafe, 21 U.S.C. 346a(a)(1), and such 
food, which is then rendered ``adulterated'' under FFDCA section 
402(a), 21 U.S.C. 342(a), may not be distributed in interstate 
commerce, 21 U.S.C. 331(a).
    Section 408(b)(2) of the FFDCA directs that EPA may establish or 
leave in effect a tolerance for a pesticide only if it finds that the 
tolerance is safe, and EPA must revoke or modify tolerances determined 
to be unsafe. FFDCA 408(b)(2)(A)(i) (21 U.S.C. 346a(b)(2)(A)(i)). 
Section 408(b)(2)(A)(ii) defines ``safe'' 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.'' This includes exposure through food, drinking water and 
all non-occupational exposures (e.g., in residential settings), but 
does not include occupational exposures to workers (i.e., 
occupational). Risks to infants and children are given special 
consideration. Specifically, pursuant to section 408(b)(2)(C), EPA must 
assess the risk of the pesticide chemical based on available 
information concerning the special susceptibility of infants and 
children to the pesticide chemical residues, including neurological 
differences between infants and children and adults, and effects of in 
utero exposure to pesticide chemicals; and available information 
concerning the cumulative effects on infants and children of such 
residues and other substances that have a common mechanism of toxicity. 
(21 U.S.C. 346a(b)(2)(C)(i)(II) and (III)).
    This provision further directs that ``in the case of threshold 
effects, . . . an additional tenfold margin of safety for the pesticide 
chemical residue and other sources of exposure shall be applied for 
infants and children to take into account potential pre- and postnatal 
toxicity and completeness of the data with respect to exposure and 
toxicity to infants and children.'' (21 U.S.C. 346a(b)(2)(C)). EPA is 
permitted to ``use a different margin of safety for the pesticide 
chemical residue only if, on the basis of reliable data, such margin 
will be safe for infants and children.'' (21 U.S.C. 346a(b)(2)(C)). Due 
to Congress's focus on both pre- and postnatal toxicity, EPA has 
interpreted this additional safety factor as pertaining to risks to 
infants and children that arise due to prenatal exposure as well as to 
exposure during childhood years. This section providing for the special 
consideration of infants and children in section 408(b)(2)(C) was added 
to the FFDCA through the Food Quality Protection Act (FQPA) (Pub. L. 
104-170, 110 Stat. 1489 (1996)); therefore, this additional margin of 
safety is often referred to as the ``FQPA safety factor (SF)''.
    Section 408(d) of the FFDCA, 21 U.S.C. 346a(d), authorizes EPA to 
revoke tolerances in response to an administrative petition submitted 
by any person. As explained in more detail in Unit IV, PANNA and NRDC 
submitted a petition in 2007 requesting revocation of all chlorpyrifos 
tolerances. The Ninth Circuit has directed EPA to grant that petition 
and issue a rule revoking or modifying those tolerances. EPA is issuing 
this rule in response to that petition and revoking all chlorpyrifos 
tolerances because EPA is unable to determine, based on data available 
at this time, that aggregate exposures to chlorpyrifos are safe.

B. Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) 
Registration Review

    Under FIFRA, a pesticide may not be sold or distributed in the 
United States unless it is registered. (7.U.S.C. 136a(a)). EPA must 
determine that a pesticide ``will not generally cause unreasonable 
adverse effects on the environment in order to register a pesticide.'' 
7 U.S.C. 136a(c)(5). The term ``unreasonable adverse effects on the 
environment'' is defined to include ``a human dietary risk from 
residues that result from a use of a pesticide in or on any food 
inconsistent with the standard under section 346a of Title 21.'' 7 
U.S.C. 136(bb). Thus, the FIFRA registration standard incorporates the 
FFDCA safety standard and requires consideration of safety at the time 
of registration and during the registration review process.
    Under section 3(g) of FIFRA (7 U.S.C. 136(a)(g)), EPA is required 
to re-evaluate existing registered pesticides every 15 years in a 
process called ``registration review.'' The purpose of registration 
review is ``to ensure that each pesticide registration continues to 
satisfy the FIFRA standard for registration,'' 40 CFR 155.40(a)(1), 
taking into account changes that have occurred since the last 
registration decision, including any new relevant scientific 
information and any changes to risk-assessment procedures, methods, and 
data requirements. 40 CFR 55.53(a). To ensure that a pesticide 
continues to meet the standard for registration, EPA must determine, 
based on the available data, including any additional information that 
has become available since the pesticide was originally registered or 
re-evaluated, that the pesticide does not cause ``unreasonable adverse 
effects on the environment.'' 7 U.S.C. 136a(c)(1), (5); see also 40 CFR 
152.50.
    Chlorpyrifos is currently undergoing registration review, which 
must be completed by October 1, 2022. 7 U.S.C. 136a(g)(1)(A)(iv). For 
information about the ongoing registration review process for 
chlorpyrifos, see https://www.regulations.gov/docket/EPA-HQ-OPP-2008-0850.

IV. FFDCA Petition and Related Litigation

A. 2007 FFDCA Petition

    In 2006, EPA issued the Registration Eligibility Decision (RED) for 
chlorpyrifos, which concluded that chlorpyrifos was eligible for 
reregistration as it continued to meet the FIFRA standard for 
registration. In September 2007, PANNA and NRDC submitted to EPA a 
petition (the Petition) seeking revocation of all chlorpyrifos 
tolerances under FFDCA section 408 and cancellation of all chlorpyrifos 
pesticide product registrations under FIFRA. (Ref. 1). That petition 
raised several claims regarding EPA's 2006 FIFRA reregistration 
decision for chlorpyrifos and the active registrations in support of 
the request for tolerance revocations and product cancellations. Those 
claims are described in detail in EPA's earlier order denying the 
petition (82 FR 16581, April 5, 2017) (FRL-9960-77).

B. Agency Responses and 2017 Order Denying Petition

    On March 29, 2017, EPA denied the Petition in full (82 FR 16581, 
April 5, 2017) (FRL-9960-77). Prior to issuing that order, EPA provided 
the Petitioners with two interim responses on July 16, 2012 and July 
15, 2014, which denied six of the Petition's claims. 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, and EPA therefore finalized its response to those 
claims in the March 29, 2017 Denial Order.
    As background, three of the Petition's claims all related to the 
same issue: Whether the potential exists for chlorpyrifos to cause 
neurodevelopmental effects in children

[[Page 48319]]

at exposure levels below EPA's existing regulatory standard (10% RBC 
AChE inhibition). Because the claims relating to the potential for 
neurodevelopmental effects in children raised novel, highly complex 
scientific issues, EPA originally decided it would be appropriate to 
address these issues in connection with the registration review of 
chlorpyrifos under FIFRA section 3(g) and decided to expedite that 
review, intending to finalize it in 2015, well in advance of the 
October 1, 2022 registration review deadline (Ref. 2). EPA decided as a 
policy matter that it would address the Petition claims raising these 
matters on a similar timeframe. Id. at 16583.
    The complexity of these scientific issues precluded EPA from 
finishing its review according to EPA's original timeline, and the 
Petitioners brought legal action in the Ninth 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. The result 
of that litigation was that on August 10, 2015, the Court ordered EPA 
to ``issue either a proposed or final revocation rule or a full and 
final response to the administrative [P]etition by October 31, 2015.'' 
In re Pesticide Action Network N. Am., 798 F.3d 809, 815 (9th Cir. 
2015).
    In response to that 2015 order, EPA issued a proposed rule to 
revoke all tolerances for chlorpyrifos on October 28, 2015 (published 
in the Federal Register on November 6, 2015 (80 FR 69080)), based on 
its unfinished registration review risk assessment. EPA acknowledged 
that it had had insufficient time to complete its drinking water 
assessment and its review of data addressing the potential for 
neurodevelopmental effects. Although EPA noted that further evaluation 
might enable more tailored risk mitigation, EPA was unable to conclude, 
based on the information before EPA at the time, that the tolerances 
were safe, since the aggregate exposure to chlorpyrifos exceeded safe 
levels.
    On December 10, 2015, the Ninth Circuit issued a further order 
requiring EPA to take final action on its proposed revocation rule and 
issue its final response to the Petition by December 30, 2016. In re 
Pesticide Action Network N. Am., 808 F.3d 402 (9th Cir. 2015). In 
response to EPA's request for an extension of the deadline in order to 
be able to fully consider the July 2016 FIFRA Scientific Advisory Panel 
(SAP) report regarding chlorpyrifos toxicology, the Ninth Circuit 
ordered EPA to complete its final action by March 31, 2017. In re 
Pesticide Action Network of North America v. EPA, 840 F.3d 1014 (9th 
Cir. 2016). Following that order, EPA published a Notice of Data 
Availability (NODA), seeking comment on EPA's revised risk assessment 
and water assessment and reopening the comment period on the proposal 
to revoke tolerances. (81 FR 81049, November 17, 2016) (FRL-9954-65).
    On March 29, 2017, and as published in the Federal Register on 
April 5, 2017, the EPA issued an order denying the Petition (the Denial 
Order) (82 FR 16581). The specific responses are described in full in 
that Denial Order and summarized again in the Agency's denial of 
objections (84 FR 35555, July 24, 2019) (FRL-9997-06). EPA's Denial 
Order did not issue a determination concerning the safety of 
chlorpyrifos. Rather, EPA concluded that, despite several years of 
study, the science addressing neurodevelopmental effects remained 
unresolved and that further evaluation of the science on this issue 
during the remaining time for completion of registration review was 
warranted. EPA therefore denied the remaining Petition claims, 
concluding that it was not required to complete--and would not 
complete--the human health portion of the registration review or any 
associated tolerance revocation of chlorpyrifos without resolution of 
those issues during the ongoing FIFRA registration review of 
chlorpyrifos.

C. Objections and EPA's Denial of Objections

    In June 2017, several public interest groups and states filed 
objections to the Denial Order pursuant to the procedures in FFDCA 
section 408(g)(2). Specifically, Earthjustice submitted objections on 
behalf of the following 12 public interest groups: Petitioners PANNA 
and NRDC, United Farm Workers, California Rural Legal Assistance 
Foundation, Farmworker Association of Florida, Farmworker Justice, 
GreenLatinos, Labor Council for Latin American Advancement, League of 
United Latin American Citizens, Learning Disabilities Association of 
America, National Hispanic Medical Association and Pineros y Campesinos 
Unidos del Noroeste. Another public interest group, the North Coast 
River Alliance, submitted separate objections. With respect to the 
states, New York, Washington, California, Massachusetts, Maine, 
Maryland, and Vermont submitted a joint set of objections (Ref. 1). The 
objections focused on three main topics: (1) The Objectors asserted 
that the FFDCA requires that EPA apply the FFDCA safety standard in 
reviewing any petition to revoke tolerances and that EPA's decision to 
deny the Petition without making a safety finding failed to apply that 
standard; (2) The Objectors contended that the risk assessments EPA 
conducted in support of the 2015 proposed rule and the 2016 Revised 
Human Health Risk Assessment (HHRA) demonstrated that chlorpyrifos 
results in unsafe drinking water exposures and adverse 
neurodevelopmental effects and that EPA therefore was required to issue 
a final rule revoking all chlorpyrifos tolerances; and (3) The 
Objectors claimed that EPA committed procedural error in failing to 
respond to comments, and they specifically pointed to comments related 
to neurodevelopmental effects, inhalation risk, and Dow AgroSciences' 
(now doing business as Corteva AgriScience) physiologically based 
pharmacokinetic model (PBPK model) used in EPA's 2014 and 2015 human 
health risk assessments, which are discussed further in Unit V.
    On July 18, 2019, EPA issued a final order denying all objections 
to the Denial Order and thereby completing EPA's administrative denial 
of the Petition (the Final Order) (84 FR 35555). Again, the Final Order 
did not issue a determination concerning the safety of chlorpyrifos. 
Rather, EPA denied the objections in part on the grounds that the data 
concerning neurodevelopmental toxicity were not sufficiently valid, 
complete, and reliable to meet the petitioners' burden.

D. Judicial Challenge to Objections Denial and 2021 Ninth Circuit Order

    On August 7, 2019, the Objectors (LULAC Petitioners) and States 
petitioned the Ninth Circuit for review of the Denial Order and the 
Final Order. The LULAC Petitioners and States argued that EPA was 
compelled to grant the 2007 Petition and revoke chlorpyrifos tolerances 
because (1) EPA lacked authority to maintain chlorpyrifos tolerances 
without an affirmative finding that chlorpyrifos is safe, (2) EPA's 
findings that chlorpyrifos is unsafe in the Agency's risk assessments 
from 2014 and 2016, compel it to revoke chlorpyrifos tolerances, and 
(3) The 2007 Petition provided a sufficient basis for EPA to reconsider 
the question of chlorpyrifos's safety and was not required to prove 
that a pesticide is unsafe.
    On April 29, 2021, the Ninth Circuit issued its decision, finding 
that when EPA denied the 2007 Petition to revoke chlorpyrifos 
tolerances, it was essentially leaving those chlorpyrifos tolerances in 
effect, which, the Court noted, the FFDCA only permits if EPA has made 
a determination that such tolerances were safe. League of United

[[Page 48320]]

Latin Am. Citizens v. Regan, 996 F.3d. 673 (9th Cir. 2021). Although 
EPA argued that it was not compelled to reconsider its safety 
determination because the 2007 Petition had failed to meet the 
threshold requirement of providing reliable evidence that the 
tolerances were unsafe, the Court found that the Petition provided the 
necessary ``reasonable grounds,'' which triggered EPA's duty to ensure 
the tolerances were safe. Id. at 695. Since EPA's Denial Order and 
Final Order failed to make any safety determinations for chlorpyrifos, 
the Court concluded that EPA violated the FFDCA by leaving those 
tolerances in place without the requisite safety findings. Id. at 695-
96. Moreover, in light of the record before the Court, including the 
2016 HHRA indicating that the current chlorpyrifos tolerances are not 
safe, the Court found EPA's denial of the 2007 Petition to be arbitrary 
and capricious. Id. at 697. Based on the available record, the Court 
concluded that EPA must grant the Petition and issue a final rule 
modifying or revoking the tolerances under FFDCA section 
408(d)(4)(A)(i). Id. at 701.
    The Court recognized that EPA had been continuing to evaluate 
chlorpyrifos in registration review and had issued additional 
regulatory documents concerning chlorpyrifos after the record closed in 
the litigation, e.g., the 2020 Proposed Interim Registration Review 
Decision and 2020 SAP, both of which are discussed in more detail in 
Unit V. below, and noted that such information could be relevant to a 
safety determination. Id. at 703. The Court allowed that if the new 
information could support a safety determination, EPA might issue a 
final rule modifying chlorpyrifos tolerances rather than revoking them, 
although the Court directed EPA to act ``immediately'' and not engage 
in ``further factfinding.'' Id. at 703. As a result, the Court ordered 
EPA to: (1) Grant the 2007 Petition; (2) Issue a final rule within 60 
days of the issuance of the mandate that either revokes all 
chlorpyrifos tolerances or modifies chlorpyrifos tolerances, provided 
that such modification is supported by a safety finding, and (3) Modify 
or cancel related FIFRA registrations for food use in a timely fashion. 
Id. at 703-04. Since the mandate was issued on June 21, 2021, the 
deadline for issuing this final rule is August 20, 2021.

V. Chlorpyrifos Background and Regulatory History

    Chlorpyrifos (0,0-diethyl-0-3,5,6-trichloro-2-pyridyl 
phosphorothioate) is a broad-spectrum, chlorinated organophosphate (OP) 
insecticide. Given the complex scientific nature of the issues 
reflected in this rule, EPA is alerting the reader that many of the 
technical terms used in this unit will be described more fully in a 
subsequent unit.
    Chlorpyrifos, like other OP pesticides, affects the nervous system 
by inhibiting acetylcholinesterase (AChE), an enzyme necessary for the 
proper functioning of the nervous system. This can ultimately lead to 
signs of neurotoxicity. As discussed in more detail below, while there 
are data that indicate an association between chlorpyrifos and 
neurodevelopmental outcomes, there remains uncertainty in the dose-
response relationship and the levels at which these outcomes occur. In 
an effort to resolve this scientific uncertainty, evaluation of 
toxicology and epidemiology studies of chlorpyrifos, specific to 
determining the appropriate regulatory endpoint, has been the focus of 
EPA's work on chlorpyrifos for over a decade.
    Chlorpyrifos has been registered for use in the United States since 
1965. Currently registered use sites include a large variety of food 
crops (including fruit and nut trees, many types of fruits and 
vegetables, and grain crops), and non-food use settings (e.g., golf 
course turf, industrial sites, greenhouse and nursery production, sod 
farms, and wood products). Public health uses include aerial and 
ground-based fogger mosquito adulticide treatments, roach bait 
products, and individual fire ant mound treatments. 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. 
See, e.g., 65 FR 76233, December 6, 2000) (FRL-6758-2); 66 FR 47481, 
September 12, 2001) (FRL-6799-7).
    In 2006, EPA completed FIFRA section 4 reregistration and FFDCA 
tolerance reassessment for chlorpyrifos and the OP class of pesticides, 
concluding that the existing tolerances were safe and that chlorpyrifos 
continued to meet the FIFRA standard for registration. In that effort, 
EPA relied on RBC AChE inhibition as the endpoint for examining risk.
    Subsequently, given ongoing scientific developments in the study of 
the OPs generally, EPA chose to prioritize the FIFRA section 3(g) 
registration review (the subsequent round of re-evaluation following 
reregistration) of chlorpyrifos and the OP class. The registration 
review of chlorpyrifos and the OPs has presented EPA with numerous 
novel scientific issues which the Agency has taken to multiple 
independent FIFRA SAP reviews. (Note: The SAP is a federal advisory 
committee created by FIFRA section 25(d), 7 U.S.C. 136w(d), and serves 
as EPA's primary source of peer review for significant regulatory and 
policy matters involving pesticides.)
    These SAPs, which have included the review of new worker and non-
occupational exposure methods, experimental toxicology and 
epidemiology, and the evaluation of a chlorpyrifos-specific 
physiologically-based pharmacokinetic-pharmacodynamic (PBPK-PD, see 
Unit VII. for definitions) model. These FIFRA SAP reviews have resulted 
in significant developments in EPA's risk assessments generally, and, 
more specifically, in the study of chlorpyrifos's effects. In 
particular, and partly in response to the issues raised in the 2007 
Petition, EPA has conducted extensive reviews of available data to 
evaluate the possible connection between chlorpyrifos and adverse 
neurodevelopmental effects, and to assess whether the 
neurodevelopmental effects could be used to determine points of 
departure (PoDs) for assessing chlorpyrifos. On this particular topic, 
EPA has convened three FIFRA SAP reviews. EPA has taken FIFRA SAP 
recommendations into consideration as it has developed risk assessments 
and regulatory documents for chlorpyrifos. The remainder of this Unit 
provides a brief regulatory overview for chlorpyrifos by presenting a 
summary of the chronology of the FIFRA SAPs and Agency assessments of 
chlorpyrifos.
    The 2008 FIFRA SAP evaluated the Agency's preliminary review of 
available literature and research on epidemiology in mothers and 
children following exposures to chlorpyrifos and other OPs, laboratory 
studies on animal behavior and cognition, AChE inhibition, and 
mechanisms of action. (Ref. 3) The 2008 FIFRA SAP recommended that AChE 
inhibition remain as the source of data for the points of departure 
(PoDs, see Unit VII. for definitions), but noted that despite some 
uncertainties, the Columbia Center for Children's Environmental Health 
(CCCEH) epidemiologic studies ``is epidemiologically sound'' and 
``provided extremely valuable information'' for evaluating the 
potential neurodevelopmental effects of chlorpyrifos (Ref. 3). See Unit 
VI.A.2. for neurodevelopmental toxicity.
    The 2010 FIFRA SAP favorably reviewed EPA's 2010 draft epidemiology 
framework. (Ref. 4, 5) This draft framework, titled ``Framework for 
Incorporating Human

[[Page 48321]]

Epidemiologic & Incident Data in Risk Assessments in Pesticides,'' 
described the use of the Bradford Hill Criteria as modified in the Mode 
of Action Framework to integrate epidemiology information with other 
lines of evidence. As suggested by the 2010 FIFRA SAP, EPA did not 
immediately finalize the draft framework but instead used it in several 
pesticide evaluations prior to making revisions and finalizing it. 
EPA's Office of Pesticide Program's (OPP) finalized this epidemiology 
framework in December 2016 (Ref. 5).
    In 2011, EPA released its preliminary human health risk assessment 
(2011 HHRA) for the registration review of chlorpyrifos. The 2011 HHRA 
used 10% RBC AChE inhibition from laboratory rats as the critical 
effect (or PoD) for extrapolating risk. It also used the default 10X 
uncertainty factors for inter- and intra-species extrapolation. The 10X 
FQPA SF was removed with a note to the public that a weight of evidence 
(WOE) evaluation would be forthcoming, as described in the 2010 draft 
``Framework for Incorporating Human Epidemiologic & Incident Data in 
Health Risk Assessment.''
    In 2011, EPA convened a meeting of the FIFRA SAP to review the 
PBPK-PD model for chlorpyrifos. The panel made numerous recommendations 
for the improvement of the model for use in regulatory risk assessment, 
including the inclusion of dermal and inhalation routes. From 2011-
2014, Dow AgroSciences, in consultation with EPA, refined the PBPK-PD 
model, and those refinements were sufficient to allow for use of the 
PBPK-PD model in the next HHRA.
    In 2012, the Agency convened another meeting of the FIFRA SAP to 
review the latest experimental data related to RBC AChE inhibition, 
cholinergic and non-cholinergic adverse outcomes, including 
neurodevelopmental studies on behavior and cognition effects. The 
Agency also performed an in-depth analysis of the available 
chlorpyrifos biomonitoring data and of the available epidemiologic 
studies from three major children's health cohort studies in the United 
States, including those from the CCCEH, Mount Sinai, and University of 
California, Berkeley. The Agency explored plausible hypotheses on mode 
of actions/adverse outcome pathways (MOAs/AOPs) leading to 
neurodevelopmental outcomes seen in the biomonitoring and epidemiology 
studies.
    The 2012 FIFRA SAP described the Agency's epidemiology review as 
``very clearly written, accurate'' and ``very thorough review''. (Ref. 
6 at 50-52, 53) It went further to note that it ``believes that the 
[Agency's] epidemiology review appropriately concludes that the studies 
show some consistent associations relating exposure measures to 
abnormal reflexes in the newborn, pervasive development disorder at 24 
or 36 months, mental development at 7-9 years, and attention and 
behavior problems at 3 and 5 years of age. . . . .'' The 2012 FIFRA SAP 
concluded that the RBC AChE inhibition remained the most robust dose-
response data, though expressed significant concerns about the degree 
to which 10% RBC AChE inhibition is protective for neurodevelopmental 
effects, pointing to evidence from epidemiology, in vivo animal 
studies, and in vitro mechanistic studies, and urged the EPA to find 
ways to use the CCCEH data.
    In 2014, EPA released a revised human health risk assessment (2014 
HHRA. (Ref. 7). The revised assessment used the chlorpyrifos PBPK-PD 
model for deriving human PoDs for RBC AChE inhibition, thus obviating 
the need for the inter-species extrapolation factor (as explained later 
in this Unit) and providing highly refined PoDs which accounted for 
gender, age, duration and route specific exposure considerations. The 
PBPK-PD model was also used to develop data derived intra-species 
factors for some lifestages. The 10X FQPA SF was retained based on the 
outcome of the 2012 FIFRA SAP and development of a WOE analysis on 
potential for neurodevelopmental outcomes according to EPA's 
``Framework for Incorporating Human Epidemiologic & Incident Data in 
Risk Assessments for Pesticides.'' The 2014 HHRA, taken together with 
the Agency's drinking water assessment, identified estimated aggregate 
risks exceeding the level of concern for chlorpyrifos.
    On November 6, 2015, EPA issued a proposed rule to revoke all 
tolerances of chlorpyrifos, based on the aggregate risks exceeding the 
level of concern (80 FR 69079) (FRL-9935-92). In this proposed 
rulemaking, EPA specified that it was unable to conclude that aggregate 
exposures from use of chlorpyrifos met the FFDCA's ``reasonable 
certainty of no harm'' standard due to risks identified from the 
drinking watering using a national-scale assessment (i.e., using 
default values and conservative assumptions). At that time, the EPA had 
not completed a refined drinking water assessment (i.e., a higher-tier 
and more resource-intensive assessment relying on more targeted inputs) 
or an additional analysis of the hazard of chlorpyrifos that was 
suggested by several commenters to the 2014 HHRA. Those commenters 
raised the concern that the use of 10% RBC AChE inhibition for deriving 
PoDs for chlorpyrifos may not provide a sufficiently health protective 
human health risk assessment given the potential for neurodevelopmental 
outcomes.
    In 2015, EPA conducted additional hazard analyses using data on 
chlorpyrifos levels in fetal cord blood reported by the CCCEH study 
investigators. The Agency convened another meeting of the FIFRA SAP in 
April 2016 to evaluate a proposal of using cord blood data from the 
CCCEH epidemiology studies as the source of data for the PoDs. The 2016 
SAP did not support the ``direct use'' of the cord blood and working 
memory data for deriving the regulatory endpoint, due in part to 
insufficient information about timing and magnitude of chlorpyrifos 
applications in relation to cord blood concentrations at the time of 
birth, uncertainties about the prenatal window(s) of exposure linked to 
reported effects, lack of a second laboratory to reproduce the 
analytical blood concentrations, and lack of raw data from the 
epidemiology study. (Ref. 8)
    Despite its critiques of uncertainties in the CCCEH studies, the 
2016 FIFRA SAP expressed concern that 10% RBC AChE inhibition is not 
sufficiently protective of human health. Specifically, the FIFRA SAP 
stated that it ``agrees that both epidemiology and toxicology studies 
suggest there is evidence for adverse health outcomes associated with 
chlorpyrifos exposures below levels that result in 10% RBC AChE 
inhibition (i.e., toxicity at lower doses).'' (Id. at 18). (Ref. 8)
    Taking into consideration the conclusions of the 2016 SAP, EPA 
issued another HHRA using a dose reconstruction approach to derive the 
PoD based on the neurodevelopmental effects observed in the CCCEH 
study. In 2016, EPA also issued a revised drinking water assessment 
(2016 DWA). EPA issued a Notice of Data Availability seeking public 
comment on the 2016 HHRA and 2016 DWA. (81 FR 81049, November 17, 2016) 
(FRL-9954-65).
    In 2017, in response to a Ninth Circuit order, EPA denied the 2007 
Petition on the grounds 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.'' (82 FR at 16583). As part of this 
commitment to further evaluate the science, EPA evaluated the new 
laboratory animal studies with results

[[Page 48322]]

suggesting effects on the developing brain occur at doses lower than 
doses that cause AChE inhibition, and concluded that they are not 
sufficient for setting a PoD. While EPA sought to verify the 
conclusions of the epidemiology studies conducted by Columbia 
University it has been unable to confirm the findings of the CCCEH 
papers or conduct alternative statistical analyses to evaluate the 
findings. In summary, while EPA sought to address the potential 
neurodevelopmental effects associated with chlorpyrifos exposure over 
the past decade, these efforts ultimately concluded with the lack of a 
suitable regulatory endpoint based on these potential effects. However, 
these efforts do not alleviate the Agency's concerns regarding 
potential neurodevelopmental effects.
    In October 2020, EPA released its latest human health risk 
assessment (2020 HHRA) and drinking water assessment (2020 DWA). (Ref. 
9 and 10) Due to the shortcomings of the data upon which the 2016 HHRA 
was based and the uncertainty surrounding the levels around which 
neurodevelopmental effects may occur, the 2020 HHRA uses the same 
endpoint and PoDs as those used in the 2014 HHRA (i.e., the PBPK-PD 
model has been used to estimate exposure levels resulting in 10% RBC 
AChE inhibition following acute (single day, 24 hours) and steady state 
(21-day) exposures for a variety of exposure scenarios for chlorpyrifos 
and/or chlorpyrifos oxon). The 2020 HHRA retained the default 10X FQPA 
SF, but also presented risk estimates at a reduced 1X FQPA SF, though 
it did not adopt or attempt to justify use of this approach.
    Then, in December 2020, as part of its FIFRA registration review, 
EPA issued its Proposed Interim Registration Review Decision (2020 PID) 
for chlorpyrifos (85 FR 78849, December 7, 2020) (FRL-10017-13). The 
2020 PID was based on comparing estimates in the 2020 HHRA with the 
values from the 2020 DWA, and retaining the 10X FQPA safety factor, the 
PID proposed to limit applications of chlorpyrifos in this country 
would be reduced to certain uses in certain regions of the United 
States. The PID proposed to conclude that the Agency could make a 
safety finding for the approach in this path forward, as risk would be 
based on limited uses in limited geographic areas, as specified. This 
proposed path forward was intended to offer to stakeholders a way to 
mitigate the aggregate risk from chlorpyrifos, which the Agency had 
determined would exceed risk levels of concern without the proposed use 
restrictions.
    In December 2020, EPA requested public comment on the 2020 PID, 
2020 HHRA, and 2020 DWA. EPA extended the 60-day comment period by 30 
days and it closed on March 7, 2021.

VI. EPA's Hazard Assessment for Chlorpyrifos

A. General Approach to Hazard Identification, Dose-Response Assessment, 
and Extrapolation

    Any risk assessment begins with an evaluation of a chemical's 
inherent properties, and whether those properties have the potential to 
cause adverse effects (i.e., a hazard identification). In evaluating 
toxicity or hazard, EPA reviews toxicity data, typically from studies 
with laboratory animals, to identify any adverse effects on the test 
subjects. Where available and appropriate, EPA will also take into 
account studies involving humans, including human epidemiological 
studies. The animal toxicity database for a conventional, food use 
pesticide usually consists of studies investigating a broad range of 
endpoints including potential for carcinogenicity, mutagenicity, 
developmental and reproductive toxicity, and neurotoxicity. These 
studies include gross and microscopic effects on organs and tissues, 
functional effects on bodily organs and systems, effects on blood 
parameters (such as red blood cell count, hemoglobin concentration, 
hematocrit, and a measure of clotting potential), effects on the 
concentrations of normal blood chemicals (including glucose, total 
cholesterol, urea nitrogen, creatinine, total protein, total bilirubin, 
albumin, hormones, and enzymes such as alkaline phosphatase, alanine 
aminotransferase and cholinesterases), and behavioral or other gross 
effects identified through clinical observation and measurement. EPA 
examines whether adverse effects are caused by different durations of 
exposure ranging from short-term (acute) to long-term (chronic) 
pesticide exposure and different routes of exposure (oral, dermal, 
inhalation). Further, EPA evaluates potential adverse effects in 
different age groups (adults as well as fetuses and juveniles). (Ref. 
11 at 8-10).
    Once a pesticide's potential hazards are identified, EPA determines 
a toxicological level of concern for evaluating the risk posed by human 
exposure to the pesticide. In this step of the risk assessment process, 
EPA essentially evaluates the levels of exposure to the pesticide at 
which effects might occur. An important aspect of this determination is 
assessing the relationship between exposure (dose) and response (often 
referred to as the dose-response analysis). In evaluating a chemical's 
dietary risks, EPA uses a reference dose (RfD) approach, which 
typically involves a number of considerations including:
     A ``point of departure'' (PoD): Typically, the PoD is the 
value from a dose-response curve that is at the low end of the 
observable data in laboratory animals and that is the toxic dose that 
serves as the `starting point' in extrapolating a risk to the human 
population, although a PoD can also be derived from human data as well. 
PoDs are selected to be protective of the most sensitive adverse toxic 
effect for each exposure scenario, and are chosen from toxicity studies 
that show clearly defined No Observed Adverse Effect Levels (NOAELs) or 
Lowest Observed Adverse Effect Levels (LOAELs), dose-response 
relationships, and relationships between the chemical exposure and 
effect. EPA will select separate PoDs, as needed, for each expected 
exposure duration (e.g., acute, chronic, short-term, intermediate-term) 
and route of exposure (e.g., oral, dermal, inhalation). For 
chlorpyrifos, as discussed later in this Unit, EPA derived PoDs based 
on 10% RBC AChE inhibition.
     Interspecies extrapolation: Because most PoDs are derived 
from toxicology studies in laboratory animals, there is a need to 
extrapolate from animals to humans. In typical risk assessments, a 
default tenfold (10X) uncertainty factor is used to address the 
potential for a difference in toxic response between humans and animals 
used in toxicity tests. For chlorpyrifos, as described further below, 
EPA used a sophisticated model called a physiologically based 
pharmacokinetic-pharmacodynamic (PBPK-PD) model that accounts for 
differences in laboratory animals and humans, thereby obviating the 
need for the default interspecies factor.
     Intraspecies extrapolation: To address the potential for 
differences in sensitivity in the toxic response across the human 
population, EPA conducts intraspecies extrapolation. In typical risk 
assessments, a 10X default uncertainty factor is used. For 
chlorpyrifos, the PBPK-PD model used to derive PoDs also accounts for 
differences in metabolism and toxicity response across the human 
population for some age groups and some subpopulations, which allows 
the default factor of 10X to be refined in accordance with EPA's 2014 
Guidance for Applying Quantitative Data to Develop Data-Derived 
Extrapolation Factors for Interspecies and Intraspecies Extrapolation.

[[Page 48323]]

     Food Quality Protection Act safety factor (FQPA SF)): The 
FFDCA section 408(b)(2)(C) instructs EPA, in making its ``reasonable 
certainty of no harm'' finding, that in ``the case of threshold 
effects, an additional tenfold margin of safety for the pesticide 
chemical residue and other sources of exposure shall be applied for 
infants and children to take into account potential pre- and post-natal 
toxicity and completeness of data with respect to exposure and toxicity 
to infants and children.'' Section 408(b)(2)(C) further states that 
``the Administrator may use a different margin of safety for the 
pesticide chemical residue only if, on the basis of reliable data, such 
margin will be safe for infants and children.'' For chlorpyrifos, as 
discussed later in this Unit, EPA is retaining the default 10X FQPA SF.
    In the human health risk assessment process, as indicated above, 
EPA uses the selected PoD to calculate a RfD for extrapolating risk. 
The RfD is calculated by dividing the selected PoD by any applicable 
interspecies and intraspecies factors and other relevant uncertainty 
factors such as LOAEL to NOAEL factor or database uncertainty factor.\
    After calculating the RfD, as indicated above, EPA retains an 
additional safety factor of 10X to protect infants and children (the 
FQPA safety factor), unless reliable data support selection of a 
different factor, as required under the FFDCA. As described in EPA's 
policy for determining the appropriate FQPA safety factor, this 
additional safety factor often overlaps with other traditional 
uncertainty factors (e.g., LOAEL to NOAEL factor or database 
uncertainty factor), but it might also account for residual concerns 
related to pre- and postnatal toxicity or exposure. (Ref. 35 at 13-16) 
In implementing FFDCA section 408, EPA calculates a variant of the RfD 
referred to as a Population Adjusted Dose (PAD), by dividing the RfD by 
the FQPA SF. Risk estimates less than 100% of the PAD are safe.

B. Toxicological Effects of Chlorpyrifos

    Consistent with FFDCA section 408(b)(2)(D), EPA has reviewed the 
available scientific data and other relevant information for 
chlorpyrifos in support of this action. For over a decade, EPA has 
evaluated the scientific evidence surrounding the different health 
effects associated with chlorpyrifos. The Agency has conducted 
extensive reviews of the scientific literature on health outcomes 
associated with chlorpyrifos and presented approaches for evaluating 
and using that information to the FIFRA SAP on several occasions, as 
discussed above in Unit V. Chlorpyrifos has been tested in 
toxicological studies for the potential to cause numerous different 
adverse outcomes (e.g., reproductive toxicity, developmental toxicity, 
cancer, genotoxicity, dermal toxicity, endocrine toxicity, inhalation 
toxicity, and immunotoxicity). The inhibition of AChE leading to 
cholinergic neurotoxicity and the potential for effects on the 
developing brain (i.e., neurodevelopmental effects) are the most 
sensitive effects seen in the available data. (2020 HHRA p. 6). The SAP 
reports have rendered numerous recommendations for additional study and 
sometimes conflicting advice for how EPA should consider (or not 
consider) the data in conducting EPA's registration review human health 
risk assessment for chlorpyrifos.
    Unit VI. discusses the Agency's assessment of the science relating 
to AChE inhibition and the potential for neurodevelopmental effects. 
Other adverse outcomes besides AChE inhibition and neurodevelopment are 
less sensitive and are thus not discussed in detail here. Further 
information concerning those effects can be found in the 2000 human 
health risk assessment which supported the RED and the 2011 preliminary 
human health risk assessment. (Ref. 12 and 13).
1. Acetylcholinesterase (AChE) Inhibition
    Chlorpyrifos, like other OP pesticides, affects the nervous system 
by inhibiting AChE, an enzyme necessary for the proper functioning of 
the nervous system and ultimately leading to signs of neurotoxicity. 
This mode of action, in which AChE inhibition leads to neurotoxicity, 
is well-established, and thus has been used as basis for the PoD for OP 
human health risk assessments, including chlorpyrifos. This science 
policy is based on decades of work, which shows that AChE inhibition is 
the initial event in the pathway to acute cholinergic neurotoxicity.
    The Agency has conducted a comprehensive review of the available 
data and public literature regarding this adverse effect from 
chlorpyrifos. (Ref. 8 at 24-25, Ref. 13 at 25-27) There are many 
chlorpyrifos studies evaluating RBC AChE inhibition or the brain in 
multiple lifestages (gestational, fetal, post-natal, and non-pregnant 
adult), multiple species (rat, mouse, rabbit, dog, human), methods of 
oral administration (oral gavage with corn oil, dietary, gavage via 
milk) and routes of exposure (oral, dermal, inhalation via vapor and 
via aerosol). In addition, chlorpyrifos is unique in the availability 
of AChE data from peripheral tissues in some studies (e.g., heart, 
lung, liver). There are also literature studies comparing the in vitro 
AChE response to a variety of tissues which show similar sensitivity 
and intrinsic activity. Across the database, brain AChE tends to be 
less sensitive than RBC AChE or peripheral AChE. In oral studies, RBC 
AChE inhibition is generally similar in response to peripheral tissues. 
Thus, the in vitro data and oral studies combined support the continued 
use of RBC AChE inhibition as the critical effect for quantitative 
dose-response assessment.
    Female rats tend to be more sensitive than males to these AChE 
effects. For chlorpyrifos, there are data from multiple studies which 
provide robust RBC AChE data in pregnant, lactating, and non-pregnant 
female rats from oral exposure (e.g., developmental neurotoxicity 
(DNT), reproductive, and subchronic data).
    In addition, studies are available in juvenile pups which show age-
dependent differences, particularly following acute exposures, in 
sensitivity to chlorpyrifos and its oxon. As discussed above, this 
sensitivity is not derived from differences in the AChE enzyme itself 
but instead are derived largely from the immature metabolic clearance 
capacity in the juveniles.
2. Neurodevelopmental Toxicity
    In addition to information on the effects of chlorpyrifos on AChE, 
there is an extensive body of information (in the form of laboratory 
animal studies, epidemiological studies, and mechanistic studies) 
studying the potential effects on neurodevelopment in infants and 
children following exposure to OPs, including chlorpyrifos.
    There are numerous laboratory animal studies on chlorpyrifos in the 
literature that have evaluated the impact of chlorpyrifos exposure in 
pre- and post-natal dosing on the developing brain. These studies vary 
substantially in their study design, but all involve gestational and/or 
early postnatal dosing with behavioral evaluation from adolescence to 
adulthood. The data provide qualitative support for chlorpyrifos to 
potentially impact the developing mammalian brain with adverse outcomes 
in several neurological domains including cognitive, anxiety and 
emotion, social interactions, and neuromotor function. It is, however, 
important to note that there is little consistency in patterns of 
effects across studies. In addition, most of these studies use doses 
that far exceed EPA's 10% benchmark response level for RBC AChE 
inhibition. There are only a few studies with doses at or near the 10% 
brain or RBC AChE inhibition levels;

[[Page 48324]]

among these only studies from Carr laboratory at Mississippi State 
University are considered by EPA to be high quality. EPA has concluded 
that the laboratory animal studies on neurodevelopmental outcomes are 
not sufficient for quantitatively establishing a PoD. Moreover, EPA has 
further concluded that the laboratory animal studies do not support a 
conclusion that adverse neurodevelopmental outcomes are more sensitive 
than 10% RBC AChE inhibition. (Ref. 8 at 25-31, Ref. 9 at 88-89).
    EPA evaluated numerous epidemiological studies on chlorpyrifos and 
other OP pesticides in accordance with the ``Framework for 
Incorporating Human Epidemiologic & Incident Data in Health Risk 
Assessment.'' (Ref. 8, 14, and 15) The most robust epidemiologic 
research comes from three prospective birth cohort studies. These 
include: (1) The Mothers and Newborn Study of North Manhattan and South 
Bronx performed by the Columbia Children's Center for Environmental 
Health (CCCEH) at Columbia University; (2) the Mount Sinai Inner-City 
Toxicants, Child Growth and Development Study or the ``Mt. Sinai Child 
Growth and Development Study;'' and (3) the Center for Health 
Assessment of Mothers and Children of Salinas Valley (CHAMACOS) 
conducted by researchers at University of California Berkeley. (Ref. 8 
at 32-43).
    In the case of the CCCEH study, which specifically evaluated the 
possible connections between chlorpyrifos levels in cord blood and 
neurodevelopmental outcomes on a specific cohort, there are a number of 
notable associations. (Ref. 8 at 36-38). Regarding infant and toddler 
neurodevelopment, the CCCEH authors reported statistically significant 
deficits of 6.5 points on the Psychomotor Development Index at three 
years of age when comparing high to low exposure groups. Notably, these 
decrements persist even after adjustment for group and individual level 
socioeconomic variables. These investigators also observed increased 
odds of mental delay and psychomotor delay at age three when comparing 
high to low exposure groups. The CCCEH authors also report strong, 
consistent evidence of a positive association for attention disorders, 
attention deficit hyperactivity disorder (ADHD), and pervasive 
development disorder (PDD) when comparing high to low chlorpyrifos 
exposure groups. Moreover, it was reported that for children in the 
CCCEH cohort at age seven for each standard deviation increase in 
chlorpyrifos cord blood exposure, there is a 1.4% reduction in Full-
Scale IQ and a 2.8% reduction in Working Memory. In addition, the CCCEH 
authors evaluated the relationship between prenatal chlorpyrifos 
exposure and motor development/movement and reported elevated risks of 
arm tremor in children around 11 years of age in the CCCEH cohort.
    Notwithstanding the observed associations, EPA and the 2012 and 
2016 FIFRA SAPs identified multiple uncertainties in the CCCEH 
epidemiology studies (Ref. 6 and 8). Some of these include the 
relatively modest sample sizes, which limited the statistical power; 
exposure at one point in prenatal time with no additional information 
regarding postnatal exposures; representativeness of a single point 
exposure where time-varying exposures or the ability to define 
cumulative exposures would be preferable; lack of specificity of a 
critical window of effect and the potential for misclassification of 
individual exposure measures; and lack of availability of the raw data 
from the studies that would allow verification of study conclusions.
    One of the notable uncertainties in the CCCEH epidemiology studies 
identified by EPA and the 2016 FIFRA SAP is the lack of specific 
exposure information on the timing, frequency, and magnitude of 
chlorpyrifos application(s) in the apartments of the women in the 
study. Despite extensive effort by EPA to obtain or infer this exposure 
information from various sources, the lack of specific exposure data 
remains a critical uncertainty. EPA made efforts in 2014 and 2016 to 
develop dose reconstruction of the exposures to these women. These dose 
reconstruction activities represent the best available information and 
tools but are highly uncertain. In addition, the pregnant women and 
children in the CCCEH studies were exposed to multiple chemicals, 
including multiple potent AChE inhibiting OPs and N-methyl carbamates. 
Moreover, using EPA's dose reconstruction methods from 2014 suggest 
that the pregnant women likely did not exhibit RBC AChE inhibition 
above 10%. The 2012 and 2016 FIFRA SAP reports expressed concern that 
it is likely that the CCCEH findings occurred at exposure levels below 
those that result in 10% RBC AChE inhibition (Ref. 6 and 8). However, 
given the available CCCEH exposure information and the exposures to 
multiple potent AChE inhibiting pesticides, EPA cannot definitively 
conclude the level of AChE inhibition. EPA remains unable to make a 
causal linkage between chlorpyrifos exposure and the outcomes reported 
by CCCEH investigators. (Ref. 8) Moreover, given the uncertainties, 
particularly in the exposure information available from CCCEH (single 
timepoints, lack of time varying exposure, lack of knowledge about 
application timing), uncertainties remain about the dose-response 
relationships from the epidemiology studies.
    Finally, there are several lines of evidence for actions of 
chlorpyrifos distinct from the classical mode of action of AChE 
inhibition. This information has been generated from model systems 
representing different levels of biological organization and provide 
support for molecular initiating events (binding to the morphogenic 
site of AChE, muscarinic receptors, or tubulin), cellular responses 
(alterations in neuronal proliferation, differentiation, neurite 
growth, or intracellular signaling), and responses at the level of the 
intact nervous system (serotonergic tone, axonal transport). Among the 
many in vitro studies on endpoints relevant to the developing brain 
available for chlorpyrifos, only three have identified outcomes in 
picomole concentrations, including concentrations lower than those that 
elicit AChE inhibition in vitro. However, as is the case for many other 
developmental neurotoxicants, most of these studies have not been 
designed with the specific goal of construction or testing an adverse 
outcome pathway. Thus, there are not sufficient data available to test 
rigorously the causal relationship between effects of chlorpyrifos at 
the different levels of biological organization in the nervous system. 
(Ref. 8 at 27-31)
    Due to the complexity of nervous system development involving the 
interplay of many different cell types and developmental timelines, it 
is generally accepted that no single in vitro screening assay can 
recapitulate all the critical processes of neurodevelopment. As a 
result, there has been an international effort to develop a battery of 
new approach methodologies (NAMs) to inform the DNT potential for 
individual chemicals. This DNT NAM battery is comprised of in vitro 
assays that assess critical processes of neurodevelopment, including 
neural network formation and function, cell proliferation, apoptosis, 
neurite outgrowth, synaptogenesis, migration, and differentiation. In 
combination the assays in this battery provide a mechanistic 
understanding of the underlying biological processes that may be 
vulnerable to chemically-induced disruption. It is noteworthy, however, 
that to date the quantitative relationship between alterations in these

[[Page 48325]]

neurodevelopmental processes and adverse health outcomes has not been 
fully elucidated. Moreover, additional assays evaluating other critical 
neurodevelopmental processes such as myelination are still being 
developed (Ref. 15).
    In September 2020, EPA convened a FIFRA SAP on developing and 
implementing NAMs using methods such as in vitro techniques and 
computational approaches. Included in that consideration was use of the 
DNT NAM battery to evaluate OP compounds as a case study. These methods 
presented to the 2020 FIFRA SAP provide a more systematic approach to 
evaluating pharmacodynamic effects on the developing brain compared to 
the existing literature studies. Initial data from the NAM battery were 
presented to the SAP for 27 OP compounds, including chlorpyrifos and 
its metabolite, chlorpyrifos oxon, and, when possible, compared to in 
vivo results (by using in vitro to in vivo extrapolation). On December 
21, 2020, the SAP released its final report and recommendations on 
EPA's proposed use of the NAMs data. (Ref. 16). The advice of the SAP 
is currently being taken into consideration as EPA develops a path 
forward on NAMs, but analysis and implementation of NAMs for risk 
assessment of chlorpyrifos is in progress and was unable to be 
completed in time for use in this rulemaking. The Agency is continuing 
to explore the use of NAMs for the OPs, including chlorpyrifos, and 
intends to make its findings available as soon as it completes this 
work.

C. Hazard Identification: Using AChE as the Toxicological Endpoint for 
Deriving PADs

    The RED for chlorpyrifos was completed in 2006 and relied on RBC 
AChE inhibition results from laboratory animals to derive PoDs and 
retained the FQPA 10X safety factor due to concerns over age-related 
sensitivity and uncertainty associated with potential 
neurodevelopmental effects observed in laboratory animals. Based on a 
review of all the studies (guideline data required, peer reviewed 
literature, mechanistic), AChE inhibition remains the most robust 
quantitative dose-response data and thus continues to be the critical 
effect for the quantitative risk assessment. This approach is 
consistent with the advice of the SAP from 2008 and 2012. The Agency 
typically uses a 10% response level for AChE inhibition in human health 
risk assessments. This response level is consistent with the 2006 OP 
cumulative risk assessment and other single chemical OP risk 
assessments. (Ref. 17 and 18).
    In response to the 2015 proposed rule to revoke chlorpyrifos 
tolerances, as noted above, the Agency received some comments raising a 
concern that the use of the 10% AChE inhibition may not be sufficiently 
health protective. Taking those comments into consideration, EPA 
conducted an additional hazard analysis and convened the 2016 FIFRA SAP 
to evaluate a proposal of using cord blood data from the CCCEH 
epidemiology studies as the source of data for PoDs. The 2016 FIFRA SAP 
did not support the ``direct use'' of the cord blood and working memory 
data for deriving the regulatory endpoint, due to insufficient 
information about timing and magnitude of chlorpyrifos applications in 
relation to cord blood concentrations at the time of birth, 
uncertainties about the prenatal window(s) of exposure linked to 
reported effects, and lack of a second laboratory to reproduce the 
analytical blood concentrations. (Ref. 8) Despite their critiques 
regarding uncertainties in the CCCEH studies, the 2016 SAP expressed 
concern that 10% RBC AChE inhibition is not sufficiently protective of 
human health.
    The 2016 FIFRA SAP, however, did present an alternative approach 
for EPA to consider. First, it is important to note that this SAP was 
supportive of the EPA's use of the PBPK-PD model as a tool for 
assessing internal dosimetry from typical OPP exposure scenarios. Use 
of the PBPK-PD model coupled with typical exposure scenarios provides 
the strongest scientific foundation for chlorpyrifos human health risk 
assessment. Given that the window(s) of susceptibility are currently 
not known for the observed neurodevelopmental effects, and the 
uncertainties associated with quantitatively interpreting the CCCEH 
cord blood data, this SAP recommended that the Agency use a time 
weighted average (TWA) blood concentration of chlorpyrifos for the 
CCCEH study cohort as the PoD for risk assessment. Thus, in 2016 EPA 
attempted, using the PBPK-PD model, to determine the TWA blood level 
expected from post-application exposures from the chlorpyrifos indoor 
crack-and-crevice use scenario. Despite that effort, EPA's position is 
that the shortcomings of the data with regard to the dose-response 
relationship and lack of exposure information discussed above, continue 
to raise issues that make quantitative use of the CCCEH data in risk 
assessment not scientifically sound.
    Thus, taking into consideration the robustness of the available 
data at this time, EPA has determined that the most appropriate 
toxicological endpoint for deriving points of departure for assessing 
risks of chlorpyrifos is 10% RBC AChE inhibition. The Agency is not 
ignoring or dismissing the extensive data concerning the potential for 
adverse neurodevelopmental outcomes, however. As discussed later in 
this Unit, the Agency is addressing the uncertainties surrounding the 
potential for adverse neurodevelopmental outcomes by retaining the 
default 10X FQPA safety factor.
1. Durations of Exposure
    As noted in Unit VI.A., EPA establishes PoDs for each expected 
exposure duration likely to result from pesticide exposure. For 
chlorpyrifos, exposure can occur from a single event or on a single day 
(e.g., eating a meal) or from repeated days of exposure (e.g., 
residential). With respect to AChE inhibition, effects can occur from a 
single exposure or from repeated exposures. For OPs, repeated exposures 
generally result in more AChE inhibition at a given administered dose 
compared to acute exposures. Moreover, AChE inhibition in repeated 
dosing guideline toxicology studies with most OPs show a consistent 
pattern of inhibition reaching a ``steady state'' of inhibition at or 
around 2-3 weeks of exposure in adult laboratory animals (Ref. 19). 
This pattern observed with repeated dosing is a result of the amount of 
inhibition coming to equilibrium with production of new enzyme. As 
such, AChE studies of 2-3 weeks generally show the same degree of 
inhibition with those of longer duration (i.e., up to 2 years of 
exposure). Thus, for most of the human health risk assessments for the 
OPs, the Agency is focusing on the critical durations ranging from a 
single day up to 21 days (i.e., the approximate time to reach steady 
state for most OPs). As such, EPA has calculated PoDs for the acute and 
steady-state durations. As described below, these PoDs have been 
derived for various lifestages, routes, and exposure scenarios.
2. Deriving PODs, Inter- and Intra-Species Extrapolation: Use of the 
PBPK Model
    The process for developing RfDs and PADs typically involves first 
deriving PoDs directly from laboratory animal studies, followed by 
dividing the PoD by the default uncertainty factors of 10X for 
interspecies extrapolation and intraspecies extrapolation, and the FQPA 
safety factor. For chlorpyrifos, as discussed previously in Unit V, 
there is a sophisticated PBPK-PD model available for chlorpyrifos. 
Numerous

[[Page 48326]]

Federal Advisory Committees and external review panels have encouraged 
the use of such a modeling approach to reduce inherent uncertainty in 
the risk assessment and facilitate more scientifically sound 
extrapolations across studies, species, routes, and dose levels. The 
PBPK-PD model for chlorpyrifos has undergone extensive peer review by 
various individual or groups, including the FIFRA SAPs. Significant 
improvements have been made to the model over the years in response to 
recommendations from the 2008, 2011, and 2012 FIFRA SAPs and comments 
from both internal and external peer reviewers. (Ref. 9 at 20). As a 
result, EPA has concluded that the current PBPK-PD model is 
sufficiently robust and is using it for deriving PoDs for chlorpyrifos.
a. Derivation of PoDs
    As noted above, the PoDs for chlorpyrifos are based on the levels 
at which 10% RBC AChE inhibition is observed. The PBPK-PD model 
accounts for pharmacokinetic and pharmacodynamic characteristics to 
derive age-, duration-, and route-specific PoDs. Separate PoDs have 
been calculated for dietary (food, drinking water) and residential 
exposures by varying inputs on types of exposures and populations 
exposed. Specifically, the following characteristics have been 
evaluated: Duration [24-hour (acute), 21-day (steady state)]; route 
(dermal, oral, inhalation); body weights which vary by lifestage; 
exposure duration (hours per day, days per week); and exposure 
frequency [events per day (eating, drinking)]. For each exposure 
scenario, the appropriate body weight for each age group or sex was 
modeled as identified from the Exposure Factors Handbook (Ref. 21) for 
residential exposures and from the U.S. Department of Agriculture's 
(USDA) National Health and Nutrition Examination Survey (NHANES)/What 
We Eat in America (WWEIA) Survey for dietary exposures.
    Within the PBPK-PD model, the Agency evaluated the following 
exposure scenarios: Oxon (chlorpyrifos metabolite) exposures via 
drinking water (acute and steady-state exposures for infants, children, 
youths, and female adults); chlorpyrifos exposures via food (acute and 
steady-state exposures for infants, children, youths, and female 
adults); steady-state residential exposures to chlorpyrifos via skin 
for children, youths, and female adults; steady-state residential 
exposures to chlorpyrifos via hand-to-mouth ingestion for children 1-2 
years old; steady-state residential exposures to chlorpyrifos via 
inhalation for children 1-2 years old and female adults. (Ref. 9 at 22-
25).
    Steady-state dietary exposure was estimated daily for 21 days. For 
drinking water exposure, infants and young childrens (infants <1 year 
old, children between 1-2 years old, and children between 6-12 years 
old) were assumed to consume water 6 times per day, with a total 
consumption volume of 0.69 L/day. For youths and female adults, they 
were assumed to consume water 4 times per day, with a total consumption 
volume of 1.71 L/day.
    For all residential dermal exposures to chlorpyrifos the dermal 
PoDs were estimated assuming 50% of the skin's surface was exposed. 
Exposure times for dermal exposure assessment were consistent with 
those recommended in the 2012 Residential Standard Operating Procedures 
(SOPs) (Ref. 18). For residential inhalation exposures following public 
health mosquitocide application, the exposure duration was set to 1 
hour per day for 21 days. The incidental oral PoDs for children 1 to <2 
years old for other turf activities were estimated assuming that there 
were six events, 15 minutes apart, per day.
    The PBPK-modeled PoDs derived for the various lifestages, routes, 
and exposure scenarios discussed above, can be found in Table 4.2.2.1.2 
of the 2020 HHRA (Ref 8).
b. Inter-Species Extrapolation
    As indicated above, the PBPK-PD model directly predicts human PoDs 
based on human physiology and biochemistry, and thus there is no need 
for an inter-species uncertainty factor to extrapolate from animal 
PoDs.
c. Intra-Species Extrapolation
    The PBPK-PD model can account for variability of critical 
physiological, pharmacokinetic, and pharmacodynamic parameters in a 
population to estimate, using the Monte Carlo analysis, the 
distribution of doses that result in 10% RBC AChE inhibition. 
Therefore, Data-Derived Extrapolation Factors (DDEF) for intra-species 
extrapolation have been estimated to replace the default intra-species 
uncertainty factor for some groups (Ref. 22).
    According to EPA's DDEF guidance (Ref. 22), when calculating a DDEF 
intra-species extrapolation factor, administered doses leading to the 
response level of interest (in the case of chlorpyrifos, the 10% change 
in RBC AChE inhibition) are compared between a measure of average 
response and response at the tail of the distribution representing 
sensitive individuals. The tail of the distribution may be selected at 
the 95th, 97.5th, and 99th percentile.
    As to chlorpyrifos, the 99th percentile was used in risk assessment 
to provide the most conservative measure (Ref. 7). In addition to 
estimating DDEF using the above approach for specific age groups, 
intra-species DDEF was also calculated by comparing between average 
responses between adults and 6-month old infants. For the 2020 HHRA, 
the largest calculated DDEFs, 4X for chlorpyrifos and 5X for the oxon 
metabolite, were used for intraspecies extrapolation for all groups 
except women of childbearing age. There was a slightly higher 
variability between adults and infants when considering the 
distributions for the oxon metabolite, thus, the slightly higher intra-
species factor. For women of childbearing age, the Agency is applying 
the standard 10X intra-species extrapolation factor due to limitations 
in the PBPK-PD model to account for physiological, anatomical, and 
biochemical changes associated with pregnancy. (Ref. 9 at 21-22).
d. Summarizing the PoDs, Inter- and Intra-Species Extrapolation Factors
    In summary, for assessing the risks from exposure to chlorpyrifos, 
the human PBPK-PD model has been used to derive PoDs based on 10% RBC 
AChE inhibition for various populations, durations, and routes. The 
model, which calculates a human PoD directly, obviates the need for an 
interspecies extrapolation factor since animal data are not used. To 
account for variations in sensitivities, the Agency has determined that 
an intra-species factor of 4X for chlorpyrifos and 5X for the oxon is 
appropriate for all groups except women of childbearing age. For women 
of childbearing age, the typical 10X intra-species factor is being 
applied, due the lack of appropriate information and algorithms to 
characterize physiological changes during pregnancy.
3. FQPA Safety Factor
    As noted above, the FFDCA requires EPA, in making its ``reasonable 
certainty of no harm'' finding, that in ``the case of threshold 
effects, an additional tenfold margin of safety for the pesticide 
chemical residue and other sources of exposure shall be applied for 
infants and children to take into account potential pre- and postnatal 
toxicity and completeness of data with respect to exposure and toxicity 
to infants and children.'' 21 U.S.C. 346A(b)(2)(C). Section 
408(b)(2)(C) further states that ``the Administrator may use a 
different margin of safety for the pesticide chemical residue only if, 
on the basis of

[[Page 48327]]

reliable data, such margin will be safe for infants and children.''
    In applying the FQPA safety factor provision, EPA has interpreted 
it as imposing a presumption in favor of retaining it as an additional 
10X safety factor. (Ref. 5 at 4, 11). Thus, EPA generally refers to the 
10X factor as a presumptive or default 10X factor. EPA has also made 
clear, however, that this presumption or default in favor of the 10X is 
only a presumption. The presumption can be overcome if reliable data 
demonstrate that a different factor is safe for children. (Id.). In 
determining whether a different factor is safe for children, EPA 
focuses on the three factors listed in FFDCA section 408(b)(2)(C)--the 
completeness of the toxicity database, the completeness of the exposure 
database, and potential pre- and post-natal toxicity. In examining 
these factors, EPA strives to make sure that its choice of a safety 
factor, based on a weight-of-the-evidence evaluation, does not 
understate the risk to children. (Id. at 24-25, 35).
    EPA's 2020 HHRA assessed the potential risks from exposures to 
chlorpyrifos in two ways--with one scenario being the retention of the 
default 10X FQPA SF, and the other scenario being the reduction of the 
FQPA SF to 1X. The purpose of using both values was to provide an 
indication of what the potential risk estimates would be under either 
scenario. The 2020 document, however, retained the 10X and did not 
adopt or offer support for reducing to 1X. To reduce the FQPA safety 
factor to 1X, the FFDCA requires that EPA determine that reliable data 
demonstrate that the 1X would be safe for infants and children. The 
2020 document did not make that determination. For chlorpyrifos, of the 
three factors mentioned in the previous paragraph, the primary factor 
that undercuts a determination that a different safety factor would be 
safe for children is the uncertainty around the potential for pre- and 
post-natal toxicity for infants and children in the area of 
neurodevelopmental outcomes.
    Based on the weight of the evidence concerning the potential for 
neurodevelopmental outcomes as discussed in Unit VI.B.2. above, there 
is ample qualitative evidence of a potential effect on the developing 
brain; however, there remains uncertainty around the levels at which 
these potential neurodevelopmental outcomes occur. Although the 
laboratory animal studies do not support a conclusion that 
neurodevelopmental outcomes are more sensitive than AChE inhibition, 
the mechanistic data are, at this time, incomplete in their 
characterization of dose-response. This conclusion may be further 
evaluated upon EPA's completion of the review of the 2020 FIFRA SAP 
report concerning NAMs; however, due to the time constraints of this 
rule, EPA has not been able to include that information in the current 
assessment of chlorpyrifos. Finally, while the epidemiology data 
indicates an association between chlorpyrifos and adverse 
neurodevelopmental outcomes, there remains some uncertainty in the 
dose-response relationship. As such, because the data available at this 
time indicate remaining uncertainties concerning pre- and post-natal 
toxicity due to insufficient clarity on the levels at which these 
outcomes occur, the Agency is unable to conclude, at this time, that a 
different safety factor would be safe for infants and children; thus, 
the Agency is retaining the default 10X FQPA safety factor.
4. Total Uncertainty Factors and PADs
    In conclusion, the Agency used a total uncertainty factor of 100X 
for determining the food and drinking water PADs for females of 
childbearing age (1X interspecies factor, 10X intra-species factor, and 
10X FQPA safety factor); 40X for determining the food PADs for 
remaining populations (1X interspecies factor, 4X intra-species factor, 
and 10X FQPA safety factor); and 50X for determining the PADs for 
drinking water for remaining populations (1X interspecies factor, 5X 
intra-species factor, and 10X FQPA safety factor).
    Taking into consideration the PoDs, intra-species extrapolation 
factors, and FQPA safety factor, the Agency calculated acute PADs 
(aPADs) and steady state PADs (ssPADs) for infants (less than 1 year 
old), children (1 to 2 years old), children (6 to 12 years old), youths 
(13 to 19 years old), and females (13-49 years old); these 
subpopulations will be protective of other subpopulations. (Ref. 9 at 
30-32.) Values may be found in table 5.0.1 in the 2020 HHRA.

VII. EPA's Exposure Assessment for Chlorpyrifos

    Risk is a function of both hazard and exposure. Thus, equally 
important to the risk assessment process as determining the hazards 
posed by a pesticide and the toxicological endpoints for those hazards 
is estimating human exposure. Under FFDCA section 408, EPA must 
evaluate the aggregate exposure to a pesticide chemical residue. This 
means that EPA is concerned not only with exposure to pesticide 
residues in food but also exposure resulting from pesticide 
contamination of drinking water supplies and from use of pesticides in 
the home or other non-occupational settings. (See 21 U.S.C. 
346a(b)(2)(D)(vi)).
    Pursuant to FFDCA section 408(b), EPA has evaluated chlorpyrifos's 
risks based on ``aggregate exposure'' to chlorpyrifos. By ``aggregate 
exposure,'' EPA is referring to exposure to chlorpyrifos by multiple 
pathways of exposure, i.e., food, drinking water, and residential. EPA 
uses available data and standard analytical methods, together with 
assumptions designed to be protective of public health, to produce 
separate estimates of exposure for a highly exposed subgroup of the 
general population, for each potential pathway and route of exposure.
    The following reflect a summary of the Agency's exposure assessment 
from the 2020 HHRA unless otherwise specified. (Ref. 10).

A. Exposure From Food

1. General Approach for Estimating Food Exposures
    There are two critical variables in estimating exposure in food: 
(1) The types and amount of food that is consumed; and (2) The residue 
level in that food. Consumption is estimated by EPA based on scientific 
surveys of individuals' food consumption in the United States conducted 
by the U.S. Department of Agriculture (USDA), (Ref. 11 at 12). 
Information on residue values can come from a range of sources 
including crop field trials; data on pesticide reduction (or 
concentration) due to processing, cooking, and other practices; 
information on the extent of usage of the pesticide; and monitoring of 
the food supply. (Id. at 17).
    Data on the residues of chlorpyrifos in foods are available from 
both field trial data and monitoring data, primarily the USDA's 
Pesticide Data Program (PDP) monitoring data. Monitoring data generally 
provide a characterization of pesticide residues in or on foods 
consumed by the U.S. population that closely approximates real world 
exposures because they are sampled closer to the point of consumption 
in the chain of commerce than field trial data, which are generated to 
establish the maximum level of legal residues that could result from 
maximum permissible use of the pesticide immediately after harvest.
    EPA uses a computer program known as the Dietary Exposure 
Evaluation Model and Calendex software with the Food Commodity Intake 
Database

[[Page 48328]]

(DEEM-FCID version 3.16/Calendex) to estimate exposure by combining 
data on human consumption amounts with residue values in food 
commodities. The model incorporates 2003-2008 consumption data from 
USDA's NHANES/WWEIA. The data are based on the reported consumption of 
more than 20,000 individuals over two non-consecutive survey days. 
Foods ``as consumed'' (e.g., apple pie) are linked to EPA-defined food 
commodities (e.g., apples, peeled fruit--cooked; fresh or N/S (Not 
Specified); baked; or wheat flour--cooked; fresh or N/S, baked) using 
publicly available recipe translation files developed jointly by USDA 
Agricultural Research Service (ARS) and EPA. For chronic exposure 
assessment (or in the case of chlorpyrifos, for steady-state exposure 
assessment), consumption data are averaged for the entire U.S. 
population and within population subgroups; however, for acute exposure 
assessment, consumption data are retained as individual consumption 
events. Using this consumption information and residue data, the 
exposure estimates are calculated for the general U.S. population and 
specific subgroups based on age, sex, ethnicity, and region.
    For chlorpyrifos, EPA determined that acute and steady-state 
exposure durations were relevant for assessing risk from food 
consumption. EPA calculates potential risk by using probabilistic 
techniques to combine distributions of potential exposures in sentinel 
populations. The resulting probabilistic assessments present a range of 
dietary exposure/risk estimates.
    Because probabilistic assessments generally present a realistic 
range of residue values to which the population may be exposed, EPA's 
starting point for estimating exposure and risk for such assessments is 
the 99.9th percentile of the population under evaluation. When using a 
probabilistic method of estimating acute dietary exposure, EPA 
typically assumes that, when the 99.9th percentile of acute exposure is 
equal to or less than the aPAD, the level of concern for acute risk has 
not been exceeded. By contrast, where the analysis indicates that 
estimated exposure at the 99.9th percentile exceeds the aPAD, EPA would 
generally conduct one or more sensitivity analyses to determine the 
extent to which the estimated exposures at the high-end percentiles may 
be affected by unusually high food consumption or residue values. (The 
same assumptions apply to estimates for steady state dietary exposure 
and the ssPAD.) To the extent that one or a few values seem to 
``drive'' the exposure estimates at the high-end of exposure, EPA would 
consider whether these values are reasonable and should be used as the 
primary basis for regulatory decision making (Ref. 20).
2. Estimating Chlorpyrifos Exposures in Food
    The residue of concern, for tolerance expression and risk 
assessment, in plants (food and feed) and livestock commodities is the 
parent compound chlorpyrifos. EPA has determined that the metabolite 
chlorpyrifos oxon is not a residue of concern in food or feed, based on 
available field trial data and metabolism studies that indicate that 
the oxon is not present in the edible portions of the crops. In 
addition, the chlorpyrifos oxon is not found on samples in the USDA PDP 
monitoring data. Furthermore, the oxon metabolite was not found in milk 
or livestock tissues (Ref. 9 at 33).
    Acute and steady-state dietary (food only) exposure analyses for 
chlorpyrifos were conducted using the DEEM-FCID version 3.16/Calendex 
software (Ref. 23). These analyses were performed for the purpose of 
obtaining food exposure values for comparison to the chlorpyrifos doses 
predicted by the PBPK-PD model to cause RBC AChE Inhibition. The acute 
and steady-state dietary (food only) exposure analyses do not include 
drinking water exposures, which were assessed separately, see Unit 
VII.B.2.
    Both the acute and steady state dietary exposure analyses are 
highly refined. The large majority of food residues used were based 
upon PDP monitoring data except in a few instances where no appropriate 
PDP data were available. In those cases, field trial data or tolerance 
level residues were assumed. EPA also used food processing factors from 
submitted studies as appropriate. In addition, EPA's acute and steady 
state dietary exposure assessments used percent crop treated (PCT) 
information. (Ref. 23)
    The chlorpyrifos acute dietary exposure analysis was conducted 
using the DEEM-FCID, version 3.16, which incorporates 2003-2008 survey 
consumption data from USDA's NHANES/WWEIA. The acute risk estimates 
were presented for the sentinel populations for infants (less than 1 yr 
old); children (1-2 years old); youths (6-12 years old); and adults 
(females 13-49 years old). The assessment of these index lifestages is 
protective of other population subgroups.
    The chlorpyrifos steady-state dietary exposure analysis was 
conducted using the Calendex component of DEEM-FCID (with 2003-2008 
survey consumption data from USDA's NHANES/WWEIA). Calendex provides a 
focus detailed profile of potential exposures to individuals across a 
calendar year. A calendar-based approach provides the ability to 
estimate daily exposures from multiple sources over time to an 
individual and is in keeping with two key tenets of aggregate risk 
assessment: (1) That exposures when aggregated are internally 
consistent and realistic; and (2) that appropriate temporal and 
geographic linkages or correlations/associations between exposure 
scenarios are maintained.
    The chlorpyrifos steady state assessment considers the potential 
risk from a 21-day exposure duration using a 3-week rolling average 
(sliding by day) across the year. For this assessment, the same food 
residue values used in the acute assessment were used for the 21-day 
duration. In the Calendex software, one diary for each individual in 
the WWEIA is selected to be paired with a randomly selected set of 
residue values for each food consumed. The steady-state analysis 
calculated exposures for the sentinel populations for infants (less 
than 1 year old); children (1-2 years old); youths (6-12 years old); 
and adults (females 13-49 years old). The assessment of these index 
lifestages is protective of other population subgroups.

B. Exposure From Drinking Water

1. General Approach for Assessing Exposure From Drinking Water
a. Modeling and Monitoring Data
    Monitoring and modeling are both important tools for estimating 
pesticide concentrations in water and can provide different types of 
information. Monitoring data can provide estimates of pesticide 
concentrations in water that are representative of the specific 
agricultural or residential pesticide practices in specific locations, 
under the environmental conditions associated with a sampling design 
(i.e., the locations of sampling, the times of the year samples were 
taken, and the frequency by which samples were collected). Although 
monitoring data can provide a direct measure of the concentration of a 
pesticide in water, it does not always provide a reliable basis for 
estimating spatial and temporal variability in exposures because 
sampling may not occur in areas with the highest pesticide use, and/or 
when the pesticides are being used and/or at an appropriate sampling 
frequency to detect high concentrations of a pesticide that occur over 
the period of a day to several days.

[[Page 48329]]

    Because of the limitations in most monitoring studies, EPA's 
standard approach is to use water exposure models as the primary means 
to estimate pesticide exposure levels in drinking water. Modeling is a 
useful tool for characterizing vulnerable sites and can be used to 
estimate upper-end pesticide water concentrations from infrequent, 
large rain events. EPA's computer models use detailed information on 
soil properties, crop characteristics, and weather patterns to estimate 
water concentrations in vulnerable locations where the pesticide could 
be used according to its label (Ref. 24 at 27-28). EPA's models 
calculate estimated water concentrations of pesticides using laboratory 
data that describe how fast the pesticide breaks down to other 
chemicals and how it moves in the environment at these vulnerable 
locations. The modeling provides an estimate of pesticide 
concentrations in ground water and surface water. Depending on the 
modeling algorithm (e.g., surface water modeling scenarios), daily 
concentrations can be estimated continuously over long periods of time, 
and for places that are of most interest for any particular pesticide.
    EPA relies on models it has developed for estimating pesticide 
concentrations in both surface water and groundwater. The most common 
model used to conduct drinking water assessments is the Pesticide in 
Water Calculator (PWC). PWC couples the Pesticide Root Zone Model 
(PRZM) and Variable Volume Water Model (VVWM) models together to 
simulate pesticide fate and transport from the field of application to 
an adjacent reservoir. (Ref. 24 at 27-28). The PWC estimates pesticide 
concentrations for an index reservoir that is modeled for site-specific 
scenarios (i.e., weather and soil data) in different areas of the 
country. A detailed description of the models routinely used for 
exposure assessment is available from the EPA OPP Aquatic Models 
website: https://www.epa.gov/pesticide-science-and-assessing-pesticide-risks/models-pesticide-risk-assessment#aquatic.
    In modeling potential surface water concentrations, EPA attempts to 
model areas of the country that are vulnerable to surface water 
contamination rather than simply model ``typical'' concentrations 
occurring across the nation. Consequently, EPA models exposures 
occurring in small highly agricultural watersheds in different growing 
areas throughout the country, over a 30-year period. The scenarios are 
designed to capture residue levels in drinking water from reservoirs 
with small watersheds with a large percentage of land use in 
agricultural production. EPA believes these assessments are likely 
reflective of a small subset of the watersheds across the country that 
maintain drinking water reservoirs, representing a drinking water 
source generally considered to be more vulnerable to frequent high 
concentrations of pesticides than most locations that could be used for 
crop production.
    When monitoring data meet certain data quantity criteria, EPA has 
tools available to quantify the uncertainty in available monitoring 
data such that it can be used quantitively to estimate pesticide 
concentrations in drinking water. (Ref. 25) Furthermore, monitoring 
data can be used in a weight of evidence approach with model estimated 
concentrations to increase confidence in the conclusions of a drinking 
water assessment.
b. Drinking Water Level of Comparison (DWLOC)
    The drinking water level of comparison (DWLOC) is a benchmark that 
can be used to guide refinements of the drinking water assessment 
(DWA). This value relates to the concept of the ``risk cup,'' which EPA 
developed to facilitate risk refinement when considering aggregate 
human health risk to a pesticide. (Ref. 26). The risk cup is the total 
exposure allowed for a pesticide considering its toxicity and required 
safety factors. The risk cup is equal to the maximum safe exposure for 
the duration and population being considered. Exposures exceeding the 
risk cup are of potential concern. There are risk cups for each 
pertinent duration of exposure (e.g., acute, short-term, chronic). The 
exposure durations most commonly of interest for acute or short-term 
pesticide exposure risk assessments are 1-day, 4-day, and 21-day 
averages. For example, the relevant exposure duration for AChE 
reversible inhibition from exposure to carbamate insecticides is 1-day, 
while AChE irreversible inhibition resulting from exposure to OP 
insecticides is usually 21-days based on steady-state kinetics. (Ref. 
19)
    In practice, EPA calculates the total exposure from food 
consumption and residential (or other non-occupational) exposures and 
subtracts this value from the maximum safe exposure level. The 
resulting value is the allowable remaining exposure without the 
potential for adverse health effect. Knowing this allowable remaining 
exposure and the water consumption for each population subgroup (e.g., 
infants), the Agency can calculate the DWLOC, which is the estimate of 
safe concentrations of pesticides in drinking water. Using this process 
of DWLOC calculation allows EPA to determine a target maximum safe 
drinking water concentration, thereby identifying instances where 
drinking water estimates require refinement. (Ref. 24 at 19-20).
c. Scale of Drinking Water Assessment
    Although food is distributed nationally, and residue values are 
therefore not expected to vary substantially throughout the country, 
drinking water is locally derived and concentrations of pesticides in 
source water fluctuate over time and location for a variety of reasons. 
Pesticide residues in water fluctuate daily, seasonally, and yearly 
because of the timing of the pesticide application, the vulnerability 
of the water supply to pesticide loading through runoff, spray drift 
and/or leaching, and changes in the weather. Concentrations are also 
affected by the method of application, the location, and 
characteristics of the sites where a pesticide is used, the climate, 
and the type and degree of pest pressure, which influences the 
application timing, rate used, and number of treatments in a crop 
production cycle.
    EPA may conduct a drinking water assessment (DWA) for a national 
scale depending on the pesticide use under evaluation. A national scale 
DWA may use a single upper-end pesticide concentration as a starting 
point for assessing whether additional refinements are needed or 
estimated pesticide concentrations for certain site-specific scenarios 
that are associated with locations in the United States vulnerable to 
pesticide contamination based on pesticide use patterns. (Ref. 24 at 
22.)
    EPA may also conduct a regional scale DWA to focus on areas where 
pesticide concentrations may be higher than the DWLOC. Under this 
assessment, EPA estimates pesticide concentrations across different 
regions in the United States that are subdivided into different areas 
called hydrologic units (HUCs). There are 21 HUC 2 regions with 18 in 
the contiguous United States. These areas contain either the drainage 
area of a major river or a combined drainage of a series of rivers. 
This information can eb found at: https://water.usgs.gov/GIS/huc.html. 
Estimated pesticide concentrations under this approach would be 
associated with a vulnerable pesticide use area somewhere within the 
evaluated region. (Ref. 24 at 23).

[[Page 48330]]

d. Drinking Water Refinements
    EPA has defined four assessment tiers for drinking water 
assessments. Lower tiered assessments are more conservative based on 
the defaults or upper bound assumptions and may compound conservatisms, 
while higher tiers integrate more available data and provide more 
realistic estimates of environmental pesticide concentrations.
    These four tiers are generally based on the level of effort, the 
amount of data considered, the spatial scale, and the certainty in the 
estimated pesticide concentration. Tier 1 requires the least amount of 
effort and the least amount of data, whereas Tier 4 is resource 
intensive, considers a wide range of sources and types of data, and is 
spatially explicit, resulting in high confidence in the reported 
pesticide concentration. Each successive tier integrates more focused 
pesticide, spatial, temporal, agronomic, and crop-specific information. 
The order in which refinements are considered (i.e., the order in which 
the assessment is refined) is pesticide-specific and depends on the 
nature and quality of the available data used to support the 
refinement. Additional information on the conduct of drinking water 
assessments can be found in the ``Framework for Conducting Pesticide 
Drinking Water Assessment for Surface Water'' (USEPA, 2020).
    As discussed in the Framework document, EPA can incorporate several 
refinements in higher tiered modeling. Two such refinements are the 
percent cropped area (PCA) and the percent crop treated (PCT). These 
are described in the recently completed document titled ``Integrating a 
Distributional Approach to Using Percent Crop Area (PCA) and Percent 
Crop Treated (PCT) into Drinking Water Assessment'' (Ref. 27) The PCA 
refers to the amount of area in a particular community water system 
that is planted with the crop of interest (e.g., the default assumption 
is that the entire watershed is planted with a crop of interest). The 
PCT refers to the amount of the cropped area that is treated with the 
pesticide of interest (e.g., the default is that the entire cropped 
area is treated with the pesticide of interest). With additional use 
and usage data, EPA can refine assumptions about the application rate 
and PCT for use in modeling to generate estimated drinking water 
concentrations (EDWCs) that are appropriate for human health risk 
assessment and more accurately account for the contribution from 
individual use patterns in the estimation of drinking water 
concentrations.
2. Drinking Water Assessment for Chlorpyrifos.
    For the chlorpyrifos drinking water assessment, the metabolite 
chlorpyrifos oxon, which forms because of drinking water treatment and 
is more toxic than chlorpyrifos, was chosen as the residue of concern. 
(Ref. 28 and 29) The range of conversion from parent to oxon depends 
upon the type of water treatment and other conditions. Based on 
available information regarding the potential effects of certain water 
treatments (e.g., chlorination appears to hasten transformation of 
chlorpyrifos to chlorpyrifos oxon), EPA assumed that all chlorpyrifos 
in source water is converted to chlorpyrifos oxon upon treatment.
    The Agency used a DWLOC approach for assessing aggregate risk from 
chlorpyrifos. As such, EPA calculated DWLOCs for different age groups 
for both the acute aggregate assessment and the steady-state aggregate 
assessment, taking into consideration the food and residential 
contributions to the risk cup. These numbers were provided as a 
benchmark for evaluating drinking water contributions from uses of 
chlorpyrifos across the United States, and whether such concentrations 
would result in aggregate exposures to chlorpyrifos that exceeded the 
Agency's levels of concern. The lowest acute DWLOC calculated was for 
exposure to chlorpyrifos oxon to infants (<1 year old) at 23 ppb; the 
lowest steady state DWLOC calculated was also for exposure to 
chlorpyrifos oxon to infants (<1 year old) at 4.0 ppb. (Ref. 9 at 45-
45). In other words, EDWCs of chlorpyrifos oxon greater than 4.0 ppb 
for a 21-day average would exceed EPA's DWLOC and present a risk that 
exceeds the Agency's level of concern.
    In its 2014 drinking water assessment, EPA concluded that there 
were multiple uses of chlorpyrifos that could lead to exposures to 
chlorpyrifos oxon in drinking water that exceed the DWLOC identified at 
that time. (Ref. 29). This assessment provided the basis for the 
Agency's proposal to revoke tolerances in 2015. (Ref. 30). In 2016, EPA 
conducted a refined drinking water assessment that estimated drinking 
water concentrations based on modeling of all registered uses, as well 
as all available surface water monitoring data. That assessment 
considered several refinement strategies in a two-step process to 
derive exposure estimates for chlorpyrifos and chlorpyrifos oxon across 
the country. The first step was an assessment of potential exposure 
based on the current maximum label rates at a national level. This 
indicated that the EDWCs could be above the DWLOC.
    Because estimated concentrations at the national level exceeded the 
DWLOC, the Agency conducted a more refined assessment of uses on a 
regional level. (Ref. 28 at 73-86). This more refined analysis derived 
EDWCs using the PWC modeling for maximum labeled rates and 1 pound per 
acre by region for each use. The analysis indicated that approved uses 
of chlorpyrifos in certain vulnerable watersheds in every region of the 
country would result in EDWCs that exceed the DWLOC. For example, Table 
25 of EPA's 2016 DWA, which provides the range of estimated 
concentrations of chlorpyrifos in drinking water from uses on golf 
courses and agricultural or production crops, shows EDWCs that exceed 
the DWLOC in vulnerable watersheds in every region in the country. 
While the lower end of some of the ranges provided in that table are 
below the DWLOC, those lower numbers reflect a single use (i.e., single 
crop) and do not reflect potential exposure from other uses where 
applications occur at higher rates, more frequently, or in more 
locations made more vulnerable due to soil type, weather, or agronomic 
practices. The relevant estimated concentration for risk assessment 
purposes is the highest concentration across all uses because it 
reflects concentrations that may occur in vulnerable sources of 
drinking water (Ref. 28 at 73-74).
    In addition, a robust quantitative analysis of the monitoring data 
was conducted resulting in concentrations consistent with model-
estimated concentrations above the DWLOC. (Ref. 28 at 90-121). 
Considering both monitoring data and modeling estimates together 
supports the conclusion that drinking water concentrations in regions 
across the country will exceed the DWLOC. (Ref. 28 at 121-123).
    After the EPA's 2016 DWA showed that the DWLOC exceedances are 
possible from several uses, EPA developed refinement strategies to 
examine those estimated regional/watershed drinking water 
concentrations to pinpoint community drinking water systems where 
exposure to chlorpyrifos oxon as a result of chlorpyrifos applications 
may pose an exposure concern. At that time, EPA was anticipating that a 
more refined drinking water assessment might allow EPA to better 
identify where at-risk watersheds are located throughout the country to 
support more targeted risk mitigation through the registration review 
process. The refinements better account for variability in the use area 
treated within a watershed that may

[[Page 48331]]

contribute to a drinking water intake (referred to as PCA or percent 
use area when considering non-agricultural uses) and incorporate data 
on the amount of a pesticide that is actually applied within a 
watershed for agricultural and non-agricultural uses (referred to as 
PCT). These refinement approaches underwent external peer review and 
were issued for public comment in January 2020: https://www.epa.gov/pesticide-science-and-assessing-pesticide-risks/about-water-exposure-models-used-pesticide. In addition, EPA used average application rates, 
average numbers of annual applications for specific crops, and 
estimated typical application timing at the state-level based on 
pesticide usage data derived from a statistically reliable private 
market survey database, publicly available survey data collected by the 
USDA, and state-specific scientific literature from crop extension 
experts.
    The recently developed refinements were integrated in the Updated 
Chlorpyrifos Refined Drinking Water Assessment for Registration Review, 
which was issued in September 2020. (2020 DWA) (Ref. 10) The updated 
assessment applied the new methods for considering the entire 
distribution of community water systems PCA adjustment factors, 
integrated state level PCT data, incorporated refined usage and 
application data, and included quantitative use of surface water 
monitoring data in addition to considering state level usage rate and 
data information. In addition, given the 2016 DWA calculation of 
estimated drinking water concentrations exceeding the DWLOC of 4.0 ppb, 
the Agency decided to focus its refinements for the 2020 updated 
drinking water assessment on a subset of uses in specific regions of 
the United States. The purpose of the focus on this subset of uses was 
to determine, if these were the only uses permitted on the label, 
whether or not the resulting estimated drinking water concentrations 
would be below the DWLOC. The subset of uses assessed were selected 
because they were identified as critical uses by the registrant and/or 
high-benefit uses to growers. That subset of currently registered uses 
included alfalfa, apple, asparagus, cherry, citrus, cotton, peach, 
soybean, sugar beet, strawberry, and wheat in specific areas of the 
country. The results of this analysis indicated that the EDWCs from 
this subset of uses limited to certain regions are below the DWLOC. 
(Ref. 10 at 16-17). However, the 2020 DWA refined estimates did not 
include chlorpyrifos exposures from uses beyond that subset. In the 
2020 DWA, EPA stated that if additional uses were added or additional 
geographic areas included, a new separate assessment would need to be 
prepared in order to evaluate whether concentrations would remain below 
the DWLOC. In addition to the modeling of the EDWCs for the specific 
subset of uses, the 2020 DWA conducted a quantitative surface water 
monitoring data analysis. That analysis indicated that monitored 
chlorpyrifos concentrations, which reflect existing uses, are above the 
DWLOC. (Ref. 10 at 62, 75). These data would need to be considered in 
the context of any additional uses beyond the subset evaluated.

C. Residential Exposure to Pesticides

1. General Approach to Assessing Non-Occupational Exposures
    Residential assessments examine exposure to pesticides in non-
occupational or residential settings (e.g., homes, parks, schools, 
athletic fields or any other areas frequented by the general public), 
based on registered uses of the pesticide. Exposures to pesticides may 
occur to persons who apply pesticides (which is referred to as 
residential handler exposure) or to persons who enter areas previously 
treated with pesticides (which is referred to as post-application 
exposure). Such exposures may occur through oral, inhalation, or dermal 
routes and may occur over different exposure durations (e.g., short-
term, intermediate-term, long-term), depending on the type of pesticide 
and particular use pattern.
    Residential assessments are conducted through examination of 
significant exposure scenarios (e.g., children playing on treated lawns 
or homeowners spraying their gardens) using a combination of generic 
and pesticide-specific data. To regularize this process, EPA has 
prepared SOPs for conducting residential assessments on a wide array of 
scenarios that are intended to address all major possible means by 
which individuals could be exposed to pesticides in a non-occupational 
environment (e.g., homes, schools, parks, athletic fields, or other 
publicly accessible locations). (Ref. 18) The SOPs identify relevant 
generic data and construct algorithms for calculating exposure amounts 
using these generic data in combination with pesticide-specific 
information. The generic data generally involve survey data on behavior 
patterns (e.g., activities conducted on turf and time spent on these 
activities) and transfer coefficient data. Transfer coefficient data 
measure the amount of pesticide that transfers from the environment to 
humans from a defined activity (e.g., hand contact with a treated 
surface or plant). Specific information on pesticides can include 
information on residue levels as well as information on environmental 
fate such as degradation data.
    Once EPA assesses all the potential exposures from all applicable 
exposure scenarios, EPA selects the highest exposure scenario for each 
exposed population to calculate representative risk estimates for use 
in the aggregate exposure assessment. Those specific exposure values 
are then combined with the life stage appropriate exposure values 
provided for food and drinking water to determine whether a safety 
finding can be made.
2. Residential Exposure Assessment for Chlorpyrifos
    Most chlorpyrifos products registered for residential treatment 
were voluntarily cancelled or phased out by the registrants between 
1997 and 2001; however, some uses of chlorpyrifos remain that may 
result in non-occupational, non-dietary (i.e., residential) exposures. 
Based on the remaining registered uses, the Agency has determined that 
residential handler exposures are unlikely. Chlorpyrifos products 
currently registered for residential use are limited to roach bait 
products or ant mound treatments. Exposures from the application of 
roach bait products are expected to be negligible. The roach bait 
product is designed such that the active ingredient is contained within 
a bait station, which eliminates the potential for contact with the 
chlorpyrifos containing bait material. Since the ant mound treatments 
can only be applied professionally, residential handler exposure is 
also not anticipated. (Ref. 9 at 36-44).
    There is a potential for residential post-application exposures. 
Chlorpyrifos is registered for use on golf courses and as an aerial and 
ground-based ultra-low volume (ULV) mosquito adulticide applications 
made directly in residential areas. Based on the anticipated use 
patterns reviewed under the SOP, EPA assessed these exposures as 
steady-state residential post-application exposures, which would be 
protective of shorter durations of exposure. There is a potential for 
dermal post-application exposures from the golf course uses for adults 
(females 13-49 years old); youths (11 to less than 16 years old); and 
children (6 to less than 11 years old). There is also a potential for 
dermal, incidental oral, and inhalation post-application exposures

[[Page 48332]]

for children (1 to less than 2 years old) and dermal and inhalation 
post-application exposures for adults from exposure to mosquitocide 
uses. The Agency combined post-application exposures for children (1 to 
less than 2 years old) for dermal, inhalation, and incidental oral 
exposure routes because these routes all share a common toxicological 
endpoint. EPA used the post-application exposures and risk estimates 
resulting from the golfing scenarios in its aggregate exposure and risk 
assessment.

VIII. Aggregate Risk Assessment and Conclusions Regarding Safety for 
Chlorpyrifos

    The final step in the risk assessment is the aggregate exposure 
assessment and risk characterization. In this step, EPA combines 
information from the first three steps (hazard identification, level of 
concern (LOC)/dose-response analysis, and human exposure assessment) to 
quantitatively estimate the risks posed by a pesticide. The aggregated 
exposure assessment process considers exposure through multiple 
pathways or routes of exposure (e.g., food, water, and residential) for 
different sub-populations (e.g., infants, children ages 1-6) and 
exposure duration or types of effects (e.g., acute noncancer effects 
(single dose), chronic noncancer effects, and cancer). The aggregated 
exposure assessments can be deterministic (levels of exposure for each 
pathway are point estimates), probabilistic (levels of exposure are a 
distribution for a given population), or a combination of the two and 
are dependent on the level of refinement or assessment tier.
    As noted above, EPA evaluates aggregate exposure by comparing 
combined exposure from all relevant sources to the safe level. Where 
exposures exceed the safe level, those levels exceed the risk cup and 
are of potential concern. There are risk cups for each pertinent 
duration of exposure for a pesticide because the amount of exposure 
that can be incurred without adverse health effects will vary by 
duration (e.g., acute, short-term, chronic). The risk cup is equal to 
the PAD (either acute, chronic, or steady-state), or the maximum safe 
exposure for short- and intermediate-term durations.
    Whether risks will exceed the risk cup (i.e., whether exposures are 
expected to exceed safe levels) is expressed differently, depending on 
the type of level of concern the Agency has identified. For dietary 
assessments, the risk is expressed as a percentage of the acceptable 
dose (i.e., the dose which EPA has concluded will be ``safe''). Dietary 
exposures greater than 100% of the percentage of the acceptable dose 
are generally cause for concern and would be considered ``unsafe'' 
within the meaning of FFDCA section 408(b)(2)(B). For non-dietary (and 
combined dietary and non-dietary) risk assessments of threshold 
effects, the toxicological level of concern is typically not expressed 
as an RfD/PAD, but rather in terms of an acceptable (or target) Margin 
of Exposure (MOE) between human exposure and the PoD. The ``margin'' 
that is being referred to in the term MOE is the ratio between the PoD 
and human exposure which is calculated by dividing human exposure into 
the PoD. An acceptable MOE is generally considered to be a margin at 
least as high as the product of all applicable safety factors for a 
pesticide. For example, when the Agency retains the default uncertainty 
factors for dietary or aggregate risk (a 10X interspecies uncertainty 
factor, a 10X intraspecies uncertainty factor, and a 10X FQPA safety 
factor), the total uncertainty factors (or level of concern) is 1000, 
and any MOE above 1000 represents exposures that are not of concern. 
Like RfD/PADs, specific target MOEs are selected for exposures of 
different durations and routes. For non-dietary exposures, EPA 
typically examines short-term, intermediate-term, and long-term 
exposures. Additionally, target MOEs may be selected based on both the 
duration of exposure and the various routes of non-dietary exposure--
dermal, inhalation, and oral. Target MOEs for a given pesticide can 
vary depending on the characteristics of the studies relied upon in 
choosing the PoD for the various duration and route scenarios.
    In addition, in a DWLOC aggregate risk assessment, the calculated 
DWLOC is compared to the EDWC. Where EPA has calculated a DWLOC, EPA 
can determine whether drinking water exposures will result in aggregate 
risks of concern by comparing estimated pesticide concentrations in 
drinking water to the DWLOC. As noted above, an aggregate DWLOC 
represents the amount of allowable safe residues of pesticide in 
drinking water because it represents the room remaining in the risk cup 
after accounting for the food and residential exposures. The DWLOC 
provides an estimate of the allowable safe concentrations of pesticides 
in drinking water for comparison to EDWCs. When the EDWC is less than 
the DWLOC, there are no risk concerns for aggregate exposures because 
the Agency can conclude that the contribution from drinking water when 
aggregated with food and non-occupational exposures will not exceed 
save levels of exposure. Conversely, an EDWC at or exceeding the DWLOC 
would indicate a risk of concern, as those exposures to chlorpyrifos in 
drinking water, when aggregated with exposures from food and 
residential exposures, would exceed safe levels of exposure. (Ref. 31).

A. Dietary Risks From Food Exposures

    As noted above, EPA's acute and steady state dietary exposures 
assessments for chlorpyrifos were highly refined and incorporated 
monitoring data for almost all foods. The Agency assessed food 
exposures based on approved registered uses of chlorpyrifos. This 
includes field uses of chlorpyrifos but not potential exposure from 
food handling establishment uses since the Agency did not identify any 
registered food handling establishment uses. (Ref. 9 at 33-36).
    Considering food exposures alone, the Agency did not identify risks 
of concern for either acute or steady state exposures. Acute dietary 
(food only) risk estimates, which are based on risk from a single 
exposure event in the 2020 HHRA were all below 100 percent of the acute 
population adjusted dose for food (aPADfood) at the 99.9th 
percentile of exposure and are not of concern. The population with the 
highest risk estimate was females (13-49 years old) at 3.2% 
aPADfood. Steady-state dietary (food only) risk estimates, 
which are based on the potential risk from a 21-day exposure duration 
using a 3-week rolling average (sliding by day) across the year, were 
also all below 100% of the steady state PAD for food 
(ssPADfood) at the 99.9th percentile of exposure and are not 
of concern. The population with the highest risk estimate was children 
(1-2 years old) at 9.7% ssPADfood.
    Although EPA's most recent risk assessment calculated two sets of 
risk estimates as a result of the dual approach to assess the range of 
risks that would occur if the Agency determined reliable data existed 
to support a 1X FQPA safety factor, EPA has determined that it is 
appropriate to retain the 10X FQPA safety factor, see Unit VI.C.3. 
Therefore, the risk estimates associated with the 1X FQPA are not 
relevant to today's action.

B. Non-Occupational, Non-Dietary (Residential) Risks

    Because there are some uses of chlorpyrifos that may result in 
residential exposures, EPA assessed risk from those uses. All 
residential post-application risk estimates for the registered uses of 
chlorpyrifos were

[[Page 48333]]

below the Agency's level of concern. (Ref. 9 at 38). The residential 
post-application LOC for children is 40, and the lowest risk estimate 
for children (11 to less than 16 years old) was 1,200; the residential 
post-application LOC for adults is 100, and the MOE is 1,000. Because 
the calculated MOEs are above the Agency's level of concern, there are 
no risks of concern from residential exposures.

C. Risks From Drinking Water

    As noted above, the Agency aggregated exposures to chlorpyrifos 
from food and residential exposures and calculated the DWLOC, i.e., the 
amount of drinking water exposures that would be considered safe. The 
Agency calculated acute and steady state DWLOCs for infants (less than 
1 year old); children (1 to 2 years old); youths (6-12 years old), and 
adults (females 13-49 years old), which would be protective of other 
subpopulations. The most sensitive acute DWLOC was 23 ppb chlorpyrifos 
oxon, and the most sensitive steady state DWLOC was 4 ppb.
    As indicated above in Unit VII.B.2., the Agency estimated drinking 
water contributions from registered uses of chlorpyrifos in its 2016 
DWA. That document indicated that EDWCs exceed the DWLOC of 4.0 ppb on 
a national level and in every region of the United States. (Ref. 28).
    While the 2020 DWA produced estimated drinking water concentrations 
that were below the DWLOC of 4.0 ppb, those EDWCs were contingent upon 
a limited subset of chlorpyrifos use. When assessing different 
combinations of only those 11 uses in specific geographic regions, the 
modeling assumed that chlorpyrifos would not be labeled for use on any 
other crops and would not otherwise be used in those geographic 
regions. At this time, however, the currently registered chlorpyrifos 
uses go well beyond the 11 uses in the specific regions assessed in the 
2020 DWA. Because the Agency is required to assess aggregate exposure 
from all anticipated dietary, including food and drinking water, as 
well as residential exposures, the Agency cannot rely on the 2020 DWA 
to support currently labeled uses. When one assesses the potential of 
all currently registered uses nationwide and in specific geographical 
areas, as was done in the 2016 DWA, the estimates of drinking water 
concentrations exceed the DWLOC of 4.0 ppb, in certain vulnerable 
watersheds across the United States.

D. Aggregate Exposure and Determination Concerning Safety

    As noted above, in accordance with FFDCA section 408(b)(2), EPA 
must, when establishing or leaving in effect tolerances for residues of 
a pesticide chemical, determine that the tolerances are safe. That is, 
EPA must determine 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.'' (21 U.S.C. 346a(b)(2)).
    As discussed earlier in this Unit, exposures from food and non-
occupational exposures individually or together do not exceed EPA's 
levels of concern. The Agency determined that risks from exposures to 
chlorpyrifos residues in food comprised 3.2% of the aPAD for females 
(13-49 years old) and 9.7% of the ssPAD for children (1-2 years old), 
the highest exposed subpopulations. Combining those exposures with 
relevant residential exposures, the Agency calculated the allowable 
levels of drinking water concentrations. Based on the Agency's 
assessment of drinking water concentrations based on the currently 
registered uses, however, drinking water exposures significantly add to 
those risks. When considering the drinking water contribution from 
currently registered uses, the Agency's levels of concern are exceeded 
when combined with food and residential exposures.
    As indicated above, the Agency calculated acute and steady-state 
DWLOCs, and the lowest DWLOC is for steady-state exposures to infants 
at 4.0 ppb; therefore, any EDWCs of chlorpyrifos oxon exceeding 4.0 ppb 
indicate that aggregate exposures of chlorpyrifos would be unsafe. The 
Agency's 2016 DWA demonstrates that DWLOC will be exceeded for some 
people whose drinking water is derived from certain vulnerable 
watersheds throughout the United States, which means that drinking 
water contributions will result in aggregate exposures that exceed the 
Agency's determined safe level of exposure. When taking into 
consideration aggregate exposures based on current labeled uses, the 
EDWCs exceed the DWLOC of 4.0 ppb. For example, as noted above in Unit 
VII.B.2., the 2016 DWA presented EDWCs for uses of chlorpyrifos, 
including concentrations based on use on golf courses and agricultural 
crops. For those uses alone, the Agency estimated concentrations 
exceeding 4.0 ppb in every region in the country; See Table 25 of the 
2016 DWA. (Ref. 28 at 73-74.) Comparing the calculated EDWCs from the 
2016 DWA with the DWLOC calculated in the 2020 HHRA shows that drinking 
water concentrations from chlorpyrifos uses will exceed the safe 
allowable level for contributions from drinking water. This means that 
aggregate exposure (food, drinking water, and residential exposures) 
exceeds the Agency's safe level for chlorpyrifos exposure. Because the 
FFDCA requires EPA to aggregate all dietary and non-occupational 
exposure, EPA cannot conclude that there is a reasonable certainty that 
no harm will result from aggregate exposure to chlorpyrifos residues 
when taking into consideration all labeled uses.
    It is worth noting that the Agency's Proposed Interim Registration 
Review Decision (PID) recognized that there might be limited 
combinations of uses in certain geographic areas that could be 
considered safe, if the assessment only includes those specific uses in 
those areas. The PID noted that ``[w]hen considering all currently 
registered agricultural and non-agricultural uses of chlorpyrifos, 
aggregate exposures are of concern. If considering only the uses that 
result in DWLOCs below the EDWCs, aggregate exposures are not of 
concern.'' (Ref. 32 at 19). The PID proposed limiting chlorpyrifos 
applications to specific crops in certain regions where the EDWCs for 
those uses were calculated to be lower than the DWLOC. (Id. at 40). The 
Agency's ability to make the safety finding for any remaining uses 
would be contingent upon significant changes to the existing 
registrations, including use cancellations, geographical limitations, 
and other label changes.
    Consequently, while the 2020 PID suggested that there may be 
limited combinations of uses that could be safe, FFDCA section 
408(b)(2) requires EPA to aggregate all dietary and non-occupational 
exposures to chlorpyrifos in making a safety finding. Without effective 
mitigation upon which to base a reduced aggregate exposure calculation, 
the products as currently registered present risks above the Agency's 
levels of concern. Based on the data available at this time and the 
aggregate exposures expected from currently registered uses, the Agency 
cannot, at this time, determine that aggregate exposures to residues of 
chlorpyrifos, including all anticipated dietary exposures and all other 
non-occupational exposures for which there is reliable information, are 
safe. Accordingly, as directed by the statute and in compliance with 
the Court's order, EPA is revoking all chlorpyrifos tolerances.

[[Page 48334]]

IX. Procedural Matters

A. When do these actions become effective?

    The revocations of the tolerances for all commodities will become 
effective on February 28, 2022. The Agency has set the expiration date 
for these tolerances to satisfy its international trade obligations 
described in Unit X.
    Any commodities listed in this rule treated with the pesticide 
subject to this rule, and in the channels of trade following the 
tolerance revocations, shall be subject to FFDCA section 408(l)(5). 
Under this section, any residues of these pesticides in or on such food 
shall not render the food adulterated so long as it is shown to the 
satisfaction of the Food and Drug Administration that:
    1. The residue is present as the result of an application or use of 
the pesticide at a time and in a manner that was lawful under FIFRA, 
and
    2. The residue does not exceed the level that was authorized at the 
time of the application or use to be present on the food under a 
tolerance or exemption from tolerance that was in effect at the time of 
the application. Evidence to show that food was lawfully treated may 
include records that verify the dates when the pesticide was applied to 
such food.

B. Response to Comments

    Today's action responds to the Ninth Circuit's order to issue a 
final rule in response to the 2007 Petition. As such this rule is not 
finalizing the proposal published in the Federal Register issue of 
November 6, 2015, nor is it implementing or resolving any registration 
review activity. Thus, this document is not responding to comments 
received on the 2015 proposal or the most recent registration review 
documents. Those activities are separate and apart from the procedural 
posture of this final rule action. Moreover, as the registration review 
process is ongoing, including a separate review of the comments 
submitted, the Agency intends to respond to the most recent comments in 
as part of that process, rather than in this rule.

C. Are the Agency's actions consistent with international obligations?

    The tolerance revocations in this final rule are not discriminatory 
and are designed to ensure that both domestically produced and imported 
foods meet the food safety standard established by the FFDCA. The same 
food safety standards apply to domestically produced and imported 
foods.
    EPA considers Codex Maximum Residue Limits (MRLs) in setting U.S. 
tolerances and in reassessing them. Codex MRLs are established by the 
Codex Committee on Pesticide Residues, a committee within the Codex 
Alimentarius Commission, an international organization formed to 
promote the coordination of international food standards. The FFDCA 
requires EPA to take Codex MRLs into consideration when establishing 
new tolerances, and it is EPA's policy to harmonize U.S. tolerances 
with Codex MRLs to the extent possible, provided that the MRLs achieve 
the level of protection required under FFDCA. In the current instance, 
EPA has determined that the current U.S. tolerances for chlorpyrifos 
are not safe and must be revoked. EPA has developed guidance concerning 
submissions for import tolerance support (65 FR 35069, June 1, 2000) 
(FRL-6559-3).
    Under the World Trade Organization Agreement on the Application of 
Sanitary and Phytosanitary Measures (SPS Agreement), to which the 
United States is a party, Members are required to, except in urgent 
circumstances, ``allow a reasonable interval between the publication of 
a sanitary or phytosanitary regulation and its entry into force in 
order to allow time for producers in exporting Members, and 
particularly in developing country Members, to adapt their products and 
methods of production to the requirements of the importing Member.'' 
(Ref. 33). The WTO has interpreted the phrase ``reasonable interval'' 
to mean normally a period of not less than six months. (Ref. 34). In 
accordance with its obligations, EPA intends to notify the WTO of this 
regulation and is providing a ``reasonable interval'' by establishing 
an expiration date for the existing tolerances to allow those 
tolerances to remain in effect for a period of six months after the 
effective date of this final rule. After the six-month period expires, 
the tolerances for residues chlorpyrifos in or on food will no longer 
be in effect.

X. Statutory and Executive Order Reviews

    Additional information about these statutes and Executive Orders 
can be found at https://www.epa.gov/laws-regulations-and-executive-orders.

A. Executive Order 12866: Regulatory Planning and Review and Executive 
Order 13563: Improving Regulations and Regulatory Review

    The Office of Management and Budget (OMB) has exempted tolerance 
regulations from review under Executive Order 12866, entitled 
Regulatory Planning and Review (58 FR 51735, October 4, 1993). Because 
this action has been exempted from review under Executive Order 12866, 
this final rule is not subject to Executive Order 13563 (76 FR 3821, 
January 21, 2011).

B. Paperwork Reduction Act (PRA)

    This final rule does not contain any information collection 
activities subject to OMB review and approval under the PRA, 44 U.S.C. 
3501 et seq. An agency may not conduct or sponsor, and a person is not 
required to respond to a collection of information that requires OMB 
approval under PRA, unless it has been approved by OMB and displays a 
currently valid OMB control number. The OMB control numbers for EPA's 
regulations in title 40 of the CFR, after appearing in the Federal 
Register, are listed in 40 CFR part 9, and included on the related 
collection instrument or form, if applicable.

C. Regulatory Flexibility Act (RFA)

    The RFA, 5 U.S.C. 601 et seq., generally requires an agency to 
prepare a regulatory flexibility analysis of any rule subject to notice 
and comment rulemaking requirements under the Administrative Procedures 
Act or any other statute. Since this rule, which is issued under FFDCA 
section 408(d)(4)(A)(i) (21 U.S.C. 346a(d)(4)(A)(i)) directly in 
response to a petition under FFDCA section 408(d), does not require the 
issuance of a proposed rule, the RFA requirements do not apply.

D. Unfunded Mandates Reform Act (UMRA)

    EPA has determined that this action does not impose any enforceable 
duty, contain any unfunded mandate, or otherwise have any effect on 
small governments subject to the requirements of UMRA sections 202, 
203, 204, or 205 (2 U.S.C. 1501 et seq.).

E. Executive Order 13132: Federalism

    This action will not have federalism implications because it is not 
expected to have a substantial direct effect on States, on the 
relationship between the national government and the States, or on the 
distribution of power and responsibilities among the various levels of 
government, as specified in Executive Order 13132 (64 FR 43255, August 
10, 1999). This final rule directly regulates growers, food processors, 
food handlers and food retailers, not States. This action does not 
alter the relationships or distribution of power and responsibilities 
established

[[Page 48335]]

by Congress in the preemption provisions of section 408(n)(4) of the 
FFDCA.

F. Executive Order 13175: Consultation and Coordination With Indian 
Tribal Governments

    For the same reasons, this action will not have Tribal implications 
because it is not expected to have substantial direct effects on Indian 
Tribes, significantly or uniquely affect the communities of Indian 
Tribal governments, and does not involve or impose any requirements 
that affect Indian Tribes. Accordingly, the requirements of Executive 
Order 13175 (65 FR 67249, November 9, 2000), do not apply to this 
action.

G. Executive Order 13045: Protection of Children From Environmental 
Health and Safety Risks

    This action is not subject to Executive Order 13045 (62 FR 19885, 
April 23, 1997), because this is not an economically significant 
regulatory action as defined by Executive Order 12866, and this action 
does not address environmental health or safety risks 
disproportionately affecting children.

H. Executive Order 13211: Actions Concerning Regulations That 
Significantly Affect Energy Supply, Distribution, or Use

    This action is not subject to Executive Order 13211 (66 FR 28355, 
May 22, 2001), because this action is not a significant regulatory 
action under Executive Order 12866.

I. National Technology Transfer and Advancement Act (NTTAA)

    In addition, since this action does not involve any technical 
standards, NTTAA section 12(d), 15 U.S.C. 272 note, does not apply to 
this action.

J. Executive Order 12898: Federal Actions To Address Environmental 
Justice in Minority Populations and Low-Income Populations

    This action does not entail special considerations of environmental 
justice related issues as delineated by Executive Order 12898 (59 FR 
7629, February 16, 1994). Nevertheless, the revocation of the 
tolerances will reduce exposure to the pesticide and lead to a 
reduction in chlorpyrifos use on food crops. While EPA has not 
conducted a formal EJ analysis for this rule, the revocation of 
tolerances will likely reduce disproportionate impacts on EJ 
communities that are impacted by chlorpyrifos applications on crops.

K. Congressional Review Act (CRA)

    This action is subject to the CRA (5 U.S.C. 801 et seq.), and EPA 
will submit a rule report containing this rule and other required 
information to each House of the Congress and to the Comptroller 
General of the United States. This action is not a ``major rule'' as 
defined by 5 U.S.C. 804(2).

XI. References

    The following is a list of the documents that are specifically 
referenced in this document. The docket, identified by docket ID number 
docket number EPA-HQ-OPP-2021-0523, 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. All 
records in docket are part of the record for this rulemaking. 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, EPA's various responses to it, 
and the objections submitted on the Petition denial are available in 
docket number EPA-HQ-OPP-2007-1005 available at https://www.regulations.gov.
2. U.S. EPA. Chlorpyrifos Final Work Plan. 2009. Available at: 
https://www.regulations.gov/document/EPA-HQ-OPP-2008-0850-0020.
3. FIFRA Scientific Advisory Panel (2008). ``The Agency's Evaluation 
of the Toxicity Profile of Chlorpyrifos.'' Report from the FIFRA 
Scientific Advisory Panel Meeting of September 16-19, 2008. 
Available at: https://www.regulations.gov/docket/EPA-HQ-OPP-2008-0274/document.
4. U.S. EPA (2010). Draft Framework and Case Studies on Atrazine, 
Human Incidents, and the Agricultural Health Study: Incorporation of 
Epidemiology and Human Incident Data into Human Health Risk 
Assessment available at: https://www.regulations.gov/document/EPA-HQ-OPP-2009-0851-0004.
5. U.S. EPA (2016). Office of Pesticide Programs' Framework for 
Incorporating Human Epidemiologic & Incident Data in Risk 
Assessments for Pesticides. (2016) Available at: https://www3.epa.gov/pesticides/EPA-HQ-OPP-2008-0316-DRAFT-0075.pdf.
6. FIFRA Scientific Advisory Panel (2012). ``Scientific Issues 
Associated with Chlorpyrifos''. Available at: https://www.regulations.gov/document/EPA-HQ-OPP-2012-0040-0029.
7. U.S. EPA (2014). Chlorpyrifos: Revised Human Health Risk 
Assessment for Registration Review. Available in docket number EPA-
HQ-OPP-2008-0850, https://www.regulations.gov/document/EPA-HQ-OPP-2008-0850-0195.
8. U.S. EPA (2016). Scientific Advisory Panel for Chlorpyrifos: 
Analysis of Biomonitoring Data. Available at: https://www.epa.gov/sites/default/files/2016-07/documents/chlorpyrifos_sap_april_2016_final_minutes.pdf.
9. U.S. EPA (2020). Chlorpyrifos Human Health Risk Assessment. 
Available at: https://www.regulations.gov/document/EPA-HQ-OPP-2008-0850-0944.
10. U.S. EPA (2020). Updated Chlorpyrifos Refined Drinking Water 
Assessment for Registration Review. Available at: https://www.regulations.gov/document/EPA-HQ-OPP-2008-0850-0941.
11. A User's Guide to Available EPA Information on Assessing 
Exposure to Pesticides in Food (June 21, 2000). Available at: 
https://www.doh.wa.gov/Portals/1/Documents/4000/PASW_exposurefood.pdf.
12. U.S. EPA (2000). Chlorpyrifos Human Health Risk Assessment. 
Available at: https://archive.epa.gov/scipoly/sap/meetings/web/pdf/hed_ra.pdf.
13. U.S. EPA (2011). Chlorpyrifos: Preliminary Human Health Risk 
Assessment for Registration Review. Available in docket number EPA-
HQ-OPP-2008-0850, https://www.regulations.gov/document/EPA-HQ-OPP-2008-0850-0025.
14. U.S. EPA (2016). Summary Reviews for Additional Epidemiological 
Literature Studies from Prospective Birth Cohort Studies. Available 
in docket number EPA-HQ-OPP-2015-0653 at https://www.regulations.gov/document/EPA-HQ-OPP-2015-0653-0438.
15. U.S. EPA (2020). The Use of New Approach Methodologies (NAMs) to 
Derive Extrapolation Factors and Evaluate Developmental 
Neurotoxicity for Human Health Risk Assessment. Available in docket 
number EPA-HQ-OPP-2020-0263 at https://www.regulations.gov/document/EPA-HQ-OPP-2020-0263-0033.
16. U.S. EPA (2020). Transmittal of Meeting Minutes and Final Report 
of the Federal Insecticide, Fungicide, and Rodenticide Act, 
Scientific Advisory Panel (FIFRA SAP) Virtual Meeting held on 
September 15-18, 2020. Available in docket number EPA-HQ-2020-0263 
at https://www.regulations.gov/document/EPA-HQ-OPP-2020-0263-0054.
17. U.S. EPA (2006). Revised Organophosphorous Pesticide Cumulative 
Risk Assessment. Available at https://www.epa.gov/pesticides/cumulative/2006-op/index.htm.
18. U.S. EPA (2012). Standard Operating Procedures for Residential 
Pesticide Exposure Assessment https://www.epa.gov/sites/default/files/2015-08/documents/usepa-opp-hed_residential_sops_oct2012.pdf.
19. FIFRA Scientific Advisory Panel (2002). ``Organophosphate 
Pesticides: Preliminary OP Cumulative Risk Assessment.'' Information 
on how to obtain the meeting report is available at https://www2.epa.gov/sap/fifra-scientific-advisory-panel-meetings.
20. U.S. EPA (2000). Choosing a Percentile of Acute Dietary Exposure 
as a Threshold of Regulatory Concern. Available at:

[[Page 48336]]

https://www.epa.gov/sites/production/files/2015-07/documents/trac2b054_0.pdf.
21. EPA's Exposure Factors Handbook. Available at: https://www.epa.gov/expobox/about-exposure-factors-handbook.
22. 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/sites/default/files/2015-01/documents/ddef-final.pdf.
23. U.S. EPA (2014). Chlorpyrifos Acute and Steady Dietary (Food 
Only) Exposure Analysis to Support Registration Review. Available 
at: https://www.regulations.gov/document/EPA-HQ-OPP-2008-0850-0197.
24. U.S. EPA (2020). Framework for Conducting Pesticide Drinking 
Water Assessments for Surface Water. Environmental Fate and Effects 
Division. Office of Pesticide Programs. Office of Chemical Safety 
and Pollution Prevention. U.S. Environmental Protection Agency. 
Available at: https://www.epa.gov/sites/default/files/2020-09/documents/framework-conducting-pesticide-dw-sw.pdf.
25. FIFRA Scientific Advisory Panel (2019) ``Approaches for 
Quantitative Use of Surface Water Monitoring Data in Pesticide 
Drinking Water Assessments.'' Available at: https://www.regulations.gov/document/EPA-HQ-OPP-2019-0417-0019.
26. U.S. EPA (2001). General Principles for Performing Aggregate 
Exposure and Risk Assessments. Available at: https://www.epa.gov/sites/default/files/2015-07/documents/aggregate.pdf.
27. U.S. EPA (2020). Appendix B. Case Study for Integrating a 
Distributional Approach to Using Percent Crop Area (PCA) and Percent 
Crop Treated (PCT) into Drinking Water Assessment. Available at: 
https://www.regulations.gov/document/EPA-HQ-OPP-2020-0279-0002.
28. U.S. EPA (2016). Chlorpyrifos Refined Drinking Water Assessment 
for Registration Review. Available at: https://www.regulations.gov/document/EPA-HQ-OPP-2015-0653-0437.
29. U.S. EPA (2014). Chlorpyrifos Updated Drinking Water Assessment 
for Registration Review. Available at: https://www.regulations.gov/document/EPA-HQ-OPP-2008-0850-0198.
30. U.S. EPA (2015). Proposed Rule: Tolerance Revocations: 
Chlorpyrifos. Available at: https://www.regulations.gov/document/EPA-HQ-OPP-2015-0653-0001.
31. U.S. EPA (2011). Finalization of Guidance on Incorporation of 
Water Treatment Effects on Pesticide Removal and Transformations in 
Drinking Water Exposure Assessments. Available at: https://www.epa.gov/pesticide-science-and-assessing-pesticide-risks/finalization-guidance-incorporation-water-treatment.
32. U.S. EPA (2020). Chlorpyrifos Proposed Interim Registration 
Review Decision. Available at: https://www.regulations.gov/document/EPA-HQ-OPP-2008-0850-0971.
33. For more information on World Trade Organization's Agreement on 
the Application of Sanitary and Phytosanitary Measures (SPS 
Agreement), please see: https://www.wto.org/english/tratop_e/sps_e/spsagr_e.htm.
34. For more information on World Trade Organization (2001) 
Implementation-Related Issues and Concerns, please see: https://docs.wto.org/dol2fe/Pages/SS/directdoc.aspx?filename=Q:/WT/Min01/17.pdf&Open=True.

List of Subjects in 40 CFR Part 180

    Environmental protection, Administrative practice and procedure, 
Agricultural commodities, Pesticides and pests, Reporting and 
recordkeeping requirements.

    Dated: August 18, 2021.
Edward Messina,
Director, Office of Pesticide Programs.

    Therefore, for the reasons set forth in the preamble, 40 CFR part 
180 is amended as follows:

PART 180--[AMENDED]

0
1. The authority citation for part 180 continues to read as follows:

    Authority:  21 U.S.C. 321(q), 346a and 371.


0
2. In Sec.  180.342, add introductory text to read as follows:


Sec.  180.342  Chlorpyrifos; tolerances for residues.

    This section and all tolerances contained herein expire and are 
revoked on February 28, 2022.
* * * * *
[FR Doc. 2021-18091 Filed 8-27-21; 8:45 am]
BILLING CODE 6560-50-P