[Federal Register Volume 77, Number 162 (Tuesday, August 21, 2012)]
[Notices]
[Pages 50510-50511]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2012-20549]



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DEPARTMENT OF HEALTH AND HUMAN SERVICES


Federal Agency Responses to Interagency Coordinating Committee on 
the Validation of Alternative Methods (ICCVAM) Recommendations on the 
Usefulness and Limitations of the LUMI-CELL[supreg] ER (BG1Luc ER TA) 
Test Method, An In Vitro Assay for Identifying Human Estrogen Receptor 
Agonist and Antagonist Activity of Chemicals

AGENCY: Division of the National Toxicology Program (DNTP), National 
Institute of Environmental Health Sciences (NIEHS), National Institutes 
of Health (NIH), HHS.

ACTION: Availability of Agency Responses.

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SUMMARY: The NTP Interagency Center for the Evaluation of Alternative 
Toxicological Methods (NICEATM) announces availability of U.S. Federal 
agency responses to ICCVAM test method recommendations on the 
usefulness and limitations of the LUMI-CELL[supreg] ER (BG1Luc ER TA) 
test method to identify human estrogen receptor (ER) agonist and 
antagonist activity of chemicals. ICCVAM forwarded the recommendations 
to Federal agencies and made these recommendations available to the 
public (77 FR 8258). ICCVAM agencies responded with their concurrence 
on the technical aspects of the BG1Luc ER transcriptional activation 
(TA) test method recommendations and their agreement that the ICCVAM 
BG1Luc ER TA test method is a validated screening test to identify 
substances with in vitro ER agonist activity or ER antagonist activity. 
The U.S. Environmental Protection Agency (EPA) responded that they 
regard the BG1Luc ER TA test method as an alternative to the Office of 
Chemical Safety and Pollution Prevention (OCSPP) 890.1300 (Organization 
for Economic Co-operation and Development [OECD] TG455) test guideline 
for transcriptional activation currently used in their Endocrine 
Disruptor Screening Program (EDSP). Several agencies also indicated 
that they would communicate the ICCVAM recommendations to stakeholders 
and encourage their appropriate use. Complete Federal agency responses 
are available at http://iccvam.niehs.nih.gov/methods/endocrine/end_eval.htm. The ICCVAM recommendations are provided in the ICCVAM test 
method evaluation report (ICCVAM, 2011), available at: http://iccvam.niehs.nih.gov/methods/endocrine/ERTA-TMER.htm.

FOR FURTHER INFORMATION CONTACT: Dr. Warren M. Casey, Deputy Director, 
NICEATM, NIEHS, P.O. Box 12233, Mail Stop: K2-16, Research Triangle 
Park, NC 27709, (telephone) 919-316-4729, (fax) 919-541-0947, (email) 
[email protected]. Courier address: NICEATM, NIEHS, Room 2032, 530 
Davis Drive, Morrisville, NC 27560.

SUPPLEMENTARY INFORMATION:

Background

    In 2002, ICCVAM evaluated the validation status of in vitro ER and 
androgen receptor (AR) binding and TA test methods for potential use in 
the EPA EDSP. The evaluation indicated that no in vitro ER- or AR-based 
test methods were adequately validated for this purpose. In response to 
an ICCVAM request for nominations, Xenobiotic Detection Systems, Inc. 
(XDS, Durham, NC) nominated the in vitro LUMI-CELL[supreg] ER (BG1Luc 
ER TA) test method for an interlaboratory validation study. ICCVAM and 
the Scientific Advisory Committee on Alternative Toxicological Methods 
(SACATM) recommended that the nominated method should be considered a 
high priority based on the lack of adequately validated test methods 
and the regulatory and public health need for such test methods. 
NICEATM led the international validation study with its partners in 
Japan (JaCVAM) and Europe (ECVAM), using laboratories sponsored by each 
validation organization. ICCVAM also proposed the development of BG1Luc 
ER TA test method performance standards.
    Following completion of the validation study, the ICCVAM 
Interagency Endocrine Disruptor Working Group, working with NICEATM, 
prepared a draft background review document (BRD) and draft 
recommendations for use of the BG1Luc ER TA test method.
    The draft BRD and draft ICCVAM recommendations were reviewed in a 
public meeting (76 FR 4113) of an international independent scientific 
peer review panel in March 2011. The peer review panel agreed with the 
draft ICCVAM recommendations that the BG1Luc ER TA test method could be 
used as a screening test to identify substances with in vitro ER 
agonist activity or ER antagonist activity and that the accuracy of 
this assay is at least equivalent to that of EPA OCSPP 890.1300, part 
of the EDSP Tier 1 screening battery.
    The final ICCVAM recommendations are included in the ICCVAM Test 
Method Evaluation Report: The LUMI-CELL[supreg] ER (BG1Luc ER TA) Test 
Method, An In Vitro Assay for Identifying Human Estrogen Receptor 
Agonist and Antagonist Activity of Chemicals (NIH Publication No. 11-
7850). The test method evaluation report also includes the updated 
ICCVAM-recommended BG1Luc ER TA test method protocol and performance 
standards that are applicable to functionally and mechanistically 
similar test methods. The final BRD, including the data and analyses on 
which the recommendations are based, is included as an appendix to the 
test method evaluation report.

Agency Responses to ICCVAM Recommendations

    In February 2012, ICCVAM forwarded final test method 
recommendations on the BG1Luc ER TA test method to U.S. Federal 
agencies for consideration (77 FR 8258), in accordance with the ICCVAM 
Authorization Act of 2000 (42 U.S.C. 285l-3). The ICCVAM Authorization 
Act requires member agencies to review ICCVAM test method 
recommendations and notify ICCVAM in writing of their findings no later 
than 180 days after receipt of recommendations. The Act also requires 
ICCVAM to make ICCVAM recommendations and agency responses available to 
the public. Agency responses are to include identification of relevant 
test methods for which the ICCVAM test method recommendations may be 
added or substituted and indicate any revisions or planned revisions to 
existing guidelines, guidances, or regulations to be made in response 
to these recommendations.
    ICCVAM agencies responded with their concurrence on the technical 
aspects of the BG1Luc ER TA test method recommendation and their 
agreement that the ICCVAM BG1Luc ER TA test method is a validated 
screening test to identify substances with in vitro ER agonist activity 
or ER antagonist activity. The EPA responded that they regard the 
BG1Luc ER TA test method as an alternative to the OCSPP 890.1300 test 
guideline for transcriptional activation currently used in their EDSP. 
Several agencies also indicated that they would communicate the ICCVAM 
recommendations to stakeholders and encourage their appropriate use. 
Complete agency responses are available at http://iccvam.niehs.nih.gov/methods/endocrine/end_eval.htm.

Background Information on ICCVAM, NICEATM, and SACATM

    ICCVAM is an interagency committee composed of representatives from 
15 Federal regulatory and research agencies that require, use, 
generate, or disseminate toxicological and safety

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testing information. ICCVAM conducts technical evaluations of new, 
revised, and alternative safety testing methods with regulatory 
applicability and promotes the scientific validation and regulatory 
acceptance of toxicological and safety-testing methods that more 
accurately assess the safety and hazards of chemicals and products and 
that reduce, refine (enhance animal welfare and lessen or avoid 
unrelieved pain and distress), or replace animal use. The ICCVAM 
Authorization Act of 2000 (42 U.S.C. 285l-3) established ICCVAM as a 
permanent interagency committee of the NIEHS under NICEATM. NICEATM 
administers ICCVAM, provides scientific and operational support for 
ICCVAM-related activities, and conducts independent validation studies 
to assess the usefulness and limitations of new, revised, and 
alternative test methods and strategies. NICEATM and ICCVAM work 
collaboratively to evaluate new and improved test methods and 
strategies applicable to the needs of U.S. Federal agencies. NICEATM 
and ICCVAM welcome the public nomination of new, revised, and 
alternative test methods and strategies applicable to the needs of 
Federal agencies. Additional information about NICEATM and ICCVAM can 
be found on the NICEATM-ICCVAM Web site (http://iccvam.niehs.nih.gov).
    SACATM was established in response to the ICCVAM Authorization Act 
(42 U.S.C. 285l-3) and is composed of scientists from the public and 
private sectors. SACATM advises ICCVAM, NICEATM, and the Director of 
the NIEHS and NTP regarding statutorily mandated duties of ICCVAM and 
activities of NICEATM. SACATM provides advice on priorities and 
activities related to the development, validation, scientific review, 
regulatory acceptance, implementation, and national and international 
harmonization of new, revised, and alternative toxicological test 
methods. Additional information about SACATM, including the charter, 
roster, and records of past meetings, can be found at http://ntp.niehs.nih.gov/go/167.

References

    ICCVAM. 2011. ICCVAM Test Method Evaluation Report: The LUMI-
CELL[supreg] ER (BG1Luc ER TA) Test Method: An In Vitro Assay for 
Identifying Human Estrogen Receptor Agonist and Antagonist Activity 
of Chemicals. NIH Publication No. 11-7850. Research Triangle Park, 
NC: NIEHS. Available: http://iccvam.niehs.nih.gov/methods/endocrine/ERTA-TMER.htm.

    Dated: August 13, 2012.
John R. Bucher,
Associate Director, National Toxicology Program.
[FR Doc. 2012-20549 Filed 8-20-12; 8:45 am]
BILLING CODE 4140-01-P