QSAR approach for the selection of congeneric compounds with a similar toxicological mode of action

The selection of compounds with a similar toxicological mode of action is a key problem in the study of chemical mixtures. In this paper, an approach for the selection of chemicals with similar mode of action, based on the an alysis of structural similarities by means of QSAR and chemometric methods, is described. As a first step, a complete representation of chemical struc tures for examined chemicals (phenylureas and triazines) by different sets of molecular descriptors allows a preliminary exploration of similarity usi ng multi-dimensional scaling (MDS). The use of genetic algorithm (GA) to se lect the most relevant molecular descriptors in modeling toxicity data make s it possible to develop predictive toxicity models. The final step is a si milarity analysis, based again on MDS, using selected molecular descriptors , really relevant in describing the toxicological effect. (C) 2001 Elsevier Science Ltd. All rights reserved.