[Federal Register Volume 88, Number 12 (Thursday, January 19, 2023)]
[Notices]
[Pages 3406-3408]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2023-00940]


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ENVIRONMENTAL PROTECTION AGENCY

[EPA-HQ-OPP-2021-0756; FRL-10116-01-OCSPP]


Availability of New Approach Methodologies in the Endocrine 
Disruptor Screening Program; Notice of Availability and Opportunity for 
Comment

AGENCY: Environmental Protection Agency (EPA).

ACTION: Notice of availability.

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SUMMARY: The Environmental Protection Agency (EPA) is announcing the 
availability of and soliciting public comment on a draft White Paper 
entitled ``Availability of New Approach Methodologies (NAMs) in the 
Endocrine Disruptor Screening Program (EDSP).'' This draft White Paper 
was developed pursuant to the Federal, Food, Drug and Cosmetic Act 
(FFDCA), which requires 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 
other endocrine effects. This draft White Paper announces that certain 
NAMs have been validated and may now be accepted by the EPA as 
alternatives for certain EDSP Tier 1 assays while others are useful for 
prioritization purposes and for use as other scientifically relevant 
information, where appropriate, in weight of evidence evaluations.

DATES: Comments must be received on or before March 20, 2023.

ADDRESSES: Submit your comments, identified by docket identification 
(ID) number EPA-HQ-OPP-2021-0756, through 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/dockets.

FOR FURTHER INFORMATION CONTACT: Natalie Bray, Pesticide Reregistration 
Division (7508M), Office of Pesticide Programs, Environmental 
Protection Agency; telephone number: (202) 566-2222; email address: 
[email protected].

SUPPLEMENTARY INFORMATION:

I. General Information

A. Does this action apply to me?

    This action is directed to the public in general and may be of 
interest to a wide range of stakeholders including environmental, human 
health, farm worker, and agricultural advocates; the chemical industry; 
pesticide users; and members of the public interested in the sale, 
distribution, or use of pesticides. Since others also may be 
interested, the agency has not attempted to describe all the specific 
entities that may be affected by this action. If you have any questions

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regarding the applicability of this action to a particular entity, 
contact the person listed under FOR FURTHER INFORMATION CONTACT.

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

    1. Submitting CBI. Do not submit CBI information to EPA through 
regulations.gov or email. 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.
    2. Multimedia submissions. Multimedia submissions (audio, video, 
etc.) must be accompanied by a written comment. The written comment is 
considered the official comment and should include discussion of all 
points you wish to make. The EPA will generally not consider comments 
or comment contents located outside of the primary submission (i.e., on 
the web, cloud, or other file sharing system).
    3. Tips for preparing your comments. When preparing and submitting 
your comments, see the commenting tips at https://www.epa.gov/dockets/comments.html. Please note that once submitted, comments cannot be 
edited or removed from the docket. The EPA may publish any comment 
received to its public docket.

II. Executive Summary

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

    Section 408(p)(1) of the Federal, Food, Drug and Cosmetic Act 
(FFDCA), 21 U.S.C. 408, requires EPA to ``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 endocrine effects as [EPA] 
may designate.''

B. What action is the Agency taking?

    The Agency is releasing the draft document entitled ``Availability 
of New Approach Methodologies (NAMs) in the Endocrine Disruptor 
Screening Program (EDSP)'' [herein called the draft ``White Paper'']. 
This draft White Paper announces that certain NAMs have been validated 
and may now be accepted by the EPA as alternatives for certain EDSP 
Tier 1 assays while others are useful for prioritization purposes and 
for use as other scientifically relevant information, where 
appropriate, in weight of evidence evaluations. The draft White Paper 
provides further details concerning when specified NAMs may be used.
    In 1998, pursuant to FFDCA section 408(p)(1), EPA introduced the 
EDSP including the use of a two-tiered screening framework consisting 
of a battery of in vitro and in vivo assays (63 FR 42852, August 11, 
1998 (FRL-6021-3) and 63 FR 71542, December 28, 1998 (FRL-6052-9)). The 
purpose of Tier 1 screening is to identify chemicals that have 
potential biological activity (``bioactivity'') in the estrogen, 
androgen or thyroid hormone pathways using a battery of assays. For 
more than a decade at the EPA, research efforts have focused on the 
development and evaluation of high-throughput in vitro assays and in 
silico methods as NAMs, including databases and computational models, 
for use as alternatives to the current suite of assays in the EDSP Tier 
1 battery to accelerate the pace of screening, add efficiencies, 
decrease costs, and reduce animal testing.
    EPA has determined that the Estrogen Receptor (ER) pathway model 
based on the full 18-assay ToxCast/Tox21 battery may be used as an 
alternative to performing certain EDSP Tier 1 screening assays: ER 
binding in vitro assay (OCSPP 890.1250), ER transcriptional activation 
in vitro assay (ERTA; OCSPP 890.1300), and the in vivo Uterotrophic 
assay (rat) (OCSPP 890.1600). EPA has further determined that the 
Androgen Receptor (AR) pathway model based on the full 11-assay 
ToxCast/Tox21 battery may be used as an alternative for the AR binding 
in vitro assay (OCSPP 890.1150). The data from these NAMs will be 
evaluated on a chemical-by-chemical basis (each assay evaluated 
independently).
    The following models and assays are not yet accepted by the EDSP as 
alternatives per se for Tier 1 screening assays, but may be used for 
priority setting for EDSP Tier 1 screening or for consideration for use 
as other scientifically relevant information, where appropriate in 
weight of evidence evaluations:
    (1) ER and AR pathway models using assay subsets (also referred to 
as reduced or minimal assay data sets); (2) In Silico Qualitative 
Structure Activity Relationship Consensus Models for ER and AR (https://ntp.niehs.nih.gov/whatwestudy/niceatm/comptox/ct-opera/opera.html); 
(3) Integration of Bioactivity and Exposure (Integrated Bioactivity 
Exposure Ratio), which compares an estimated external dose threshold 
for a biological effect, based on an internal dose (i.e., plasma 
concentration) derived from bioactivity data (e.g., ER and AR pathway 
model outputs), with estimates of exposure; and, (4) The Sequence 
Alignment to Predict Across Species Susceptibility (SeqAPASS) tool for 
interspecies extrapolation.
    EPA requests the public provide comment on the clarity and 
completeness of the draft document. Given the strengths and 
uncertainties of these methods, EPA also requests the public provide 
comment on the draft conclusions that certain NAMs have been validated 
and may now be accepted by the EPA as alternatives for certain EDSP 
Tier 1 assays while others are useful for prioritization purposes and 
for consideration for use as other scientifically relevant information.
    Included in the docket for this action are two documents that 
respond to comments on related subject matter. One document responds to 
comments received in response to a notice issued in the Federal 
Register of June 19, 2015 (80 FR 35350 (FRL-9928-69), see also docket 
ID No. EPA-HQ-OPPT-2015-0305) requesting comment on EPA's document 
titled ``Endocrine Disruptor Screening Program: Use of High Throughput 
Assays and Computational Tools.'' The other document contains EPA's 
responses to comments regarding the Federal Insecticide, Fungicide, and 
Rodenticide Act (FIFRA) Scientific Advisory Panel (SAP) Meeting from 
November 28-30, 2017 (82 FR 26097, June 6, 2017 (FRL-9962-79) and 82 FR 
36137, August 3, 2017 (FRL-9965-61), see also docket ID No. EPA-HQ-OPP-
2017-0214). EPA is including these documents in the docket for this 
action because they provide useful context on past public input on the 
EDSP which EPA considered when developing the draft White Paper. EPA is 
not requesting public comment on these response to comments documents.

III. Do guidance documents contain binding requirements?

    As guidance, the draft White Paper is not binding on the Agency or 
any outside parties, and the Agency may depart from it where 
circumstances warrant and without prior notice. While EPA has made 
every effort to ensure the accuracy of the discussion in the guidance, 
the obligations of EPA and the regulated community are determined by 
statutes, regulations, or other legally binding documents. In the event 
of a conflict between the discussion in the guidance documents and any 
statute,

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regulation, or other legally binding document, the guidance documents 
will not be controlling.
    Authority: 21 U.S.C. 408.

    Dated: January 13, 2023.
Michal Freedhoff,
Assistant Administrator, Office of Chemical Safety and Pollution 
Prevention.
[FR Doc. 2023-00940 Filed 1-18-23; 8:45 am]
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