[Federal Register: June 1, 2009 (Volume 74, Number 103)]
[Notices]               
[Page 26242-26243]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr01jn09-45]                         

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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); Independent 
Scientific Peer Review Panel Report: Updated Validation Status of New 
Versions and Applications of the Murine Local Lymph Node Assay: A Test 
Method for Assessing the Allergic Contact Dermatitis Potential of 
Chemicals and Products: Notice of Availability and Request for Public 
Comments

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

ACTION: Request for comments.

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SUMMARY: NICEATM, in collaboration with the Interagency Coordinating 
Committee on the Validation of Alternative Methods (ICCVAM), convened 
an independent, international, scientific peer review panel (hereafter, 
Panel) on April 28-29, 2009, to evaluate three non-radioactive modified 
versions and new applications for the Murine Local Lymph Node Assay 
(LLNA). The LLNA is an alternative test method that can be used to 
determine the allergic contact dermatitis potential of chemicals and 
products. The Panel report from this meeting is now available. The 
report contains (1) the Panel's evaluation of the updated validation 
status of the methods and (2) the Panel's comments on the updated draft 
ICCVAM test method recommendations. NICEATM invites public comment on 
the Panel's report. The report is available on the NICEATM-ICCVAM Web 
site at http://iccvam.niehs.nih.gov/docs/immunotox_docs/
LLNAPRPRept2009.pdf or by contacting NICEATM at the address given 
below.

DATES: Written comments on the Panel report should be received by July 
15, 2009.

ADDRESSES: Comments should be submitted preferably electronically via 
the NICEATM-ICCVAM Web site at http://iccvam.niehs.nih.gov/contact/FR_
pubcomment.htm. Comments can also be submitted by e-mail to 
niceatm@niehs.nih.gov. Written comments can 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; (fax) 919-541-0947. 
Courier address: NIEHS, NICEATM, 530 Davis Drive, Room 2035, Durham, NC 
27713.

FOR FURTHER INFORMATION CONTACT: Dr. William S. Stokes (telephone) 919-
541-2384, (fax) 919-541-0947 and (e-mail) niceatm@niehs.nih.gov.

SUPPLEMENTARY INFORMATION:

Background

    In January 2007, the Consumer Product Safety Commission submitted a 
nomination to NICEATM and ICCVAM to assess the validation status of (1) 
the use of the LLNA to determine potency for hazard classification 
purposes, (2) LLNA protocols using non-radioactive procedures, (3) the 
LLNA limit dose procedure, and (4) the use of the LLNA to test 
mixtures, aqueous solutions, and metals (i.e., an updated assessment of 
the applicability domain of the LLNA). In June 2007, the Scientific 
Advisory Committee on Alternative Toxicological Methods (SACATM) 
endorsed these activities as high priorities for ICCVAM. NICEATM, on 
behalf of ICCVAM, also sought input from the public on these activities 
and requested data from studies using the LLNA or modified versions of 
the LLNA (72 FR 27815). After considering all comments received, ICCVAM 
endorsed carrying out these activities as high priorities. ICCVAM also 
developed draft LLNA performance standards to facilitate evaluation of 
modified LLNA protocols that are functionally and mechanistically 
similar to the traditional LLNA. These draft LLNA performance standards 
were made public and comments were requested in September 2007 (72 FR 
52130).
    ICCVAM and NICEATM prepared draft background review documents 
(BRDs) that provided comprehensive reviews of available data and 
relevant information for each of the modifications and new applications 
of the LLNA. ICCVAM also developed draft test method recommendations 
regarding the proposed usefulness and limitations, standardized 
protocols, and future studies. NICEATM announced availability of the 
draft BRDs and draft recommendations for public comment and the public 
peer review meeting in January 2008 (73 FR 1360).
    The Panel met in public session on March 4-6, 2008, to review these 
topics, and their report was made available in May 2008 (73 FR 29136). 
The draft BRDs and draft test method recommendations, the draft ICCVAM 
LLNA test method performance standards, the Panel's report, and all 
public comments were made available to SACATM for comment at their 
meeting on June 18-19, 2008 (73 FR 25754).
    As a result of additional data received by ICCVAM subsequent to the 
March 2008 Panel meeting, the draft BRDs for the following were 
updated:
     The validation status of three modified LLNA test method 
protocols that do not require the use of radioactive substances.
     The use of the LLNA for testing pesticide formulations, 
other products, and aqueous solutions.

Second Meeting of the Peer Review Panel

    The Panel met again in public session on April 28-29, 2009 (74 FR 
8974). The Panel reviewed the revised draft ICCVAM documents for 
completeness, errors, and omissions of any existing relevant data or 
information. The Panel evaluated the information in the revised draft 
documents to determine the extent to which each of the applicable 
criteria for validation and acceptance of toxicological test methods 
(ICCVAM, 2003) had been appropriately addressed. The Panel then 
considered the ICCVAM draft recommendations for test method uses and 
limitations, proposed standardized protocol, proposed plans for 
development of test method performance standards, and proposed 
additional studies, and commented on the extent that the 
recommendations were supported by the information provided in the draft 
BRDs.

Availability of the Peer Panel Report

    The Panel's conclusions and recommendations are detailed in the

[[Page 26243]]

Independent Scientific Peer Review Panel Report: Updated Validation 
Status of New Versions and Applications of the Murine Local Lymph Node 
Assay: A Test Method for Assessing the Allergic Contact Dermatitis 
Potential of Chemicals and Products (available at http://
iccvam.niehs.nih.gov/docs/immunotox_docs/LLNAPRPRept2009.pdf). The 
revised draft documents reviewed by the Panel and the draft ICCVAM test 
method recommendations are available at http://iccvam.niehs.nih.gov/
methods/immunotox/llna_PeerPanel.htm.

Request for Public Comments

    NICEATM invites the submission of written comments on the Panel's 
report. When submitting written comments, please refer to this Federal 
Register notice and include appropriate contact information (name, 
affiliation, mailing address, phone, fax, e-mail, and sponsoring 
organization, if applicable). All comments received will be made 
publicly available via the NICEATM-ICCVAM Web site at http://
iccvam.niehs.nih.gov/methods/immunotox/llna_PeerPanel.htm. In 
addition, there will be an opportunity for oral public comments on the 
Panel's report during an upcoming meeting of SACATM scheduled for June 
25-26, 2009 (74 FR 19562). Information concerning the SACATM meeting is 
available at http://ntp.niehs.nih.gov/go/7441. ICCVAM will consider the 
Panel report along with SACATM and public comments when finalizing test 
method recommendations. An ICCVAM test method evaluation report, which 
will include the final ICCVAM recommendations, will be forwarded to 
relevant Federal agencies for their consideration. The evaluation 
report will also be available to the public on the NICEATM-ICCVAM Web 
site at http://iccvam.niehs.nih.gov/methods/immunotox/llna.htm and by 
request from NICEATM (see ADDRESSES above).

Background Information on ICCVAM, NICEATM, and SACATM

    ICCVAM is an interagency committee composed of representatives from 
15 Federal regulatory and research agencies that use, generate, or 
disseminate 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) 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 U.S. Federal agencies. 
Additional information about ICCVAM and NICEATM can be found on their 
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/ see ``Advisory Board & Committees'' (or directly at 
http://ntp.niehs.nih.gov/go/167).

Reference

    ICCVAM. 2003. ICCVAM Guidelines for the Nomination and 
Submission of New, Revised, and Alternative Test Methods. NIH 
Publication No. 03-4508. Research Triangle Park, NC: NIEHS. 
Available at: http://iccvam.niehs.nih.gov.

    Dated: May 19, 2009.
John R. Bucher,
Associate Director, NTP.
[FR Doc. E9-12360 Filed 5-29-09; 8:45 am]

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