Mechanism-based comparisons of acute toxicities elicited by industrial organic chemicals in procaryotic and eucaryotic systems.

Comparisons of toxicities elicited by nonpolar and polar narcotics, weak acid uncouplers of oxidative phosphorylation, and bioreactive chemicals between the eucaryotic systems Pimephales promelas and Tetrahymena pyriformis and the procaryotic systems Escherichia coli and Photobacterium phosphoreum were performed. Each chemical had been a priori assigned a mechanism/mode of action based on the results from previous studies with eucaryotic systems. Hydrophobicity-dependent QSARs for nonpolar narcosis for both the E. coli and the P. phosphoreum endpoints was developed. However, due to the lack of a significant relationship between P. phosphoreum toxicity and log Kow, such a QSAR for polar narcosis was developed only for the E. coli endpoint. Except for 4-nitroaniline (the only chemical in the examined group that required activation to become the Michael receptor), all chemicals containing reactive substructures revealed excess toxicity over polar narcosis QSAR for E. coli endpoints. Moreover, chloroacidic acid and ethyl chloroacetate in this system also appear to be bioreactive. The only mechanism that seemed to not exist in the procaryotic system was uncoupling of oxidative phosphorylation. Chemicals from this group, except 2,4-dinitroaniline, did not exhibit excess toxicity over polar narcosis QSAR. This was thought to be explained by the lack of mitochondria in procaryotes, the target site of uncoupling agents in eucaryotes. In addition, evaluation of toxicities of halogen-substituted short-chain carboxylic alcohols indicated that their mechanisms vary, depending upon the type of substitution and the system.