Validation and development of the DEREK skin sensitisation rulebase by analysis of the BgVV list of contact allergens

The DEREK knowledge-based computer system contains a sub-set of 57 rules describing chemical substructures (toxophores) responsible for skin sensitisation. This rulebase has been subjected to extensive validation and is undergoing continuous refinement in the course of its development. As part of an ongoing programme of validation and testing, the predictive ability of the sensitisation rule set was assessed by processing the structures of the first 84 chemical substances in the list of contact allergens issued by the German Federal Institute for Health Protection of Consumers (BgVV). This list of chemicals was considered important, because the biological data for each of the chemicals were carefully scrutinised and peer reviewed. The existing DEREK rulebase for skin sensitisation identified toxophores for skin sensitisation in the structures of 71 out of the 84 chemicals. The exercise highlighted areas of chemistry in which 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. After refinement, the rulebase was able to identify toxophores for skin sensitisation for 82 of the 84 chemicals in the BgVV list. A further 55 chemicals have now been added to the BgVV list of contact allergens. The DEREK rulebase identified toxophores in 35 of the 36 chemicals described as important contact allergens and those with established evidence of contact-allergic effects, and in 12 out of 19 chemicals described as insignificant contact allergens, or those causing questionable contact-allergic effects.