Structure-Toxicity Relationships for the Effects to Tetrahymena pyriformis of Aliphatic,Carbonyl-Containing,alpha,beta-Unsaturate Chemicals

摘要

Toxicity data for 82 aliphatic chemicals with an alpha,beta-unsaturated substructure were compiled.Toxicity was assessed in the 2-day Tetrahymena pyriformis population growth impairment assay.Toxic potency [log(IGC_(50)~(-1))] for most of these chemicals was in excess of baseline narcosis as quantified by the 1-octanol/water partition coefficient (log K_(ow)).The toxicity of the alpha,beta-unsaturated aldehydes was modeled well by log K_(ow) in conjunction with the sum of partial charges on the vinylene carbon atoms (Q_(C4)+Q_(C3)) and the energy of the lowest unoccupied molecular orbital (E_(lumo)).These electronic descriptors were also successful at modeling the toxicity of alpha,beta-unsaturated ketones.The toxicity of a range of acrylates was constant within about 0.2 of a log unit.Conversely,the toxicity of methacrylates and esters containing the vinylene group varied considerably and was explained by their hydrophobicity.The comparison of the quantitative structure-activity relationship (QSAR) for the methacrylates and esters with that for non-polar narcosis showed little significant difference and hence suggested that substitution on the carbon-carbon double bond in the methacrylates and vinylene unsaturated esters does not enhance toxicity over that of baseline.Substitution on the carbon-carbon double bond in the alpha,beta-unsaturated aldehydes resulted in toxicity that was similar to that for saturated derivatives.Although an excellent hydrophobicity-dependent QSAR was developed for the esters containing ethynylene group,these compounds are considered to act as Michael-type acceptors.Attempts to combine different groups of Michael-type acceptors into a single QSAR,based on mechanistically derived descriptors,were unsuccessful.Thus,the modeling of the toxicity of the alpha,beta-unsaturated carbonyl domain is currently limited to models for narrow subdomains.