Endocrine Disruptor Screening Program (EDSP); Near-Term Strategies for Implementation; Notice of Availability and Request for Comment, 73841-73853 [2023-23721]

Agencies

• ENVIRONMENTAL PROTECTION AGENCY

[Federal Register Volume 88, Number 207 (Friday, October 27, 2023)]
[Notices]
[Pages 73841-73853]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2023-23721]


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ENVIRONMENTAL PROTECTION AGENCY

[EPA-HQ-OPP-2023-0474; FRL-11384-01-OCSPP]


Endocrine Disruptor Screening Program (EDSP); Near-Term 
Strategies for Implementation; Notice of Availability and Request for 
Comment

AGENCY: Environmental Protection Agency (EPA).

ACTION: Notice.

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SUMMARY: The Environmental Protection Agency (EPA) is announcing the 
availability of and soliciting comment on the near-term strategies 
described in this document to help the Agency meet its obligations and 
commitments under the Federal Food, Drug, and Cosmetic Act (FFDCA), 
which requires, among other things, that EPA screen for and protect 
against endocrine disrupting effects in humans. An important part of 
these obligations and commitments is the Endocrine Disruptor Screening 
Program (EDSP), which EPA established in 1998 as a two-tier endocrine 
screening and testing process for pesticides and other chemicals. After 
over two decades of implementing the EDSP and other aspects of the 
mandate in FFDCA, EPA has developed near-term strategies to begin 
addressing the challenges it has encountered and to rebuild the EDSP. 
This document covers only the initial strategies that EPA is taking 
over the next several years to generate momentum toward its longer-term 
goal of timely addressing all its endocrine screening data needs and 
decisions. Through this notice and to help implement its strategies, 
EPA is also seeking additional endocrine data on two groups of active 
ingredients currently undergoing registration review, or explanations 
of why the additional data are unnecessary for EPA to make its FIFRA 
and FFDCA decisions.

DATES: Comments must be received on or before December 26, 2023.

ADDRESSES: Submit your comments, identified by docket identification 
(ID) number EPA-HQ-OPP-2023-0474, 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 Confidential Business Information (CBI) or other 
information whose disclosure is restricted by statute. Additional 
instructions on commenting or visiting the docket, along with more 
information about dockets generally, is available at https://www.epa.gov/.

FOR FURTHER INFORMATION CONTACT: Catherine Aubee, Endocrine Disruptor 
Screening Program (7505T), Office of Pesticide Programs, Environmental 
Protection Agency, 1200 Pennsylvania Ave. NW, Washington, DC 20460-
0001; main telephone number: (202) 566-1030; email address: 
[email protected].

SUPPLEMENTARY INFORMATION:

I. Executive Summary

A. Does this action apply to me?

    You may be potentially affected by this action if you produce, 
manufacture, use, or import pesticide/agricultural chemicals and other 
chemical substances; or if you are or may otherwise be involved in the 
testing of chemical substances for potential endocrine effects. 
Potentially affected entities, identified by the North American 
Industrial Classification System (NAICS) codes, may include, but are 
not limited to:
     Chemical manufacturers, importers and processors (NAICS 
code 325), e.g., persons who manufacture, import or process chemical 
substances.
     Pesticide, fertilizer, and other agricultural chemical 
manufacturing (NAICS code 3253), e.g., persons who manufacture, import 
or process pesticide, fertilizer and agricultural chemicals.
     Scientific research (NAICS code 5417).

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

    FFDCA section 408(p)(1) requires, among other things, that EPA 
``develop a screening program, using appropriate validated test systems 
and other scientifically relevant information to determine whether 
certain substances may have an effect in humans that is similar to an 
effect produced by a naturally occurring estrogen, or such other 
effects as [EPA] may designate.'' (21 U.S.C. 346a(p)). FFDCA sections 
408(p)(2) and (p)(7) require EPA to implement the EDSP by August 1999 
and report to Congress on the program's progress by August 2000, 
respectively.
    FFDCA section 408(p)(3) requires that EPA ``shall provide for the 
testing of all pesticide chemicals.'' FFDCA section 201 defines 
``pesticide chemical'' as ``any substance that is a pesticide within 
the meaning of the Federal Insecticide, Fungicide, and Rodenticide Act 
(FIFRA), including all active and pesticide inert ingredients of such 
pesticide.'' (21 U.S.C. 231(q)(1)). However, FFDCA section 408(p)(4) 
authorizes EPA to, by order, exempt a substance from the EDSP if the 
EPA ``determines that the substance is anticipated not to produce any 
effect in humans similar to an effect produced by a naturally occurring 
estrogen.'' FFDCA section 408(p)(5) identifies the requirements and 
processes for issuing test orders, requiring testing under the EDSP, 
and submitting information obtained from the testing to EPA. (21 U.S.C. 
346a(p)(5)). Finally, FFDCA section 408(p)(6) requires EPA to ``as 
appropriate, take action under such statutory authority as is available 
to the Administrator, including consideration under other sections of 
this chapter, as is necessary to ensure the protection of public 
health'' for ``any substance that is found, as a result of testing and 
evaluation under this section, to have an endocrine effect on humans.''
    The Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) 
precludes the distribution and sale of any pesticide that is not 
registered under FIFRA. (7 U.S.C. 136a(a)). Applications for 
registration of a pesticide may be submitted to EPA but must meet the 
requirements in FIFRA sections 3(c) and 33, which include providing 
complete data in support of that registration request. (7 U.S.C. 136a 
and 136w-8). The data required to support these applications are 
identified in EPA regulations at 40 CFR part 158. EPA may issue Data 
Call-In (DCI) notices under FIFRA section 3(c)(2)(B) to require 
additional data during the registration process to address a risk or 
after registration to maintain a registered pesticide. (7 U.S.C. 
136a(c)(2)(B)). To grant a pesticide registration, FIFRA requires EPA 
to consider whether the pesticide has ``unreasonable adverse effects'' 
to human health and the environment. (7 U.S.C. 136a(c)(5)). FIFRA 
section 2(bb) defines ``unreasonable adverse effects on the

[[Page 73842]]

environment'' to mean, among other things, ``any unreasonable risk to 
man or the environment, taking into account the economic, social, and 
environmental costs and benefits of the use of any pesticide.'' (7 
U.S.C. 136(bb)). EPA is required to review each pesticide registration 
every 15 years to determine whether the pesticide continues to satisfy 
this FIFRA standard for registration. (7 U.S.C. 136a(g)). EPA 
regulations at 40 CFR part 155, subpart C apply to the conduct of this 
registration review process.

C. What action is the Agency taking?

    This document describes three near-term strategies the Agency is 
taking to further implement its obligations and commitments under FFDCA 
section 408(p) relating to the EDSP, which EPA established in 1998 as a 
two-tier endocrine screening and testing process for pesticides and 
other chemicals. EPA is pursuing these strategies to generate momentum 
toward its longer-term goal of timely addressing all its endocrine data 
needs and decisions.
    Under strategy one, EPA will prioritize addressing potential human 
estrogen, androgen, and thyroid effects for conventional pesticide 
active ingredients. Although the Agency will continue to address 
wildlife endocrine effects and endocrine effects from other pesticide 
chemicals (e.g., inert ingredients and active ingredients intended 
solely for biological or antimicrobial uses), updates and activities 
relating to that work are on a longer-term timeline for the reasons 
discussed in the strategy. Under strategy two, EPA will use existing 
data, routinely obtained through FIFRA registration and registration 
review, to determine whether additional human health-related endocrine 
data are needed and to make endocrine decisions under FIFRA and FFDCA 
section 408(p). This strategy also describes the endocrine data that 
EPA considers sufficient to register a new conventional active 
ingredient and how EPA will address endocrine data deficiencies for 
those registration submissions and for registration review cases. Under 
strategy three, EPA will phase into its registration review processes 
any new data requirements to address potential human estrogen, 
androgen, and thyroid effects for conventional pesticide active 
ingredients, starting with 30 registration review cases (``Group 1'' 
cases) that EPA has identified using a new framework for prioritizing 
estrogen and androgen data needs. In this notice, EPA is requesting 
comments and the voluntary submittal of existing information on these 
30 cases and, during the comment period, plans to begin preparing DCIs 
with the goal of issuing those them in spring of 2024 for specified 
EDSP Tier 1 data for these cases.
    To support the strategies described in this document, EPA has 
posted the following three reference documents in the docket:
    1. Use of Existing Mammalian Data to Address Data Needs and 
Decisions for Endocrine Disruptor Screening Program (EDSP) for Humans 
under FFDCA Section 408(p) (Ref. 1). This endocrine science paper 
explains when and how EPA will rely on data it has already received 
under FIFRA to address the data needs and decisions under FFDCA section 
408(p), providing the scientific support for strategies two and three.
    2. List of Conventional Registration Review Chemicals for Which an 
FFDCA Section 408(p)(6) Determination is Needed (Ref. 2). This paper 
lists each currently registered conventional pesticide active 
ingredient, and how the types of data EPA has for each active 
ingredient inform where it fits within EPA's priorities for obtaining 
any additional endocrine data for those pesticides in registration 
review. Commenters should use this list to identify the active 
ingredients for which EPA is seeking information through this document.
    3. Status of Endocrine Disruptor Screening Program (EDSP) List 1 
Screening Conclusions (Ref. 3). This paper explaining EPA's decisions 
under FFDCA section 408(p) relating to the human endocrine system 
(estrogen, androgen, and thyroid endpoints) for all 52 EDSP List 1 
chemicals. In 2009, EPA published the List 1 chemicals and issued test 
orders for them (the original List 1 had 67 chemicals). The Agency 
later revised the list to 52 chemicals because 15 were canceled or 
discontinued. The actions to address the remaining List 1 chemicals are 
unrelated to the development of Group 1 chemicals in this document.
    Many aspects of this document overlap with policies described in a 
notice issued in the Federal Register of August 11, 1998 (63 FR 42852) 
(FRL-6021-3) (hereinafter referred to as the ``1998 Notice''), that 
established the basic components of the EDSP. EPA views this document 
as consistent with the policies in the 1998 Notice and thus is not 
rescinding or modifying those policies. Rather, this document augments 
the notice with complementary strategies and priorities that reflect 
advances in science, EPA's experience administering the EDSP, and the 
Agency's recent efforts to more quickly meet its FFDCA section 408(p) 
obligations and commitments.

D. Why is the Agency taking this action?

    After over two decades of implementing FFDCA section 408(p), EPA 
has developed the near-term strategies in this document to begin to 
transparently address the challenges it has encountered and rebuild the 
EDSP. This document explains how the Agency currently obtains and will 
obtain data needed to assess a conventional pesticide active 
ingredient's interaction with the human estrogen, androgen, and thyroid 
pathways, and when and how EPA intends to make the requisite FFDCA 
section 408(p)(6) finding that the pesticide use adequately protects 
human health. This document also addresses the confusion about when and 
how EPA obtains data in the registration and registration review 
processes to assess the potential for effects to the endocrine system 
from use of a conventional pesticide active ingredient. These near-term 
strategies also help EPA respond to specific recommendations in a 2021 
EPA Office of Inspector General (OIG) Report to develop a strategic 
plan for the EDSP and to a legal complaint filed in the Federal 
District Court for the Northern District of California raising similar 
issues.

E. Does this document contain binding requirements?

    This document describes EPA's near-term strategies over the next 
several years to accelerate how the Agency meets its FFDCA section 
408(p) obligations and commitments. The requirements in the statutes 
and any future FIFRA DCIs or FFDCA test orders are binding on EPA and 
the order recipients, respectively, but this document does not impose 
any binding requirements on EPA or outside parties. The strategies 
outlined in this document further the general goals of the program, and 
EPA may depart from the strategies where circumstances warrant and 
without prior notice. In general, however, EPA will continue to offer 
notice and comment on chemical-specific proposed decisions that 
implement these strategies.

F. What should I consider as I prepare my comments for EPA?

1. Scope of Request for Comments
    As discussed further in strategy three of this document, EPA 
encourages the public to submit any relevant estrogen, androgen, and 
thyroid data for the Group 1 and Group 2 cases of pesticide

[[Page 73843]]

active ingredients currently in registration review. The public may 
also submit any explanations for why additional endocrine data are 
unnecessary to inform the Agency's findings under FIFRA and FFDCA 
section 408(p) for potential endocrine effects in humans.
    Please submit any relevant endocrine data, Other Scientifically 
Relevant Information (OSRI), or explanations of why the additional data 
are unnecessary for EPA to make its FIFRA and FFDCA section 408(p) 
decisions to the ``Registration Review'' section of EPA's Pesticide 
Submission Portal (PSP). The PSP can be accessed through EPA's Central 
Data Exchange (CDX) using the link https://cdx.epa.gov/.
2. Submitting CBI
    Do not submit CBI to EPA through https://www.regulations.gov or 
email. If you wish to include CBI in your comment, please follow the 
applicable instructions at https://www.epa.gov/dockets/commenting-epa-dockets#rules and clearly mark the part or all of the information that 
you claim to be CBI. In addition to one complete version of the comment 
that includes information claimed as CBI, a copy of the comment that 
does not contain the information claimed as CBI must be submitted for 
inclusion in the public docket. Information so marked will not be 
disclosed except in accordance with procedures set forth in 40 CFR part 
2.
3. Tips for Preparing Your Comments
    When preparing and submitting your comments, see the commenting 
tips at https://www.epa.gov//commenting-epa-dockets.

II. Background

A. What is the endocrine system?

    Endocrine systems, also referred to as hormone systems, are found 
in all mammals, birds, fish, and many other living organisms. These 
systems are made up of glands located throughout the body, the hormones 
synthesized by these glands and released into the bloodstream or the 
fluid surrounding cells, and the receptors in various organs and 
tissues that recognize and respond to the hormones.

B. What is the relevant history of the EDSP?

    In 1996, Congress amended the FFDCA with the Food Quality 
Protection Act, 21 U.S.C. 346a(p), requiring EPA to develop a screening 
program ``to determine whether certain substances may have an effect in 
humans that is similar to an effect produced by a naturally occurring 
estrogen, or such other endocrine effects as [EPA] may designate.'' In 
response, EPA established the EDSP, the basic components of which were 
described in the 1998 Notice (63 FR 42852). Further, when carrying out 
the EDSP, EPA ``shall provide for the testing of all pesticide 
chemicals,'' which includes active and inert ingredients, and ``may 
provide for the testing of any other substance that may have an effect 
that is cumulative to an effect of a pesticide chemical if the 
Administrator determines that a substantial population may be exposed 
to such a substance.'' The FFDCA required EPA to implement the EDSP by 
August 1999 and report to Congress on the program's progress by August 
2000. EPA met both requirements on time, as the Agency began 
implementing the EDSP after issuing the 1998 Federal Register Notice 
(the statute does not specify when implementation ends nor steps for 
implementing the EDSP, and thus EPA views implementation as an ongoing 
activity) and the Agency issued its report to Congress in August 2000.
    FFDCA section 408(p) requires EPA to screen only for estrogen 
effects in humans that are similar to an effect produced by a naturally 
occurring estrogen. Through the 1998 Federal Register Notice, however, 
EPA permissibly expanded the scope of the EDSP in two important ways. 
One is to include screening for androgen and thyroid effects, based on 
the recommendations of the Endocrine Disruptor Screening and Testing 
Advisory Committee (EDSTAC), which EPA formed to advise on designing a 
screening and testing program for chemicals. EPA had explained that it 
will focus on estrogen, androgen, and thyroid because they are among 
the most studied of the approximately 50 known vertebrate hormones, 
with a relatively large body of relevant data and screening tests. EPA 
also explained that including these three hormone systems will help the 
Agency understand effects on reproduction, development, and growth. 
Further, EPA adopted the EDSTAC recommendation to screen for effects in 
the same endocrine systems in wildlife because adverse effects on 
wildlife can forewarn of potential risks to humans and because strong 
evidence existed for endocrine disruption from pesticides in natural 
wildlife and fish populations. Throughout this document, when EPA 
refers to section 408(p) ``obligations and commitments,'' the Agency is 
describing both the mandatory aspects of this section (obligations) and 
the discretionary aspects (commitments), as summarized in Table 1.

   Table 1--Summary of FFDCA Section 408(p) Mandatory Obligations and
       Discretionary Commitments for Pesticide Active Ingredients
------------------------------------------------------------------------
                                                               EPA
                         Mandatory         Status of      discretionary
  FFDCA provision       obligation        obligation      commitment and
                                                              status
------------------------------------------------------------------------
408(p)(1)..........  Must create       Completed when    In 1998,
                      estrogen          EPA created the   expanded
                      screening         EDSP in 1998.     screening
                      program.                            program to
                                                          include
                                                          androgen,
                                                          thyroid, and
                                                          wildlife.
408(p)(2)..........  Must implement    Completed the     Ongoing
                      screening         deadline          (currently
                      program by Aug.   obligation, but   implementing
                      1999.             ongoing           expanded
                                        implementation.   screening).
408(p)(3)..........  Must provide for  Ongoing           Ongoing
                      testing of all    (currently        (currently
                      pesticide         obtaining data    obtaining data
                      chemicals and     through FIFRA     through FIFRA
                      may provide for   regulations and   regulations
                      testing of        processes).       and
                      other substance                     processes).
                      with cumulative
                      effect to a
                      pesticide
                      chemical.
408(p)(4)..........  None, but EPA     Ongoing           Ongoing
                      may exempt        (established      (established
                      chemical from     the Endocrine     the EDSPOC to
                      408(p).           Disruptor         make
                                        Science Policy    recommendation
                                        Council           s on
                                        (EDSPOC) to       exemptions).
                                        make
                                        recommendations
                                        on exemptions).
408(p)(5)..........  Must issue test   Ongoing           Ongoing
                      orders.           (currently        (currently
                                        implementing      implementing
                                        for pesticide     for pesticide
                                        active            active
                                        ingredients       ingredients
                                        through FIFRA     through FIFRA
                                        regulations and   regulations
                                        processes).       and
                                                          processes).

[[Page 73844]]

 
408(p)(6)..........  Must take action  Ongoing (working  Through this
                      to protect        to address        notice, EPA
                      public health     protections for   will begin
                      against a         pesticide         issuing
                      substance with    active            determinations
                      endocrine         ingredients in    for pesticide
                      effect.           FIFRA             active
                                        decisions).       ingredients
                                                          when 408(p)(6)
                                                          is met for
                                                          human
                                                          estrogen,
                                                          androgen, and
                                                          thyroid.
408(p)(7)..........  Must report to    Completed.......  N/A.
                      Congress by
                      August 2000.
------------------------------------------------------------------------

C. What is the screening and testing process under the EDSP?

    Through the 1998 Notice, EPA also adopted the EDSTAC recommendation 
to create a two-tier EDSP screening and testing process. The purpose of 
the first tier of testing (Tier 1) is to screen chemicals for the 
potential to interact with the estrogen, androgen, or thyroid systems 
and inform the need for any additional data (e.g., Tier 2) to evaluate 
possible adverse effects in humans or wildlife. The purpose of Tier 2 
testing is to identify, characterize, and quantify those adverse 
effects for risk assessment. The Tier 1 screening battery consists of 
11 assays, six of which are in vivo (performed with living organisms) 
and five of which are in vitro (performed outside of living organisms, 
with biological material such as cells or tissues).
    As described in its January 2023 white paper on new approach 
methodologies (NAMs; Ref. 4), EPA has now validated two computational 
models that integrate bioactivity data from multiple in vitro assays, 
referred to as the ToxCast Pathway Models for estrogen and androgen 
receptors, which can serve as alternatives to four of the 11 assays. 
Specifically, the validated estrogen receptor ToxCast Pathway Model can 
serve as an alternative for three of the Tier 1 assays that detect 
estrogen activity and the validated androgen receptor ToxCast Pathway 
Model can serve as an alternative for one of the Tier 1 assays that 
detect androgen activity. Research is ongoing to develop validated 
models as alternatives for other Tier 1 and Tier 2 assays.
    Under the EDSP two-tier process, analysis of Tier 1 screening data, 
in conjunction with OSRI on the endocrine system, results in one of two 
outcomes: a recommendation for additional data (e.g., through Tier 2 
testing of the chemical) to establish a dose-response relationship for 
any adverse effects that may result from interactions with the 
endocrine system, or an explanation for why no further testing is 
needed to assess the chemical for potential impacts to the estrogen, 
androgen, and thyroid hormone pathways. If more testing is recommended, 
the Tier 1 analysis also informs which tests may be performed.

D. How is FIFRA involved in EPA's implementation of the EDSP?

    FFDCA section 408(p) is not limited to EDSP screening and testing, 
as paragraph (p)(6) also requires EPA to ``as appropriate, take action 
under such statutory authority as is available to the Administrator, 
including consideration under other sections of this chapter, as is 
necessary to ensure the protection of public health'' for ``any 
substance that is found, as a result of testing and evaluation under 
this section, to have an endocrine effect on humans.'' Because FFDCA 
section 408(p) does not itself provide legal authority to ``ensure the 
protection of public health,'' EPA must rely on authorities in other 
sections of FFDCA and other laws, such as FIFRA, to satisfy FFDCA 
section 408(p)(6). In this respect, EPA's implementation of FFDCA 
section 408(p) and FIFRA are closely linked.
    The two are closely linked in another important manner. To meet the 
FIFRA requirement of ensuring that a pesticide will not cause 
``unreasonable adverse effects on the environment,'' EPA reviews 
numerous studies to assess potential adverse outcomes from exposure to 
chemicals. These studies include acute, sub-chronic, and chronic 
toxicity, including assessments of a wide range of potential toxic 
effects for carcinogenicity, neurotoxicity, developmental, 
reproductive, and general or systemic toxicity, and other effects. 
These studies include endpoints that may be susceptible to endocrine 
influence, including effects on endocrine target organ weights and 
histopathology, estrus cyclicity, sexual maturation, fertility, 
pregnancy rates, reproductive loss, and sex ratios in offspring.
    In the past, however, EPA's Office of Pesticide Programs (OPP) has 
generally focused on endocrine-related activities under FIFRA separate 
from the EDSP testing strategy. Thus, OPP's FIFRA decisions have not 
been explicit about how its review of required and submitted data for 
FIFRA informs EPA's obligations and commitments under FFDCA section 
408(p). For instance, OPP amended its FIFRA data requirements at 40 CFR 
part 158 to incorporate an updated reproductive study, which is the 
same study identified in EDSP Tier 2 and which allows the Agency to 
fully evaluate the potential for a conventional pesticide active 
ingredient to interact with the estrogen and androgen pathways. 
However, EPA did not explain how that effort informs the obligations 
and commitments under FFDCA section 408(p).
    In addition, while prior FIFRA decisions often referred to the 
FFDCA section 408(p) screening program, those decisions have not 
expressly discussed whether or how the data EPA reviews for its FIFRA 
decisions address FFDCA section 408(p) obligations or commitments. For 
example, FIFRA actions protect for the most sensitive endpoints in 
humans, which in many cases are not endocrine endpoints. In these 
situations, EPA did not take the final step of explaining whether or 
how the FIFRA decision fully addresses the data needs and decisions 
under FFDCA section 408(p) and protects the public from potential 
endocrine effects.
    One reason EPA has not completed these FFDCA section 408(p) actions 
is that it had focused on developing the science and technology to 
rapidly screen for chemicals that may have the potential to disrupt the 
estrogen, androgen, and thyroid systems of humans and wildlife. In 
recent years, for example, the Agency has focused on NAMs, particularly 
with high-throughput testing approaches, because of their central role 
in supporting the screening of the thousands of chemicals covered by 
the EDSP. This includes EPA testing of over 1,800 chemicals using the 
estrogen receptor and androgen receptor ToxCast Pathway Models, which, 
as explained in a separate white paper previously released, fulfill the 
data

[[Page 73845]]

needs for four separate EDSP Tier 1 assays for those chemicals. Through 
the strategies in this document, EPA is planning to expand the scope of 
its EDSP work to emphasize obtaining any additional human endocrine 
data as part of the Agency's FIFRA decisions and to issue FFDCA section 
408(p)(6) decisions where possible.

E. What concerns have been raised about EPA's implementation of the 
EDSP?

    The issues discussed earlier have led to confusion and criticism 
about the extent to which EPA has implemented FFDCA section 408(p) for 
pesticides. These criticisms have included concerns that EPA has been 
failing to obtain data and assess whether a pesticide active ingredient 
may cause adverse endocrine effects at the regulated levels and failing 
to make decisions under FFDCA section 408(p)(6) that consider those 
data and effects. In addition, EPA understands that some stakeholders 
have heard different messages over the years about whether EPA would 
require Tier 1 data when it has adequate Tier 2 data to make FIFRA 
determinations and FFDCA section 408(p) findings. Through this notice, 
EPA seeks to transparently address some of these criticisms and 
concerns.
    In July 2021, EPA's OIG issued a report concluding that the Agency 
has made limited progress in implementing the EDSP (Ref. 5). The report 
identified several reasons for this limited progress, including delays 
in testing pesticides for endocrine disruption, and lack of strategic 
guidance, performance measures, and other actions needed to implement 
the EDSP. The report offered ten recommendations for OCSPP, which the 
office generally agreed with and proposed to address. This document 
represents the Agency's strategic plan for rebuilding the EDSP that 
OCSPP will augment in the future. OCSPP has also begun implementing 
several other OIG recommendations, including publishing an EDSP white 
paper on NAMs, conducting an annual internal program review, and 
periodically updating the program website.
    In December 2022, EPA received a complaint in Alianza Nacional de 
Campesinas et al. v. EPA, alleging that EPA has violated the FFDCA and 
Administrative Procedures Act by not implementing the EDSP and not 
testing all pesticide chemicals for possible endocrine effects. (Ref. 
6).

III. Strategies To Further Implement FFDCA Section 408(p)

    EPA recognizes that its past practice has created questions about 
whether and how the Agency has been implementing FFDCA section 408(p), 
and now seeks to address these questions and accelerate progress in 
further implementing the EDSP, beginning with the three strategies 
described in this section. Before discussing the strategies, EPA is 
identifying the two overall approaches for expediting its ability to 
meet its FFDCA section 408(p) obligations and commitments.

A. Obtain Needed Endocrine Data During FIFRA Registration or 
Registration Review

    EPA will use the FIFRA registration and registration review 
processes to obtain data as needed to assess potential human estrogen, 
androgen, and thyroid effects for its FIFRA and FFDCA section 408(p) 
decisions. In general, EPA is already receiving some endocrine data 
through these processes as part of its standard FIFRA processes and 
regulatory data requirements. For example, for over a decade, EPA has 
routinely received data on mammalian estrogen and androgen effects for 
new conventional pesticide registrations through either a two-
generation reproductive study (typically performed in the rat (Ref. 7)) 
or an extended one-generation reproductive toxicity (EOGRT) study (also 
normally performed in the rat) (Organization for Economic Cooperation 
and Development (OECD) TG443) (Ref. 8). In these situations, EPA will 
generally not need to obtain additional data for these endpoints, 
including Tier 1 data, as explained in strategy three. Further, EPA 
understands that some registrants may have generated endocrine data to 
meet registration requirements in other countries but never submitted 
those data to EPA. EPA will consider those data, if submitted, to 
assess the need for additional endocrine data and to make the relevant 
FIFRA and FFDCA section 408(p) decisions, while avoiding unnecessary 
duplicative testing.
    Where EPA has identified outstanding endocrine data needs for a 
pesticide active ingredient, it will generally obtain the data through 
the FIFRA registration or registration review process, rather than 
through the FFDCA section 408(p)(5) process for issuing FFDCA test 
orders, as EPA already has a well-established process of seeking data 
through FIFRA. Further, EPA will generally obtain the data based on 
prioritized lists of pesticide active ingredients that it has begun 
developing and describes in strategy three.

B. Integrate FFDCA Data and Decisions into FIFRA Decisions

    For conventional pesticide active ingredients, EPA will integrate 
its FFDCA section 408(p) endocrine data and decisions into its FIFRA 
decisions, so that the Agency can efficiently use its FIFRA process and 
timelines to also address its FFDCA obligations and commitments for 
those chemicals. This approach will significantly increase EPA's 
consistency and transparency about how and when the Agency is meeting 
its FFDCA section 408(p) obligations and commitments as part of FIFRA 
decisions.
    Moving forward, when EPA has addressed those obligations and 
commitments for a pesticide active ingredient, it will clearly indicate 
that it has sufficient endocrine data and completed taking action under 
FFDCA section 408(p)(6) to ``ensure the protection of public health.'' 
This can occur in one of three scenarios. In scenario one, the most 
sensitive human endpoint identified in the pesticide's database is not 
an endocrine endpoint and is protective of endocrine effects at higher 
doses, if any are present. In scenario two, EPA exempts a pesticide 
active ingredient from the requirements of FFDCA section 408(p) because 
the Agency determines that the chemical meets the section 408(p)(4) 
statutory standard that it ``is anticipated not to produce any effect 
in humans similar to an effect produced by a naturally occurring 
estrogen.'' In its 2023 decision for citric acid, for instance, EPA 
concluded the acid is not anticipated to produce in humans or other 
organisms any effect similar to an effect produced by naturally 
occurring estrogen, androgen, or thyroid hormones, because it has no 
endocrine activity and no toxic effects at levels that people consume 
(Ref. 9).
    In both scenarios, EPA will issue a determination as part of a 
FIFRA decision for a pesticide that the Agency has completed taking 
action under FFDCA section 408(p)(6) to ``ensure the protection of 
public health'' by regulating exposure based on the most sensitive 
endpoint. Although FFDCA section 408(p)(6) does not obligate EPA to 
issue this determination and explanation, EPA is committing to do so 
because the Agency recognizes the benefits of more clarity and 
transparency about how it implements FFDCA section 408(p). This is 
another example where EPA distinguishes between mandatory obligations 
and

[[Page 73846]]

discretionary commitments, as summarized in Table 1.
    In scenario three, an endocrine effect is the most sensitive 
endpoint, so EPA would directly regulate to protect against that effect 
and issue a determination that it has completed taking action under 
FFDCA section 408(p)(6) through its FIFRA decision that uses the 
endocrine endpoint to regulate exposure to that pesticide. For example, 
the thyroid is a target organ for the insecticide fipronil, and thyroid 
effects were used as the basis for deriving most of the risk assessment 
endpoints and points of departure in the most recent human health risk 
assessment for this chemical (Ref. 10).
    Throughout this document, when EPA refers to a FFDCA section 
408(p)(6) ``decision,'' it is referring to one of these three 
scenarios. Strategies two and three explain when and how EPA will 
integrate these FFDCA section 408(p) data and decisions into its FIFRA 
registration and registration review decisions for conventional 
pesticide active ingredients.
    In implementing these strategies, EPA recognizes that it cannot 
address all past and present challenges simultaneously. For example, 
EPA is concerned about overwhelming the capacity of testing 
laboratories if it were to immediately impose testing for the hundreds 
of pesticide active ingredients in registration review. In addition, 
EPA does not have the resources to immediately assess each active 
ingredient case to identify all endocrine data gaps and to begin 
obtaining all outstanding data immediately. Thus, EPA developed this 
document to help prioritize how the Agency will implement these 
strategies. To summarize, the three strategies discussed are as 
follows:
     EPA will prioritize addressing potential human estrogen, 
androgen, and thyroid effects for conventional pesticide active 
ingredients (see strategy one), starting with the use of existing data 
routinely obtained through FIFRA registration and registration review 
activities, to determine whether additional endocrine data are needed 
(see strategy two).
     If existing data are adequate to inform the FFDCA section 
408(p)(6) and FIFRA decisions for any of the three endocrine pathways, 
EPA will make those decisions without obtaining additional endocrine 
data for that pathway (e.g., Tier 1), because any additional data would 
be duplicative and would not alter those decisions (see strategy 
three).
     EPA will continue to require that all applications for 
conventional new active ingredient registrations include adequate data 
to assess potential interaction with the human estrogen, androgen, and 
thyroid pathways. Those data will inform the FIFRA registration 
decision, which will include whether or how it addresses FFDCA section 
408(p) endocrine data and decisions (see strategy two).
    Similarly, to ensure all existing registrations for conventional 
pesticide active ingredients are supported by adequate human health-
related endocrine data, EPA will phase into the registration review 
process, using the framework discussed in this document (see strategy 
three), any additional data needs for evaluating potential interaction 
with human estrogen, androgen, and thyroid pathways. For 30 high 
priority conventional pesticide active ingredients, however, EPA is 
seeking any comments, existing endocrine data, and explanations on the 
need for additional endocrine data for any chemical on this list. 
During the public comment period, EPA will initiate the process for 
issuing DCIs in spring 2024 to require specified data for each of these 
active ingredients to address gaps in the data. EPA expects to include 
in the DCIs for these chemicals the requirement for the following EDSP 
Tier 1 studies or equivalent data: steroidogenesis, aromatase, 
Hershberger, female rat pubertal, and male rat pubertal studies. EPA 
also expects to include in the DCIs the potential for requiring 
submission of Tier 2 studies, based on the results of the Tier 1 
studies submitted and any OSRI that may inform the weight-of-evidence 
analyses on those data. In the alternative, EPA expects to accept Tier 
2 data in response to the DCIs to assess for potential effects to the 
estrogen and androgen pathways. Thus, if EPA receives an acceptable 
two-generation reproductive or EOGRT study, the study would fully 
satisfy the EDSP Tier 1 DCI for estrogen and androgen endpoints. As 
discussed in strategy three, EPA has prioritized the 30 chemicals 
because it lacks sufficient Tier 2 data for the chemicals but does have 
screening-level data indicating potential activity in the mammalian 
estrogen and/or androgen system. Further, as with new conventional 
active ingredient applications, EPA will explain in registration review 
documents for conventional active ingredients whether or how EPA's 
assessment or decision addresses FFDCA section 408(p) data and 
decisions.
1. Scope
    EPA's resources for the EDSP are limited, so the Agency must 
prioritize which aspects of the EDSP to address first. For these near-
term strategies, EPA has prioritized the registration of new 
conventional active ingredients and the registration review of 
conventional active ingredients, because they comprise the majority of 
registered active ingredients. The strategies are not intended to apply 
at this time to pesticide active ingredients that are solely intended 
for biological and antimicrobial uses or inert ingredients. Those 
ingredients span a wider range of uses and modes of action and can 
often present very different chemistries than conventional pesticides. 
EPA is still evaluating how best to prioritize human endocrine 
assessments for those active and inert ingredients and to develop 
strategies for the chemicals.
2. Strategy One: Prioritize Human Endocrine Effects
    The FFDCA section 408(p)(1) mandate is limited to developing a 
screening program to identify potential estrogen effects in humans, but 
EPA in 1998 expanded the scope of the program to include potential 
androgen and thyroid effects in humans and potential wildlife estrogen, 
androgen, and thyroid effects. Because of limited resources, however, 
EPA will initially focus on ensuring that the potential for human 
endocrine effects is transparently and sufficiently addressed for 
conventional pesticide active ingredients.
    Meanwhile, EPA will maintain its current approach in its FIFRA 
decisions of addressing wildlife endocrine effects if it already has 
adequate endocrine data for a species or group of species, supported by 
multiple lines of scientific evidence, as part of a new conventional 
registration or registration review action. EPA will also prioritize 
resources for research and risk assessment methods development to 
better understand endocrine effects in wildlife.
    There are several reasons for this decision to first address EPA's 
statutory requirement to more fully assess human endocrine effects 
before assessing discretionary wildlife effects. First, EPA's 
scientific understanding of the impacts of chemical interactions on the 
human endocrine system is generally more developed than for most 
wildlife. Thus, the data and science currently available to EPA enable 
the Agency to make progress in evaluating effects on humans using the 
approaches presented in this document. This is especially true 
considering the large number of non-mammalian species that are covered 
by the EDSP (e.g., birds, fish, amphibians). Second, EPA is already 
taking unprecedented steps to reduce pesticide

[[Page 73847]]

exposure to wildlife through its work under FIFRA and the Endangered 
Species Act (ESA) (16 U.S.C. 1531 et seq.). Through its ESA-FIFRA 
Workplan released in April 2022 and subsequent updates, EPA has 
prioritized mitigating pesticide effects on endangered species earlier 
in the FIFRA registration and registration review processes (Ref. 11). 
In addition, EPA has developed and will be implementing FIFRA Interim 
Ecological Mitigation measures for agricultural crop uses of 
conventional pesticide active ingredients in registration review. EPA 
expects that these mitigation measures will reduce pesticide exposures 
for ESA-listed species. EPA is also pursuing several pilot projects to 
expedite mitigation for listed species (e.g., herbicide strategy, 
Hawaiian species initiative) and continuing to implement the mitigation 
measures from ESA biological opinions for individual pesticide active 
ingredients, such as certain organophosphates (Ref. 11). These 
mitigation measures are also expected to reduce pesticide exposure to 
wildlife, which will also reduce the potential for endocrine 
disruption.
    EPA will continue to advance the science and develop strategies to 
consider the potential for endocrine effects on wildlife under the 
EDSP. For example, as outlined in the EDSP NAMs white paper, EPA is 
continuing to refine and apply species extrapolation processes and 
tools, which will help EPA understand how test results on laboratory 
animals extrapolate to effects on wildlife (Ref. 4). EPA is also 
involved in international efforts to assess the addition of thyroid 
endpoints to fish assays and tests that are commonly submitted to 
support pesticide registrations. Lastly, EPA is building datasets to 
support the development and validation of models that would allow in 
vitro to in vivo extrapolation for Tier 1 ecological studies. EPA will 
further discuss its approach to wildlife under the EDSP in future 
strategy documents. For the remainder of this document, all discussions 
are limited to the human endocrine system.
3. Strategy Two: Use Existing Data To Determine Whether Additional 
Endocrine Data Are Needed and To Inform FIFRA and FFDCA Endocrine 
Findings
    As a key part of rebuilding the EDSP, EPA is committing to 
transparency when assessing the adequacy of data on whether a 
conventional pesticide active ingredient has the potential to interact 
with the estrogen, androgen, and thyroid pathways. EPA is also 
committing to ensure that when it authorizes a new pesticide through 
registration and reauthorizes its use through registration review, 
those decisions adequately protect human health, as required by FFDCA 
section 408(p)(6). EPA can make these determinations more promptly when 
they are based on existing data, supplemented by targeted requests for 
additional data and explanations to address any potential data gaps. In 
most cases, the existing data will already have been submitted through 
registration or registration review to inform the FIFRA unreasonable 
adverse effects finding.
    In this strategy, EPA explains the overall status of what data are 
already typically available to the Agency on conventional pesticide 
active ingredients as part of its registration and registration review 
program. If EPA determines that available Tier 2 or other data are 
sufficient to fully inform the FIFRA registration/registration review 
and FFDCA section 408(p)(6) decisions for estrogen, androgen, and 
thyroid pathways, EPA will make the decisions without seeking 
additional EDSP Tier 1 data. In contrast, if EPA determines that 
additional data are needed to make the decisions, EPA will base the 
next steps and timing for those steps on the priority group in which 
the chemical belongs, as further discussed subsequently in this 
document.
    To inform when and how EPA will use existing FIFRA data or OSRI to 
determine whether a pesticide has a potential endocrine effect under 
FFDCA section 408(p), EPA has prepared a science support paper (Ref. 
1), which is available in the docket and briefly summarized in this 
strategy. That paper explains the data typically submitted to EPA that 
will meet EPA's needs for evaluating potential interaction with human 
estrogen, androgen, and thyroid pathways. EPA is separating its 
discussion of estrogen and androgen data from thyroid data because the 
data on estrogen and androgen are often generated together and separate 
from thyroid data. As discussed further subsequently in this document, 
EPA plans to reevaluate its approach to assessing any additional 
thyroid data needs in the coming years.
a. Human Estrogen and Androgen Data
    EPA created the two-tier EDSP system in 1998 as one way to screen 
and prioritize testing for the thousands of chemicals that required 
screening. The goal was to limit the more expensive and lengthier Tier 
2 testing by using Tier 1 screening to eliminate Tier 2 testing 
requirements for chemicals that had no potential to affect the human 
endocrine system. Since 1998, however, EPA has obtained additional data 
for many pesticide active ingredients through registration or 
registration review, because those data are also important to evaluate 
whether a pesticide meets the FIFRA registration standard. 
Specifically, in 1998, EPA updated its guidelines for the two-
generation reproductive study (OCSPP 850.3800). Soon after this update, 
EPA required the updated study to be submitted for all new 
registrations of conventional pesticide active ingredients. In 
addition, in some cases EPA may have also received the updated study 
for pesticides registered before the guideline update. The updated 
reproductive study is the same as what EPA would have required through 
Tier 2 testing to determine effects on human estrogen and androgen 
pathways, as explained in the science support paper (Ref. 1). 
Similarly, for some newer pesticide active ingredients, EPA has 
received a rodent EOGRT study instead of an updated two-generation 
reproductive study. The EOGRT study provides the same estrogen and 
androgen data as the updated reproductive study, and thus EPA also 
considers the EOGRT study as a validated alternative to satisfy the 
Tier 2 and FIFRA data needs (Ref. 1). There may also be OSRI (such as a 
study submitted to meet other countries' regulatory requirements) that 
might meet the data needs that the Tier 2 mammalian study is designed 
to fulfill.
    Further, if EPA has adequate Tier 2 data, it does not expect that 
Tier 1 data are needed to inform FFDCA section 408(p)(6) decisions for 
human estrogen and androgen effects and FIFRA unreasonable adverse 
effects determinations. EPA recognized this relationship between EDSP 
Tier 1 and Tier 2 data in the 1998 Federal Register Notice (Ref. 12) 
with the conceptual framework for the EDSP, which states that ``the 
outcome of Tier 2 is designed to be conclusive in relation to the 
outcome of Tier 1 and any other prior information. Thus, a negative 
outcome in Tier 2 will supersede a positive outcome in Tier 1.'' 
Consistent with this statement, when EPA has either an updated two-
generation reproductive or EOGRT study, only in exceptional situations 
would the Agency need to consider OSRI or require more data (e.g., Tier 
1 data) to assess for interaction with the estrogen or androgen 
pathway. For example, if the outcome of a two-generation reproductive 
study is ambiguous or inconclusive for one or more endocrine endpoints, 
EPA may consider whether OSRI addresses the

[[Page 73848]]

ambiguity or inconclusiveness. This strategy clarifies that when EPA 
concludes that the two-generation reproductive study, EOGRT study, or 
OSRI are adequate to assess a conventional pesticide active ingredient 
for interaction with the estrogen or androgen pathway, it will 
explicitly make that determination as part of a FIFRA assessment and 
the accompanying registration or registration review decision. In those 
situations, EPA will not need or require EDSP Tier 1 data under FIFRA 
or FFDCA section 408(p)(5).
    Based on this analysis, for new pesticide active ingredient 
registrations, EPA will continue to require the updated two-generation 
reproductive study, the alternative EOGRT study, or equivalent data. 
Applications for new conventional pesticide active ingredients that are 
not accompanied by either study or equivalent data will be deemed 
incomplete and unacceptable for further review.
    For conventional active ingredients in registration review, EPA 
will first determine whether an updated reproductive or EOGRT study is 
available and adequate to assess for interaction with the estrogen and 
androgen pathways. Among the approximately 460 conventional active 
ingredient cases currently in registration review, EPA has received 
acceptable updated two-generation reproductive or EOGRT studies for 
approximately 90 (20%) cases. This is only an estimate based on EPA's 
initial analysis and will change over time.
    For the remaining conventional registration review cases without 
the updated two-generation reproductive or EOGRT study, EPA's approach 
will depend on which of three groups the chemical belongs to, as 
discussed in strategy three. To help implement these next steps, EPA 
will use its Endocrine Disruptor Science Policy Council (EDSPOC), 
established in 2022 to review hazard and exposure data and to recommend 
whether to exempt a pesticide under FFDCA section 408(p)(4). The EDSPOC 
will recommend whether additional Tier 2 data are needed based on its 
review of comments and data submitted in response to this document, 
future DCIs for endocrine data, and all existing data for pesticides 
for which the Agency lacks either an updated two-generation 
reproductive or EOGRT study. This issue is discussed in the science 
support paper (Ref. 1).
b. Human Thyroid Data
    Unlike the estrogen and androgen pathways, a Tier 2 assay for 
thyroid was not established at the time of the EDSP's creation in 1998. 
At the time, only the Tier 1 rat pubertal assays provided thyroid 
evaluation in the EDSP battery. In 2005, EPA released its ``Guidance 
for Thyroid Assays in Pregnant Animals, Fetuses and Postnatal Animals, 
and Adult Animals'' (Ref. 13), which was used to develop studies to 
evaluate lifestage sensitivity to thyroid effects. This includes the 
EOGRT study that the OECD adopted in 2011 and the comparative thyroid 
assay (CTA). Both studies evaluate the same endpoints as the Tier 1 rat 
pubertal assays for adult animals, while providing additional 
information on thyroid toxicity at various stages of an animal's life. 
If a registrant has submitted an acceptable EOGRT study with a thyroid 
evaluation or a CTA, EPA does not expect to need Tier 1 or other data 
to inform its FFDCA section 408(p)(6) decision for thyroid effects, 
unless the Agency identifies an issue that warrants additional 
lifestage information.
    EPA recognizes that studies such as the EOGRT and CTA are animal 
and resource intensive, and certain endpoint data may be difficult to 
obtain (e.g., advanced techniques necessary for small blood volumes 
particularly in young animals, limited number of laboratories capable 
of properly conducting studies). As a result, EPA does not require 
either of these studies for all pesticide active ingredients unless 
data indicate such a need. Currently, EPA evaluates all available 
thyroid data during registration or registration review to assess 
whether evidence exists that a chemical may cause adverse thyroid 
effects and determine whether additional thyroid information is needed. 
This includes data from several studies required under FIFRA (e.g., 
subchronic, chronic, and carcinogenicity) for conventional pesticide 
active ingredients that evaluate potential thyroid toxicity. 
Measurements in these studies typically include thyroid organ weights 
and histopathology (e.g., colloid amount, follicular cell height and 
shape) that can detect changes associated with thyroid hormone 
perturbations. For some of these conventional pesticide active 
ingredients, registrants also submit optional thyroid hormone data to 
EPA to provide additional characterization of potential thyroid 
toxicity. Additionally, EPA may also consider data from EDSP Tier 1 rat 
pubertal assays or OSRI that provide thyroid evaluation. These data are 
predominantly obtained from guideline studies in rats, which are 
recognized as a sensitive animal model for humans, as discussed in the 
science support paper (Ref. 9). Thus, a lack of thyroid toxicity in 
these rat studies provides a strong basis for concluding a lack of 
concern for thyroid toxicity in humans and thus a sufficient basis for 
FIFRA and FFDCA section 408(p)(6) findings. This strategy clarifies 
that if EPA finds no evidence of thyroid toxicity, then it will 
conclude that no further data are needed at that time under FIFRA and 
FFDCA section 408(p) to assess the conventional pesticide active 
ingredient for thyroid toxicity. The registration and registration 
review documents will explain that conclusion.
    In contrast, if EPA determines that there is evidence of thyroid 
toxicity, EPA will refer the case to the Hazard and Science Policy 
Council (HASPOC), an internal peer review council that addresses 
whether additional data may be necessary to evaluate the potential of 
an active ingredient to interact with the thyroid pathway. HASPOC takes 
a weight-of-evidence approach to determine whether additional thyroid 
information is needed considering data from multiple lines of evidence, 
such as physical-chemical properties, toxicity of the chemical and any 
structurally related chemicals, exposure from the registered use 
pattern, and estimated risks. HASPOC has predominantly considered the 
need for a CTA to obtain lifestage specific thyroid measurements, 
including thyroid hormones. Depending on the available data, however, 
EPA may seek additional thyroid data for screening the chemical before 
requiring lifestage information. If the HASPOC concludes that no 
further data are needed at that time under FIFRA and FFDCA section 
408(p) to assess the conventional pesticide active ingredient for 
thyroid effects, the EPA registration or registration review documents 
will explain that conclusion. If substantial new information is raised 
in the future calling into question these FIFRA and FFDCA findings, EPA 
can address the issue at that time, as appropriate to the 
circumstances.
    EPA believes that there may be existing studies with thyroid 
measurements, such as EDSP Tier 1 rat pubertal assays or EOGRT studies, 
that EPA had not yet specifically requested. Additionally, although 
thyroid hormone and organ weight measures are not required as part of 
the EPA rat subchronic toxicity test guidelines (OCSPP 870.3050, 
870.3100), registrants may submit existing or future studies that 
follow the OECD guidelines to support pesticide registrations. In 2018, 
the OECD updated its guidelines for the 28-day and 90-day rat 
subchronic studies (TGs 407 and 408 (Refs. 14 and 15, respectively)) to 
measure thyroid hormones and organ weight, in addition

[[Page 73849]]

to the previously required thyroid histopathology evaluations in those 
guidelines, to detect perturbations to the thyroid pathway. EPA 
anticipates that as more pesticide applications are submitted 
consistent with the OECD guidelines, EPA will receive additional 
thyroid-related data, which will be consistent with the data obtained 
from the Tier 1 rat pubertal assays.
    As of 2023, most new conventional pesticide active ingredient 
registration submissions that EPA receives have not followed the 
voluntary 2018 OECD guidelines for the subchronic rodent oral toxicity 
studies. One reason is that EPA regulations allow registrants, 
consistent with the OECD agreement on Mutual Acceptance of Data, to 
decide whether to follow the EPA or the OECD guidelines for the 
subchronic rodent oral toxicity studies. A second reason is that 
registrants typically perform these types of studies many years before 
they submit a registration application package to EPA. The Agency 
expects within the next few years to begin receiving more FIFRA new 
pesticide active ingredient applications with studies that follow the 
2018 OECD guidelines for subchronic rodent oral toxicity studies that 
will contain these additional thyroid-related measures.
    EPA is actively considering potential revisions to its current 
framework for thyroid data needs, including scientific advancements and 
potential to require additional thyroid measures. As described in the 
EDSP white paper on NAMs (Ref. 4), EPA has ongoing research to develop 
high-throughput screening assays for thyroid-relevant targets, and 
models to predict thyroid-related apical outcomes (e.g., growth, 
reproduction). Further, EPA is collaborating in international efforts 
to advance NAMs for thyroid effects. EPA needs additional research and 
peer review before it can include these NAMs in the EDSP. Thus, EPA 
expects to convene a FIFRA Scientific Advisory Panel (SAP) (anticipated 
in 2025) to obtain external peer review on potential revisions to the 
thyroid framework and may alter its approach after the FIFRA SAP 
review.
c. Where Endocrine Data Are Inadequate or Absent
    Strategy two pertains to situations where EPA can clearly use 
existing endocrine data, but in some situations further analysis of 
available data will lead EPA to determine that data gaps exist. For 
example, EPA estimates approximately 317 conventional pesticide cases 
in registration review that lack an updated, post-1998 two-generation 
reproductive or EOGRT study. Compared to the updated guideline 
reproductive study that provides Tier 2 test data (Ref. 7), the pre-
1998 study likely did not evaluate all the endocrine-related endpoints 
that were added to the test guideline in 1998. As a result, for these 
pesticides, EPA will need to assess the results of the pre-1998 study 
along with any OSRI to determine the need for additional data on the 
potential for estrogen and androgen effects. What constitutes 
additional data will depend on the extent of missing information as 
described in more detail in strategy three. In general, EPA will seek 
Tier 1 data or OSRI to augment the data obtained from the pre-1998 
reproductive study. Although both FIFRA section 3(c) and FFDCA section 
408(p) provide authority for EPA to obtain any additional needed 
endocrine data, EPA already has an established FIFRA process under 
section 3(c) to obtain data, so the Agency will generally use this 
process rather than the FFDCA process.
d. Other Potential Uses of Tier 1 Data Unrelated to the EDSP
    Thus far, the discussion of Tier 1 data has been limited to whether 
EPA needs those data when it has adequate Tier 2 data or OSRI to assess 
potential effects on the human endocrine system. This is a result of 
the structure of the two-tier EDSP that EPA developed in 1998. More 
generally, however, the data listed in EDSP Tier 1 may be developed 
independently of the EDSP and, thus, may also inform aspects of risk 
assessment unrelated to FFDCA section 408(p). One potential role is to 
inform the required FFDCA cumulative effects analysis of whether a 
substance ``may have an effect that is cumulative to the effect of a 
pesticide chemical.'' To the extent such Tier 1 data has already been 
submitted (or is submitted) to EPA for purposes of the EDSP, EPA may 
find that data useful for informing other aspects of risk assessment. 
If EPA needs similar data in those or other situations, it can obtain 
them under FIFRA or provisions of the FFDCA unrelated to the EDSP, 
although it would not be called ``Tier 1 data'' per se. Because this 
document covers only the initial rebuilding of the EDSP, it does not 
address potential uses of that type of data for non-EDSP uses.
    To summarize, the key parts of strategy two are as follows:
     For human estrogen and androgen effects, if EPA has an 
adequate updated two-generation or EOGRT study to support a new 
conventional pesticide active ingredient application or a currently 
registered conventional pesticide active ingredient in registration 
review, then it will likely conclude that it has sufficient data to 
inform its FIFRA and its FFDCA section 408(p)(6) decisions for 
potential human estrogen and androgen effects. In those case, EPA will 
not seek Tier 1 data to complete those decisions.
     Consistent with current practice, new conventional 
pesticide active ingredient applications will be deemed incomplete if 
EPA has neither an adequate updated two-generation or EOGRT study, or 
equivalent data. Those applications will not proceed through the 
registration process.
     For currently registered conventional pesticide active 
ingredients, strategy three explains how EPA will prioritize these 
pesticides to determine whether and what additional data it needs. In 
general, EPA will prioritize an active ingredient that lacks an 
adequate updated two-generation or EOGRT study (which will likely be 
the case for pesticides registered before 1998), if EPA determines 
available data are inadequate or insufficient to address interaction on 
the estrogen and androgen pathway.
     For human thyroid effects, if EPA has an acceptable CTA or 
EOGRT study with thyroid evaluations, then it will likely have 
sufficient thyroid toxicity data to inform its FIFRA and FFDCA 
408(p)(6) decisions for potential human thyroid effects, and EPA will 
not seek Tier 1 data to support those decisions. When neither of these 
studies are available, EPA will continue with its current approach of 
evaluating the available data for each pesticide active ingredient. If 
no evidence exists of thyroid-related toxicity or if HASPOC has not 
recommended requiring additional data (e.g., CTA) based on the weight-
of-the evidence evaluation, then EPA will include in its FIFRA 
assessments and accompanying registration or registration review 
decision an explanation for why the available data are sufficient to 
inform its FIFRA and its FFDCA section 408(p)(6) decisions for thyroid. 
In these cases, EPA will not need Tier 1 data for thyroid. If HASPOC 
recommends additional thyroid data, OPP's regulatory divisions will 
review the recommendation during the registration or registration 
review process for the pesticide to determine whether or when to issue 
a DCI for the additional needed thyroid data. EPA may alter its 
approach to determining additional thyroid data needs following the 
FIFRA SAP review (anticipated in 2025) of potential revisions to its 
thyroid framework.

[[Page 73850]]

4. Strategy Three: Through Registration Review, Phase in Any New Data 
Requirements To Address Potential Human Estrogen, Androgen, and Thyroid 
Effects for Registered Conventional Pesticide Active Ingredients, 
Starting with Priority Chemicals
    EPA's longstanding goal is for its registration review final 
decisions to include decisions under FFDCA section 408(p) for potential 
human estrogen, androgen, and thyroid effects. To continue fulfilling 
this goal, EPA has created a framework for conventional pesticides 
awaiting human endocrine decisions that prioritizes obtaining new data 
based on whether EPA already has data for the pesticide and, if so, 
whether the data indicate a potential for endocrine disruption. 
Depending on the answers to these questions, EPA has assigned each 
conventional active ingredient in registration review into one of three 
groups. For example, Group 1, which consists of 30 cases, is the 
highest priority for potential data collection.
    Where possible, EPA's goal is to incorporate any data requirements 
for additional estrogen, androgen, and thyroid data into the start of 
registration review cases, as EPA does for other potential human health 
effects. Where the current registration review case is farther along in 
registration review, EPA will address any additional endocrine data 
needs by issuing a DCI, as appropriate, in later stages of registration 
review for a chemical.
    The number of registration review cases presented in this section 
is an approximation and subject to change. Readers should not focus on 
the number of cases for exactness and instead use them to gain a 
general understanding of the number of cases currently in registration 
review that are priorities for further human endocrine screening and 
decisions. In the future, EPA plans to revise the registration review 
website to include updates of the number of cases presented in this 
section.
a. How EPA Prioritized Conventional Active Ingredients Undergoing 
Registration Review for Obtaining Additional Estrogen-Androgen Data
    EPA has developed the framework that EPA will be using to determine 
which conventional pesticides in registration review require additional 
estrogen and androgen data for human health effects and how the Agency 
will prioritize obtaining additional data through DCIs (as discussed in 
strategy two, EPA will continue its current approach for thyroid). The 
framework represents EPA's initial approach to organize and prioritize 
the large number of registration review pesticides for any additional 
estrogen and androgen data and regulatory decisions, and may evolve as 
EPA gains experience implementing it. See Figure 1. in Ref. 2 for a 
diagram of the framework used for prioritizing the 403 conventional 
pesticide cases currently in registration review for which an FFDCA 
section 406(p)(6) determination is needed.
    EPA has 459 conventional pesticide cases currently in registration 
review that have neither a registration review final decision nor an 
FFDCA section 408(p)(6) decision. These cases cover pesticides 
registered before October 2007 (with a current registration review 
deadline of October 2026) and some pesticides registered after this 
date. There are seven cases for which EPA has exempted the pesticide 
active ingredient from testing under FFDCA section 408(p)(4), and 49 
cases from List 1 that EPA is addressing separate from this framework 
(see List 1 decision memo (Ref. 3)). That leaves 403 cases currently in 
registration review for further consideration of whether and when to 
require additional endocrine data. A pesticide registration review case 
is comprised of one or multiple pesticide active ingredients depending 
on the case. Many conventional pesticide cases have only one active 
ingredient.
    Table 2 includes estimates of the number of conventional pesticide 
cases currently in registration review for which an FFDCA section 
406(p)(6) determination is needed. EPA is addressing List 1 pesticides 
separately in the List 1 decision memo (Ref. 3).

     Table 2--Categorization of the 403 Conventional Pesticide Cases
  Currently in Registration Review for Which an FFDCA Section 406(p)(6)
                         Determination is Needed
------------------------------------------------------------------------
                     Description                       Number of cases *
------------------------------------------------------------------------
No further testing for estrogen or androgen.........                  86
    Cases with updated 2-gen. repro. study..........                  82
    Cases with EOGRT study..........................                   4
May need further estrogen or androgen data:.........                 317
    Group 1 cases...................................                  30
    Group 2 cases...................................                 126
    Group 3 cases...................................                 161
------------------------------------------------------------------------
* Numbers as of 8/25/2023.

    As previously stated and further explained in the science support 
paper, either an updated two-generation reproductive or EOGRT study 
will generally provide sufficient data on potential estrogen and 
androgen effects in humans. The Agency has data from at least one of 
these studies for 86 of the 403 cases (82 cases with the updated 
reproductive study and 4 cases with the EOGRT study) (Ref. 2).
    , and EPA expects to make FFDCA section 408(p)(6) decisions for 
these human endocrine effects as part of registration review for these 
pesticides without seeking further estrogen or androgen data.
    For the remaining 317 cases without either study, EPA then 
determined whether it has data on the estrogen receptor and androgen 
receptor from the ToxCast Pathway Models. The ToxCast program, which 
generates high throughput data for chemicals of interest to EPA, has 
produced endocrine screening data for over 1,800 chemicals to inform 
the estrogen receptor and androgen receptor ToxCast Pathway Models. For 
191 of the 317 cases, EPA has ToxCast Pathway Model scores for the 
estrogen receptor, androgen receptor, or both. The ToxCast Pathway 
Model scores for 30 of these 191 cases show bioactivity that may 
provide evidence for a potential effect on estrogen, androgen, or both, 
indicating the need for additional data to evaluate the potential to 
interact with the estrogen, androgen, or both pathways (the remaining 
161 of the 317 cases without positive ToxCast data are discussed later 
in this section). EPA is seeking through this notice any Tier 1 data, 
OSRI, or explanation of how existing data address the ToxCast

[[Page 73851]]

Pathway Model scores, in order to determine whether there is actually a 
potential for an estrogen-androgen effect for these 30 cases. During 
the public comment period, EPA will initiate the process for issuing 
DCIs for these cases by spring 2024. Because the cases show the 
potential for endocrine activity, EPA considers them the highest 
priority for obtaining additional data and will refer to them as 
``Group 1'' cases.
    For the remaining 126 of 317 cases, ToxCast Pathway Model scores 
were not available for the estrogen receptor or androgen receptor. 
These chemicals are also high priorities for obtaining data, but not as 
high as Group 1 cases because data currently exist that demonstrate 
potential activity in the ToxCast models for the Group 1 cases. EPA 
considers these 126 cases ``Group 2'' for assessment and potential data 
collection. While the Agency prioritizes Group 1 cases, it will refine 
the Group 2 cases as follows. First, EPA will determine whether any of 
the active ingredients for those cases are exempt from further testing 
under FFDCA section 408(p)(4) because the Agency has determined that an 
active ingredient ``is anticipated not to produce any effect in humans 
similar to an effect produced by a naturally occurring estrogen.'' If 
so, EPA will exempt the active ingredient and explain its decision. 
Second, for the remaining cases, EPA will search for any existing 
estrogen or androgen data and evaluate its potential as OSRI. EPA will 
then determine whether further testing is needed for each of the 
remaining cases to make an FFDCA section 408(p) determination.
    Among the 191 cases with ToxCast data, there are 161 cases that 
show no activity for either estrogen or androgen receptors. EPA has 
assigned these pesticides a lower priority for obtaining additional 
data, given current data suggest no potential for estrogen or androgen 
activity, and is referring to these 161 cases as ``Group 3.'' In the 
docket is a document titled, ``List of Conventional Registration Review 
Chemicals for Which an FFDCA Section 408(p)(6) Determination is 
Needed,'' that lists the pesticide cases that fall within each group, 
accounting for all 403 registration review cases discussed in this 
strategy (Ref. 2).
b. How EPA Will Obtain Additional Data and Integrate the New Data Into 
Registration Review
i. For Group 1 Cases: 30 Cases Without an Updated Two-Generation 
Reproductive or EOGRT Study but for Which ToxCast Data Show Activity 
for Estrogen, Androgen, or Both
    For the 30 Group 1 cases, EPA will seek additional data to better 
understand the positive findings in the ToxCast data for estrogen, 
androgen, or both. Specifically, for each pesticide, EPA is seeking 
through this notice any Tier 1 data, OSRI, or explanation of how 
existing data address the existing ToxCast Pathway Model scores. During 
this public comment period, EPA will begin the process for issuing DCIs 
for these 30 cases with the goal to begin issuing them in spring 2024. 
The DCIs will cover all the Tier 1 data relevant to mammals, except the 
assays for which the ToxCast Pathway Model scores may serve as 
alternatives (i.e., estrogen receptor binding in vitro assay, estrogen 
receptor transcriptional activation in vitro assay, in vivo 
uterotrophic assay, and androgen receptor binding in vitro assay). 
Thus, as part of a DCI, EPA will require data from the following five 
Tier 1 assays to complete screening for estrogen and androgen effects 
in humans: Steroidogenesis, aromatase, Hershberger, female rat 
pubertal, and male rat pubertal (see Table 3). In lieu of all five Tier 
1 assays, EPA expects to allow a registrant, in response to a DCI, to 
submit an updated two-generation reproductive or EOGRT study, or 
equivalent data, which will generally provide conclusive data for 
potential estrogen and androgen effects in humans. The DCIs will be 
based on the Pesticide Data Call-Ins Information Collection Request 
(EPA No. 2288.04).

       Table 3--Additional EDSP Tier 1 Data EPA Expects To Request
------------------------------------------------------------------------
                                  Estrogen      Androgen       Thyroid
          Assay name               pathway       pathway       pathway
------------------------------------------------------------------------
                             In vitro Assays
------------------------------------------------------------------------
OCSPP 890.1550--                    [ssquf]       [ssquf]
 Steroidogenesis (Human Cell
 Line--H295R).................
OCSPP 890.1200--Aromatase           [ssquf]
 (Human Recombinant)..........
------------------------------------------------------------------------
                             In vivo Assays
------------------------------------------------------------------------
OCSPP 890.1400--Hershberger                       [ssquf]
 (Rat)........................
OCSPP 890.1450--Pubertal            [ssquf]                     [ssquf]
 Development and Thyroid
 Function in Intact Juvenile/
 Peripubertal Female Rats.....
OCSPP 890.1500--Pubertal                          [ssquf]       [ssquf]
 Development and Thyroid
 Function in Intact Juvenile/
 Peripubertal Male Rats.......
------------------------------------------------------------------------

    As EPA receives data for the Group 1 cases through public comments 
and any DCIs, it will determine the most efficient way to review the 
data and integrate them into the registration review process so that 
the Agency can issue its FIFRA and FFDCA section 408(p) findings for 
potential human estrogen, androgen, and thyroid effects. EPA must 
consider multiple factors when developing this timeline, including 
efficiencies in batching similar chemicals, the timing of when the 
Agency will receive and review data for other EDSP priority pesticides, 
the length of time needed to generate the data, the deadlines to 
complete other aspects of registration review for a pesticide, and the 
timeframe for amending pesticide labels to reflect any needed updated 
mitigation measures. EPA expects to release a more detailed timeline in 
2024.
ii. For Group 2 Cases: 126 Cases Without Updated Two-Generation 
Reproductive or EOGRT Study, and No ToxCast Pathway Model Scores
    EPA is not initiating the process for issuing DCIs for Group 2 
cases at this time because the Agency's resources are currently limited 
to obtaining and reviewing additional data for the Group 1 cases. The 
more immediate focus on Group 1 cases will also allow EPA to apply any 
lessons learned in collecting and reviewing data for Group 1 to Group 2 
cases. Although EPA does not yet have

[[Page 73852]]

a precise timeframe for issuing FIFRA DCIs for these cases, it expects 
to begin drafting them in 2025.
    In the meantime, the Agency will make some progress on Group 2 
cases in two ways. One is to consider any endocrine data or OSRI that 
registrants of these pesticides submit to EPA. As with Group 1 cases, 
EPA is particularly interested in any existing Tier 1 or Tier 2 data 
that the Agency is unaware of, endocrine data submitted to support 
distribution and use of the pesticide in other countries, or data from 
well-conducted studies addressing the pesticide active ingredient's 
endocrine effects. Although EPA cannot yet commit to reviewing these 
data within a specific timeframe, the Agency believes it may be useful 
to, at a minimum, gain a better understanding of the breadth and depth 
of available data for these pesticides before issuing DCIs. Thus, as 
with the Group 1 cases, EPA encourages registrants of Group 2 
pesticides to identify and submit any relevant endocrine data that have 
not been submitted to EPA or any explanations for why further testing 
should not be required.
    Second, given the large number of pesticides in the Group 2 list, 
EPA will identify the pesticides within this group that are higher 
priorities for endocrine testing. EPA will use comments, data, and 
explanations submitted, as well as the tools for prioritization 
described in its January 2023 EDSP NAMs white paper (Ref. 4), to 
determine which Group 2 pesticides will receive DCIs first. EPA will 
also use these same data and tools to determine whether to exempt any 
pesticides on the list from further testing under FFDCA section 
408(p)(4) using its current approach to exemptions. In 2024, EPA will 
provide more information on its timeline for Group 2 chemicals.
iii. For Group 3: All Remaining Conventional Registration Review Cases 
Not in Group 1 or Group 2
    As explained earlier, a main goal of rebuilding the EDSP is to 
incorporate the FFDCA section 408(p) obligations and commitments into 
the FIFRA process, including the registration review of existing 
pesticides. EPA will thus begin phasing into registration review those 
obligations and commitments for the 161 Group 3 cases. By phasing Group 
3 cases into the existing registration review schedule, EPA may also 
need to shift where a case currently stands in registration review.
    Most Group 3 cases (approximately 154 out of 161 cases) have active 
ingredients that were registered before October 2007 and have a current 
registration review deadline of October 2026. Typically, EPA issues 
DCIs before the draft risk assessment (DRA) phase of registration 
review. The pre-2007 cases, however, are generally past the DRA phase, 
often by several years. EPA will thus likely address its endocrine data 
needs as part of its continuous work plan (CWP) for these cases. Like a 
preliminary work plan (PWP), a CWP will provide an overview of the 
registration review case status, list registrations, and provide other 
pertinent data or information. As a continuation of an existing 
registration review case, the CWP will explain any new developments 
that EPA knows about a case, including any newly identified data or 
other information needed for a final registration review decision. 
Thus, EPA currently plans to prioritize the Group 3 cases and use the 
CWP to notify the public of when additional endocrine data are needed 
for each case and then issue a DCI to obtain the necessary data before 
completing a final decision for registration review. Consistent with 
existing EPA policy, a final decision will include an FFDCA section 
406(p)(6) decision for human estrogen, androgen, and thyroid.
    For the approximately seven other Group 3 cases with active 
ingredients registered after October 2007, EPA will determine whether 
to address its endocrine data needs through a CWP or a PWP. EPA will 
use the latter approach when it can integrate endocrine data needs into 
the registration review process from the outset, such as for cases 
without a PWP yet. Thus, for these cases, EPA will likely address the 
endocrine data needs before it does so for many Group 2 case, because 
the Group 3 case happens to be at an early enough stage of registration 
review where EPA can incorporate those data needs into the normal 
review process.

V. References

    The following is a listing of the documents that are specifically 
referenced in this document. The docket includes these documents and 
other information considered by EPA, including documents that are 
referenced within the documents that are included in the docket, even 
if the referenced document is not physically located in the docket. For 
assistance in locating these other documents, please consult the 
technical person listed under FOR FURTHER INFORMATION CONTACT.

1. US EPA. Use of Existing Mammalian Data to Address Data Needs and 
Decisions for Endocrine Disruptor Screening Program (EDSP) for 
Humans under FFDC Section 408(p). October 2023.
2. US EPA. List of Conventional Registration Review Chemicals for 
Which an FFDCA Section 408(p)(6) Determination is Needed. October 
2023.
3. US EPA. Status of Endocrine Disruptor Screening Program (EDSP) 
List 1 Screening Conclusions. October 2023.
4. US EPA. Availability of New Approach Methodologies (NAMs) in the 
Endocrine Disruptor Screening Program (EDSP). December 12, 2022. 
https://www.regulations.gov/document/EPA-HQ-OPP-2021-0756-0002.
4. US EPA Office of Inspector General (OIG). EPA's Endocrine 
Disruptor Screening Program Has Made Limited Progress in Assessing 
Pesticides. Report No. 21-E-0186. Report Type: Audit. July 28, 2021. 
https://www.epaoig.gov/reports/audit/epas-endocrine-disruptor-screening-program-has-made-limited-progress-assessing.
5. The United States District Court for the Northern District of 
California. Case No. 22-cv-9030. Filed December 20, 2022.
6. US EPA. Health Effects Test Guidelines: OPPTS 870.3800 
Reproduction and Fertility Effects [EPA 712-C-98-208]. August 1, 
1998. https://www.regulations.gov/document/EPA-HQ-OPPT-2009-0156-0018.
6. Organisation for Economic Co-operation and Development (OECD). 
OECD Guideline for the Testing of Chemicals, Extended One-Generation 
Reproductive Toxicity Study. OECD/OCDE 443. Adopted: June 25, 2018. 
https://www.oecd-ilibrary.org/docserver/9789264185371-en.pdf?expires=1695671098&id=id&accname=guest&checksum=F8B12F13B2F19A2731C51FA392B78716.
7. US EPA. Exemption of Citric Acid from the Requirements of the 
Endocrine Disruptor Screening Program. January 19, 2023. https://www.regulations.gov/document/EPA-HQ-OPP-2020-0558-0008.
8. US EPA. Fipronil: Draft Human Health Risk Assessment for 
Registration Review. March 20, 2020. https://www.regulations.gov/document/EPA-HQ-OPP-2011-0448-0076.
9. US EPA. EPA's Workplan and Progress Toward Better Protections for 
Endangered Species. EPA website. https://www.epa.gov/endangered-species/epas-workplan-and-progress-toward-better-protections-endangered-species.
10. US EPA. Endocrine Disruptor Screening Program; Proposed 
Statement of Policy. Federal Register. 63 FR 71542, December 28, 
1998 (FRL-6052-9). https://www.epa.gov/sites/default/files/2015-08/documents/122898frnotice.pdf.
11. US EPA. Guidance for Thyroid Assays in Pregnant Animals, Fetuses 
and Postnatal Animals, and Adult Animals. October 24, 2005. https://www.epa.gov/sites/default/files/2015-06/documents/thyroid_guidance_assay.pdf.

[[Page 73853]]

12. OECD. OECD Guidelines for the Testing of Chemicals, Repeated 
Dose 28-Day Oral Toxicity Study in Rodents. OECD/OCDE 407. Adopted: 
October 3, 2008. https://www.oecd-ilibrary.org/docserver/9789264070684-en.pdf?expires=1695669052&id=id&accname=guest&checksum=B2CCC35058D14B03AFA5C29EBB5D1CE5.
13. OECD. OECD Guideline for the Testing of Chemicals, Repeated Dose 
90-Day Oral Toxicity Study In Rodents. OECD/OCDE 408 Adopted: June 
25, 2018. https://www.oecd-ilibrary.org/docserver/9789264070707-en.pdf?expires=1695668998&id=id&accname=guest&checksum=19E7679541E3927AE5066BBB8CFA0F54.

VI. Paperwork Reduction Act (PRA)

    The strategies outlined in this document describe information 
collection activities that do not create any new paperwork burdens that 
require additional approval by OMB under the PRA, 44 U.S.C. 3501 et 
seq. The information collection activities associated with pesticide 
registration are already approved by OMB under OMB Control No. 2070-
0226, entitled ``Consolidated Pesticide Registration Submission 
Portal'' (EPA ICR No. 2624.01). Information collection activities 
associated with data call-in activities, including the generation of 
data for registration review, are approved under OMB Control No. 2070-
0174, entitled ``Pesticides Data Call-In Program Information Collection 
Request'' (EPA ICR No. 2288.06).
    Authority: 7 U.S.C. 136 et seq. and 21 U.S.C. 346a.

    Dated: October 20, 2023.
Michal Freedhoff,
Assistant Administrator, Office of Chemical Safety and Pollution 
Prevention.
[FR Doc. 2023-23721 Filed 10-26-23; 8:45 am]
BILLING CODE 6560-50-P