Overview
The Murine Local Lymph Node Assay (LLNA) is a method for assessing the potential of a test
substance to induce allergic
contact dermatitis. In January 2007, the U.S. Consumer Product Safety Commission (CSPC) requested 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. In response to comments received from its
scientific advisory committee (SACATM) and
from the public, ICCVAM endorsed these activities as high priorities.
NICEATM and ICCVAM prepared draft Background Review Documents and draft recommendations for each
topic, which were peer reviewed in a public meeting in March 2008.
The Peer Review Panel's Report is now available, and final ICCVAM recommendations
are expected in fall 2008.
Peer Review Panel Report on the Validation Status of New Versions and Applications of
the Murine Local Lymph Node Assay (LLNA): A Test Method for Assessing the Allergic Contact Dermatitis
Potential of Chemicals and Products: Notice of Availability and Request for Public Comments
Announcement of an Independent Scientific Peer Review Panel Meeting on the Murine Local Lymph
Node Assay; Availability of Draft Background Review Documents; Request for Comments
Murine Local Lymph Node Assay: Request for Comments, Nominations of Scientific Experts, and
Submission of Data
The LLNA was the first test method to be validated under the ICCVAM process by a panel
of peer reviewers. On Sep. 17, 1998, NICEATM hosted a meeting to review the Murine Local
Lymph Node Assay (LLNA) as an alternative test method for assessing the
allergic contact dermatitis potential of chemicals. The final
peer review report was published in February 1999. The peer review panel
concluded that the LLNA is a valid alternative to currently accepted
guinea pig test methods, and that the LLNA reduces the number of animals
required for testing and eliminates animal pain and distress. Compared
to the traditional test, the LLNA can also be completed in a shorter
timeframe and provides dose-response information. Additional
recommendations on the usefulness and limitations of the LLNA are
provided in the peer review report.
Based on the recommendations of ICCVAM and the independent scientific
peer review panel, the LLNA has been accepted as an alternative to the
guinea pig maximization test for assessing allergic contact dermatitis
by the U.S. EPA, FDA, and OSHA, who all announced their
acceptance of the LLNA in October 1999. An
implementation workshop co-sponsored by ICCVAM and the International
Life Sciences Institute (ILSI) was convened in January 2001. The
workshop discussed how to conduct the assay and interpret the results in
order to meet regulatory agency requirements. The LLNA was considered as an
international test guideline by the 30-member countries of the Organisation for
Economic Cooperation and Development (OECD) in their Test Guidelines Programme.
The updated OECD Test Guideline 429 - Skin Sensitisation: LLNA, was
adopted on the 24th of April 2002.
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