Development of an expert system rulebase for the prospective identification of photoallergens

Relationships between the structure and properties of chemicals can be programmed into knowledge-based systems such as DEREK (an acronym for 'Deductive Estimation of Risk from Existing Knowledge'). The DEREK knowledge-based computer system contains a sub-set of over 50 rules describing chemical substructures (toxophores) responsible for skin sensitization. This rulebase, based originally on Unilever historical in-house guinea pig maximisation test data, is largely complete and is undergoing refinement as the next stage of its development. As part of an ongoing program of validation and testing, the predictive ability of the sensitization rule set was assessed by processing the structures of over 100 chemical substances in the list of contact allergens identified by the BgVV (German Federal Institute for Health Protection of Consumers). The exercise highlighted areas of chemistry where further development of the rulebase was required, either by extension of the scope of existing rules or by generation of new rules where a sound mechanistic rationale for the biological activity could be established. Several chemicals likely to be acting as photoallergens were identified and rules for photoallergenicity were written covering three classes of chemicals. This paper describes work to extend the DEREK rules for photoallergenicity as part of the European Phototox Project.