Development of an expert system rulebase for identifying contact allergens.

There are currently no in vitro methods for the identification of skin sensitizers (contact allergens). Knowledge relating chemical structure to toxicity can be programmed into expert systems. An historical database containing results of 294 defined single substances tested in the guinea pig maximization test to a single protocol has been used to derive a set of structural alerts for skin sensitization. Where possible, the approach used was to group the substances according to their most likely mechanism of reaction with skin proteins. Where no mechanism could be identified, structural alerts were derived empirically for groups of molecules with similar chemical functionality. This process has currently resulted in the production of 40 structure-activity rules, which have been incorporated into the expert system DEREK. Rulebases of this type have potential for use as a preliminary screen in toxicological hazard identification and may ultimately lead to a reduction in the use of laboratory animals.