[Federal Register Volume 66, Number 88 (Monday, May 7, 2001)]
[Notices]
[Pages 23022-23027]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 01-11412]


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ENVIRONMENTAL PROTECTION AGENCY

[OPPTS-42212C; FRL-6778-2]


Endocrine Disruptor Screening Program; Establishment of an 
Endocrine Disruptor Methods Validation Subcommittee under the National 
Advisory Council for Environmental Policy and Technology; Request for 
Nominations for Membership

AGENCY:  Environmental Protection Agency (EPA).

ACTIONS:  Notice; request for nominations for membership.

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SUMMARY:  As mandated by the Federal Food, Drug, and Cosmetic Act, as 
amended by the Food Quality Protection Act of 1996, EPA is implementing 
an Endocrine Disruptor Screening Program (EDSP). This notice proposes 
the establishment of an Endocrine Disruptor Methods Validation 
Subcommittee (EDMVS) as a Subcommittee under the National Advisory 
Council for Environmental Policy and Technology (NACEPT), and requests 
nominations for members of the EDMVS from interested organizations. 
NACEPT is a chartered federal advisory committee subject to the 
provisions of the Federal Advisory Committee Act. Through NACEPT, the 
EDMVS will provide technical advice an recommendations to EPA regarding 
validation of the Tier 1 Screening and Tier 2 Testing methods for its 
Endocrine Disruptor Screening Program (EDSP). Background information 
regarding the Agency's Endocrine Disruptor Screening Program (EDSP) and 
the mission of the EDMVS are discussed in Unit IV. of SUPPLEMENTARY 
INFORMATION. This information is being provided to allow interested 
organizations to review the scope of proposed activities to nominate 
qualified individuals for membership on the EDMVS.

DATES:  Nominations must be received on or before June 6, 2001.

ADDRESSES:  Nominations for membership may be submitted by mail, 
electronically, or in person. Please follow the detailed instructions 
for each method as provided in Unit III. of the SUPPLEMENTARY 
INFORMATION. To ensure proper receipt by EPA, your request must 
identify docket control number OPPTS-42212C in the subject line on the 
first page of your response.

FOR FURTHER INFORMATION CONTACT:  For general information contact: TSCA 
Hotline, Environmental Assistance Division (7408), Office of Pollution 
Prevention and Toxics, Environmental Protection Agency, 401 M St., SW., 
Washington, DC 20460. Telephone: 202-554-1404; TDD: 202-554-0551; e-
mail: <a href="/cdn-cgi/l/email-protection#c195928280ec89aeb5ada8afa481a4b1a0efa6aeb7"><span class="__cf_email__" data-cfemail="297d7a6a680461465d4540474c694c5948074e465f">[email protected]</span></a>.
    For technical information contact: Anthony Maciorowski, Senior 
Technical Advisor, Office of Prevention, Pesticides and Toxic 
Substances; telephone: 202-260-3048; e-mail address: 
<a href="/cdn-cgi/l/email-protection#6b060a08020419041c180002450a051f030405122b0e1b0a450c041d"><span class="__cf_email__" data-cfemail="610c0002080e130e16120a084f000f15090e0f18210411004f060e17">[email protected]</span></a> or
    Gary Timm, Senior Technical Advisor, Office of Prevention, 
Pesticides and Toxic Substances; telephone: 202-260-1859; e-mail 
address: <a href="/cdn-cgi/l/email-protection#3e4a57535310595f4c477e5b4e5f10595148"><span class="__cf_email__" data-cfemail="d6a2bfbbbbf8b1b7a4af96b3a6b7f8b1b9a0">[email protected]</span></a>.

SUPPLEMENTARY INFORMATION:

I. Does This Notice Apply to Me?

    This action is directed to the public in general. You may be 
interested in nominating members to the subcommittee set forth in this 
notice if you produce, manufacture, use, consume, work with, or import 
pesticide chemicals, substances that may have an effect cumulative to 
an effect of a pesticide, or substances found in sources of drinking 
water. To determine whether you or your business may have an interest 
in this notice you should carefully examine section 408(p) of the 
Federal Food, Drug, and Cosmetic Act (FFDCA), as amended by the Food 
Quality Protection Act (FQPA) of 1996 (Public Law 104-170), 21 U.S.C. 
346a(p) and amendments to the Safe Drinking Water Act (SDWA) (Public 
Law 104-182), 42 U.S.C. 300j-17. Since other entities may also 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 
regarding the applicability of this action to a particular entity, 
consult the technical persons listed under FOR FURTHER INFORMATION 
CONTACT.

II. How Can I Get Additional Information, Including Copies of This 
Document or Other Related Documents?

    1. Electronically. You may obtain electronic copies of this 
document, and certain other related documents that might be available 
electronically, from the EPA Internet Home Page at http://www.epa.gov/scipoly. To access this document, on the Home Page select ``Endocrine 
Disruptors'' which will take you to the OSCP Endocrine Disruptor 
Screening Program web site.
    2. In person. The Agency has established an administrative record 
for the EDMVS under docket control number OPPTS-42212C. The 
administrative record consists of the documents specifically referenced 
in this notice, any public comments received during an applicable 
comment period, and other information related to the Endocrine 
Disruptor Methods Validation Subcommittee Organizational Meeting. This 
administrative record includes the documents that are physically 
located in the docket, as well as the documents that are referenced in 
those documents. The public version of the administrative record, which 
includes printed, paper versions of any electronic comments that may be 
submitted during an applicable comment period, is available for 
inspection in the TSCA Nonconfidential Information Center, North East 
Mall Rm. B-607, Waterside Mall, 401 M St., SW., Washington, DC. The 
Center is open from noon to 4 p.m., Monday through Friday, excluding 
legal holidays. The telephone number of the Center is (202) 260-7099.

[[Page 23023]]

III. How Can I Nominate Potential Members to the Endocrine 
Disruptor Methods Validation Subcommittee?

    You may nominate technically qualified persons for membership to 
the Endocrine Disruptor Methods Validation Subcommittee through the 
mail, in person, or electronically. Nominations for membership should 
be submitted by the nominating organization, and must include a 
curriculum vitae of the nominee detailing his or her specific area of 
relevant scientific expertise. Members of the EDMVS will be selected on 
the basis of their relevant scientific expertise and diversity of 
perspectives on mammalian, ecological, and in vitro endocrine disruptor 
screening and testing methods and procedures, toxicity test methods 
standardization and validation, and chemical and pesticide regulatory 
processes. Members will be appointed for 2 years. Subcommittee members 
shall be appointed with balanced representation from among the 
following sectors: the agrichemical and commodity chemical industries; 
environmental/public interest organizations; public health 
organizations; animal welfare organizations; Federal agencies; State, 
local and tribal governments; academia; consumers, and the public. Your 
nomination must be received by EPA on or before June 6, 2001. To ensure 
proper receipt by EPA, it is imperative that you identify docket 
control number OPPTS-42212C in the subject line on the first page of 
your request.
    1. By mail. You may submit a written nomination to: Document 
Control Office (7407), Office of Pollution Prevention and Toxics 
(OPPT), Environmental Protection Agency, 1200 Pennsylvania Ave., NW., 
Washington, DC 20460.
    2. In person or by courier. You may deliver a written nomination 
to: OPPT Document Control Office (DCO) in the East Tower Rm. G-099, 
Waterside Mall, 401 M St., SW., Washington, DC. The DCO is open from 8 
a.m. to 4 p.m., Monday through Friday, excluding legal holidays. The 
telephone number for the DCO is (202) 260-7093.
    3. Electronically. You may submit your nomination electronically by 
e-mail to: <a href="/cdn-cgi/l/email-protection#345b4444401a5a575d57745144551a535b42"><span class="__cf_email__" data-cfemail="452a3535316b2b262c26052035246b222a33">[email protected]</span></a>. Use Wordperfect 6.1/8.0 or ASCII file 
format and avoid the use of special characters and any form of 
encryption. All comments in electronic form must be identified by 
docket control number OPPTS-42212C.

IV. Background

A. Authorities

    Two laws enacted in 1996 authorize the Agency to screen pesticides 
and other chemicals found in food or in drinking water sources to 
determine whether they may cause estrogenic or other endocrine effects 
in humans. The impetus for development of EPA's Endocrine Disruptor 
Screening Program was an amendment to FFDCA, contained in the FQPA of 
1996 (Public Law 104-170). The FFDCA (21 U.S.C. 346a(p) as amended 
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 the Administrator may designate.

21 U.S.C. 346a(p)(3), also states that in carrying out its screening 
program, EPA

    (A) shall provide for the testing of all pesticide chemicals and 
(B) 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.

    Additionally, Congress amended the SDWA (42 U.S.C. 300j-17) 
authorizing EPA to provide for the testing under the screening program 
authorized in the FFDCA

    . . .of any other substance that may be found in sources of 
drinking water if the Administrator determines that a substantial 
population may be exposed to such substance. (42 U.S.C. 300j-17).

Through the amended FFDCA, Congress directed EPA to develop an 
endocrine disruptor screening program using appropriate validated test 
systems and other scientifically relevant information by August 3, 
1998, implement the program by August 3, 1999, and report progress to 
Congress by August 3, 2000.
    EPA may rely upon FIFRA and TCSA testing authority. Under FIFRA 
section 3(c)(2)(B), if EPA determines that additional data are required 
to maintain in effect an existing pesticide registration, it can 
require pesticide registrants to provide EPA with additional data in 
support of the registrant. Likewise, TSCA section 4 provides EPA 
authority to require testing of certain industrial chemicals.

B. Development of EPA's Endocrine Disruptor Screening Program

    Prior to the passage of the FQPA and SDWA, the Agency initiated 
several endocrine disruptors investigations including: the development 
of a special report and effects assessment (Ref. 6); a series of 
endocrine disruptor methods workshops funded by the World Wildlife 
Fund, Chemical Manufacturer's Association, and the Agency (Refs. 1, 3, 
and 7); and co-sponsorship (with the National Institute of 
Environmental Health Sciences and Department of the Interior) of an 
independent critical analysis of the literature on hormonally active 
agents in the environment by the National Academy of Sciences (Ref. 5). 
The foregoing activities coincided with the establishment and 
deliberationsof the Endocrine Disruptor Screening and Testing Advisory 
Committee (Ref. 2).
    The complexity of the scientific and regulatory issues surrounding 
the endocrine disruptor issue led EPA to seek broad expert advice and 
counsel beyond the Agency. EPA held a public meeting in May of 1996 
requesting advice on how to develop a scientifically defensible, 
pragmatic approach to endocrine disruptor screening and testing. The 
stakeholder feedback indicated that a broad based multi-sector 
stakeholder committee should be established under the Federal Advisory 
Committee Act. Following a second public meeting and analysis of 
stakeholder interests (Keystone Center Convening Report, see 
www.epa.gov/scipoly/oscpendo), the Agency chartered the Endocrine 
Disruptor Screening and Testing Advisory Committee (EDSTAC).
    EDSTAC was charged with providing advice and recommendations to the 
Agency regarding a strategy for testing chemical substances to 
determine whether they may have an effect in humans similar to an 
effect produced by naturally occurring hormones. EDSTAC consisted of 39 
representatives from industry, environmental and public health advocacy 
groups, state government, other Federal agencies, and academic 
scientists. Over a 2-year period, EDSTAC held eight meetings. To 
facilitate regional public comment on the process, the meetings were 
held in different parts of the country (Chicago, San Francisco, New 
York, Houston, Orlando, Baltimore and Washington) and provided 
opportunities for public comment. In its final report, EDSTAC (Ref. 2, 
available at www.epa.gov/scipoly/oscpendo) provided 71 consensus 
recommendations regarding an endocrine disruptor screening program. 
Considering the EDSTAC's diverse membership, EPA found its consensus 
recommendations compelling and scientifically rigorous. Therefore, EPA 
closely followed EDSTAC's advice and recommendations in developing its 
Endocrine Disruptor Screening Program (EDSP).

[[Page 23024]]

    EPA's EDSP is outlined in the August 11, 1998 Federal Register (63 
FR 42852) (FRL-6021-3), and further developed as a proposed statement 
of policy in the December 28, 1998 Federal Register (63 FR 71542) (FRL-
6052-9), available at www.epa.gov/fedrgstr/EPA-TOX/1998/December/Day-28/t34298.htm). The EDSP proposed statement of policy, including public 
comments, was subsequently reviewed by a joint panel of the FIFRA 
Scientific Advisory Panel (SAP) and the EPA Science Advisory Board 
(SAB) in May 1999. Like Gray et al. (Ref. 3), EDSTAC (Ref. 2) and the 
NRC (Ref. 5), the SAP/SAB (Ref. 8) final report concluded that a tiered 
approach relying on a combination of in vivo and in vitro screens for 
Tier 1 and a set of in vivo Tier 2 tests was scientifically reasonable. 
This conclusion was based upon each group's assessment of the current 
state-of-the-science on the evaluation of agents impacting the 
endocrine system. Another consistent conclusion was the need to 
validate the individual screens and tests in EDSP. The validation and 
peer review are science-based process steps, which are prerequisite to 
the final development and approval of test guidelines for regulatory 
use (Ref. 4).
    EPA also received public comments on the proposed statement of 
policy which were considered by the SAP/SAB joint panel review. The 
Agency will respond to these public comments in a future Federal 
Register notice and final statement of policy prior to requiring 
regulatory testing.

C. Implementation of EPA's Endocrine Disruptor Screening Program

    EPA's ongoing implementation of Endocrine Disruptor Screening 
Program (EDSP) is science-driven, and based on the recommendations and 
comments of EDSTAC (Ref. 2), the FIFRA SAP/SAB Joint Panel (Ref. 8), 
and the NAS (Ref. 5). In keeping with its FFDCA-mandated deadline, the 
Agency forwarded a Report to Congress in August 2000, providing the 
Agency's progress on implementation of the EDSP. The above referenced 
Federal Register Notices, SAB/SAP report, Endocrine Disruptor Screening 
Program Report to Congress, and other EPA EDSP-related information are 
available at www.epa.gov/scipoly/oscpendo. The Agency's Implementation 
is currently proceeding on two fronts. EPA is completing development of 
the Endocrine Disruptor Priority Setting Database and the compartment-
based approach that the Agency will use to establish priorities for 
screening chemicals at a later stage of implementation. EPA has also 
initiated prevalidation and validation studies on some of the of Tier 1 
and Tier 2 assays that are likely to be part of the EDSP. The Endocrine 
Disruptor Methods Validation Subcommittee will provide advice and 
comment on both the ongoing and new studies necessary to validate the 
EDSP assays.
    1. Priority setting. Priority setting processes will not be 
included in the mission statement to the EDMVS, but EPA's ongoing 
activities are briefly summarized here for background information 
purposes. As many as 87,000 chemicals may be sorted into categories for 
priority setting. However, EPA anticipates that tens of thousands of 
chemicals will be exempted from screening. Priority setting tools and 
processes are being developed by EPA, its contractors and cooperators. 
Until the Agency completely finalizes its priority setting tools and 
process, accurate estimates of how many chemicals may actually be 
candidates for screening remain premature. Yet, EPA expects that 10% or 
less of the universe of chemicals will undergo actual screening.
    Public review and comment during development of the EDSP priority 
setting process has been provided through two public workshops held in 
January 1999 and June 2000 (Federal Register notices and workshop 
reports are available at www.epa.gov/scipoly/oscpendo). The priority 
setting approach is based on development and application of a 
relational database titledThe Endocrine Disruptor Priority Setting 
Database (EDPSD). The EDPSD consolidates existing information and data 
on exposure and effects to rank chemicals. The chemicals are ranked 
within compartments. A number of compartments may be configured on the 
basis of exposure and effects characteristics, separately or in 
combination. The current version of the EDPSD may be examined at http://www.ergweb.com/endocrine.
    Recognizing that little relevant effects information for endocrine 
disruption exists for the vast majority of chemicals, the Agency is 
considering approaches for providing additional information to assist 
priority setting. Initially, high throughput pre-screening (HTPS) 
technology was viewed as an approach to provide information on the 
ability of a chemical to bind with hormone receptors, thereby improving 
the assignment of a high screening priority for endocrine active 
chemicals. An HTPS feasibility study was completed by the Agency in 
1999. Following external scientific peer review by the FIFRA SAP/EPA 
SAB Joint Panel (Ref. 8), the HTPS reporter gene methods used in the 
feasibility study were deemed unreliable for routine regulatory use. 
Presently, EPA is not conducting any Agency-sponsored studies on HTPS. 
The Agency is continuing discussions with the Japanese Government on 
the development of a different reporter gene based HTPS system. 
However, the Japanese studies remain ongoing, and must await completion 
and scientific evaluation before being further considered.
    EPA has also engaged in the development of QSAR models to predict 
endocrine receptor binding activity from the molecular structure of 
chemicals. The Agency is presently working with the Food and Drug 
Administration to refine and validate two-dimensional pharmacophore 
screening models and three-dimensional CoMFA (comparative molecular 
field analysis) models, as well as the Unversity of Bourgas on three 
dimensional COREPA (Common Reactivity Pattern) models. The Agency is 
developing estrogen and androgen receptor binding data to verify the 
model results. The QSAR model approaches have the potential to be 
incorporated in the EDPSD, provided they prove to be reliable upon 
completion of ongoing studies and scientific peer review.
    Priority setting is not part of the charge to the EDMVS. However, 
the Agency will keep the subcommittee informed of these activities, in 
that the results have implications for the development of in vitro 
screening and pre-screening methods. The latter will be part of the 
charge to the subcommittee.
    2. Validation of EDSP assays. The EDSP assays that EPA is 
developing and validating on a priority basis are identified below:
Tier 1 Screening Battery Methods
    <bullet> Estrogen (ER) and androgen receptor (AR) binding assays
    <bullet> ER and AR assays with w/transcriptional activation
    <bullet> Steroidogenesis assay
    <bullet> Uterotrophic assay
    <bullet> Hershberger assay
    <bullet> Pubertal female assay w/thyroid endpoints
    <bullet> Frog metamorphosis
    <bullet> Fish reproductive screening assay
Tier 1 Screening Battery Alternate Methods
    <bullet> Pubertal male assay w/thyroid endpoints
    <bullet> Aromatase assay
    <bullet> Rodent in utero through lactation assay
Tier 2 Testing Battery Methods
    <bullet> Two-generation mammalian reproductive toxicity study with 
endocrine endpoints

[[Page 23025]]

    <bullet> Two-generation avian reproductive toxicity study with 
endocrine endpoints
    <bullet> Two-generation fish reproductive study with endocrine 
endpoints
    <bullet> Two-generation mysid shrimp reproductive study with 
endocrine endpoints
    3. The Validation Process. As a charter member and co-chair of the 
Interagency Coordinating Committee on the Validation of Alternative 
Methods (ICCVAM), EPA (and the EDMVS) will follow the interagency 
validation framework outlined in Validation and Regulatory Acceptance 
of Toxicological Test Methods (Ref. 4) for validating the EDSP 
screening and testing methods. The National Institute of Environmental 
Health Sciences (NIEHS) established ICCVAM as a standing committee of 
Federal agencies to coordinate and facilitate interagency validation, 
acceptance, and harmonization of toxicological test methods with an 
emphasis on reducing animal use, refining procedures involving animals 
to make them less stressful and replacing animals where scientifically 
appropriate.
    The ICCVAM validation process was designed as a flexible, adaptable 
framework applicable to conventional and alternative methods, and to 
meet the needs of diverse test sponsors, Federal agencies and 
regulatory processes. The framework provides a number of stages and 
outcomes including research, methods development, prevalidation, 
validation, peer review, and regulatory acceptance. All stages and 
outcomes are part of the interagency ICCVAM process. However, as 
indicated in Validation and Regulatory Acceptance of Toxicological Test 
Methods: ``ICCVAM does not ordinarily address methods applicable to 
only one agency'' (Ref. 4, p. 46); and ``test method sponsors may elect 
to arrange for independent peer review by third parties prior to 
submission of a method to an agency or ICCVAM'' (Ref. 4, p. 47). 
Regulatory approval of test guidelines remains the sole responsibility 
of each regulatory agency.
    Although there is widespread interest in EPA's EDSP, the screening 
and testing methods are being developed and validated with the specific 
goal of developing test guidelines for EPA regulatory use. The test 
guidelines will ultimately be used by chemical manufacturers, pesticide 
registrants, and other entities to develop data for submission to EPA 
in support of the Agency's statutorily mandated chemical risk 
management programs.
    EPA will manage the validation process for the EDSP with 
substantial involvement of ICCVAM personnel. EPA and ICCVAM have 
mutually agreed to this administrative arrangement to ensure that EDSP 
validation meets ICCVAM interagency validation principles (Ref. 4), as 
well as EPA guideline development, review, and regulatory approval 
processes for EPA's chemical risk management programs. EPA will manage 
the process set forth by ICCVAM for the validation of all of the 
specific in vitro and in vivo EDSP methods. ICCVAM and the National 
Toxicology Program will manage and peer review a background review 
document and summarize literature derived performance criteria into a 
generic guidance document that could be used for validating estrogen 
receptor and androgen receptor binding/reporter gene assays.
    In addition to EPA's domestic EDSP validation program, certain 
screening assays and tests for international use are also being 
conducted by the Organization for Economic Cooperation and Development 
(OECD) Test Guidelines Program. EPA is an active member of the OECD 
Test Guidelines Program activities, as well as the latter's Endocrine 
Disruptor Testing and Assessment Workgroup. EPA will rely upon the OECD 
mechanism for validating those EDSP screens and tests of international 
interest. The OECD, EPA and ICCVAM have also mutually agreed to this 
administrative arrangement to ensure that all appropriate validation 
and peer review steps are achieved in both domestic and international 
efforts.
    4. Studies initiated to date by EPA. A number of studies have been 
initiated by EPA to provide the data necessary for the validation of 
individual methods. The results of these ongoing studies, as well as 
advice regarding the design of new studies will be the primary work of 
the EDMVS. A summary of studies that have been initiated by EPA is 
shown below.

----------------------------------------------------------------------------------------------------------------
                                                       Initial protocol      Prevalidation
          Assays/tests             Literature review     demonstration          studies       Validation studies
----------------------------------------------------------------------------------------------------------------
ER/AR binding assay               <bullet>            <bullet>            <bullet>            <bullet>
----------------------------------------------------------------------------------------------------------------
Uterotrophic assay                <bullet>            <bullet>            <bullet>            <bullet>
----------------------------------------------------------------------------------------------------------------
Hershberger assay                 <bullet>            <bullet>            <bullet>            <bullet>
----------------------------------------------------------------------------------------------------------------
Pubertal female assay             <bullet>            <bullet>            <bullet>
----------------------------------------------------------------------------------------------------------------
Pubertal male assay               <bullet>            <bullet>            <bullet>
----------------------------------------------------------------------------------------------------------------
Frog metamorphosis assay                              <bullet>
----------------------------------------------------------------------------------------------------------------
Fish reproductive screen                              <bullet>
----------------------------------------------------------------------------------------------------------------
Mammalian 2-generation test                           <bullet>
----------------------------------------------------------------------------------------------------------------
Avian 2-generation test                               <bullet>
----------------------------------------------------------------------------------------------------------------
Invertebrate 2-generation test                        <bullet>
----------------------------------------------------------------------------------------------------------------


[[Page 23026]]

V. Endocrine Disruptor Methods Validation Subcommittee Mission 
Statement

A. Purpose and Authority

    This mission statement establishes the Endocrine Disruptor Methods 
Validation Subcommittee (EDMVS) in accordance with the Federal Advisory 
Subcommittee Act (5 U.S.C. App. 2 section 9(c)). The EDMVS is being 
established as a subcommittee under the auspices of EPA's National 
Advisory Council for Environmental Policy and Technology. The purpose 
of the EDMVS is to provide advice and counsel to the EPA on scientific 
issues associated with the conduct of studies necessary for validation 
of Tier 1 and Tier 2 methods for the EPA's Endocrine Disruptor 
Screening Program (63 FR 71542). The EDMVS will provide advice and 
recommendations regarding: the development of initial protocols; 
prevalidation study designs; validation study designs; and synthesis of 
prevalidation and validation study results for the EDSP Tier 1 and Tier 
2 methods into documents suitable for external peer review. The EDMVS 
advice and recommendations will be forwarded to the Agency through 
NACEPT. Taking into account this advice and recommendations, EPA will 
manage and conduct prevalidation and validation laboratory studies.

B. Objectives

    EDMVS provides independent advice and counsel to the Agency through 
NACEPT, on scientific and technical issues related to validation of 
EDSP Tier 1 and Tier 2 methods, including the reduction of animal pain 
suffering and use. Following validation of the individual screening 
methods, the collective data will be integrated and evaluated to 
optimize the configuration of the Tier 1 screening battery. EDMVS may 
also examine new or innovative methods that may be applicable for 
inclusion in a second phase of validation. Specific areas for advice 
and counsel include:
    1. Initial protocol development. The development and/or review of 
Endocrine Disruptor Screening Program (EDSP) initial protocols based on 
existing information and experience (past and current research). The 
initial protocols will serve as the starting point for all subsequent 
prevalidation studies. EPA will prepare a Background Review Document 
(BRD) addressing all critical areas outlined in Validation and 
Regulatory Acceptance of Toxicological Test Methods (Ref. 4) will be 
prepared for each method to summarize, explain, and document decisions 
regarding the relevant principles, methods and techniques for the 
initial protocol.
    2. Prevalidation studies. The further development and optimization 
of specific EDSP initial protocols through targeted investigations. The 
targeted investigations will be designed to address questions necessary 
for an optimized, transferable protocol suitable for inter-laboratory 
validation studies.
    3. Validation studies. The design and interpretation of comparative 
inter-laboratory studies to establish the reliability and relevance of 
the EDSP optimized transferable protocols. Following validation, the 
optimized transferable protocols will provide the basis for endocrine 
disruptor test guidelines for regulatory use.
    4. Preparation of EDSP Method Validation documents for external 
peer review. All EDSP methods must be peer reviewed prior to approval 
for regulatory use. With advice and recommendations of the EDMVS, EPA 
will synthesize and interpret data and information generated in 
protocol development, prevalidation studies and validation studies into 
EDSP method-specific documents suitable for external peer review. 
External scientific peer review of the EDSP methods will be arranged by 
EPA through an Agency-approved external scientific peer review panel.

C. Scope of the Activity

    The EDMVS and NACEPT will provide a forum for a diverse group of 
individuals representing a broad range of interests and backgrounds 
from across the country to consult with and make recommendations to the 
Agency on matters relating to the validation and external scientific 
peer review of endocrine disruptor screening and testing methods. The 
subcommittee will analyze issues, review data and protocols, compile 
information, make recommendations to the Agency, and undertake other 
activities necessary to meet its responsibilities.

D. Composition

    The EDMVS shall be composed of 25 members approved by the 
Administrator. Members will be selected on the basis of their relevant 
scientific expertise and diversity of perspectives on endocrine 
disruptor screening and testing methods and procedures, toxicity test 
methods standardization and validation, and chemical and pesticide 
regulatory processes. Members will be appointed for 2 years. 
Subcommittee members shall be appointed with balanced representation 
from the following sectors: The agrichemical and commodity chemical 
industries; environmental/public interest organizations; public health 
organizations; animal welfare organizations; Federal agencies; State, 
local and tribal governments; academia; consumers, and the public. The 
Agency will appoint a Chair and Deputy Chair for the Subcommittee.

E. Workgroups and Ad Hoc Teams

    Workgroups and ad hoc teams may be established on an as-needed 
basis consisting of EDMVS members, or supplemented with specialists 
qualified in the technical area of the workgroup or team appointed by 
the Agency. Such teams will develop in-depth technical issues or 
analyses that may be necessary for the EDMVS to conduct its 
deliberations.

F. Meetings

    The EDMVS will hold up to six meeting a year. A regular employee of 
EPA will act as the Designated Federal Officer who will be present or 
represented at all meetings and is authorized to adjourn any such 
meetings whenever the official determines it to be in the public 
interest. All EDMVS meetings will be called, announced, and held in 
accordance with FACA and NACEPT rules, which require open meetings and 
an opportunity for interested persons to file comments before or after 
meetings, or to make statements during the public meetings to the 
extent time permits. The date, time, location and any public 
participation instructions for each meeting will be announced in the 
Federal Register at least 30 days before the meeting date. Each meeting 
shall be conducted in accordance with an agenda approved in advance by 
the Designated Federal Officer. The meeting information and agenda will 
be posted on the Agency's web site as soon as it is available, and no 
later than 15 days before the meeting date.

VI. References

    1. Ankley, G. T. et al. 1998. Overview of a workshop on screening 
methods for detecting (anti)-estrogenic/androgenic chemicals in 
wildlife. Environmental Toxicology Chemistry. 17: 68-87.
    2. Endocrine Disruptor Screening and Testing Advisory Committee: 
Final Report. 1998. U. S. Environmental Protection Agency, Office of 
Prevention, Pesticides, and Toxic Substances, Washington, DC.
    3. Gray. L. E. et al. 1997. Endocrine Screening Methods Workshop 
Report: Detection of Estrogenic and Androgenic Hormonal and 
Antihormonal Activity for Chemicals that Act via Receptor or

[[Page 23027]]

Steroidogenic Enzyme Mechanisms. Reproductive Toxicology 11:719-750.
    4. National Institute of Environmental Health Sciences. 1997. 
Validation and Regulatory Acceptance of Toxicological Test Methods: A 
report of the ad hoc Interagency Coordinating Committee on the 
Validation of Alternative Methods. NIH Publication No. 97-3981, NIEHS, 
Research Triangle Park, NC,105 pp.
    5. National Research Council. Hormonally Active Agents in the 
Environment. National Academy Press, Washington, DC, 429 pp.
    6. U. S. EPA. 1997. Special Report on Environmental Endocrine 
Disruptors: An Effects Assessment and Analysis. U. S. Environmental 
Protection Agency, Office of Research and Development, EPA/630/R-96/
012, Washington, DC, 116 pp.
    7. U.S. EPA. 1997. Screening Methods for Chemicals that Alter 
Thyroid Hormone Action, Function, and Homeostasis. U. S. Environmental 
Protection Agency, Office of Research and Development, EPA/6000/R-98/
057, Washington, DC, 44 pp.
    8. U. S. EPA. 1999. Review of the EPA's Proposed Environmental 
Endocrine Disruptor Screening Program. U. S. Environmental Protection 
Agency, Science Advisory Board, EPA-SAB-EC-99-013, Washington, DC, 35 
pp.

List of Subjects

    Environmental protection.


    Dated: April 24, 2001.
Stephen L. Johnson,
Acting Assistant Administrator, Office of Prevention, Pesticides and 
Toxic Substances.
[FR Doc. 01-11412 Filed 5-4-01 8:45 am]
BILLING CODE 6560-50-S


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