[Federal Register Volume 76, Number 96 (Wednesday, May 18, 2011)]
[Notices]
[Pages 28781-28782]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2011-12264]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES


Independent Scientific Peer Review Panel Report: Evaluation of 
the Validation Status of an In Vitro Estrogen Receptor Transcriptional 
Activation Test Method for Endocrine Disruptor Chemical Screening: 
Notice of Availability and Request for Public Comments

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

ACTION: Notice of availability and request for comments.

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SUMMARY: The NTP Interagency Center for the Evaluation of Alternative 
Toxicological Methods (NICEATM), on behalf of the Interagency 
Coordinating Committee on the Validation of Alternative Methods 
(ICCVAM), convened an independent international scientific peer review 
panel (hereafter, Panel) on March 29-30, 2011, to evaluate the 
validation status of the LUMI-CELL[supreg] (BG1Luc ER TA) test method, 
an in vitro transcriptional activation (TA) assay used to identify 
chemicals that can interact with human estrogen receptors (ERs). The 
Panel report is now available on the NICEATM-ICCVAM Web site at: http://iccvam.niehs.nih.gov/docs/endo_docs/EDPRPRept2011.pdf or by 
contacting NICEATM (see ADDRESSES). The report contains (1) the Panel's 
evaluation of the validation status of the test method and (2) the 
Panel's comments on the draft ICCVAM test method recommendations. 
NICEATM invites public comment on the Panel report.

DATES: Written comments on the Panel report should be received by July 
5, 2011.

ADDRESSES: NICEATM prefers that comments be submitted electronically by 
e-mail to [email protected]. Comments can also be submitted via the 
NICEATM-ICCVAM Web site at http://iccvam.niehs.nih.gov/contact/FR_pubcomment.htm. Written comments can be sent by mail or fax to Dr. 
Warren Casey, Deputy Director, NICEATM, NIEHS, P.O. Box 12233, Mail 
Stop: K2-16, Research Triangle Park, NC 27709; (fax) 919-541-0947. 
Courier address: NIEHS, NICEATM, 530 Davis Drive, Room 2035, Durham, NC 
27713.

FOR FURTHER INFORMATION CONTACT: Dr. Warren Casey: (telephone) 919-316-
4729, (fax) 919-541-0947, (e-mail) [email protected].

SUPPLEMENTARY INFORMATION:

Background

    In January 2011, NICEATM announced the convening of an independent 
scientific peer review panel to review and comment on the draft 
background review document (BRD) summarizing available data, 
reliability and accuracy of the BG1Luc ER TA test method, the draft 
recommendations, as well as the availability of the draft documents for 
public comment (76 FR 4113). The Panel met in public session on March 
29-30, 2011, at the Natcher Conference Center in Bethesda, MD. The 
Panel reviewed the draft ICCVAM BRD for completeness, errors, and 
omissions of any existing relevant data or information. The Panel also 
evaluated the information in the draft documents to determine the 
extent to which each of the applicable criteria for validation and 
acceptance of toxicological test methods (ICCVAM, 2003a) had been 
appropriately addressed. The Panel then considered the ICCVAM draft 
recommendations and commented on the extent that the recommendations 
were supported by the information provided in the draft BRD.
    In January 2004, Xenobiotic Detection Systems, Inc. (XDS, Durham, 
NC) nominated their LUMI-CELL[supreg] BG1Luc ER TA test method for an 
interlaboratory validation study. This method uses BG-1 cells, a human 
ovarian carcinoma cell line that is stably transfected with an 
estrogen-responsive luciferase reporter gene to measure whether and to 
what extent a substance induces or inhibits TA activity via ER mediated 
pathways (Denison and Heath-Pagliuso, 1998). Included in the nomination 
package were test results from XDS for 56 of the 78 ICCVAM reference 
substances for agonist activity and 16 of the 78 ICCVAM reference 
substances for antagonist activity. These studies were funded primarily 
by an NIEHS Small Business Innovation Research (SBIR) grant 
(SBIR43ES010533-01).
    In accordance with the ICCVAM nomination process, NICEATM conducted 
a preliminary evaluation of the nomination package to determine the 
extent to which it addressed the ICCVAM prioritization criteria and 
adherence to the ICCVAM recommendations for the standardization and 
validation of in vitro endocrine disruptor test methods (ICCVAM, 
2003b). ICCVAM and the Scientific Advisory Committee on Alternative 
Toxicological Methods (SACATM) recommended that the BG1Luc ER TA test 
method should be

[[Page 28782]]

considered a high priority for interlaboratory studies based upon the 
lack of adequately validated test methods and the regulatory and public 
health need for such test methods. Based on this evaluation, ICCVAM 
recommended that:
     The BG1Luc ER TA test method should be considered a high 
priority for interlaboratory validation studies as an in vitro test 
method for the detection of test substances with ER agonist and 
antagonist activity.
     Validation studies should include coordination and 
collaboration with the European Centre for the Validation of 
Alternative Methods (ECVAM) and the Japanese Center for the Validation 
of Alternative Methods (JaCVAM) and include one laboratory in each of 
the three respective geographic regions (United States, Europe, and 
Japan).
     In preparation for the interlaboratory validation study, 
XDS should conduct protocol standardization studies with an emphasis on 
filling data gaps in the antagonist protocol for the BG1Luc ER TA.
    The NIEHS subsequently agreed to support the validation study in 
light of its role as one of the three NTP agencies, whose mission 
includes the development and validation of improved testing methods. 
Based on the results of this study, ICCVAM is now reviewing the 
validation status of this test method for identification of substances 
with in vitro ER agonist or antagonist activity. NICEATM and the ICCVAM 
Interagency Endocrine Disruptors Working Group prepared a draft BRD 
that provides a comprehensive description and the data from the 
validation study used to assess the accuracy and reliability of the 
BG1Luc ER TA test method. ICCVAM also developed draft recommendations 
for its use.

Availability of the Peer Panel Report

    The Panel's conclusions and recommendations are detailed in the 
Independent Scientific Peer Review Panel Report: Evaluation of the 
Validation Status of the BG1Luc4E2 ER TA (LUMICELL), an In Vitro 
Transcriptional Activation Assay Used to Identify Chemicals That Can 
Interact with Human Estrogen Receptors which is available along with 
the draft documents reviewed by the Panel and the draft ICCVAM test 
method recommendations at http://iccvam.niehs.nih.gov/methods/endocrine/PeerPanel11.htm.

Request for Public Comments

    NICEATM invites the submission of written comments on the Panel 
report. When submitting written comments, please refer to this Federal 
Register notice and include appropriate contact information (name, 
affiliation, mailing address, phone, fax, e-mail, and sponsoring 
organization, if applicable). All comments received will be made 
publicly available via the NICEATM-ICCVAM Web site at http://iccvam.niehs.nih.gov/methods/endocrine/PeerPanel11.htm. ICCVAM will 
consider the Panel report along with public comments and comments made 
by SACATM at their June 16-17, 2011 meeting (67 FR 23323) when 
finalizing test method recommendations. Final ICCVAM recommendations 
will be published in an ICCVAM test method evaluation report, which 
will be forwarded to relevant Federal agencies for their consideration. 
The evaluation report will also be available to the public on the 
NICEATM-ICCVAM Web site at http://iccvam.niehs.nih.gov/methods/endocrine/ERTA-TMER.htm and by request from NICEATM (see ADDRESSES 
above).

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 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 test methods that more accurately assess the safety and 
hazards of chemicals and products and that refine (decrease or 
eliminate pain and distress), reduce, and 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 and 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 welcome the public nomination of new, revised, and alternative 
test methods and strategies applicable to the needs of U.S. Federal 
agencies. Additional information about ICCVAM and NICEATM can be found 
on the NICEATM-ICCVAM Web site (http://iccvam.niehs.nih.gov).
    SACATM was established in response to the ICCVAM Authorization Act 
[Section 285l-3(d)] 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

    Denison MS, Heath-Pagliuso S. 1998. The Ah receptor: A regulator 
of the biochemical and toxicological actions of structurally diverse 
chemicals. Bull Environ Contam Toxicol 61(5): 557-568.
    ICCVAM. 2003a. ICCVAM Guidelines for the Nomination and 
Submission of New, Revised, and Alternative Test Methods. NIH 
Publication No. 03-4508. Research Triangle Park, NC.
    ICCVAM. 2003b. ICCVAM Evaluation of In Vitro Test Methods For 
Detecting Potential Endocrine Disruptors: Estrogen Receptor and 
Androgen Receptor Binding and Transcriptional Activation Assays.


    Dated: May 11, 2011.
John R. Bucher,
Associate Director, National Toxicology Program.
[FR Doc. 2011-12264 Filed 5-17-11; 8:45 am]
BILLING CODE 4140-01-P