[Federal Register Volume 65, Number 34 (Friday, February 18, 2000)]
[Notices]
[Pages 8385-8386]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 00-4010]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Public Health Service


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 Assessing Acute Oral Toxicity; 
Evaluation of the Up-and-Down Procedure

    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: 919-541-7997; fax: 919-541-0947; e-
mail: [email protected].
    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: 703-305-7188; fax: 703-308-1805; e-mail: 
[email protected]. 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

[[Page 8386]]

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.
[FR Doc. 00-4010 Filed 2-17-00; 8:45 am]
BILLING CODE 4140-01-M