Document ID: EPA-HQ-OPPT-2007-0493-0001
Agency: epa
Document Type: Notice
Title: Endocrine Disruptor Screening Program; Assay Peer Review Process
Posted Date: 2007-07-13T04:00Z

[Federal Register: July 13, 2007 (Volume 72, Number 134)]
[Notices]               
[Page 38577-38580]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr13jy07-68]                         

-----------------------------------------------------------------------

ENVIRONMENTAL PROTECTION AGENCY

[EPA-HQ-OPPT-2007-0493; FRL-8138-4]

 
Endocrine Disruptor Screening Program; Assay Peer Review Process

AGENCY:  Environmental Protection Agency (EPA).

ACTION:  Notice.

-----------------------------------------------------------------------

SUMMARY: The purpose of this notice is to announce the approach EPA 
intends to take for conducting peer reviews of the Tier 1 screening 
assays and Tier 2 testing assays that are being validated by the 
Agency's Endocrine Disruptor Screening Program (EDSP), as well as EPA's 
approach for conducting the peer review of the Tier 1 battery. EPA is 
also announcing the availability of a listserver (Listserv) that will 
allow interested parties to sign up to receive e-mail notifications of 
EDSP peer review updates, including information on the availability of 
peer review materials to be posted on the EDSP website. These materials 
may include the documents to be peer reviewed, background documents, 
the charge to the peer reviewers, and reports that summarize the 
results of peer reviews.

FOR FURTHER INFORMATION CONTACT:  Linda Phillips, Office of Science 
Coordination and Policy (7203M), Environmental Protection Agency, 1200 
Pennsylvania Ave., NW., Washington, DC 20460-0001; telephone number: 
(202) 564-1264; e-mail address: phillips.linda@epa.gov.

SUPPLEMENTARY INFORMATION:

I. General Information

A. Does this Action Apply to Me?

    This action is directed to the public in general. You may be 
potentially affected by this action if you produce, manufacture, use, 
consume, work with, or import commercial or pesticide chemicals. To 
determine whether you or your business may be affected by this action, 
you should carefully examine section 408(p) of FFDCA, 21 U.S.C. 
346a(p). Potentially affected entities, using the North American 
Industrial Classification System (NAICS) codes to assist you and others 
in determining whether this action might apply to certain entities, may 
include, but are not limited to:
     Chemical Manufacturers, Importers and Processors (NAICS 
code 325), e.g., entities who manufacture, import or process chemical 
substances.
     Pesticide, Fertilizer, and Other Agricultural Chemical 
Manufacturing (NAICS code 3253), e.g., entities who manufacture, import 
or process pesticide, fertilizer and agricultural chemicals.
     Scientific Research and Development Services (NAICS code 
5417), e.g., persons who conduct testing of chemical substances for 
endocrine affects.
    This listing is not intended to be exhaustive, but rather provides 
a guide for readers regarding entities likely to be affected by this 
action. Other types of entities not listed in this unit could also be 
affected. If you have any questions regarding the applicability of this 
action to a particular entity, consult the person listed under FOR 
FURTHER INFORMATION CONTACT.

B. How Can I Get Copies of this Document and Other Related Information?

    1. Docket. Materials cited in this notice are available in docket 
number EPA-HQ-OPPT-2007-0493. All documents in the docket are listed in 
the regulations.gov index. To access the electronic docket, go to 
http://www.regulations.gov, select ``Advanced Search,'' then ``Docket 

Search.'' Insert the docket ID number where indicated and select the 
``Submit'' button. Follow the instructions on the regulations.gov 
website to view the docket index or access available documents. 
Although listed in the index, some information is not publicly 
available, e.g., Confidential Business Information (CBI) or other 
information whose disclosure is restricted by statute. Certain other 
material, such as copyrighted material, will be publicly available only 
in hard copy. Publicly available docket materials are available 
electronically athttp://www.regulations.gov, or, if only available in 

hard copy, at the OPPT Docket. The OPPT Docket is located in the EPA 
Docket Center (EPA/DC) at Rm. 3334, EPA West Bldg., 1301 Constitution 
Ave., NW., Washington, DC. The EPA/DC Public Reading Room hours of 
operation are 8:30 a.m. to 4:30 p.m., Monday through Friday, excluding 
Federal holidays. The telephone number of the EPA/DC Public Reading 
Room is (202) 566-1744, and the telephone number for the OPPT Docket is 
(202) 566-0280. Docket visitors are required to show photographic 
identification, pass through a metal detector, and sign the EPA visitor 
log. All visitor bags are processed through an X-ray machine and 
subject to search. Visitors will be provided an EPA/DC badge that must 
be visible at all times in the building and returned upon departure.
    2. Electronic access. You may access thisFederal Register document 
electronically through the EPA Internet

[[Page 38578]]

under the ``Federal Register'' listings athttp://www.epa.gov/fedrgstr/.

II. Introduction

A. What Action is the Agency Taking?

    EPA is announcing its approach for conducting peer reviews of Tier 
1 screening assays and Tier 2 testing assays that are being validated 
by the Agency's Endocrine Disruptor Screening Program (EDSP), as well 
as its approach for conducting the peer review of the Tier 1 battery. 
EPA is also announcing the availability of a listserver (Listserv). To 
subscribe to the EDSP Listserv send a blank e-mail message to: 
join-edsp@lists.epa.gov from the location at which you normally send or 

receive mail. For more information on the listserv, go tohttp://www.epa.gov/scipoly/oscpendo.
 Using the Listserv, interested parties 

may sign up to receive e-mail notifications of EDSP peer review 
updates, including information on the availability of peer review 
materials to be posted at the EDSP website. These materials may include 
the documents to be peer reviewed, background documents, the charge to 
the peer reviewers, and reports that summarize the results of peer 
reviews. EPA is not at this time soliciting public comment on the 
individual Tier 1 assays. Rather, EPA will solicit comments on the Tier 
1 battery once the individual peer reviews have been completed as 
discussed in Unit IV.D.

B. What is the Agency's Authority for Taking this Action?

    Section 408(p) of FFDCA 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 
effect as [EPA] may designate.'' (FFDCA 21 U.S.C. 346a(p)). These test 
systems are being validated under EPA's EDSP. EPA's validation process 
includes peer review as its final step.

III. Background

    EPA initially set forth the EDSP in the August 11, 1998, Federal 
Register notice (63 FR 42852) (FRL-6021-3) and solicited public comment 
on the program in the December 28, 1998, Federal Register notice (63 FR 
71541) (FRL-6052-9). The program set forth in these notices was based 
on the recommendations of the Endocrine Disruptor Screening and Testing 
Advisory Committee (EDSTAC), which was chartered under the Federal 
Advisory Committee Act (FACA), 5 U.S.C. App. 2, section 9(c). The 
EDSTAC was comprised of members representing the commercial chemical 
and pesticides industries, Federal and State agencies, worker 
protection and labor organizations, environmental and public health 
groups, and research scientists.
    EDSTAC recommended that EPA's program address both potential human 
and ecological effects; examine effects on estrogen, androgen, and 
thyroid hormone-related processes; and include non-pesticide chemicals, 
contaminants, and mixtures in addition to pesticides (Ref. 1). Based on 
these recommendations, EPA developed a two tiered approach, referred to 
as the EDSP. The purpose of Tier 1 is to identify substances that have 
the potential to interact with the estrogen, androgen, or thyroid 
hormone systems using a battery of relatively short-term screening 
assays. The purpose of Tier 2 is to identify and establish a dose-
response relationship for any adverse effects that might result from 
the interactions identified through the Tier 1 assays. The Tier 2 tests 
are multi-generational assays that will provide the Agency with more 
definitive testing data. EDSTAC also recommended that EPA establish a 
priority-setting approach for choosing chemicals to undergo Tier 1 
screening.
    EPA currently is implementing its EDSP in three major parts that 
are being developed in parallel and with substantial work on each well 
underway. This document deals only with the peer review component of 
the validation process (item 3 in the following discussion). EPA is 
addressing the other aspects of the EDSP in separate documents 
published in the Federal Register. The three parts are briefly 
summarized as follows:
    1. Priority setting. EPA is prioritizing chemicals to undergo 
screening in the battery of Tier 1 assays. EPA described its priority 
setting approach for the first 50-100 chemicals to be tested in the 
Federal Register of September 27, 2005 (70 FR 56449) (FRL-7716-9). The 
draft initial list of chemicals to undergo Tier 1 screening was 
published in the Federal Register for public review on June 18, 2007 
(72 FR 33486) (FRL-8129-3). The Agency expects to finalize this initial 
list of chemicals before screening is implemented in 2008. More 
information on EPA's priority setting approach for the EDSP is 
available at http://www.epa.gov/scipoly/oscpendo/prioritysetting.

    2. Procedures. EPA intends to commence Tier 1 screening of the 
first group of pesticide chemicals by issuing test orders under FFDCA 
section 408(p) to chemical companies identified as the manufacturer or 
processor of the identified chemicals, including the pesticide 
registrant. EPA is developing a draft implementation policy that will 
describe the procedures that EPA will use to issue orders, the 
procedures that order recipients would use to respond to the order, how 
data protection and compensation will be addressed in the test orders, 
and other related procedures or policies. In addition, EPA is 
developing a draft template for the test order and a draft information 
collection request (ICR) to obtain the necessary clearances under the 
Paperwork Reduction Act (PRA). The Agency expects to seek public 
comment on the draft implementation policy and related documents in 
late summer 2007, and after considering those comments, EPA expects to 
finalize the policy by the end of 2007.
    3. Assay validation. EPA is validating assays that are candidates 
for inclusion in the Tier 1 screening battery, selecting the 
appropriate screening assays for the screening battery based on the 
validation data, and developing and validating Tier 2 tests. Validation 
is defined as the process by which the reliability and relevance of 
test methods are evaluated for a specific use (Ref. 2). EPA has 
implemented the validation process in several phases (Ref. 3), 
including the following:
     Preparation of detailed review papers (DRPs) that involve 
a search of the relevant scientific literature and development of a 
document that discusses the scientific basis of each assay and 
critically evaluates candidate protocols.
     Conduct of pre-validation studies that demonstrate and 
optimize the assay, with the end result being a standardized protocol 
for use in the multi-laboratory validation phase.
     Conduct of validation studies in multiple laboratories. 
The purpose of this phase is to demonstrate the transferability of the 
protocol, measure lab-to-lab variability, and help establish final 
performance characteristics for the assay.
     Peer review of the data to determine strengths and 
weaknesses of the assays. Peer review is the critical evaluation of 
scientific and technical work products by independent experts. Its 
purpose is to improve the quality, credibility, and acceptability of 
regulatory decisions. According to EPA's Peer Review Handbook (Ref. 4), 
peer review is an important component of the scientific process. It 
provides a focused, objective evaluation of a research proposal, 
publication, risk assessment, health advisory, guidance

[[Page 38579]]

or other document submitted for review. The criticisms, suggestions and 
new ideas provided by the peer reviewers ensure objectivity, stimulate 
creative thought, strengthen the reviewed document and confer 
scientific credibility on the product. Comprehensive, objective peer 
review leads to good science and product acceptance within the 
scientific community.
    EPA plans to peer review the following EDSP work products:

------------------------------------------------------------------------
                                     Tier 1 Assay
          Tier 1 Assays                 Battery          Tier 2 Assays
------------------------------------------------------------------------
Adult Male                        Battery To be       Amphibian Growth
Androgen Receptor Binding.......   Determined          and Reproduction
Aromatase.......................                      Two-generation
Estrogen Receptor Binding.......                       Avian
Female Pubertal.................                      Two-generation
Fish Screen.....................                       Fish
Frog Metamorphosis..............                      Two-generation
Hershberger\1\..................                       Mysid
Male Pubertal...................
Steroidogenesis H295R...........
Uterotrophic\2\.................
------------------------------------------------------------------------
\1\The Hershberger assay has been peer reviewed by the Organization for
  Economic Cooperation and Development (OECD). EPA will not conduct a
  separate peer review of this assay.
\2\The Uterotrophic assay has been peer reviewed by OECD. EPA will not
  conduct a separate peer review of this assay.

    The primary product to be peer reviewed for each assay will be an 
Integrated Summary Report (ISR) that summarizes and synthesizes the 
information compiled from the validation process (i.e., DRPs, pre-
validation studies, and inter-lab validation studies, with a major 
focus on inter-laboratory validation results).

IV. Peer Review Process

     The approaches that EPA intends to use for conducting peer reviews 
of the Tier 1 and Tier 2 assays, and the Tier 1 battery are described 
in the following sections.

A. Tier 1 Assays

    The mechanism that will be used to peer review Tier 1 Assays will 
be an external letter review organized under an EPA peer review 
contract. The procedures used for peer review of the Tier 1 assays will 
be in accordance with EPA's Peer Review Handbook (Ref. 4). For each 
assay, the contractor will compile a list of qualified peer review 
candidates who are independent of those who performed the work or who 
have been involved in the development or refinement of the protocol, 
including those who have provided EPA with expert advice throughout the 
validation process. The potential peer reviewers will be identified 
from among academia, government, and the private sector, based on their 
subject matter expertise, availability, and lack of conflict of 
interest or past involvement in the project. From this pool of 
candidate reviewers, the contractor will establish a balanced peer 
review panel consisting of 3 to 10 peer reviewers. EPA will be notified 
of the identity of the peer reviewers, but will not have contact with 
them before or during the peer review process to ensure that an 
independent review is performed. The contractor will provide the 
reviewers with the ISR for the assay to be reviewed and any supporting 
documentation that is needed for the peer review, along with a list of 
charge questions that will be developed by EPA. The ISR will summarize 
and synthesize the information compiled from the validation process 
(i.e., DRPs, pre-validation studies, and inter-lab validation studies), 
with a major focus on inter-laboratory validation results. The charge 
to the reviewers will be designed to address the following types of 
issues:
    1. Clarity of the stated purpose of the assay.
    2. Clarity, comprehensiveness, and consistency of the data 
interpretation with the stated purpose of the assay.
    3. Biological and toxicological relevance of the assay as related 
to its stated purpose.
    4. Clarity and conciseness of the protocol in describing the 
methodology of the assay such that the laboratory can:
    a. Comprehend the objective;
    b. Conduct the assay;
    c. Observe and measure prescribed endpoints;
    d. Compile and prepare data for statistical analyses; and
    e. Report the results.
    5. Strengths and/or limitations of the assay.
    6. Impacts of the choice of:
    a. Test substances,
    b. Analytical methods, and
    c. Statistical methods in terms of demonstrating the performance of 
the assay.
    7. Repeatability and reproducibility of the results obtained with 
the assay, considering the variability inherent in biological and 
chemical test methods.
     The panel will review and comment on the assay, and the contractor 
will compile the peer review record. The peer review record will 
include the peer review document and all supporting materials given to 
the peer reviewers; the instructions/charge to the peer reviewers; all 
comments, information, and materials received from the peer reviewers; 
and names, affiliations, qualifications of the peer review panel 
members. EPA will use the peer review record to make a final 
determination as to a Tier 1 assay's suitability for use in the 
screening program, and finalize the assay for consideration for 
inclusion in the Tier 1 battery. EPA plans to begin peer reviewing Tier 
1 assays by mid-2007. This schedule is dependent upon the successful 
completion of studies that are currently underway.

B. Tier 1 Battery

    As recommended by the Endocrine Disruptor Screening and Testing 
Advisory Committee (EDSTAC), EPA's EDSP testing strategy will consist 
of a battery of Tier I assays. The battery is expected to be comprised 
of screening assays that, when used in combination, will identify 
substances that have the potential to interact with the estrogen, 
androgen, and thyroid hormone systems.
    Prior to initiating testing, EPA intends to propose a battery of 
Tier 1 screening assays. The battery will be peer reviewed by the 
Scientific Advisory Panel (SAP) established under the Federal 
Insecticide, Fungicide, and

[[Page 38580]]

Rodenticide Act (FIFRA). The FIFRA SAP is structured to provide 
scientific advice, information and recommendations to EPA on pesticides 
and pesticide-related issues as to the impact of regulatory actions on 
health and the environment. The FIFRA SAP is a Federal advisory 
committee established in 1975 under FIFRA that operates in accordance 
with requirements of the FACA. The FIFRA SAP is composed of a permanent 
panel consisting of seven members who are appointed by the EPA 
Administrator from nominees provided by the National Institutes of 
Health and the National Science Foundation. In addition, FIFRA, as 
amended by the FQPA of 1996, established a Science Review Board 
consisting of at least 60 scientists who are available to the FIFRA SAP 
on an ad hoc basis to assist in reviews conducted by the Panel. As a 
peer review mechanism, the FIFRA SAP provides comments, evaluations and 
recommendations to improve the effectiveness and quality of analyses 
made by Agency scientists. Members of the FIFRA SAP are scientists who 
have sufficient professional qualifications, including training and 
experience, to provide expert advice and recommendation to the Agency. 
More information about the FIFRA SAP is available at http://www.epa.gov/scipoly/sap
.

    The proposed battery along with the materials supporting its 
composition will be provided to a panel of approximately 15 to 20 SAP 
reviewers. Some of the panel members may be individuals who 
participated in review of one or more Tier 1 assays, and some 
individuals will be new to the EDSP peer review process. Use of some of 
the same reviewers for both the Tier 1 assays and the Tier 1 battery is 
intended to ensure that individuals familiar with the individual assays 
are represented when the battery is discussed. This should not present 
a conflict of interest because the context of the review and the 
questions being asked of the battery reviewers will differ from what is 
asked of the reviewers for the individual Tier 1 assays (e.g., 
questions posed to the SAP reviewers would pertain to whether the 
proposed battery adequately covers the endpoints of interest for 
estrogen, androgen, and thyroid while questions posed to the Tier 1 
assay reviewers would focus on the strengths and weaknesses of 
individual assays.

C. Tier 2 Assays

    The peer review strategy for the Tier 2 assays will follow a 
pattern similar to that used for Tier 1 battery. These assays will be 
peer reviewed by the FIFRA SAP.

D. Public Comment

    The formal peer review process described above is intended to 
ensure a systematic and unbiased review of the scientific basis for 
including an assay in the EDSP. Although the Agency recognizes that 
other qualified scientists may also wish to offer opinions to the 
Agency on the merits of the assays, EPA is not soliciting public 
comments during the period in which the individual Tier 1 assays are 
being peer reviewed. Instead, the Agency will accept comments on the 
overall Tier 1 battery from the public when the composition of the Tier 
1 battery is being peer reviewed by the SAP. A separateFederal Register 
notice will announce the SAP review of the Tier 1 battery and provide 
information on opportunities for public comment.

V. Listserv

    The EDSP has created a listserver (Listserv) or ``mailing group.'' 
A Listserv is an electronic mailing list that makes it possible to 
reach all individuals in a mailing group with a single e-mail message 
sent over the Internet. By adding your name to the EDSP Listserv, you 
will periodically receive an e-mail announcing the availability of 
materials on the EDSP website and other timely information. To 
subscribe to the EDSP Listserv send a blank e-mail message to: 
join-edsp@lists.epa.gov from the location at which you normally send or 

receive mail.

VI. References

    The following is a list of the documents that are specifically 
referenced in this document. These references are available in the 
docket as identified under ADDRESSES.
    1. U.S. EPA. Endocrine Disruptor Screening and Testing Advisory 
Committee Final Report. August 1998. Available at:http://www.epa.gov/scipoly/oscpendo/edspoverview/finalrpt.htm
.

    2. National Institute of Environmental Health Sciences (NIEHS). 
Validation and Regulatory Acceptance of Toxicological Test Methods, A 
Report of the ad hoc Interagency Coordinating Committee on the 
Validation of Alternative Methods. Research Triangle Park, NC. NIH 
Report 97-3981. March 1997.
    3. U.S. EPA. Validation of Screening and Testing Assays Proposed 
for the EDSP, Draft Version 5.3. October 23, 2006. Available at:http://www.epa.gov/scipoly/sap/meetings/2007/february/edsp-validation-paper.pdf
.

    4. U.S. EPA. Science Policy Council Handbook: Peer Review, 3rd 
Edition. Office of Science Policy, U.S. Environmental Protection 
Agency, Washington, DC. EPA/100/B-06/002. Available at: http://www.nheerl.epa.gov/nheerl_science/peer/about_peer/files/3rd_Edition_PR_Handbook.pdf
.

List of Subjects

    Environmental protection, Chemicals, Endocrine disruptors, 
Pesticides.

    Dated: July 2, 2007.
James B. Gulliford,
Assistant Administrator for Prevention, Pesticides and Toxic 
Substances.
[FR Doc. E7-13672 Filed 7-12-07; 8:45 am]

BILLING CODE 6560-50-S