Notice2023-00940
Availability of New Approach Methodologies in the Endocrine Disruptor Screening Program; Notice of Availability and Opportunity for Comment
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Published
January 19, 2023
Issuing agencies
Environmental Protection Agency
Abstract
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.
Full Text
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<title>Federal Register, Volume 88 Issue 12 (Thursday, January 19, 2023)</title>
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[Federal Register Volume 88, Number 12 (Thursday, January 19, 2023)]
[Notices]
[Pages 3406-3408]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[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 <a href="https://www.regulations.gov">https://www.regulations.gov</a>. 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 <a href="https://www.epa.gov/dockets">https://www.epa.gov/dockets</a>.
FOR FURTHER INFORMATION CONTACT: Natalie Bray, Pesticide Reregistration
Division (7508M), Office of Pesticide Programs, Environmental
Protection Agency; telephone number: (202) 566-2222; email address:
<a href="/cdn-cgi/l/email-protection#7a18081b0354141b0e1b16131f3a1f0a1b541d150c"><span class="__cf_email__" data-cfemail="553727342c7b3b342134393c30153025347b323a23">[email protected]</span></a>.
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
[[Page 3407]]
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
<a href="http://regulations.gov">regulations.gov</a> 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 <a href="https://www.epa.gov/dockets/comments.html">https://www.epa.gov/dockets/comments.html</a>. 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 (<a href="https://ntp.niehs.nih.gov/whatwestudy/niceatm/comptox/ct-opera/opera.html">https://ntp.niehs.nih.gov/whatwestudy/niceatm/comptox/ct-opera/opera.html</a>);
(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,
[[Page 3408]]
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]
BILLING CODE 6560-50-P
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