[Federal Register Volume 72, Number 176 (Wednesday, September 12, 2007)]
[Notices]
[Pages 52130-52131]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E7-18011]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES


National Toxicology Program (NTP) Interagency Center for the 
Evaluation of Alternative Toxicological Methods (NICEATM); Draft 
Performance Standards for the Murine Local Lymph Node Assay: Request 
for Comments

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

ACTION: Request for comments.

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SUMMARY: The Murine Local Lymph Node Assay (LLNA) is the first 
alternative test method evaluated and recommended by the Interagency 
Coordinating Committee on the Validation of Alternative Methods 
(ICCVAM). It was subsequently accepted by regulatory authorities to 
determine the allergic contact dermatitis potential of chemicals and 
products. In January 2007, the U.S. Consumer Product Safety Commission 
(CSPC) submitted a nomination requesting that NICEATM and ICCVAM assess 
the validation status of (1) The LLNA as a stand-alone assay for 
potency determination for hazard classification purposes; (2) modified 
LLNA protocols; (3) the LLNA limit test; (4) the use of LLNA to test 
mixtures, aqueous solutions, and metals; and (5) the applicability 
domain for LLNA. In order to facilitate the review of the modified LLNA 
protocols, ICCVAM proposed developing performance standards for the 
LLNA. In May 2007, a Federal Register notice was published (Vol. 72, 
No. 95, pages 27815-27817, May 17, 2007) requesting comments and data 
relevant to these nominated activities. In June 2007, the Scientific 
Advisory Committee on Alternative Toxicological Methods (SACATM) 
endorsed the nominated activities as high priorities for ICCVAM. In 
response to SACATM comments, along with those provided by the public in 
response to the previous Federal Register notice, ICCVAM also endorsed 
these activities as high priorities. ICCVAM subsequently prepared draft 
performance standards for the LLNA and now requests public comments on 
this draft document, which is available on the NICEATM/ICCVAM Web site 
at: (http://iccvam.niehs.nih.gov/methods/immunotox/immunotox.htm) or by 
contacting NICEATM (see FOR FURTHER INFORMATION CONTACT below).

DATES: Submit comments on or before October 29, 2007.

ADDRESSES: Dr. William S. Stokes, NICEATM Director, NIEHS, P.O. Box 
12233, MD EC-17, Research Triangle Park, NC 27709, (fax) 919-541-0947, 
(e-mail) [email protected]. Courier address: NICEATM, 79 T.W. 
Alexander Drive, Building 4401, Room 3128, Research Triangle Park, NC 
27709. Responses can be submitted electronically at the ICCVAM-NICEATM 
Web site: http://iccvam.niehs.nih.gov/contact/FR_pubcomment.htm or by 
e-mail, mail, or fax.

FOR FURTHER INFORMATION CONTACT: Other correspondence should be 
directed to Dr. William S. Stokes (919-541-2384 or 
[email protected]).

SUPPLEMENTARY INFORMATION: 

Background

    The LLNA is an alternative test method used for skin sensitization 
testing that reduces the number of animals needed, reduces the time 
required for testing, and can substantially reduce or avoid pain and 
distress associated with traditional guinea pig testing methods. The 
LLNA was the first alternative test method evaluated and recommended by 
ICCVAM and based on the recommendations of ICCVAM and an independent 
scientific peer review panel, the LLNA has been accepted by U.S. and 
international regulatory authorities as an alternative to the guinea 
pig maximization test and Buehler test for assessing allergic contact 
dermatitis (EPA 2003; ISO 2002; OECD 2002). Since 2003, ICCVAM has 
routinely developed performance standards for test methods; however, 
because the concept of performance standards was not developed by 
ICCVAM until 2003, they were not developed during the ICCVAM evaluation 
of the LLNA in 1998 (NIH Publication No. 99-4494, available: (http://iccvam.niehs.nih.gov/docs/immunotox_docs/llna/llnarep.pdf).
    In January 2007, CSPC submitted a nomination requesting that 
NICEATM and ICCVAM assess the validation status of (1) The LLNA as a 
stand-alone assay for potency determination for classification 
purposes; (2) modified LLNA protocols; (3) the LLNA limit test; (4) the 
use of LLNA to test mixtures, aqueous solutions, and metals; and (5) 
the applicability domain for LLNA. ICCVAM endorsed the nomination and 
also decided to develop performance standards to facilitate evaluation 
of modified LLNA protocols to the traditional LLNA. In May 2007, a 
Federal Register notice was published requesting comments and data 
relevant to these activities (Vol. 72, No. 95, pages 27815-27817, May 
17, 2007; available,

[[Page 52131]]

http://iccvam.niehs.nih.gov/SuppDocs/FedDocs/FR/FR_E7_9544.pdf). In 
June 2007, SACATM endorsed these activities as high priorities for 
ICCVAM. In response to SACATM comments, along with those provided by 
the public in response to the previous Federal Register notice, ICCVAM 
endorsed these activities, including the development of performance 
standards, as high priorities. ICCVAM subsequently prepared draft 
performance standards for the LLNA, which are available on the NICEATM/
ICCVAM Web site at: (http://iccvam.niehs.nih.gov/methods/immunotox/immunotox.htm).
    These draft test method performance standards are proposed to 
evaluate the performance of LLNA test methods that incorporate specific 
modifications to the measurement of lymphocyte proliferation in the 
traditional LLNA. These modifications focus specifically on 
incorporating non-radioactive procedures to evaluate lymphocyte 
proliferation in the draining auricular lymph nodes rather than 
incorporation of radioactivity (i.e., 3H-thymidine), which 
is used in the traditional LLNA.
    Public comments received in response to the draft LLNA performance 
standards will be considered by ICCVAM during development of a revised 
draft version of this document. A public meeting is planned for early 
2008 where an international, independent, peer review panel will 
evaluate the revised draft LLNA performance standards and review the 
other nominated LLNA related activities. Following this meeting, the 
recommendations of the peer review panel will be made available for 
public and SACATM comment. ICCVAM will consider the panel report and 
public and SACATM comments in preparing final LLNA performance 
standards.

Request for Public Comments

    NICEATM invites the submission of written comments on the draft 
LLNA performance standards. 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 by 
the deadline listed above will be placed on the NICEATM/ICCVAM Web site 
(http://ntp-apps.niehs.nih.gov/iccvampb/searchPubCom.cfm) and made 
available to the peer review panel and ICCVAM.

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, or replace 
animal use. The ICCVAM Authorization Act of 2000 (42 U.S.C. 285l-3, 
available at http://iccvam.niehs.nih.gov/about/PL106545.htm) 
establishes 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 federal agencies. Additional information 
about ICCVAM and NICEATM is available on the following Web site: http://iccvam.niehs.nih.gov.

    Dated: September 5, 2007.
Samuel H. Wilson,
Acting Director, National Institute of Environmental Health Sciences 
and National Toxicology Program.
 [FR Doc. E7-18011 Filed 9-11-07; 8:45 am]
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