Overview
The murine local lymph node assay (LLNA) is a stand-alone test 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
new versions and applications of the LLNA.
The ICCVAM Immunotoxicity Working Group (IWG), working with NICEATM, prepared draft background review
documents (BRDs) and draft recommendations for application of the LLNA for evaluating pesticide
formulations and other products, and for three modified versions of the LLNA not requiring the use
of radioactive markers. The draft BRDs and draft ICCVAM recommendations were reviewed in a public meeting
of an international independent scientific peer review panel (“Panel”) in March 2008. The Panel agreed
with the ICCVAM assessment that more data were needed to
evaluate these new versions and applications of the LLNA. Additional data were submitted to
NICEATM; NICEATM and the IWG revised the BRDs,
and updated test method recommendations were developed by ICCVAM. A second Panel
meeting to consider the revised documents was held on April 28-29, 2009; the Panel's report
will be available in June.
View a summary of the April 2009 Panel meeting
[PDF]
The Panel concluded that the available data and test method performance support the use of
two of the non-radioactive modified versions of the LLNA, the
LLNA: DA and the LLNA: BrdU-ELISA, to identify substances as potential skin sensitizers and
nonsensitizers, with certain limitations. They agreed with ICCVAM’s proposal that, based on the
current validation database, multiple stimulation index (SI) decision criteria should be used to
identify sensitizers and nonsensitizers for each of the two methods. The Panel also noted that the
limitation of these test methods when using the proposed multiple decision criteria is the
indeterminate classification of substances that fall in the range of SI values for which a
classification is uncertain. The Panel recommended that when such results are obtained, users should
carefully interpret the results in an integrated decision strategy in conjunction with all other
available information (e.g., dose response and QSAR information, statistical analyses,
peptide-binding activity, molecular weight, results from related chemicals, other testing data) to
determine if there is adequate information for an accurate sensitization hazard classification or if
additional testing is necessary. The Panel agreed with the ICCVAM proposal to defer a formal
recommendation on the validity of the LLNA: BrdU-FC until an independent audit of all data
supporting the analysis has been conducted and until transferability has been demonstrated
in an interlaboratory validation study.
With regard to the applicability of the LLNA for testing pesticide formulations and other
products (e.g., natural complex substances, dyes, aqueous solutions), the Panel concluded that
any material should be suitable for testing in the LLNA unless there is a biologically-based
rationale for exclusion, such as unique physicochemical properties that might affect the ability
of the material to interact with immune processes. The Panel therefore concluded that the LLNA should
be considered appropriate for testing pesticide formulations and other products, unless there
is a biologically-based rationale for exclusion.
ICCVAM will consider the Panel’s report along with all public and SACATM comments received,
and prepare final test method recommendations that will be forwarded to Federal agencies for
their consideration later in 2009.
Announcement of a Second Meeting of the Independent Scientific Peer Review Panel on the Murine
Local Lymph Node Assay; Availability of Draft Background Review Documents (BRD); Request for Comments
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View Federal Register Notice
(Vol. 74, No. 38, pages 8974-8975, February 27, 2009) [PDF] |
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More information about the Peer Panel meeting and links to draft documents |
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
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View Federal Register Notice
(Vol. 73, No. 98, pages 29136-29137, May 20, 2008) [PDF] |
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Read the Peer Panel Report [PDF] |
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Information about the Peer Panel meeting |
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
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View Federal Register Notice
(Vol. 73, No. 5, pages 1360-1362, January 8, 2008) [PDF] |
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Details about the meeting |
Murine Local Lymph Node Assay: Request for Comments, Nominations of Scientific Experts, and
Submission of Data
Information about the 1998 LLNA Peer Panel meeting
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