A quantitative structure-activity/dose relationship for contact allergenic potential of alkyl group transfer agents.

Since no in vitro model is available, or indeed likely, to predict or investigate skin sensitization potential of substances, an approach based on a model using physicochemical criteria is the most likely route to a reduced requirement for animal testing. As part of the investigation of structure-activity relationships in contact allergy, it was shown that methyl transfer agents are capable of acting as skin sensitizers. This work has now been extended to a more general examination of alkyl transfer reactions. In vivo dose responses to challenge and the patterns of cross reactivity between C(12), C(16), unsaturated C(16) and methyl transfer agents were examined to form the basis of the mathematical model. All alkyl transfer agents examined were potent sensitizers, with evidence of mutual cross reactivity between them. The sensitization data have been accurately modelled using a mathematical equation. Analysis in terms of a modified relative alkylation index model showed evidence of an overload effect.