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 th e prediction of skin sensitization potential, based on structural aler ts (substructures associated with a toxicological mechanism), and suit able for incorporation as rules into a knowledge-based system is descr ibed. 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 penetrati on. The proposed structural alerts were tested on a data set of divers e chemicals. The results showed that the alerts have potential as prel iminary indicators of skin sensitization potential for a wide range of low molecular weight chemicals.