05-5564. National Toxicology Program; National Toxicology Program (NTP) Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM); Request for Nominations for an Independent Peer Review Panel To Evaluate In Vitro Testing ...

AGENCY:

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

ACTION:

Request for nominations for an independent peer review panel and request for in vivo and in vitro data.

SUMMARY:

The NTP Interagency Center for Evaluation of Alternative Toxicological Methods (NICEATM) in collaboration with the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) is planning to convene an independent peer review panel (hereafter, Panel) to evaluate the validation status of two in vitro cytotoxicity assays for estimating in vivo acute oral toxicity. The Panel will evaluate the usefulness, limitations, accuracy, and reliability of these test methods for their intended purpose. NICEATM requests nominations of expert scientists for consideration as potential Panel members. ICCVAM will consider the conclusions and recommendations from the Panel in developing test method recommendations and performance standards for these test methods. Data from standard in vivo acute oral toxicity testing and in vitro cytotoxicity testing also is requested.

DATES:

Nominations and data should be received by noon on May 6, 2005.

ADDRESSES:

Nominations and data should be sent by mail, fax, or e-mail to Dr. William S. Stokes, Director of NICEATM, at NICEATM, NIEHS, P.O. Box 12233, MD EC-17, Research Triangle Park, NC 27709, (phone) 919-541-2384, (fax) 919-541-0947, (e-mail) [e-mail]. Courier address: NICEATM, 79 T.W. Alexander Drive, Building 4401, Room 3128, Research Triangle Park, NC 27709.

FOR FURTHER INFORMATION CONTACT:

NICEATM, NIEHS, P.O. Box 12233, MD EC-17, Research Triangle Park, NC 27709, (phone) 919-541-2384, (fax) 919-541-0947, (e-mail) [e-mail].

SUPPLEMENTARY INFORMATION:

Background

NICEATM and the European Committee on the Validation of Alternative Methods (ECVAM) conducted a collaborative validation study to independently evaluate the usefulness of two in vitro basal cytotoxicity assays proposed for estimating in vivo rat acute oral toxicity. Neutral red uptake assays using both a mouse cell line (i.e., BALB/c 3T3 fibroblasts) and a primary human cell type (i.e., normal human epithelial keratinocytes) were evaluated in a multi-laboratory validation study. Cytotoxicity results are proposed for use in predicting starting doses for in vivo acute oral lethality assays, which may reduce the number of animals required for such determinations.

NICEATM is preparing Background Review Documents on the two in vitro test methods that will contain comprehensive summaries of available data, an analysis of the accuracy and reliability of standardized test method protocols, and related information characterizing the current validation status of these assays. Once completed, the Background Review Documents will be provided to the Panel and made available to the public. Meeting information, including date and location, and public availability of the Background Review Documents will be announced in a future Federal Register notice and posted on the ICCVAM/NICEATM Web site (http://iccvam.niehs.nih.gov).

Request for the Nomination of Scientists for the Peer Review Panel

NICEATM invites nominations of scientists with relevant knowledge and experience to serve on the Panel. Areas of relevant expertise include, but are not limited to: physiology and pharmacology, acute systemic toxicity testing in animals, evaluation and treatment of acute toxicity in humans, development and use of in vitro methodologies, biostatistical data analysis, knowledge of chemical data sets useful for validation of acute toxicity studies, and hazard classification of chemicals and products. Each nomination should include the person's name, affiliation, contact information (i.e. mailing address, e-mail address, telephone and fax numbers), and a brief summary of relevant experience and qualifications. Nominations should be sent to NICEATM by mail, fax, or e-mail within 45 days of the publication of this notice. Correspondence should be directed to Dr. William Stokes, Director, NICEATM, at the address given above.

Request for Data

NICEATM invites the submission of data from standard in vivo acute oral toxicity testing and in vitro cytotoxicity testing. Two previous requests for existing in vivo and in vitro acute toxicity data have been made (Federal Register, Vol. 69, No. 201, pp. 61504-5, October 19, 2004 and Vol. 65, No. 115, pp. 37400-3, June 14, 2000). In vivo and in vitro acute toxicity testing data for chemicals or products should be sent to NICEATM by mail, fax, or e-mail to the address given above. Data submitted by the deadline listed in this notice will be considered during an evaluation of the validation status of the two cytotoxicity methods, anticipated in late 2005; however, data will be accepted at any time. Chemical and protocol information/test data submitted in response to this notice may be incorporated in future NICEATM and ICCVAM reports and publications as appropriate.

When submitting chemical and protocol information/test 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 data to be submitted as copies of pages from study notebooks and/or study reports, if available. Raw data and analyses available in electronic format may also be submitted. Each submission for a chemical should preferably include the following information, as appropriate:

• Common and trade name.
• Chemical Abstracts Service Registry Number (CASRN).
• Chemical class.
• Product class.
• Commercial source.
• In vitro basal cytotoxicity test protocol used.
• In vitro cytotoxicity test results.
• In vivo acute oral toxicity test protocol used.
• Individual animal responses at each observation time (if available).
• The extent to which the study complied with national or international Good Laboratory Practice (GLP) guidelines.
• Date and testing organization.

Those persons submitting data on chemicals tested for in vitro basal cytotoxicity are referred to the standard test-reporting template recommended for the High Production Volume (HPV) program at http://www.epa.gov/​chemrtk/​toxprtow.htm or at http://iccvam.niehs.nih.gov/​methods/​invitro.htm. In vivo data for the same chemicals should be reported as recommended in the test reporting section of the current Environmental Protection Agency (EPA) guideline for acute oral toxicity (EPA, 2002).

Submitted data will be used to further evaluate the usefulness and limitations of in vitro cytotoxicity data for estimating acute oral toxicity and will be included in a database to support the investigation of other test methods necessary to improve the accuracy of in vitro assessments of acute systemic toxicity.

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, and replace animal use. The ICCVAM Authorization Act of 2000 (Pub. L. 106-545, available at http://iccvam.niehs.nih.gov/​about/​PL106545.htm) 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 NICEATM can be found at the following Web site: http://iccvam.niehs.nih.gov.

Dated: March 11, 2005.

Samuel H. Wilson,

Deputy Director, National Institute of Environmental Health Sciences.