[Federal Register Volume 75, Number 89 (Monday, May 10, 2010)]
[Notices]
[Pages 25866-25867]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2010-10954]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health


National Toxicology Program (NTP); NTP Interagency Center for the 
Evaluation of Alternative Toxicological Methods (NICEATM); Federal 
Agency Responses to Interagency Coordinating Committee on the 
Validation of Alternative Methods Recommendations on the Murine Local 
Lymph Node Assay, An Alternative Test Method for Assessing the Allergic 
Contact Dermatitis Potential of Chemicals and Products: Notice of 
Availability

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

ACTION: Notice of Availability.

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SUMMARY: U.S. Federal agency responses to Interagency Coordinating 
Committee on the Validation of Alternative Methods (ICCVAM) test method 
recommendations on the murine local lymph node assay (LLNA), an 
alternative safety testing method used to assess the potential of 
chemicals and products to cause allergic contact dermatitis (ACD), are 
now available. ICCVAM recommended an updated LLNA test method protocol, 
a reduced LLNA procedure (rLLNA), and LLNA test method performance 
standards. In accordance with the ICCVAM Authorization Act, ICCVAM 
previously forwarded recommendations to Federal agencies and made these 
recommendations available to the public (74 FR 50212). Agencies have 
now 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/rLLNA.htm and http://iccvam.niehs.nih.gov/methods/immunotox/llna_PerfStds.htm. The ICCVAM 
recommendations are provided in ICCVAM Test Method Evaluation Reports, 
which are available on the NICEATM-ICCVAM Web site at http://iccvam.niehs.nih.gov/methods/immunotox/LLNA-LD/TMER.htm and http://iccvam.niehs.nih.gov/methods/immunotox/PerfStds/llna-ps.htm.

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, (e-mail) 
[email protected]. Courier address: NICEATM, NIEHS, Room 2034, 530 
Davis Drive, Morrisville, NC 27560.

SUPPLEMENTARY INFORMATION:

[[Page 25867]]

Background

    ICCVAM originally recommended the LLNA as a valid stand-alone 
alternative method to existing ACD test methods in 1999 (NIH 
publication No. 99-4494; available at http://iccvam.niehs.nih.gov/docs/immunotox_docs/llna/llnarep.pdf). ICCVAM recommended that the LLNA 
could be used as a substitute for the existing guinea pig based test 
methods for most testing situations, which would reduce the number of 
animals required and avoid pain and distress. The Environmental 
Protection Agency (EPA), the Food and Drug Administration (FDA), and 
the Consumer Product Safety Commission (CPSC) subsequently accepted the 
method as a valid substitute. The Organization for Economic Co-
operation and Development (OECD) adopted the LLNA as international OECD 
Test Guideline 429 and the International Standards Organization (ISO) 
adopted the LLNA as ISO Test 10993-10.
    The updated LLNA test method protocol uses 20% fewer animals than 
the original LLNA protocol recommended by ICCVAM in 1999, and provides 
improved guidance on dose selection and other procedures to improve 
assay accuracy and reproducibility. The rLLNA procedure can further 
reduce the number of animals required by 40% compared to the updated 
LLNA protocol multi-dose procedure. ICCVAM recommends that the rLLNA 
test method should be routinely considered before conducting the 
traditional multi-dose LLNA, and should be used as the initial test for 
ACD where determined appropriate. ICCVAM evaluation and complete 
recommendations for the updated LLNA test method protocol and the rLLNA 
procedure are provided in the ICCVAM Test Method Evaluation Report: The 
Reduced Murine Local Lymph Node Assay: An Alternative Test Method Using 
Fewer Animals to Assess the Allergic Contact Dermatitis Potential of 
Chemicals and Products (NIH Publication No. 09-6439, available at 
http://iccvam.niehs.nih.gov/methods/immunotox/LLNA-LD/TMER.htm).
    ICCVAM also recommends that the LLNA test method performance 
standards can be used to efficiently evaluate the validity of modified 
test methods that are mechanistically and functionally similar to the 
traditional LLNA. The LLNA test method performance standards are 
provided in the ICCVAM report, Recommended Performance Standards: 
Murine Local Lymph Node Assay (NIH Publication No. 09-7357, available 
at http://iccvam.niehs.nih.gov/methods/immunotox/PerfStds/llna-ps.htm).
    ICCVAM evaluated the updated versions of the LLNA in response to a 
2007 nomination from the CPSC (http://iccvam.niehs.nih.gov/methods/immunotox/llnadocs/CPSC_LLNA_nom.pdf). The nomination also requested 
that ICCVAM evaluate the validation status of (1) new versions of the 
LLNA test method protocol that do not require the use of radioactive 
materials; (2) use of the LLNA to test mixtures, aqueous solutions, 
metals, and other substances; and (3) use of the LLNA to determine ACD 
potency categories for hazard classification and labeling purposes. 
ICCVAM recommendations on these new versions and applications are 
undergoing finalization and will be forwarded to Federal agencies in 
2010.

Agency Reponses to ICCVAM Recommendations

    In September 2009, ICCVAM forwarded final test method 
recommendations for the rLLNA, the updated LLNA test method protocol, 
and LLNA performance standards to U.S. Federal agencies for 
consideration, in accordance with the ICCVAM Authorization Act of 2000 
(42 U.S.C. 285l-3(e)(4)) (74 FR 50212). 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.

Background Information on ICCVAM and NICEATM

    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 
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://www.iccvam.niehs.nih.gov).

    Dated: April 30, 2010.
John R. Bucher,
Associate Director, National Toxicology Program.
[FR Doc. 2010-10954 Filed 5-7-10; 8:45 am]
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