In vivo and in vitro nephrotoxicity of aniline and its monochlorophenyl derivatives in the Fischer 344 rat.

Aniline (A) and its monochlorophenyl derivatives (2-CA, 3-CA and 4-CA) are widely-used chemical intermediates. In the present study, the in vivo and in vitro nephrotoxic potential of these compounds was assessed in Fischer 344 rats. In the in vivo experiments, rats were administered a single intraperitoneal (i.p.) injection of an aniline (0.4, 1.0 or 1.5 mmol/kg) or 0.9% saline (2.0 ml/kg, i.p.), and renal function monitored at 24 and 48 h. 2-CA was the only compound tested which decreased urine volume, elevated the blood urea nitrogen (BUN) concentration and depressed both basal and lactatestimulated p-aminohippurate (PAH) accumulation by renal cortical slices at the 1.0 mmol/ kg dose. Similar results were produced following 3- and 4-CA administration, but these compounds required a dose of 1.5 mmol/kg. Aniline had little effect on renal function at the doses used in this study. In the in vitro experiments, 2-CA (10(-4) M or greater) depressed basal PAH accumulation. Tetraethylammonium (TEA) uptake was decreased by all compounds with an incubate concentration of the aniline at 10(-3) M. Lactatestimulated PAH uptake was not decreased by any test compound. These results indicate that chlorine substitution on the phenyl ring of aniline enhances nephrotoxic potential, and that 2-substitution produces the greatest increase.