[Federal Register Volume 71, Number 188 (Thursday, September 28, 2006)]
[Notices]
[Pages 56997-56998]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E6-15972]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health


National Toxicology Program (NTP), NTP Interagency Center for the 
Evaluation of Alternative Toxicological Methods (NICEATM); Notice of 
Availability of a Revised List of Recommended Reference Substances for 
Validation of In Vitro Estrogen and Androgen Receptor Binding and 
Transcriptional Activation Assays

AGENCY: National Institute of Environmental Health Sciences (NIEHS), 
National Institutes of Health (NIH).

ACTION: Notice of the availability of a revised list of recommended 
reference substances.

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SUMMARY: NICEATM announces the availability of an addendum to 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'' [NIH 
Publication 03-4503]. The addendum describes the rationale for 
revisions to the original list of recommended reference substances for 
validation of in vitro estrogen receptor (ER) and androgen receptor 
(AR) binding and transcriptional activation (TA) assays.

SUPPLEMENTARY INFORMATION:

Background

    In April 2000, the Environmental Protection Agency (EPA) asked 
ICCVAM to evaluate the validation status of in vitro ER and AR binding 
and TA assays that were proposed as possible components of the EPA 
Endocrine Disruptor Screening Program Tier 1 screening battery. ICCVAM 
agreed to evaluate these test methods based on their potential 
interagency applicability and public health significance. NICEATM 
subsequently compiled available data and information on in vitro ER and 
AR binding and TA assays in four draft Background Review Documents 
(BRDs) (available at http://iccvam.niehs.nih.gov/methods/endocrine.htm).
    In collaboration with the ICCVAM Endocrine Disruptor Working Group, 
NICEATM organized an independent scientific evaluation of the 
validation status of the four types of in vitro endocrine disruptor 
screening test methods on May 20-21, 2002, in Research Triangle Park, 
NC (Federal Register, Vol. 66, No. 57, pp. 16278-16279, March 23, 2001 
and Federal Register, Vol. 66, No. 67, pp. 16415-16416, April 5, 2002, 
available at http://iccvam.niehs.nih.gov/methods/endocrine.htm).
    The final BRDs and the ICCVAM Test Method Evaluation Report, which 
includes the expert panel report, public comments, and other relevant 
documents, were published in May 2003 and announced in the Federal 
Register notice (Vol. 68, No. 106, pp. 33171-33172, June 3, 2003, 
available at http://iccvam.niehs.nih.gov/methods/endocrine.htm).
    NICEATM recently reviewed the commercial availability and cost for 
the 78 substances recommended by ICCVAM for use in in vitro ER and AR 
binding and TA validation studies. A minimum of 44 substances are 
recommended for AR binding and TA assays, while a minimum of 53 
substances are recommended for ER binding and TA assays. This review 
indicated that three substances (anastrazole, CGS 18320B, and 
fadrozole) are not commercially available, one substance has restricted 
commercial availability (ICI 182,780) and six others (actinomycin D, 
hydroxyflutamide, 4-hydroxytamoxifen, methyltrienolone, 12-O-
tetradecanoylphorbol-13-acetate, zearalenone) have costs that are 
considered excessive. ICCVAM has replaced the four substances, which 
are not commercially available or have restricted availability, with 
ones having similar ER and AR activity profiles (4-
hydroxyandrostenedione, chrysin, dicofol, raloxifene HCl). 19-
nortestosterone and resveratrol were identified as replacements for two 
of the expensive substances, metyltrienolone and zearalenone 
respectively. NICEATM sought to replace four of the highly priced 
substances (actinomycin D, hydroxyflutamide, 4-hydroxytamoxifen, 12-O-
tetradecanoylphorbol-13-acetate), but was unable to identify suitable 
replacements because of their unique activity profiles and/or chemical/
physical properties. The proposed revisions were made available for 
public comment in March 2006 (Federal Register, Vol. 71, No. 51, pp. 
13597-13598, March 16, 2006) and no comments were received. The final 
revised list of 78 reference substances recommended for validation of 
in vitro ER and AR binding and TA validation studies and a discussion 
about the revisions are now available in the document, ``Addendum to 
the ICCVAM Evaluation of In Vitro Test Methods for Detecting Potential 
Endocrine Disruptors: Estrogen Receptor and Androgen Receptor Binding 
and Transcriptional Activation Assays.'' The addendum is available on 
the ICCVAM/NICEATM Web site at http://iccvam.niehs.nih.gov see ``Test 
Method Evaluations'' or by contacting NICEATM (requests should be sent 
by mail, fax, or e-mail to Dr. William S. Stokes, NICEATM Director, 
NIEHS, P. O. Box 12233, MD EC-17, Research Triangle Park, NC, 27709, 
(phone) 919-541-2384, (fax) 919-541-0947, (e-mail) 
[email protected].).

Background Information on ICCVAM and NICEATM

    ICCVAM is an interagency committee composed of representatives from 
15 Federal regulatory and research agencies that use or generate 
toxicological information. ICCVAM conducts technical evaluations of 
new, revised, and alternative methods with regulatory applicability and 
promotes the scientific validation and regulatory acceptance of 
toxicological test methods that more accurately assess the safety and 
hazards of chemicals and products and that refine, reduce, or replace 
animal use. The ICCVAM Authorization Act of 2000 (42 U.S.C. 285) 
establishes ICCVAM as a permanent interagency committee of the NIEHS 
under the NICEATM. NICEATM administers the ICCVAM and provides 
scientific and operational support for ICCVAM-related activities. 
NICEATM and ICCVAM work collaboratively to evaluate new and improved 
test methods applicable to the needs of Federal agencies. Additional 
information about ICCVAM and

[[Page 56998]]

NICEATM can be found at the following Web site: http://www.iccvam.niehs.nih.gov.

    Dated: September 18, 2006.
Samuel H. Wilson,
Deputy Director, National Institute of Environmental Health Sciences 
and National Toxicology Program.
 [FR Doc. E6-15972 Filed 9-27-06; 8:45 am]
BILLING CODE 4140-01-P