[Federal Register Volume 77, Number 30 (Tuesday, February 14, 2012)]
[Notices]
[Pages 8258-8260]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2012-3437]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES


Availability of ICCVAM Evaluation Report and 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 report and recommendations; Notice of 
Transmittal.

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SUMMARY: The NTP Interagency Center for the Evaluation of Alternative 
Toxicological Methods (NICEATM) announces availability of an 
Interagency Coordinating Committee on the

[[Page 8259]]

Validation of Alternative Methods (ICCVAM) test method evaluation 
report (TMER) that includes recommendations on the usefulness and 
limitations of the LUMI-CELL[supreg] estrogen receptor (ER) 
transcriptional activation (TA) test method (hereafter referred to as 
the BG1Luc ER TA test method) to identify human ER agonist and 
antagonist activity of chemicals. The report also provides (1) 
performance standards that can be used to evaluate functionally and 
mechanistically similar test methods, (2) recommended test method 
protocols, (3) a final background review document (BRD) describing the 
current validation status of this test method, and (4) recommendations 
for future studies.
    ICCVAM recommends that the BG1Luc ER TA test method can be used as 
a screening test to identify substances with in vitro estrogen agonist 
and antagonist activity. This use is based on an evaluation of results 
from an international validation study and corresponding accuracy and 
reliability.
    The report and recommendations have been transmitted to Federal 
agencies to review and respond to ICCVAM in accordance with the 
provisions of the ICCVAM Authorization Act of 2000 (42 U.S.C. 285l-2).

FOR FURTHER INFORMATION CONTACT: Dr. William S. Stokes, Director, 
NICEATM, NIEHS, P.O. Box 12233, Mail Stop: K2-16, Research Triangle 
Park, NC, 27709, (telephone) 919-541-2384, (fax) 919-541-0947, (email) 
[email protected]. Courier address: NICEATM, NIEHS, Room 2034, 530 
Davis Drive, Morrisville, NC 27560.

SUPPLEMENTARY INFORMATION:

Background

    In January 2004, Xenobiotic Detection Systems, Inc. (XDS, Durham, 
NC) nominated the BG1Luc ER TA test method for an interlaboratory 
validation study. ICCVAM and the Scientific Advisory Committee on 
Alternative Toxicological Methods (SACATM) recommended a high priority 
for the nominated study, based on the lack of adequately validated test 
methods and the regulatory and public health need for such test 
methods. NICEATM subsequently led and coordinated an international 
validation study with its counterparts in Japan (Japanese Center for 
the Validation of Alternative Methods) and Europe (European Centre for 
the Validation of Alternative Methods) in laboratories sponsored by 
each validation organization. ICCVAM also proposed the development of 
BG1Luc ER TA test method performance standards. ICCVAM assigned the 
activities a high priority after considering comments from the public 
and endorsement from SACATM.
    ICCVAM established an interagency Endocrine Disruptor Working Group 
(EDWG) composed of scientists from the 15 Federal agencies represented 
on ICCVAM to work with NICEATM to carry out the relevant evaluation 
activities. Following completion of the validation study, NICEATM, 
ICCVAM, and the EDWG prepared a draft BRD and draft test method 
recommendations. NICEATM released the ICCVAM draft documents to the 
public for comment and convened an international independent scientific 
peer review panel (hereafter referred to as the Panel) in public 
session on March 29-30, 2011, to provide their conclusions on the draft 
BRD and draft ICCVAM test method recommendations (76 FR 4113). 
Stakeholders from the public were provided opportunities to comment 
throughout the review process, including the opportunity for oral 
comments at the Panel meeting. The Panel considered these comments, as 
well as public comments submitted prior to the meeting, before 
concluding its deliberations. The Panel report was published and made 
available to the public for review and comment (76 FR 28781). The draft 
test method recommendations, the draft BRD, the draft Panel report, and 
all public comments were made available to SACATM, which provided 
comments at its public meeting on June 16-17, 2011 (76 FR 23323).
    ICCVAM considered the peer review panel report and all public and 
SACATM comments in preparing the ICCVAM final test method 
recommendations. Detailed ICCVAM recommendations are provided in the 
ICCVAM TMER, 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, 
available at http://iccvam.niehs.nih.gov/methods/endocrine/ERTA-TMER.htm). ICCVAM recommends that the BG1Luc ER TA test method can be 
used as a screening test to identify substances with in vitro estrogen 
agonist activity. This use is based on an evaluation of available 
validation study data and corresponding accuracy and reliability. 
ICCVAM recommends that the accuracy of this assay is at least 
equivalent to the current ER TA assay included in regulatory testing 
guidance. The ICCVAM TMER also includes the updated ICCVAM-recommended 
BG1Luc ER TA test method protocol, performance standards that are 
applicable to functionally and mechanistically similar test methods, 
the final BRD, relevant endocrine disruptor testing regulations and 
testing guidelines, applicable Federal Register notices, the Panel 
report, public comments, and SACATM meeting minutes.

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 methods that more accurately assess the safety and 
hazards of chemicals and products and that reduce, refine (decrease or 
eliminate 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 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 
(Section 285l-3[d]) and is composed of scientists from the public and 
private sectors (67 FR 11358). 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.

[[Page 8260]]

References

    EPA. 2009. Endocrine Disruptor Screening Program Test 
Guidelines. OPPTS 890.1300: Estrogen Receptor Transcriptional 
Activation (Human Cell Line (HeLa-9903)). Washington, DC: U.S. 
Environmental Protection Agency. Available: http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPPT-2009-0576-0006.
    ICCVAM. 2011. ICCVAM Test Method Evaluation Report: The LUMI-
CELL[reg] ER (BG1Luc ER TA) Test Method: An In Vitro Assay for 
Identifying Human Estrogen Receptor Agonist and Antagonist Activity 
of Chemicals. Research Triangle Park, NC: National Institute of 
Environmental Health Sciences. Available: http://iccvam.niehs.nih.gov/methods/endocrine/ERTA-TMER.htm.
    ICCVAM. 2006. Addendum to ICCVAM Evaluation of In Vitro Test 
Methods for Detecting Potential Endocrine Disruptors. Research 
Triangle Park, NC: National Institute of Environmental Health 
Sciences. Available: http://iccvam.niehs.nih.gov/docs/endo_docs/EDAddendFinal.pdf.
    ICCVAM. 2003a. ICCVAM Evaluation of In Vitro Test Methods For 
Detecting Potential Endocrine Disruptors: Estrogen Receptor and 
Androgen Receptor Binding and Transcriptional Activation Assays. NIH 
Publication No. 03-4503. Research Triangle Park, NC: National 
Institute of Environmental Health Sciences. Available: http://iccvam.niehs.nih.gov/methods/endocrine/end_TMER.htm.
    ICCVAM. 2002a. Background Review Document. Current Status of 
Test Methods for Detecting Endocrine Disruptors: In Vitro Estrogen 
Receptor Transcriptional Activation Assays. NIH Publication No. 03-
4505. Research Triangle Park, NC: National Institute of 
Environmental Health Sciences. Available: http://iccvam.niehs.nih.gov/methods/endocrine/end_bckgnd.htm#ERTA.
    ICCVAM. 2002b. Background Review Document. Current Status of 
Test Methods for Detecting Endocrine Disruptors: In Vitro Androgen 
Receptor Binding Assays. NIH Publication No. 03-4506. Research 
Triangle Park, NC: National Institute of Environmental Health 
Sciences. Available: http://iccvam.niehs.nih.gov/methods/endocrine/end_bckgnd.htm#ARBnd.
    ICCVAM. 2002c. Background Review Document: Current Status of 
Test Methods for Detecting Endocrine Disruptors: In Vitro Estrogen 
Receptor Binding Assays. NIH Publication No. 03-4504. Research 
Triangle Park, NC: National Institute of Environmental Health 
Sciences. Available: http://iccvam.niehs.nih.gov/methods/endocrine/end_bckgnd.htm#ERBnd.
    ICCVAM. 2002d. Background Review Document. Current Status of 
Test Methods for Detecting Endocrine Disruptors: In Vitro Androgen 
Receptor Transcriptional Activation Assays. NIH Publication No. 03-
4507. Research Triangle Park, NC: National Institute of 
Environmental Health Sciences. Available: http://iccvam.niehs.nih.gov/methods/endocrine/end_bckgnd.htm#ARTA.
    ICCVAM. 2002e. Expert Panel Evaluation of the Validation Status 
of In Vitro Test Methods for Detecting Endocrine Disruptors: 
Estrogen Receptor and Androgen Receptor Binding and Transcriptional 
Activation Assays. Expert Panel Final Report. Research Triangle 
Park, NC: National Institute of Environmental Health Sciences. 
Available: http://iccvam.niehs.nih.gov/methods/endocrine/end_EPrpt.htm.
    OECD. 2009. Test No 455: The Stably Transfected Human Estrogen 
Receptor-alpha Transcriptional Activation Assay for Detection of 
Estrogenic Agonist-Activity of Chemicals. In: OECD Guidelines for 
the Testing of Chemicals, Section 4: Health Effects. Paris: OECD 
Publishing. Available: http://www.oecd-ilibrary.org/environment/oecd-guidelines-for-the-testing-of-chemicals-section-4-health-effects_20745788.
    Rogers JM, Denison MS. 2000. Recombinant cell bioassays for 
endocrine disruptors: Development of a stably transfected human 
ovarian cell line for the detection of estrogenic and anti-
estrogenic chemicals. In Vitro Mol Toxicol 13(1):67-82.

    Dated: February 7, 2012.
John R. Bucher,
Associate Director, National Toxicology Program.
[FR Doc. 2012-3437 Filed 2-13-12; 8:45 am]
BILLING CODE 4140-01-P