[Federal Register Volume 66, Number 57 (Friday, March 23, 2001)]
[Notices]
[Pages 16278-16279]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 01-7228]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Public Health Service


National Institute of Environmental Health Sciences (NIEHS), 
National Institutes of Health (NIH), National Toxicology Program (NTP); 
Request for Data and Nominations of Expert Scientists for an 
Independent Peer Review Evaluation of In Vitro Estrogen and Androgen 
Receptor Binding and Transcriptional Activation Assays for Endocrine 
Disruptor Screening

SUMMARY: The National Toxicology Program (NTP) Interagency Center for 
the Evaluation of Alternative Toxicological Methods (NICEATM) in 
collaboration with the Interagency Coordinating Committee on the 
Validation of Alternative Methods (ICCVAM) is planning an independent 
Peer Review Panel (hereafter, Panel) evaluation of the validation 
status of in vitro estrogen receptor (ER) and androgen receptor (AR) 
binding and transcriptional activation assays. Conclusions and 
recommendations from the Panel will be considered by federal agencies 
in selecting and establishing minimum performance criteria for in vitro 
test methods used to screen chemicals for potential endocrine 
disrupting effects, including the U.S. Environmental Protection 
Agency's (EPA) Endocrine Disruptor Screening Program. At this time, 
NICEATM requests study results and data evaluating the performance and 
reliability of ER and AR binding and transcriptional activation assays, 
and other relevant information from the scientific community that 
should be considered by the Panel. NICEATM also requests nominations of 
expert scientists for consideration as potential Panel members.

BACKGROUND INFORMATION: In response to public concern that pesticides 
may interfere with endocrine processes in humans and wildlife, Congress 
directed EPA, through the 1996 Food Quality Protection Act (FQPA) (Pub. 
L. 104-170) to develop a screening program for evaluating the potential 
of pesticides and other chemicals to induce hormone-related health 
effects. Language in the1996 amendments to the Safe Drinking Water Act 
(Pub. L. 104-182) added that EPA would use this screening program to 
evaluate substances found in drinking water sources for endocrine 
effects if there is widespread human exposure to such substances. 
Consequently, in 1998, EPA proposed an Endocrine Disruptor Screening 
Program (EDSP) (Federal Register, Vol. 63, No. 248, pp. 71541-71568, 
December 28, 1998, available at http://www.epa.gov/fedrgstr/EPA-TOX/1998/December/Day-28/t34298.htm).
    The conceptual framework of the EDSP (http://www.epa.gov/scipoly/oscpendo/index.htm) consists of a Tier 1 Screening battery of tests 
that is designed to identify substances capable of interacting with the 
endocrine system, and a Tier 2 Testing level that is designed to 
confirm Tier 1 results and characterize the nature of the endocrine 
disrupting effects of the substances identified with Tier 1 Screening. 
Under the mandates of the FQPA, EPA is requiring that each screen and 
test method proposed for use in the program undergo standardization and 
scientific validation consistent with the principles of ICCVAM, as 
described in NIH Publication 97-3981, Validation and Regulatory 
Acceptance of Toxicological Test Methods: A Report of the ad hoc 
Interagency Coordinating Committee on the Validation of Alternative 
Methods (ICCVAM Report), available at http://iccvam.niehs.nih.gov/validate.pdf and the Organization for Economic Co-operation and 
Development (OECD) (Final Report of the OECD Workshop on Harmonization 
of Validation and Acceptance Criteria for Alternative Toxicological 
Test Methods: OECD, 1996, available at http://www.oecd.org//ehs/test/08e69840.pdf).
    EPA nominated the ER and AR binding assays and ER and AR 
transcriptional activation assays for review using the ICCVAM 
evaluation process, and agreed to sponsor the necessary background 
review document preparation and peer review. ICCVAM subsequently 
recommended that these methods should undergo independent scientific 
peer review based on their potential interagency applicability and 
public health significance. NICEATM, in collaboration with ICCVAM, is 
therefore convening an independent panel of scientists to assess the 
validation status of these four different types of in vitro assays. 
These assays are relevant for screening purposes in the EDSP because 
they may identify substances that alter natural endocrine processes in 
the body by binding with estrogen and/or androgen receptors, resulting 
in either activation or

[[Page 16279]]

inhibition of gene activation. As part of the evaluation, EPA requested 
the development and review of proposed minimum performance criteria 
that future methods of these types should achieve, in light of the 
performance of existing methods.
    For both the receptor binding and transcriptional activation 
assays, the Panel will evaluate the extent to which the validation and 
acceptance criteria outlined in the ICCVAM Report have been addressed. 
The Panel will be asked to provide conclusions and recommendations 
regarding the usefulness and limitations of various ER and AR binding 
and/or transcriptional activation assays, and the adequacy of proposed 
technically feasible minimum performance criteria that these types of 
assays should achieve. Finally, the Panel will address whether and what 
additional test method development and validation efforts might further 
enhance and/or characterize the usefulness of specific in vitro ER and 
AR binding and/or transcriptional activation assays.
    NICEATM is preparing background review documents on ER and AR 
binding and transcriptional activation testing methods that will 
contain comprehensive summaries of available data and related 
information characterizing the current validation status of these 
assays. The Panel will evaluate the background review documents, which 
will also be made available to the public.
    The Peer Review Panel meeting is anticipated to take place in early 
2002. Meeting information, including date and location, and public 
availability of the background review documents will be announced in a 
future Federal Register notice that will also be posted on the ICCVAM/
NICEATM website (http://iccvam.niehs.nih.gov).

Request for Nominations of Experts to Serve on the Panel

    NICEATM invites nominations of scientists with relevant knowledge 
and experience who might be considered for the independent Peer Review 
Panel. Areas of expertise that may be relevant include, but are not 
limited to, endocrinology, reproductive toxicology, cellular biology, 
molecular genetics and biostatistics. Each nomination should include 
the person's name, affiliation, contact information (i.e., mailing 
address, telephone and fax numbers, and e-mail address), and a brief 
summary of relevant experience and qualifications. Nominations should 
be sent to NICEATM by mail, fax or e-mail within 60 days of the 
publication date of this notice. Correspondence should be directed to 
Dr. William S. Stokes, Director, NTP Interagency Center for the 
Evaluation of Alternative Toxicological Methods, NIEHS, 79 T.W. 
Alexander Drive, MD EC-17, P.O. Box 12233, Research Triangle Park, NC 
27709; telephone: 919-541-7997; fax: 919-541-0947; e-mail: 
[email protected].

Request for Data

    NICEATM welcomes data from completed studies using or evaluating ER 
and AR binding and/or transcriptional activation assays, and 
information about ongoing or planned studies using these methods. 
Information should address applicable aspects of the validation and 
regulatory acceptance criteria provided in the ICCVAM Report. Where 
possible, data and information should adhere to the guidance provided 
in NIH Publication 99-4496, Evaluation of the Validation Status of 
Toxicological Methods: General Guidelines for Submissions to ICCVAM 
(http://iccvam.niehs.nih.gov/subguide.htm). Both documents are 
available by request from NICEATM at the address provided above. 
Information and data should be submitted within 60 days of the 
publication date of this notice to ensure adequate consideration during 
preparation of the background review documents for the Panel. 
Correspondence should be sent by mail, fax or e-mail to Dr. William S. 
Stokes (contact information is provided in the previous section of this 
notice).

Background Information on ICCVAM and NICEATM

    ICCVAM was established in 1997 to coordinate cross-agency issues 
relating to the validation, acceptance, and national/international 
harmonization of toxicological testing methods. Composed of 
representatives from fifteen Federal regulatory and research agencies 
that use or generate toxicological information, ICCVAM promotes the 
scientific validation and regulatory acceptance of toxicological test 
methods that enhance agencies' ability to make decisions on health 
risks, while refining, reducing, and replacing animal use wherever 
possible. ICCVAM was authorized as a permanent Federal committee on 
December 19, 2000 through passage of the ICCVAM Authorization Act of 
2000 (Pub. L. 106-545, available at http://iccvam.niehs.nih.gov/PL106545.htm). NICEATM provides operational and scientific support for 
ICCVAM and ICCVAM-related activities. NICEATM and ICCVAM work 
collaboratively to develop, validate, and achieve regulatory acceptance 
of new and improved test methods applicable to the needs of Federal 
agencies.
    Additional information about ICCVAM and NICEATM can be found at the 
following website: http://iccvam.niehs.nih.gov.

    Dated: March 9, 2001.
Samuel H. Wilson,
Deputy Director, National Toxicology Program.
[FR Doc. 01-7228 Filed 3-22-01; 8:45 am]
BILLING CODE 4140-01-P