Examination of the structure-toxicity relationships of L-cysteine-S-conjugates of halogenated alkenes and their corresponding mercapturic acids in rat renal tissue slices.

Rat kidney slices were produced using a modified version of a mechanical tissue slicer. The slices were incubated with various concentrations of L-cysteine conjugates and mercapturic acids of halogenated alkenes in a submersion incubation system. The slices showed a time- and concentration-dependent toxicity to the nephrotoxic conjugates. The five L-cysteine conjugates tested: S-(1,2-dichlorovinyl)-L-cysteine (1,2-DCVC), S-(1,1,2,2-tetrafluoroethyl)-L-cysteine (TFEC), S-(1-chloro-1,2,2-trifluoroethyl)-L-cysteine (CTFEC), S-(1,1-dichloro-2,2-difluoroethyl)-L-cysteine (DCDFEC) and S-(1,1-dibromo-2,2-difluoroethyl)-L-cysteine (DBDFEC) were more toxic compared to the corresponding mercapturic acids. Comparing the in vitro toxicity data with the in vivo data for the same compounds results in similar ranking for the relative nephrotoxicity of the conjugates.