[Federal Register Volume 72, Number 95 (Thursday, May 17, 2007)]
[Notices]
[Pages 27815-27817]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E7-9544]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES


National Toxicology Program (NTP) Interagency Center for the 
Evaluation of Alternative Toxicological Methods (NICEATM); the Murine 
Local Lymph Node Assay: Request for Comments, Nominations of Scientific 
Experts, and Submission of Data

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

ACTION: Request for comments, submission of relevant data, and 
nominations of scientific experts.

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SUMMARY: The Interagency Coordinating Committee on the Validation of 
Alternative Methods (ICCVAM) received a nomination from the U.S. 
Consumer Product Safety Commission (CPSC) to evaluate the validation 
status of: (1) The murine local lymph node assay (LLNA) as a stand-
alone assay for determining potency (including severity) for the 
purpose of hazard classification; (2) the ``cut-down'' or ``limit 
dose'' LLNA approach; (3) non-radiolabeled LLNA methods; (4) the use of 
the LLNA for testing mixtures, aqueous solutions, and metals; and (5) 
the current applicability domain (i.e., the types of chemicals and 
substances for which the LLNA has been validated). ICCVAM reviewed the 
nomination, assigned it a high priority, and proposed that NICEATM and 
ICCVAM carry out the following activities in its evaluation: (1) 
Initiate a review of the current literature and available data, 
including the preparation of a comprehensive background review 
document, and (2) convene a peer review panel to review the various 
proposed LLNA uses and procedures for which sufficient data and 
information are available to adequately assess their validation status. 
ICCVAM also recommends development of performance standards for the 
LLNA. At this time, NICEATM requests: (1) Public comments on the 
appropriateness and relative priority of these activities, (2) 
nominations of expert scientists to consider as members of a possible 
peer review panel, and (3) submission of data for the LLNA and/or 
modified versions of the LLNA.

DATES: Submit comments, data, and nominations by June 15, 2007. 
Relevant data will also be accepted after this date and considered when 
feasible.

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

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directed to Dr. William S. Stokes (919-541-2384 or 
[email protected]).

SUPPLEMENTARY INFORMATION:

Background

    ICCVAM previously evaluated the validation status of the LLNA as a 
stand-alone alternative method to the Guinea Pig Maximization Test 
(GPMT) and the Buehler Assay (NIH publication No. 99-4494; available at 
http://iccvam.niehs.nih.gov/methods/immunotox/llna.htm). Based on this 
evaluation, ICCVAM recommended the LLNA as a valid substitute for the 
guinea pig methods for most testing situations. The Environmental 
Protection Agency, Food and Drug Administration, and the CPSC 
subsequently accepted the method as a valid substitute. The OECD also 
adopted the LLNA as OECD Test Guideline 429.
    In January 2007, the CPSC submitted a nomination to NICEATM (http://iccvam.niehs.nih.gov/SuppDocs/submission.htm) requesting that ICCVAM 
assess the validation status of:
     The LLNA as a stand-alone test for potency determinations 
(including severity) for the purpose of hazard classification.
     LLNA protocols that do not require the use of radioactive 
materials.
     The LLNA ``cut-down'' or ``limit dose'' procedure.
     The ability of the LLNA to test mixtures, aqueous 
solutions, and metals.
     The current applicability domain (i.e., the types of 
chemicals and substances for which the LLNA has been determined to be 
useful).
    Since 2003, ICCVAM has routinely developed performance standards 
for test methods; however, they were not developed for the LLNA, which 
was reviewed in 1999. Accordingly, ICCVAM proposes to now develop 
performance standards for the LLNA. Performance standards communicate 
the basis by which new proprietary and nonproprietary test methods have 
been determined to have sufficient relevance and reliability for 
specific testing purposes. Performance standards based on test methods 
accepted by regulatory agencies can be used to evaluate the reliability 
and relevance of other test methods that are based on similar 
scientific principles and measure or predict the same biological or 
toxic effect. On January 24, 2007, ICCVAM unanimously endorsed with a 
high priority: (1) Developing performance standards for the LLNA and 
(2) initiating a review of the available data and information 
associated with the CPSC nominated activities. A determination of which 
(if any) of the nominated activities will move forward will be made 
subsequent to this review and after consideration of comments by the 
public and the Scientific Advisory Committee on Alternative 
Toxicological Methods (SACATM). If a decision is made to proceed with 
evaluation of these test methods, ICCVAM and NICEATM propose convening 
a peer review panel to review the usefulness and limitations of each of 
the LLNA methods listed above. The panel would also formulate 
conclusions on the adequacy of draft ICCVAM performance standards, any 
proposed future validation studies, and draft ICCVAM-proposed 
standardized test method protocols.

Request for Public Comments and Nominations of Scientific Experts

    NICEATM requests public comments on the appropriateness and 
relative priority of the nominated activities. NICEATM also requests 
the nominations of scientists with relevant knowledge and experience to 
serve on the panel if a panel meeting occurs. Areas of relevant 
expertise include, but are not limited to: physiology, pharmacology, 
immunology, skin sensitization testing in animals, development and use 
of in vitro methodologies, biostatistics, knowledge about the use of 
chemical datasets for validation of toxicity studies, and hazard 
classification of chemicals and products. Each nomination should 
include the person's name, affiliation, contact information (i.e., 
mailing address, e-mail address, telephone and fax numbers), curriculum 
vitae, and a brief summary of relevant experience and qualifications.

Request for Data

    NICEATM invites the submission of data from standard LLNA testing 
(i.e., OECD TG 429) with mixtures, aqueous solutions, and/or metals, as 
well as corresponding data from human and other animal studies. In 
addition, NICEATM invites the submission of data supporting the use of 
(1) the LLNA as a stand-alone test for determining potency (including 
severity) for the purpose of hazard classification, (2) the LLNA ``cut-
down'' or ``limit dose'' procedure, and (3) LLNA protocols that do not 
require the use of radioactivity. Although data can be accepted at any 
time, data submitted by June 15, 2007, will be considered during the 
ICCVAM evaluation process. Submitted data will be used to further 
evaluate the usefulness and limitations of the LLNA and may be 
incorporated into future NICEATM and ICCVAM reports and publications as 
appropriate. The data will also be included in a database to support 
the investigation of other test methods for assessing skin 
sensitization.
    When submitting chemical and protocol information/test data, please 
reference this Federal Register notice and provide appropriate contact 
information (name, affiliation, mailing address, phone, fax, e-mail, 
and sponsoring organization, as applicable).
    NICEATM prefers data to be submitted as copies of pages from study 
notebooks and/or study reports, if available. Raw data and analyses 
available in electronic format may also be submitted. Each submission 
for a chemical should preferably include the following information, as 
appropriate:
     Common and trade name.
     Chemical Abstracts Service Registry Number (CASRN).
     Chemical class.
     Product class.
     Commercial source.
     LLNA protocol used.
     Individual animal responses.
     The extent to which the study complied with national or 
international Good Laboratory Practice (GLP) guidelines.
     Date and testing organization.
     Sensitization data from other test methods.

Consideration by SACATM

    On June 12, 2007, SACATM will meet at the Marriott Bethesda North 
Hotel and Conference Center in Bethesda, Maryland. The agenda includes 
consideration of the nominated LLNA activities, priorities, and 
proposed activities http://ntp.niehs.nih.gov/go/7441) and an 
opportunity for oral public comments. The SACATM meeting was announced 
in a separate Federal Register notice (Federal Register Vol. 72, No. 
83, pp. 23831-32, May 1, 2007).

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

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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: May 8, 2007.
David A. Schwartz,
Director, National Institute of Environmental Health Sciences and 
National Toxicology Program.
[FR Doc. E7-9544 Filed 5-16-07; 8:45 am]
BILLING CODE 4140-01-P