Document ID: EPA-HQ-OPPT-2014-0766-0001
Agency: epa
Document Type: Notice
Title: Guidance: Endocrine Disruptor Screening Program Test Guidelines; Three Tier 2 Non-Mammalian Tests
Posted Date: 2015-01-30T05:00Z

[Federal Register Volume 80, Number 20 (Friday, January 30, 2015)]
[Notices]
[Pages 5107-5109]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2015-01836]

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ENVIRONMENTAL PROTECTION AGENCY

[EPA-HQ-OPPT-2014-0766; FRL-9919-43]

Draft Test Guidelines; Endocrine Disruptor Screening Program Test 
Guidelines (Series 890); Three Tier 2 Non-Mammalian Tests; Notice of 
Availability and Request for Comment

AGENCY: Environmental Protection Agency (EPA).

ACTION: Notice.

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SUMMARY: EPA is announcing the availability of three draft test 
guidelines for public review and comment that are being added to its 
890 Series, entitled ``Endocrine Disruptor Screening Program Test 
Guidelines.'' The draft guidelines relate to the following three non-
mammalian species tests identified under Tier 2 of the Endocrine 
Disruptor Screening Program (EDSP): Japanese quail 2-generation 
reproduction test; Medaka extended 1-generation reproduction test; and 
Larval amphibian growth and development assay. These draft test 
guidelines are part of a series of test guidelines established by the 
Office of Chemical Safety and Pollution Prevention (OCSPP) for use in 
testing pesticides and chemical substances. The test guidelines serve 
as a compendium of accepted scientific methodologies and protocols that 
are intended to provide data to inform regulatory decisions. The test 
guidelines provide guidance for conducting the test, and are also used 
by EPA, the public, and companies that submit data to EPA.

DATES: Comments must be received on or before March 31, 2015.

ADDRESSES: Submit your comments, identified by docket identification 
(ID) number EPA-HQ-OPPT-2014-0766, by one of the following methods:
     Federal eRulemaking Portal: http://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.
     Mail: Document Control Office (7407M), Office of Pollution 
Prevention and Toxics (OPPT), U.S. Environmental Protection Agency, 
1200 Pennsylvania Ave. NW., Washington, DC 20460-0001.
     Hand Delivery: To make special arrangements for hand 
delivery or delivery of boxed information, please follow the 
instructions at http://www.epa.gov/dockets/contacts.html.
Additional instructions on commenting or visiting the docket, along 
with more information about dockets generally, is available at http://www.epa.gov/dockets.

FOR FURTHER INFORMATION CONTACT: Sharlene Matten, telephone number: 
(202) 564-0130, email address: matten.sharlene@epa.gov; or Steven 
Knott, telephone number: (202) 564-0103, email address: 
knott.steven@epa.gov. Mailing address: Office of Science Coordination 
and Policy (7201M), Environmental Protection Agency, 1200 Pennsylvania 
Ave. NW., Washington, DC 20460-0001.

SUPPLEMENTARY INFORMATION:

I. Introduction

    EPA is announcing the availability of three draft test guidelines 
for public review and comment that are being added to its 890 Series, 
entitled ``Endocrine Disruptor Screening Program Test Guidelines.'' The 
draft guidelines relate to the following three non-mammalian species 
tests identified under Tier 2 of the EDSP: Japanese quail 2-generation 
reproduction test; Medaka

[[Page 5108]]

extended 1-generation reproduction test; and Larval amphibian growth 
and development assay.
    These draft test guidelines are part of a series of test guidelines 
established by OCSPP for use in testing pesticides and chemical 
substances to develop data for submission to the Agency under the 
Federal Food, Drug and Cosmetic (FFDCA) section 408 (21 U.S.C. 346a), 
the Federal Insecticide, Fungicide and Rodenticide Act (FIFRA) (7 
U.S.C. 136 et seq.), and the Toxic Substances Control Act (TSCA) (15 
U.S.C. 2601 et seq.). The test guidelines serve as a compendium of 
accepted scientific methodologies and protocols that are intended to 
provide data to inform regulatory decisions under TSCA, FIFRA, and/or 
FFDCA.
    The test guidelines provide guidance for conducting the test, and 
are also used by EPA, the public, and companies that are subject to 
data submission requirements under TSCA, FIFRA, and/or FFDCA. As 
guidance documents, the test guidelines are not binding on either EPA 
or any outside parties, and EPA may depart from the test guidelines 
where circumstances warrant and without prior notice. At places in this 
guidance, the Agency uses the word ``should.'' In this guidance, use of 
``should'' with regard to an action means that the action is 
recommended rather than mandatory. The procedures contained in the test 
guidelines are recommended for generating the data that are the subject 
of the test guideline, but EPA recognizes that departures may be 
appropriate in specific situations. You may propose alternatives to the 
recommendations described in the test guidelines, and the Agency will 
assess them for appropriateness on a case-by-case basis.

II. General Information

A. Does this action apply to me?

    This action is directed to the public in general. Although this 
action may be of particular interest to those persons who are or may be 
required to conduct testing of pesticides and chemical substances for 
submission to EPA under TSCA, FIFRA, and/or FFDCA, the Agency has not 
attempted to describe all the specific entities that may be affected by 
this action.

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

    1. Submitting CBI. Do not submit this information to EPA through 
regulations.gov or email. Clearly mark the part or all of the 
information that you claim to be CBI. For CBI information in a disk or 
CD-ROM that you mail to EPA, mark the outside of the disk or CD-ROM as 
CBI and then identify electronically within the disk or CD-ROM the 
specific information that is claimed as 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. Tips for preparing your comments. When preparing and submitting 
your comments, see the commenting tips at http://www.epa.gov/dockets/comments.html.

III. Overview

A. What is the EDSP?

    The EDSP is established under FFDCA section 408(p), which requires 
EPA to develop a chemical substance screening program using appropriate 
validated test systems and other scientifically relevant information to 
determine whether certain chemical substances may have hormonal 
effects. The EDSP consists of a two-tiered approach to screen chemical 
substances for potential endocrine disrupting effects. The purpose of 
Tier 1 screening is to identify chemical substances that have the 
potential to interact with the estrogen, androgen, or thyroid hormone 
systems using a battery of assays. Chemical substances that have the 
potential to interact with the estrogen, androgen or thyroid systems 
may proceed to Tier 2 testing, which is designed to identify any 
adverse endocrine-related effects caused by the chemical substance, and 
to establish a quantitative relationship between the dose and that 
endocrine effect. Additional information about the EDSP is available at 
http://www.epa.gov/endo.
    1. Tests considered for EDSP Tier 2. In the December 1998 EDSP 
Policy Statement (Ref. 1), the Agency explained that the purpose of the 
testing stage (Tier 2) is to characterize the likelihood, nature, and 
dose-response relationship of any estrogen-, androgen-, and thyroid-
related effects caused by a chemical substance in humans or wildlife. 
At that time, EPA identified the following non-mammalian tests under 
Tier 2 of EDSP: Amphibian reproduction and developmental toxicity, 
avian reproduction, fish reproduction, and invertebrate reproduction.
    EPA followed the general validation principles of the Organization 
for Economic Co-Operation and Development (OECD) and the 
Intergovernmental Interagency Coordinating Committee on the Validation 
of Alternative Methods (ICCVAM) in the development of the four non-
mammalian Tier 2 tests. In June 2013, the FIFRA Scientific Advisory 
Panel (SAP), a Federal advisory committee chartered under the Federal 
Advisory Committee Act (5 U.S.C. Appendix), reviewed draft protocols 
and supporting data for the four non-mammalian Tier 2 tests (Ref. 2): 
Japanese quail 2-generation toxicity test; Medaka extended 1-generation 
reproduction test; Larval amphibian growth and development assay; and 
mysid 2-generation toxicity test.
    2. Status of the mysid 2-generation toxicity test. Although the 
mysid 2-generation toxicity test was generally supported by the FIFRA 
SAP, the data were not considered fully reliable across all endpoints 
and the results were not repeatable across laboratories without 
recommended improvements (Ref. 2). The FIFRA SAP and public commenters 
also stated that endpoints in the mysid 2-generation toxicity test are 
also provided to a large extent by the current mysid chronic life cycle 
test (Ref. 3), a test used effectively to assess the risk of chemical 
substances that may disrupt invertebrate growth, development, and 
reproduction, such as, insect growth regulators that disrupt 
development mediated by invertebrate hormones (Ref. 2). While concerns 
were expressed for certain aspects of the mysid 2-generation toxicity 
test, there were advancements in other features of the assay, 
particularly regarding culturing conditions and control performance.
    Based on all of these factors, the Agency intends to consider and 
potentially incorporate, as appropriate, test design features from the 
mysid 2-generation toxicity test when updating and finalizing the 
existing draft mysid chronic life cycle test guideline (Ref. 4) 
assessing development, growth, reproductive, and toxicity endpoints. 
This may include the option of extending the mysid chronic life cycle 
test to a second generation. Expansion of the mysid chronic life cycle 
test was one of the Agency's options discussed in the December 1998 
EDSP Policy Statement (Ref. 1). The existing OCSPP Test Guideline 
850.1350 is intended to meet current and future testing requirements 
for data submitted to EPA under FFDCA, FIFRA, and TSCA (Ref. 4).

B. How were the draft test guidelines developed?

    The FIFRA SAP supported the scientific rationale and purpose,

[[Page 5109]]

representative species chosen, biological and toxicological relevance 
of the major endpoints selected and measured, and the validation 
process used by EPA for all four Tier 2 non-mammalian tests (Ref. 2). 
Based on the FIFRA SAP's recommendations and public comments received, 
the EPA revised the test protocols (Ref. 3) and developed draft test 
guidelines for the following three tests: Japanese quail 2-generation 
toxicity test, Medaka extended 1-generation reproduction test, and 
Larval amphibian growth and development assay.
     The Japanese quail 2-generation reproduction test features 
a number of core apical endpoints related to survival, growth, 
reproduction and, potentially, behavior, as well as more pathway-
specific endpoints (e.g., histopathology). See draft OCSPP Test 
Guideline 890.2100, entitled ``Endocrine Disruptor Screening Program 
Test Guidelines; Avian Two-generation Toxicity Test in the Japanese 
Quail.''
     The Medaka extended 1-generation reproduction test, 
developed and evaluated primarily by scientists from the United States 
and Japan, starts with F0 adults, proceeds through the entire F1 
generation, and provides an option for an entire life cycle exposure of 
the F2 generation. The test, which features both pathway-specific 
(e.g., histopathology) and apical (e.g., growth, reproduction) 
endpoints, has been successfully evaluated using several chemical 
substances expected to have different effects on the hypothalamic-
pituitary-gonadal (HPG) axis. See draft OCSPP Test Guideline 890.2200, 
entitled ``Endocrine Disruptor Screening Program Test Guidelines; 
Medaka Extended One Generation Reproduction Test (MEOGRT).''
     The Larval amphibian growth and development assay is 
designed to assess possible risks of both HPG- and hypothalamic-
pituitary-thyroid (HPT)-active toxicants. The assay, which was also 
developed through a joint effort between the United States and Japan, 
is initiated with Nieuwkoop-Faber (NF) stage 8 embryos and proceeds 
through NF stage 62 (complete metamorphosis). The amphibian test 
considers a variety of both apical and more pathway-specific endpoints. 
See draft OCSPP Test Guideline 890.2300, entitled ``Endocrine Disruptor 
Screening Program Test Guidelines; Larval Amphibian Growth and 
Development Assay (LAGDA).''

IV. 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 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 
persons listed under FOR FURTHER INFORMATION CONTACT.
1. EPA. Endocrine Disruptor Screening Program; Proposed Statement of 
Policy; Notice. Federal Register (63 FR 71542, December 28, 1998) (FRL-
6052-9).
2. FIFRA SAP. SAP Minutes No. 2013-04. A Set of Scientific Issues Being 
Considered by the Environmental Protection Agency Regarding: Proposed 
Endocrine Disruptor Screening Program (EDSP) Tier 2 Ecotoxicity Tests, 
June 25-28, 2013. 2013. Docket ID No. EPA-HQ-OPP-2013-0182-0084.
3. EPA. Summary of EPA's Responses to Recommendations of the June 25-
28, 2013 FIFRA SAP Regarding Proposed EDSP Tier 2 Non-Mammalian Tests. 
2014.
4. EPA. OCSPP Harmonized Ecological Effects Test Guideline 850.1350 
(Public Draft): Mysid Chronic Toxicity Test, April 1996. EPA 712-C-96-
166. 1996. Docket ID No. EPA-HQ-OPPT-2009-0154.

    Authority: 7 U.S.C. 136 et seq.; 15 U.S.C. 2601 et seq.; 21 
U.S.C. 346a.

    Dated: December 23, 2014.
Louise P. Wise,
Acting Assistant Administrator, Office of Chemical Safety and Pollution 
Prevention.
[FR Doc. 2015-01836 Filed 1-29-15; 8:45 am]
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