[Federal Register Volume 65, Number 106 (Thursday, June 1, 2000)]
[Notices]
[Pages 35109-35110]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 00-13734]



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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Public Health Service


National Institute of Environmental Health Sciences (NIEHS), 
National Institutes of Health (NIH), National Toxicology Program (NTP); 
Notice of Peer Review Meeting on the Revised Up-and-Down Procedure 
(UDP) as an Alternative Test Method for Assessing Acute Oral Toxicity; 
Request for Comments

Summary

    Pursuant to Public Law 103-43, notice is hereby given of a public 
meeting coordinated by the Interagency Coordinating Committee on the 
Validation of Alternative Methods (ICCVAM) and the NTP Interagency 
Center for the Evaluation of Alternative Toxicological Methods 
(NICEATM) and sponsored by NIEHS and the NTP. The agenda topic is the 
scientific peer review of the revised Up-and-Down Procedure, a method 
proposed as a replacement for the existing LD50 test for evaluating the 
acute oral toxicity potential of chemicals. The meeting will take place 
on July 25, 2000, from 8:30 a.m. to 5:30 p.m. at the Sheraton Crystal 
City Hotel, 1800 Jefferson Davis Highway, Arlington, VA 22202. The 
meeting is open to the public.

Background

    ICCVAM, with participation by 14 Federal regulatory and research 
agencies and programs, was established in 1997 to coordinate issues 
relating to the development, validation, acceptance, and national/
international harmonization of toxicological test methods. ICCVAM seeks 
to promote the scientific validation and regulatory acceptance of new 
and improved test methods applicable to Federal agencies including 
methods that may reduce and replace animal use, or that refine animal 
use to reduce or eliminate pain and distress. The Committee's functions 
include the coordination of interagency reviews of toxicological test 
methods and communication with stakeholders throughout the process of 
test method development and validation. The following Federal 
regulatory and research agencies and organizations participate in this 
effort:

Consumer Product Safety Commission
Department of Defense
Department of Energy
Department of Health and Human Services
    Agency for Toxic Substances and Disease Registry
    Food and Drug Administration
    National Institute for Occupational Safety and Health/CDC
    National Institutes of Health
    National Cancer Institute
    National Institute of Environmental Health Sciences
    National Library of Medicine
Department of the Interior
Department of Labor
    Occupational Safety and Health Administration
Department of Transportation
    Research and Special Programs Administration
Environmental Protection Agency

    The NTP Center for the Evaluation of Alternative Toxicological 
Methods (NICEATM) was established in 1998 and provides operational 
support for the ICCVAM. NICEATM and ICCVAM seek to promote the 
validation and regulatory acceptance of new test methods that will 
enhance agencies' abilities to assess risks, and that will refine, 
reduce, and replace animal use. NICEATM and ICCVAM collaborate to carry 
out activities associated with the development, validation, and 
regulatory acceptance of proposed new and improved test methods. These 
activities may include:
    Independent Peer Review Panel Meetings, which are typically 
convened following the completion of comprehensive validation studies 
on a test method. Independent peer review has been determined to be an 
essential prerequisite for consideration of a test method for 
regulatory acceptance. Peer Review Panels are asked to develop 
scientific consensus on the usefulness and limitations of test methods 
to generate information for specific human health and/or ecological 
risk assessment purposes. Following the independent peer review of a 
test method, ICCVAM forwards recommendations on their usefulness to 
agencies for their consideration. Federal agencies then determine the 
regulatory acceptability of a method according to their mandates.
    Expert Panel Meetings, which are typically convened to evaluate the 
validation status of a 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 enhance the 
effectiveness of a method.
    Test Method Workshops, which are convened, as needed, to evaluate 
the adequacy of current methods for assessing specific toxicities, to 
identify areas in need of improved or new testing methods, to identify 
research efforts that may be needed to develop new test methods, and to 
identify appropriate development and validation activities for proposed 
new methods.

Agenda

    The agenda topic is the scientific peer review evaluation of 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 now 
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 substitute for Guideline 401. 
An Independent Peer Review Panel will (1) evaluate the extent to which 
established validation and acceptance criteria (``Validation and 
Regulatory Acceptance of Toxicological Test Methods: A Report of the ad 
hoc Interagency Coordinating Committee on the Validation of Alternative 
Methods,'' NIH Publication No. 97-3981, http://ntpserver.niehs.nih.gov/htdocs/ICCVAM/iccvam.html) have been addressed, and (2) 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 compared to Guideline 401. A request 
for nominations of expert scientists for the Panel was previously 
published (FR 65, 8385-8386, February 18, 2000).
    The meeting will begin at 8:30 a.m. on July 25 and will conclude by 
5 p.m. There will be a brief orientation on ICCVAM and the ICCVAM 
review process, followed by a peer review of the revised UDP and 
supporting

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information. The Peer Review Panel will discuss the usefulness of the 
UDP as an alternative to the traditional LD50 methods currently 
accepted by government regulatory authorities for the assessment of 
acute oral toxicity potential of chemicals.

Background Document Available for Comment

    NICEATM has prepared a Background Review Document that includes the 
revised UDP protocol and documents supporting the basis and validity of 
the test method. Copies of the Up-and-Down Procedure Background Review 
Document and supporting documentation may be obtained from NICEATM, MD 
EC-17, P.O. Box 12233, Research Triangle Park, NC, 27709, Phone: 919-
541-3398, Fax: 919-541-0947, E-mail: [email protected]. A copy of 
the Background Review Document and comments submitted will be available 
for viewing Monday through Friday, from 12 noon to 4 p.m. EST at the U. 
S. Environmental Protection Agency, Office of Prevention, Pesticides 
and Toxic Substances, Non-Confidential Information Center, Room 607B, 
Northeast Mall, 401 M Street, SW, Washington, DC 20460. Thirty days 
prior to the meeting, a detailed agenda will be available on the web 
at: http://iccvam.niehs.nih.gov or by contacting NICEATM.
    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; E-mail: 
Meyer,[email protected]. Mail address: Ariel Rios Bldg., 1200 
Pennsylvania Ave., NW, Mail Code 7506C, Washington, DC 20460; Federal 
Express address: 1921 Jefferson Davis Highway, Room 1104H, Arlington, 
VA 22202.

Request for Comments

    NICEATM invites the submission of written comments on the revised 
Up-and-Down Procedure, and submission of other available information 
and data on the UDP, including information about completed, ongoing, or 
planned studies. Written comments and additional information should 
include name, affiliation, mailing address, phone, fax, e-mail and 
sponsoring organization (if any), and should be sent by mail, fax, or 
e-mail to NICEATM at the address listed above. Comments may be 
submitted anytime before the meeting; however, comments should be 
submitted by June 15 in order to ensure time for adequate review by the 
Panel. Written comments will be made available to the Peer Review Panel 
members, ICCVAM agency representatives and experts, and attendees at 
the meeting and will be included in the resource materials assembled on 
the UDP.
    The Expert Panel Meeting will be open to the public, and time will 
be provided for presentation of public oral comments at designated 
times during the meeting. Speakers will be assigned on a first-come, 
first-serve basis and up to seven minutes will be allotted to each 
speaker. In order to facilitate planning, members of the public who 
wish to present oral statements at the meeting should contact NICEATM 
as soon as possible, but no later than July 18, 2000. Persons 
registering to make comments are asked to provide, if possible, a 
written copy of their statement in advance so that copies can be made 
and distributed to the Peer Review Panel members for their timely 
consideration prior to the meeting. Written statements can supplement 
and expand the oral presentation, and each speaker is asked to provide 
his/her name, affiliation, mailing address, phone, fax, e-mail and 
supporting organization (if any). Registration for making public 
comments will also be available on-site. If registering on-site to 
speak and reading oral comments from printed copy, the speaker is asked 
to bring 50 copies of the text. These copies will be distributed to the 
Panel and supplement the record.
    Summary minutes from the meeting and the final report from the Peer 
Review Panel will be prepared and made available upon request to 
NICEATM (address provided above). These documents will also be made 
available via the internet at the website: http://iccvam.niehs.nih.gov.
    Additional information about ICCVAM and NICEATM can be found at the 
website:http://iccvam.niehs.nih.gov.

    Dated: May 22, 2000.
Samuel H. Wilson,
Deputy Director, National Institute of Environmental Health Sciences.
[FR Doc. 00-13734 Filed 5-31-00; 8:45 am]
BILLING CODE 4140-01-P