Overview
ICCVAM has developed recommendations for current uses and limitations of the reduced murine local
lymph node assay (rLLNA) as a modification to the traditional murine local lymph node assay (LLNA)
to reduce the use of animals in skin sensitization testing. ICCVAM concludes that the performance of
the rLLNA, when conducted in accordance with the updated ICCVAM-recommended LLNA test method
protocol, is sufficient to distinguish between skin sensitizers and non-sensitizers in cases that do
not require dose-response information. ICCVAM also concludes that the rLLNA will reduce animal use
by 40% for each test compared to the traditional LLNA. Therefore, ICCVAM recommends that the rLLNA
test method be used routinely to determine the allergic contact dermatitis potential of chemicals
and products before conducting the traditional LLNA.
The ICCVAM recommendations for current uses and limitations of the rLLNA, as well as
recommendations for standardized protocols and future studies, can be found
in the report, ICCVAM Test Method Evaluation Report: The Reduced Murine Local Lymph Node Assay: A
Test Method for Assessing the Allergic Contact Dermatitis Potential of Chemicals and Products.
View Test Method Evaluation Report Table of Contents in webpage format
Download complete report (547 pages) [PDF]
Background
The LLNA is an alternative skin-sensitization test method that requires fewer animals and less
time than traditional guinea pig tests such as the guinea pig maximization test and the Buehler
test. Compared to guinea pig tests, the LLNA can also substantially reduce or avoid animal pain and
distress. The rLLNA, also referred to as the “cut-down” or “limit dose” LLNA, was one of several
modified versions of the LLNA nominated by the U.S. Consumer Product Safety Commission in 2007 for
evaluation by ICCVAM and NICEATM. The proposed rLLNA could reduce the number of animals used for
skin-sensitization testing by 40% compared to the traditional LLNA.
The ICCVAM Immunotoxicity Working Group, working with NICEATM, prepared a draft background review
document (BRD) and draft test method recommendations for use of the rLLNA. These documents were
provided to an independent international scientific peer review panel (“Panel”) and the
public for consideration
and comment. In finalizing their test method recommendations, ICCVAM considered the conclusions and
recommendations of the Panel and ICCVAM’s
Scientific Advisory Committee on Alternative Toxicological
Methods, as well as comments from the public.
ICCVAM concluded that the scientific validity of the rLLNA has been adequately evaluated.
They also concluded that the performance of the rLLNA,
when conducted in accordance with the ICCVAM-recommended
rLLNA test method protocol, is sufficient to distinguish between skin sensitizers and non-sensitizers in cases
that do not require dose-response information. ICCVAM recommends that the rLLNA test method be used
routinely to determine the allergic contact dermatitis potential of chemicals and products before
conducting the traditional LLNA. Negative substances can be classified as non-sensitizers,
and positive substances can be classified as sensitizers. In cases that require
dose-response information, positive substances must be tested in the traditional
multiple-dose LLNA. Therefore, if dose-response information is required for a substance
that, after consideration of all available information, is also suspected of having the
potential to produce allergic contact dermatitis, it should be evaluated initially using the traditional LLNA.
View rLLNA Background Review Document (Appendix D of the Test Method Evaluation Report - 147 pages) [PDF]
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