Quantitative structure-Activity relationship (QSAR) analysis of the acute sublethal neurotoxicity of solvents.
Acute, sublethal neurotoxicity data for the neurotropic effects of some common solvents were subjected to quantitative structure-activity relationship (QSAR) analysis. Hydrophobicity was found to be important in modelling neurotoxicity; however, highly significant QSARs from regression analysis were not obtained, which may imply that metabolic activity and differing mechanisms of action play an important role in neurotoxicity. It is proposed that hydrophobicity could be used to predict a 'minimal' neurotoxic effect level, above which there will be a neurotoxic effect. Principal component analysis was applied to separate chemicals with high neurotoxicity (EC(30) less than 50 micromoles/litre) from those with low neurotoxicity. This was successful when parameters describing hydrophobicity, molecular volume and size, melting and boiling point were included and provides a potential method to predict whether a compound is highly neurotoxic. This suggests that in addition to partitioning through a membrane, aqueous solubility and volatility are also important factors governing neurotoxicity.
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School of Pharmacy and Chemistry, Liverpool John Moores University, Byrom Street, Liverpool L3 3AF, UK.