Haloaniline-induced in vitro nephrotoxicity: effects of 4-haloanilines and 3,5-dihaloanilines.

Haloanilines are widely used as chemical intermediates in the manufacture of pesticides, dyes and drugs. The purpose of this study was to examine the in vitro nephrotoxic effects of the four 4-haloaniline and four 3,5-dihaloaniline isomers using renal cortical slices obtained from the kidneys of untreated, male Fischer 344 rats. Renal cortical slices were incubated with a haloaniline hydrochloride (0.1, 0.5, 1.0 or 2.0 mM, final concentration) or vehicle for 2 h, and toxicity determined by monitoring lactate dehydrogenase (LDH) release and changes in tissue gluconeogenesis capacity. At the concentrations tested, none of the 4-haloanilines increased LDH release. 4-Bromoaniline reduced gluconeogenesis at the lowest concentration (0.1 mM), but 4-iodoaniline 2.0 mM induced the largest decrease in gluconeogenesis (92% downward arrow). Among the 3,5-dihaloanilines, 3,5-dibromoaniline proved to be the most potent nephrotoxicant and 3,5-difluoroaniline the least potent nephrotoxicant. LDH release was increased by the dibromo (1.0 and 2. 0 mM), dichloro (2.0 mM) and diiodo (2.0 mM) derivatives, but not by 3,5-difluoroaniline. These results demonstrate that 3, 5-dihaloanilines are generally more potent nephrotoxicants in vitro than the 4-haloaniline isomers, and that bromo and iodo substitutions enhanced the nephrotoxic potential of aniline to the greatest degree.