Structure-activity relationships for skin sensitization potential: development of structural alerts for use in knowledge-based toxicity prediction systems.

The development of qualitative structure-activity relationships for the prediction of skin sensitization potential, based on structural alerts (substructures associated with a toxicological mechanism), and suitable for incorporation as rules into a knowledge-based system is described. The structure dependence of the skin sensitization mechanism may be largely defined in terms of the presence or metabolic/nonmetabolic formation of protein reactive functional groups on the test compound and by the physicochemical requirements of significant skin penetration. The proposed structural alerts were tested on a data set of diverse chemicals. The results showed that the alerts have potential as preliminary indicators of skin sensitization potential for a wide range of low molecular weight chemicals.