Quantitative structure-activity relationship models correctly predict the toxic and aneuploidizing properties of six halogenated methanes in Aspergillus nidulans.

In a previous study, the relationships between the chemical structure and the ability of 35 chlorinated aliphatic hydrocarbons to induce aneuploidy and toxicity in Aspergillus nidulans were analyzed. Quantitative structure-activity relationships (QSAR) were defined for each of the biological activities under study: ARR (the dose able to block mitotic growth), D37 (the dose with 37% of survival) and LEC (the lowest efficient concentration in aneuploidy induction). In this study, these QSAR equations were used to predict the toxic and genetic activity of a further six chemicals, not included in the previous data base: bromotrichloromethane, bromoform, bromochloromethane, bromodichloromethane, dibromochloromethane and dibromochlorofluoromethane. Their ARR, D37 and LEC values were measured, and were in agreement with the predicted values, with correlation coefficients around 0.99. Furthermore, the QSAR model, which had previously been developed to discriminate between aneugenic and inactive halogenated hydrocarbons, correctly predicted the aneugenic activity of five out of six methanes. These correct predictions confirmed the validity of our QSAR model, according to which the induction of aneuploidy in A. nidulans depends on both the electrophilic and steric properties of the chemicals, whereas toxicity mainly depends on steric factors.