[Federal Register Volume 74, Number 227 (Friday, November 27, 2009)]
[Notices]
[Pages 62317-62319]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E9-28278]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES


National Toxicology Program (NTP); NTP Interagency Center for the 
Evaluation of Alternative Toxicological Methods (NICEATM); Evaluation 
of In Vitro Estrogen Receptor Transcriptional Activation and In Vitro 
Cell Proliferation Assays for Endocrine Disruptor Chemical Screening: 
Request for Nominations for an Independent Expert Peer Review Panel and 
Submission of Relevant In Vitro and In Vivo Data

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

ACTION: Request nominations for an independent expert panel and 
submission of relevant data.

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SUMMARY: NICEATM, in collaboration with the Interagency Coordinating 
Committee on the Validation of Alternative Methods (ICCVAM), is 
planning to convene an independent scientific peer review panel 
(hereafter, Panel) to assess the validation status of an in vitro 
stably-transfected estrogen receptor (ER) transcriptional activation 
(TA) Assay (LUMI-CELL[supreg] ER assay) and an in vitro cell 
proliferation assay (CertiChem MCF-7 Cell Proliferation assay) for 
their usefulness and limitations in determining whether and to what 
extent chemicals can interact with estrogen receptors in vitro.
    Validated assays that can detect the interaction of chemicals with 
specific hormone receptors including the ER are included in the U.S. 
Environmental Protection Agency (EPA) Endocrine Disruptor Screening 
Program (EDSP) (http://www.epa.gov/endo/pubs/assayvalidation/status.htm). The two assays that will undergo peer review are currently 
undergoing validation studies to determine their usefulness and 
limitations for the EDSP. Any other existing data from these two assays 
are requested to ensure that all available relevant data are considered 
by the Panel. Data from other existing in vitro and in vivo assays for 
the 78 reference substances used for the validation studies (available 
at http://iccvam.niehs.nih.gov/docs/endo_docs/EDAddendFinal.pdf) are 
requested for use in characterizing the expected in vitro and in vivo 
activity of these 78 reference substances. At this time NICEATM 
requests:
     Nominations of expert scientists for consideration as 
potential Panel members.
     Submission of existing data from the LUMI-CELL[supreg] ER 
and the CertiChem MCF-7 Cell Proliferation assays.
     Submission of data from in vivo or other in vitro 
assessments for the 78 reference substances recommended by ICCVAM for 
the validation of in vitro ER and AR binding and TA test methods 
(available at http://iccvam.niehs.nih.gov/docs/endo_docs/EDAddendFinal.pdf).

DATES: Submit nominations and data by January 11, 2010. Data submitted 
after this date will be considered in the evaluation, where feasible.

ADDRESSES: Submit nominations and data electronically by e-mail to 
[email protected], or via the NICEATM-ICCVAM Web site at http://iccvam.niehs.nih.gov/contact/FR_pubcomment.htm. Nominations and data 
may also be sent by mail or fax to 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, (e-mail). 
Courier address: NIEHS, NICEATM, 530 Davis Drive, Room 2034, 
Morrisville, NC 27560.

[[Page 62318]]


FOR FURTHER INFORMATION CONTACT: Dr. William S. Stokes, (telephone) 
919-541-2384, (fax) 919-541-0947 and (e-mail) [email protected].

SUPPLEMENTARY INFORMATION:

Background

    In April 2000, the EPA requested that ICCVAM evaluate the 
validation status of in vitro ER and AR binding and TA assays for 
potential use in the proposed EPA EDSP. ICCVAM and NICEATM compiled 
available relevant data for 137 existing assays and compiled data were 
submitted to an independent expert panel for review. This panel 
concluded that there were no adequately validated in vitro ER- or AR-
based test methods (the panel's report is available on the NICEATM-
ICCVAM Web site at http://iccvam.niehs.nih.gov/methods/endocrine/end_EPrpt.htm). Based on these conclusions and recommendations, along with 
comments from the public, ICCVAM recommended minimum procedural 
standards and a list of 78 reference substances that should be used to 
standardize and validate in vitro ER and AR binding and TA test method 
protocols. These recommendations were made publicly available in the 
report: ICCVAM Evaluation of the In Vitro Methods for Detecting 
Potential Endocrine Disruptors: Estrogen Receptor and Androgen Receptor 
Binding and Transcriptional Activation Assays (available at: http://iccvam.niehs.nih.gov/methods/endocrine/end_TMER.htm). The list of 78 
reference substances was subsequently modified because of cost and 
availability considerations and published in a separate Addendum 
(available at: http://iccvam.niehs.nih.gov/docs/endo_docs/EDAddendFinal.pdf).
    Two in vitro assays to detect ER agonists and antagonists were 
subsequently nominated to ICCVAM for validation studies in response to 
an ICCVAM request (69 FR 21564): The LUMI-CELL[supreg] ER assay 
developed by Xenobiotic Detection Systems, Inc. (XDS) and the CertiChem 
MCF-7 Cell Proliferation assay developed by CertiChem, Inc. 
(CertiChem). Based on preliminary results provided for these test 
methods and comments from the public and the Scientific Advisory 
Committee on Alternative Toxicological Methods (SACATM; 69 FR 21564 and 
71 FR 60748, respectively), ICCVAM and its Endocrine Disruptor Working 
Group recommended a high priority for validation studies for the LUMI-
CELL[supreg] ER and CertiChem MCF-7 Cell Proliferation assays.
    An international interlaboratory validation study of the LUMI-
CELL[supreg] ER assay is currently nearing completion. The study 
includes three laboratories sponsored by NICEATM, the European Centre 
for the Validation of Alternative Methods, and the Japanese Center for 
the Validation of Alternative Methods. An intralaboratory validation 
study of the MCF-7 Cell Proliferation assay has been completed by 
CertiChem in conjunction with NICEATM, and an interlaboratory study is 
planned.
    NICEATM will prepare draft background review documents (BRDs) 
following completion of the validation studies that will provide 
comprehensive summaries of available data, analyses of test method 
accuracy and reliability, and related information characterizing the 
current validation status of each of the assays. The draft BRDs will 
form the basis for draft ICCVAM test method recommendations on 
usefulness and limitations, standardized test method protocols, future 
studies, and performance standards that will subsequently be provided 
to the Panel and made available to the public. The Panel will meet in 
public session to review the validation status of the LUMI-CELL[supreg] 
ER, MCF-7 Cell Proliferation assays, and any of the other assays for 
which there are adequate data available. The Panel will comment on the 
extent to which the BRD supports draft ICCVAM test method 
recommendations. The Panel may also consider the results for other 
assays with incomplete validation databases to determine their current 
validation status and to identify data gaps that need to be addressed 
in order to further characterize their usefulness and limitations for 
the EDSP. Meeting information, including dates, locations, and public 
availability of the BRDs will be announced in future Federal Register 
notices and will also be posted on the ICCVAM/NICEATM Web site (http://iccvam.niehs.nih.gov/methods/endocrine/end_eval.htm).

Request for Nominations of Scientific Experts

    NICEATM requests nominations of scientists with relevant knowledge 
and experience to serve on the Panel. Areas of relevant expertise 
include, but are not limited to, biostatistics, cellular biology, 
endocrinology, molecular genetics, regulatory toxicology, reproductive 
toxicology, and test method validation. Each nomination should include 
the nominee's name, affiliation, contact information (i.e., mailing 
address, email address, telephone, and fax numbers), curriculum vitae, 
and a brief summary of relevant experience and qualifications.

Request for Data

    NICEATM invites the submission of relevant in vitro and in vivo 
data and information for reference substances on the list of 78 
substances recommended by ICCVAM for standardizing and validating in 
vitro ER and AR binding and TA test methods (available at http://iccvam.niehs.nih.gov/docs/endo_docs/EDAddendFinal.pdf) or other 
substances for which data exists from the two in vitro test methods 
described in this notice. Relevant in vivo data may include, but are 
not limited to: Multi-generational reproductive and developmental 
toxicity studies, uterotrophic bioassays, and short term assays 
assessing changes in phenotypic parameters such as anogenital distance, 
time of vaginal opening, nipple retention, and preputial separation 
delays in males.
    Although data can be accepted at any time, data received by January 
11, 2010 will ensure consideration during the ICCVAM evaluation 
process. Relevant data received after this date will be considered 
during the ICCVAM evaluation process where feasible. All information 
submitted in response to this notice will be made publicly available 
and may be incorporated into future NICEATM and ICCVAM reports and 
publications as appropriate.
    When submitting data, please reference this Federal Register notice 
and provide appropriate contact information (name, affiliation, mailing 
address, phone, fax, e-mail, and sponsoring organization, as 
applicable).
    NICEATM prefers that data be submitted as copies of pages from 
study notebooks and/or study reports, if available. Laboratory data and 
analyses available in electronic format may also be submitted. Each 
submission for a substance should preferably include the following 
information, as appropriate:
     Common and trade name
     Chemical Abstracts Service Registry Number (CASRN)
     Commercial source
     In vivo or in vitro test protocol used
     Individual animal or in vitro responses at each 
observation time (i.e., laboratory data)
     The extent to which the data were collected in accordance 
with national/international Good Laboratory Practice guidelines
     Date and testing organization
     Physical and chemical properties (e.g., molecular weight, 
pH, water solubility, etc.)

[[Page 62319]]

Background Information on ICCVAM, NICEATM, and SACATM

    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, and replace 
animal use. The ICCVAM Authorization Act of 2000 (42 U.S.C. 285l-3, 
available at http://iccvam.niehs.nih.gov/docs/about_docs/PL106545.pdf) 
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. NICEATM and ICCVAM 
work collaboratively to evaluate new and improved test methods 
applicable to the needs of Federal agencies. Additional information 
about ICCVAM and NICEATM is available on the NICEATM-ICCVAM Web site: 
http://iccvam.niehs.nih.gov.
    SACATM was established January 9, 2002 and is composed of 
scientists from the public and private sectors (67 FR 11358). SACATM 
provides advice to the Director of the NIEHS, ICCVAM, and NICEATM 
regarding the statutorily mandated duties of ICCVAM and activities of 
NICEATM. Additional information about SACATM, including the charter, 
roster, and records of past meetings, can be found at http://ntp.niehs.nih.gov/go/167.

    Dated: November 16, 2009.
John R. Bucher,
Associate Director, National Toxicology Program.
[FR Doc. E9-28278 Filed 11-25-09; 8:45 am]
BILLING CODE 4140-01-P