Preliminary assessment of the skin sensitizing activity of selected rodent carcinogens using the local lymph node assay.
It has been demonstrated previously that there exists an incomplete correlation between the skin sensitizing potential of chemicals and their mutagenic properties as judged by activity in the Salmonella mutation assay. More recently, it has been proposed that there may exist a broader association between carcinogenicity in rodents (including non-genotoxic carcinogenesis) and skin sensitizing activity. To explore further these putative relationships we have here examined the skin sensitizing potential of two non-genotoxic rodent carcinogens which are generally considered not to represent a carcinogenic hazard in humans (limonene and saccharin) and of three genotoxic rodent carcinogens (vinylidene dichloride, ethyl acrylate and bisphenol A diglycidyl ether). For this purpose we have used the local lymph node assay (LLNA), a method for the identification and characterization of skin sensitizing chemicals that has recently been recognized as a stand-alone method for hazard identification purposes. Activity in the LLNA was compared with the results of Salmonella tests conducted previously. This small series of investigations reveals that there exists no general relationship between skin sensitizing potential and rodent carcinogenicity. Furthermore, although a general correlation does exist between mutagenic activity and skin sensitization, this association is not universal and activity in the Salmonella mutation assay does not necessarily imply skin sensitizing potential. Collectively these data suggest that it is inappropriate currently to recommend the use of skin sensitization tests as an adjunct to conventional approaches to the evaluation of potential carcinogenicity.
Warbrick
E V
EV
Syngenta Central Toxicology Laboratory, Alderley Park, Macclesfield, SK10 4TJ, Cheshire, UK.
Dearman
R J
RJ
Ashby
J
J
Schmezer
P
P
Kimber
I
I
D000085:Acetates / Q000633:toxicity; D000818:Animals; D001559:Benzhydryl Compounds; D015197:Carcinogenicity Tests / Q000379:methods*; D002273:Carcinogens / Q000633:toxicity*; D053138:Cyclohexenes; D017449:Dermatitis, Allergic Contact / Q000209:etiology* / Q000276:immunology; D004000:Dichloroethylenes / Q000633:toxicity; D004852:Epoxy Compounds / Q000633:toxicity; D005260:Female; D000077222:Limonene; D023441:Local Lymph Node Assay; D051379:Mice; D008808:Mice, Inbred CBA; D012439:Saccharin / Q000633:toxicity; D013729:Terpenes / Q000633:toxicity; D000098826:Bisphenol A Compounds
D000085:Acetates; D001559:Benzhydryl Compounds; D002273:Carcinogens; D053138:Cyclohexenes; D004000:Dichloroethylenes; D004852:Epoxy Compounds; D000077222:Limonene; D012439:Saccharin; D013729:Terpenes; C029297:vinylidene chloride; C007650:ethyl acetate; C019273:bisphenol A diglycidyl ether; D000098826:Bisphenol A Compounds