Classification of chemicals according to mechanism of aquatic toxicity: an evaluation of the implementation of the Verhaar scheme in Toxtree.

A number of mechanisms have been identified that can lead to (acute) aquatic toxicity. The assignment of compounds to a particular mechanism of action is important in the development and utilisation of (quantitative) structure-activity relationships ((Q)SARs) for ecotoxicity. Assignment to a mechanism can be difficult; however in 1992 Verhaar et al. published a series of structural rules which aimed to classify compounds according to mechanism of action. Recent interest has seen the Verhaar rules coded into freely available software such as Toxtree available from the European Chemicals Bureau. To date, a complete critical evaluation of these rules has been lacking. Therefore, the aim of this study was to evaluate the Toxtree implementation of the Verhaar rules using two well characterised aquatic toxicity datasets (Pimephales promelas and Tetrahymena pyriformis phenol databases) for which mechanisms of toxic action are well established. The present study highlights rule, and possible coding, errors that may lead to misclassifications. Improvements to both the rules and prediction architecture are suggested. In particular further rules to improve predictions for polar narcosis (class 2) are suggested.