[Federal Register Volume 68, Number 106 (Tuesday, June 3, 2003)]
[Notices]
[Pages 33171-33172]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 03-13839]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Public Health Service


National Institute of Environmental Health Sciences (NIEHS); 
National Toxicology Program (NTP); Notice of Availability of the 
Report: ``Interagency Coordinating Committee on the Validation of 
Alternative Methods (ICCVAM) Evaluation of In Vitro Test Methods for 
Detecting Potential Endocrine Disruptors: Estrogen Receptor and 
Androgen Receptor Binding and Transcriptional Activation Assays''

Summary

    The National Toxicology Program (NTP) Interagency Center for the 
Evaluation of Alternative Toxicological Methods (NICEATM) announces the 
availability of the report entitled, ``ICCVAM Evaluation of In Vitro 
Test Methods for Detecting Potential Endocrine Disruptors: Estrogen 
Receptor and Androgen Receptor Binding and Transcriptional Activation 
Assays,'' NIH Publication 02-4503. The report contains ICCVAM's 
recommendations on minimum procedural standards and reference 
substances for standardization and validation of in vitro estrogen and 
androgen receptor binding and transcriptional activation assays.

Availability of Report

    The report is available electronically (PDF format) on the NICEATM/
ICCVAM web site at http://iccvam.niehs.nih.gov. A limited number of 
printed reports and CDs are available. To receive a printed report or 
CD, please send a request to Dr. William S. Stokes, Director, NICEATM, 
PO Box 12233, MD EC-17, Research Triangle Park, NC 27709, phone: 919-
541-2384, fax: 919-541-0947, or email [email protected]. Inquiries 
about the report or its availability should be sent to Dr. Stokes at 
the above address.

Background

    In April 2000, the EPA asked the ICCVAM to evaluate the validation 
status of in vitro estrogen receptor (ER) and androgen receptor (AR) 
binding and transcriptional activation (TA) assays that were proposed 
as possible components of the EPA Endocrine Disruptor Screening Program 
(EDSP) Tier 1 screening battery. ICCVAM, which is charged by law (Pub. 
L. 106-545) to evaluate the scientific validity of new, revised, and 
alternative test methods proposed for specific regulatory uses, agreed 
to evaluate these test methods based on their potential interagency 
applicability and public health significance.
    The NICEATM, which administers and provides scientific support for 
the ICCVAM, subsequently compiled available data and information on in 
vitro ER and AR binding and TA assays. Four draft Background Review 
Documents (BRDs) (available at http://iccvam.niehs.nih.gov/methods/endocrine.htm) were prepared according to published guidelines for 
submission of test methods to ICCVAM (ICCVAM 1999). This comprehensive 
review found that there are no adequately standardized and validated in 
vitro ER- or AR-based test methods. The NICEATM proposed minimum 
procedural standards that should be incorporated into standardized 
protocols for each of the four types of assays. In addition, NICEATM 
included within each BRD a list of proposed substances that should be 
used for the validation of in vitro ER and AR binding and TA assays.

[[Page 33172]]

    In collaboration with the ICCVAM Endocrine Disruptor Working Group 
(EDWG), NICEATM organized an independent technical evaluation of the 
four types of in vitro endocrine disruptor test methods on May 20-21, 
2002 in Research Triangle Park, NC [Federal Register. 66 FR 57: 16278-
16279, March 23, 2001 and 67 Federal Register 66: 16415-16416, April 5, 
2002). This meeting was open to the public with time set aside for 
public comment.
    A 24-member scientific expert panel reviewed the information and 
recommendations provided in the four draft BRDs and developed its own 
conclusions and recommendations for each type of test method on the 
following:
    [sbull] Specific test methods that should undergo further 
evaluation in validation studies and their relative priority for 
evaluation;
    [sbull] The adequacy of the proposed minimum procedural standards;
    [sbull] The adequacy of protocols for specific test methods 
recommended for validation; and
    [sbull] The adequacy and appropriateness of substances proposed for 
validation studies.
    The expert panel presented its evaluations, conclusions, and 
recommendations at the meeting. Following the meeting, the expert 
panel's written evaluations and consensus recommendations were 
consolidated into an independent report (http://iccvam.niehs.nih.gov/methods/endocrine.htm).
    In October 2002 (67 FR 204: 64902-64903, October 22, 2002), the 
NICEATM made available for public comment the expert panels' final 
report. This report contains the expert panel's evaluations and 
consensus recommendations for the four types of assays and a revised 
list of proposed substances for validation of in vitro ER and AR 
binding and TA test methods. Following review of this report and the 
public comments, ICCVAM finalized its recommendations and developed 
recommended minimum procedural standards and the list of proposed 
substances that should be used to standardize and validate in vitro ER 
and AR binding and TA assays. The final expert panel report, public 
comments, and other relevant documents are appended to the ICCVAM 
report. The ICCVAM report, whose availability is announced in this 
notice (see above), will be forwarded to Federal agencies for their 
consideration and information.
    The minimum procedural standards and the list of recommended 
substances for validation should facilitate standardization and 
validation of in vitro endocrine disruptor assays. Data from validation 
studies on test methods that incorporate the recommended minimum 
procedural standards will serve as the basis for developing minimum 
performance standards for acceptable in vitro ER-or AR-based test 
methods. The EDSP will use data generated from validated in vitro and 
in vivo Tier 1 screening test methods to reach weight-of-evidence 
decisions on whether to conduct large multi-generational in vivo 
studies. It is also anticipated that data obtained during the 
validation of the four different types of in vitro ER- and AR-based 
test methods will help characterize the extent to which individual or 
batteries of in vitro endocrine disruptor test methods might be used to 
prioritize chemicals for Tier 1 screening and Tier 2 testing. Finally, 
implementation of the recommendations in this report is expected to 
decrease and perhaps eventually eliminate the need to use male and 
female animals as a source of AR and ER, respectively, for in vitro 
screening assays.
    Test method developers are encouraged to submit in vitro test 
methods for evaluation by ICCVAM that adhere to the minimum procedural 
standards outlined in this report and that have undergone validation 
using the recommended substances. Following adequate validation of in 
vitro endocrine disruptor test methods, ICCVAM and NICEATM will 
coordinate their scientific peer review. Formal ICCVAM test 
recommendations will then be forwarded to Federal agencies as required 
by the ICCVAM Authorization Act of 2000 (Pub. L. 106-545).

    Dated: May 28, 2003.
Kenneth Olden,
Director, National Institute of Environmental Health Sciences.
[FR Doc. 03-13839 Filed 6-2-03; 8:45 am]
BILLING CODE 4140-01-P