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.