00-4010. National Institute of Environmental Health Sciences, National Toxicology Program: Request for Data and Nomination of Expert Scientists To Participate in the Independent Peer Review Evaluation of the Revised Up-and-Down Procedure for ...

The Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) and the National Toxicology Program (NTP) Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM) are currently planning a meeting where an Independent Peer Review Panel (hereafter, Panel) will assess the validation status of the revised Up-and-Down Procedure (UDP). This procedure is an updated version of the Organization for Economic Cooperation and Development (OECD) Test Guideline 425 (OECD Guideline for the Testing of Chemicals, Acute Oral Toxicity: Up-and-Down Procedure. Guideline 425, adopted September 21, 1998, OECD, Paris, France, http://www.oecd.org/​ehs/​test). The revised UDP is proposed as a substitute for the existing OECD Test Guideline 401 (OECD Guideline for the Testing of Chemicals, Acute Oral Toxicity, Guideline 401, adopted February 24, 1987, OECD, Paris, France). OECD has proposed that Guideline 401 should be deleted since three alternative methods are not available (OECD Document ENV/JM(99)19, Test Guidelines Programme, Acute Oral Toxicity Testing: Data Needs and Animal Welfare Considerations, 29th Joint Meeting, June 8-11, 1999, Paris, France). Prior to deletion of Guideline 401, U.S. agencies have requested that ICCVAM conduct an independent peer review of the revised UDP to determine the validity of the method as a replacement for Guideline 401. The Panel will evaluate the extent to which the validation and acceptance criteria (outline in NIH Publication 97-3981, Validation and Regulatory Acceptance of Toxicological Test Methods: A Report of the ad hoc Interagency Coordinating Committee on the Validation of Alternative Methods, http://ntpserver.niehs.nih.gov/​htdocs/​ICCVAM/​iccvam.html) have been addressed and will provide conclusions and recommendations regarding the usefulness and limitations of the method as a substitute for the traditional acute oral toxicity test method (OECD Guideline 401, 1987). The UDP has the potential to reduce the number of animals required to classify chemicals for acute oral toxicity as compared to Guideline 401.

Nomination of Experts To Serve on Review Panel and Request for Data

The Center welcomes the nomination of scientists with relevant knowledge and experience who might be considered for the Panel to review information on UDP. For each person suggested, his/her name, address, and a brief summary of relevant experience and qualifications should be provided. Where possible, telephone and fax numbers and/or e-mail address should also be provided. Nominations should be sent by mail, fax, or e-mail to NICEATM within 30 days of this notice's publication date. Correspondence should be directed to Dr. William S. Stokes, Co-Chair, ICCVAM, NTP Interagency Center for the Evaluation of Alternative Toxicological Methods, Environmental Toxicology Program, NIEHS/NTP, 79 T.W. Alexander Drive, MD EC-17, P.O. Box 12233, Research Triangle Park, NC 27709; phone: [phone]; fax: [phone]; e-mail: [e-mail].

The Center would also welcome data and information from completed, ongoing, or planned studies using or evaluating the UDP. Information should address applicable aspects of the validation and regulatory acceptance criteria provided in NIH Publication 97-3981, Validation and Regulatory Acceptance of Toxicological Test Methods: A Report of the ad hoc Interagency Coordinating Committee on the Validation of Alternative Methods (http://ntp-server.niehs.nih.gov/​htdocs/​ICCVAM/​iccvam.html). Where possible, data and information should adhere to the guidance provided in the document, Evaluation of the Validation Status of Toxicological Methods: General Guidelines for Submissions to ICCVAM (http://iccvam.niehs.nih.gov/​doc1.htm). Both documents are available by request from NICEATM at the address provided above. Information submitted in response to this request will be incorporated into the background material provided to the Panel. The Panel's peer review meeting is anticipated to take place in early to mid-summer, and meeting information (including date and location) and public availability of the background document will be announced in a future Federal Register notice and will be posted on the ICCVAM website (http://iccvam.niehs.nih.gov). Information about studies with UDP should be sent to Dr. Stokes (contact information provided above).

Persons requesting additional information regarding the rationale for the OECD proposal to delete the OECD Guideline 401 can contact William T. Meyer, U.S. Environmental Protection Agency, Office of Pesticide Programs, phone: [phone]; fax: [phone]; e-mail: [e-mail]. Mail address: Ariel Rios Bldg., 1200 Pennsylvania Avenue, NW, Mail Code 7506C, Washington, DC 20460; Federal Express address: 1921 Jefferson Davis Highway, Room 1104H, Arlington, VA 22202.

Background Information

ICCVAM, with participation by 14 Federal regulatory and research agencies, was established in 1997 to coordinate cross-agency issues relating to validation, acceptance, and national/international harmonization of toxicological test methods. ICCVAM seeks to promote the scientific validation and regulatory acceptance of toxicological test methods that will enhance the agencies' ability to assess risks and make decisions and that will refine, reduce, and replace animal use whenever possible. NICEATM provides administrative and technical support for ICCVAM and serves as a communication and information resource. NICEATM and ICCVAM collaborate to carry out related activities needed to develop, validate, and achieve regulatory acceptance of new and improved test methods applicable to Federal agencies. These activities may include:

1. Test Method Workshops are convened as needed to evaluate the adequacy of current test methods for assessing specific toxicities, to identify areas in need of improved or new testing methods, and to identify research and validation efforts that may be needed to develop a new test method.

2. Expert Panel Meetings are typically convened to evaluate the validation status of a test method following the completion of initial development and pre-validation studies. An Expert Panel is asked to recommend additional validation studies that might be helpful in further characterizing the usefulness of a method and to identify any additional research and development efforts that might support or enhance the accuracy and efficiency of a method.

3. Independent Peer Review Panel Meetings are typically convened following the completion of comprehensive validation studies on a test method. Panels are asked to develop scientific consensus on the usefulness and limitations of test methods and to generate information for specific human health and/or ecological risk assessment purposes. Following the review of a test method, ICCVAM forwards recommendations on its usefulness to agencies for their consideration. Federal agencies then determine the regulatory acceptability of a method according to their mandates.

Additional information about ICCVAM and NICEATM can be found at the website: http://iccvam.niehs.nih.gov.

Dated: February 11, 2000.

Samuel H. Wilson,

Deputy Director, National Institute of Environmental Health Sciences.