Activity of human contact allergens in the murine local lymph node assay

The murine local lymph node assay (LLNA) is a predictive test for the ident ification of chemicals that have the potential to cause skin sensitization. Since its original development, the assay has been the subject of national and international evaluation studies and extensive comparisons with guinea pig tests and human data. On the basis of these investigations, the LLNA h as recently been endorsed by ICCVAM (Interagency Coordinating Committee on the Validation of Alternative Methods) as a stand-alone method for skin sen sitization hazard identification. At the same time, ICCVAM confirmed that, although the LLNA is not an in vitro method, it does represent a refinement in the way animals are used and can provide a means for reducing the numbe r of animals used in sensitization hazard assessment. The investigations de scribed here were designed to explore further the ability of the LLNA to id entify accurately those chemicals that cause allergic contact dermatitis in humans. To that end we have measured, amongst 3 independent laboratories, LLNA responses induced by a total of 18 test chemicals, 11 of which are kno wn to cause skin sensitization and 7 of which are believed not to be associ ated with any significant evidence of allergic contact dermatitis in humans . The LLNA correctly classified 16 of the 18 materials. The 11 chemicals te sted which are associated with allergic contact dermatitis in humans were f ound to be positive in the LLNA. Of the 7 materials believed to be non-sens itizers, 5 were negative in the LLNA and 2 produced positive results. Colle ctively, these data provide additional evidence that the LLNA is able to di scriminate skin sensitizers from those chemicals which do not possess a sig nificant skin sensitization potential and thus provides a method for hazard identification that offers important animal welfare benefits.