Prediction of noninteractive mixture toxicity of organic compounds based on a fuzzy set method

Current methods for the prediction of mixture toxicity have shown to be valid for mixtures that conform to some assumptions that were ideally formulated for mixtures comprising constituents exhibiting either completely similar or dissimilar mechanisms of action. Approaches are needed that predict the toxicity of mixtures representative of real environmental occurrences i.e., those comprising constituents of mixed similar and dissimilar compounds and therefore are more complex. In this paper such a methodology is proposed which uses molecular descriptors and fuzzy set theory to characterize the degree of similarity and dissimilarity of mixture constituents, integrates the concentration addition and independent action models, and therefore is called INFCIM (INtegrated Fuzzy Concentration addition--Independent action Model). INFCIM is tested in two case studies using toxicity data of four mixtures, and its performance is compared against those of both concentration addition and independent action models. Mixture 1 consists of 18 s-triazines acting on green freshwater algae scenedemus vacuolatus. Mixture 2 comprises 16 acting constituents tested on scenedemus vacuolatus. Both mixtures inhibit reproduction in the biological assays. There are 10 quinolone compounds in mixture 3 and 16 phenol derivative compounds in mixture 4 all causing long-term inhibition of bioluminescence in the marine bacterium Vibrio fischeri. It was shown that INFCIM performed comparably or better than the best performing existing model in the original studies for all the mixtures tested.