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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
Note: EPA no longer updates this information, but it may be useful as a reference or resource.
[Federal Register: September 28, 2006 (Volume 71, Number 188)]
[Notices]
[Page 56997-56998]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr28se06-78]
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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)
niceatm@niehs.nih.gov.).
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://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