Assessment of chloroaniline toxicity by the submitochondrial particle assay

The effects on mitochondrial respiration of 15 chloroanilines were recorded by using the in vitro response of submitochondrial particles (SMP) from be ef heart mitochondria. The bioassay procedure for SMP is based on the proce ss of reverse electron transfer, which can be negatively affected by inhibi tors of electron transport, by uncouplers, and by chemicals that impair mem brane integrity. The EC50 values, determined for the tested chloroanilines, indicate a general tendency of increasing toxicity with increasing chlorin e substitution. In order to validate the results obtained and to evaluate t he capability of the SMP assay to reproduce the toxic effects of the examin ed compounds on different freshwater species, the EC50 values were compared with literature data from other biological assays regarding both in vitro systems and whole organisms. A good correlation was found in particular wit h two widely used testing systems, the Microtox((R)) and the Tetrahymena as says. In addition, quantitative structure-activity relationships (QSARs) we re established between the EC50 values and various molecular descriptors fo r hydrophobic, steric, and electronic interactions. The results obtained we re utilized to elucidate the mechanism of toxic action of chloroanilines, w hich are commonly reported to act by the polar narcosis mode of action. Mor eover, they confirmed that the SMP assay can be a useful tool for studying the toxicity of chemicals that act nonspecifically by impairing membrane st ructure and functions.