Preliminary assessment of the skin sensitizing activity of selected rodentcarcinogens using the local lymph node assay

it has been demonstrated previously that there exists an incomplete correla tion between the skin sensitizing potential of chemicals and their mutageni c properties as judged by activity in the Salmonella mutation assay. More r ecently, it has been proposed that there may exist a broader association be tween carcinogenicity in rodents (including non-genotoxic carcinogenesis) a nd skin sensitizing activity. To explore further these putative relationshi ps we have here examined the skin sensitizing potential of two non-genotoxi c rodent carcinogens which are generally considered not to represent a carc inogenic hazard in humans: (limonene and saccharin) and of three genotoxic rodent carcinogens (vinylidene dichloride. ethyl acrylate and bisphenol A d iglycidyl ether). For this purpose we have used the local lymph node assay (LLNA), a method For the identification and characterization of skin sensit izing chemicals that has recently been recognized as a stand-alone method f ur hazard identification purposes. Activity in the LLNA was compared with t he results of Salmonella tests conducted previously. This small series of i nvestigations reveals that there exists no general relationship between ski n sensitizing potential and rodent carcinogenicity. Furthermore, although a general correlation does exist between mutagenic activity and skin sensiti zation, this association is not universal and activity in the Salmonella mu tation assay does not necessarily imply skin sensitizing potential. Collect ively these data suggest that it is inappropriate currently to recommend th e use of skin sensitization tests as an adjunct to conventional approaches to the evaluation of potential carcinogenicity. (C) 2001 Elsevier Science I reland Ltd. All rights reserved.