[Federal Register Volume 77, Number 38 (Monday, February 27, 2012)]
[Notices]
[Pages 11536-11538]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2012-4541]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES


Interagency Coordinating Committee on the Validation of 
Alternative Methods (ICCVAM) Recommendations on the Use of the Murine 
Local Lymph Node Assay for Potency Categorization of Chemicals Causing 
Allergic Contact Dermatitis: Availability of Federal Agency Responses

AGENCY: Division of the National Toxicology Program (DNTP), National 
Institute of Environmental Health Sciences (NIEHS), National Institutes 
of Health (NIH).

ACTION: Availability of Agency Responses.

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SUMMARY: The NTP Interagency Center for the Evaluation of Alternative 
Toxicological Methods (NICEATM) announces availability of U.S. Federal 
agency responses to ICCVAM test method recommendations on the use of 
the murine local lymph node assay (LLNA) for potency categorization of 
chemicals causing allergic contact dermatitis (ACD). ICCVAM forwarded 
the recommendations to Federal agencies and made these recommendations 
available to the public (76 FR 45254). In accordance with the ICCVAM 
Authorization Act of 2000 (42 U.S.C. 285l-3), agencies have notified 
ICCVAM in writing of their findings, and ICCVAM is making these 
responses available to the public. Federal agency responses are 
available on the NICEATM-ICCVAM Web site at http://iccvam.niehs.nih.gov/methods/immunotox/LLNApotency.htm. The ICCVAM 
recommendations are provided in the ICCVAM test method evaluation 
report (ICCVAM, 2011).

FOR FURTHER INFORMATION CONTACT: Dr. William S. Stokes, Director, 
NICEATM, NIEHS, P.O. Box 12233, Mail Stop: K2-16, Research Triangle 
Park, NC 27709, (telephone) 919-541-2384, (fax) 919-541-0947, (email) 
<a href="/cdn-cgi/l/email-protection#ea8483898f8b9e87aa84838f8299c4848382c48d859c"><span class="__cf_email__" data-cfemail="85ebece6e0e4f1e8c5ebece0edf6abebecedabe2eaf3">[email protected]</span></a>. Courier address: NICEATM, NIEHS, Room 2034, 530 
Davis Drive, Morrisville, NC 27560.

SUPPLEMENTARY INFORMATION: 

Background

    The LLNA is accepted worldwide as a valid alternative to 
traditionally accepted guinea pig test methods for assessing ACD hazard 
potential for most testing applications. In January 2007, the U.S. 
Consumer Product Safety Commission (CPSC) requested that NICEATM and 
ICCVAM evaluate the LLNA for its usefulness for determining skin 
sensitization potency categories.

[[Page 11537]]

The CPSC, under the Federal Hazardous Substances Act, requires hazard 
labeling of products considered to be strong skin sensitizers. Results 
from tests that could be used to identify potential strong human skin 
sensitizers would support the CPSC and other agencies with an interest 
in identifying strong skin sensitizers. While guinea pig tests have 
traditionally been used to categorize the potency of skin sensitizers, 
the LLNA uses fewer animals, requires less time to perform, provides 
dose-response information, and eliminates the pain and distress 
produced by positive reactions.
    Accordingly, NICEATM and ICCVAM evaluated the extent that the LLNA 
could be used to correctly predict ``strong'' versus ``other than 
strong'' human skin sensitizers. NICEATM, working in collaboration with 
the ICCVAM Interagency Immunotoxicity Working Group (IWG), prepared a 
draft background review document (BRD) and draft recommendations for 
use of the LLNA for potency categorization of chemicals that cause ACD 
in humans. The draft BRD and draft ICCVAM recommendations were reviewed 
in a public meeting of an international independent scientific peer 
review panel in March 2008; the peer review panel report was made 
available to the public for comment in May 2008 (73 FR 29136). The 
Scientific Advisory Committee on Alternative Toxicological Methods 
(SACATM) discussed and commented on the report, draft BRD, and draft 
ICCVAM recommendations at its June 2008 meeting (73 FR 25754). ICCVAM 
considered the panel's report, comments from SACATM, and public 
comments, and finalized its recommendations.
    The final ICCVAM recommendations are provided in the ICCVAM Test 
Method Evaluation Report: Usefulness and Limitations of the Murine 
Local Lymph Node Assay for Potency Categorization of Chemicals Causing 
Allergic Contact Dermatitis in Humans (NIH Publication No. 11-7709, 
available at http://iccvam.niehs.nih.gov/methods/immunotox/LLNA-pot/TMER.htm). The test method evaluation report also includes an updated 
ICCVAM-recommended LLNA protocol and recommended future studies that 
may further characterize the usefulness and limitations of the LLNA for 
potency determinations. The final BRD, including additional analyses 
performed by NICEATM as recommended by the peer review panel, is 
included as an appendix to the test method evaluation report. ICCVAM 
recommended that positive results from ACD safety testing using the 
murine LLNA could be used to categorize some chemicals and products as 
strong skin sensitizers. However, since the current LLNA decision 
criterion only identified 52% of the strong human skin sensitizers, 
ICCVAM recommended that this criterion should not be used as the basis 
for determining that a substance is not a strong skin sensitizer. 
Therefore, the potency criterion should only be used in a screening 
approach, where chemicals that meet the criterion could be categorized 
as strong skin sensitizers, but chemicals that do not meet the 
criterion would require additional testing or information to determine 
that they are not strong skin sensitizers. In accordance with the 
Public Health Service Policy on Humane Care and Use of Laboratory 
Animals and Animal Welfare Act regulations, the LLNA should be 
routinely considered when planning animal studies to evaluate whether 
chemicals and products are strong sensitizers in order to minimize 
animal use and to avoid unrelieved pain and distress, and should be 
used when determined appropriate.

Agency Responses to ICCVAM Recommendations

    In June 2011, ICCVAM forwarded final test method recommendations on 
using the LLNA for potency categorization of chemicals to U.S. Federal 
agencies for consideration (76 FR 45254), in accordance with the ICCVAM 
Authorization Act of 2000 (42 U.S.C. 285l-3). The ICCVAM Authorization 
Act requires member agencies to review ICCVAM test method 
recommendations and notify ICCVAM in writing of their findings no later 
than 180 days after receipt of recommendations. The Act also requires 
ICCVAM to make ICCVAM recommendations and agency responses available to 
the public. Agency responses are to include identification of relevant 
test methods for which the ICCVAM test method recommendations may be 
added or substituted and indicate any revisions or planned revisions to 
existing guidelines, guidances, or regulations to be made in response 
to these recommendations. Complete agency responses are available at 
http://iccvam.niehs.nih.gov/methods/immunotox/LLNApotency.htm.

Background Information on NICEATM, ICCVAM, and SACATM

    ICCVAM is an interagency committee composed of representatives from 
15 Federal regulatory and research agencies that require, use, 
generate, or disseminate toxicological and safety testing information. 
ICCVAM conducts technical evaluations of new, revised, and alternative 
safety testing methods with regulatory applicability and promotes the 
scientific validation and regulatory acceptance of toxicological and 
safety testing methods that more accurately assess the safety and 
hazards of chemicals and products while reducing animal use, refining 
animal use by enhancing animal welfare and lessening or avoiding 
unrelieved pain and distress, or replacing animals used for testing. 
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, provides scientific and operational support 
for ICCVAM-related activities, and conducts independent validation 
studies to assess the usefulness and limitations of new, revised, and 
alternative test methods and strategies. NICEATM and ICCVAM work 
collaboratively to evaluate new and improved test methods and 
strategies applicable to the needs of U.S. Federal agencies. NICEATM 
and ICCVAM welcome the public nomination of new, revised, and 
alternative test methods and strategies for validation studies and 
technical evaluations. Additional information about ICCVAM and NICEATM 
can be found on the NICEATM-ICCVAM Web site (http://iccvam.niehs.nih.gov).
    SACATM was established in response to the ICCVAM Authorization Act 
[Section 285l-3(d)] and is composed of scientists from the public and 
private sectors (67 FR 11358). SACATM advises ICCVAM, NICEATM, and the 
Director of the NIEHS and NTP regarding statutorily mandated duties of 
ICCVAM and activities of NICEATM. SACATM provides advice on priorities 
and activities related to the development, validation, scientific 
review, regulatory acceptance, implementation, and national and 
international harmonization of new, revised, and alternative 
toxicological test methods. Additional information about SACATM, 
including the charter, roster, and records of past meetings, can be 
found at http://ntp.niehs.nih.gov/go/167.

Reference

ICCVAM. 2011. ICCVAM Test Method Evaluation Report: Usefulness and 
Limitations of the Murine Local Lymph Node Assay for Potency 
Categorization of Chemicals Causing Allergic Contact Dermatitis in 
Humans. NIH Publication No. 11-7709. Research Triangle Park, NC: 
National Institute of Environmental Health Sciences. Available: 
http://iccvam.niehs.nih.gov/methods/immunotox/LLNA-pot/TMER.htm.


[[Page 11538]]


    Dated: February 15, 2012.
John R. Bucher,
Associate Director, National Toxicology Program.
[FR Doc. 2012-4541 Filed 2-24-12; 8:45 am]
BILLING CODE 4140-01-P


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