3,5-DICHLOROANILINE TOXICITY IN FISCHER-344 RATS PRETREATED WITH INHIBITORS AND INDUCERS OF CYTOCHROME-P450

3,5-Dichloroaniline (3,5-DCA), a derivative needed in the manufacture of dyes, pesticides and industrial compounds has been reported to indu ce renal damage. This study investigated whether pretreatment with ind ucers or inhibitors of P450 altered 3,5-DCA toxicity. P450 levels were induced in male Fischer 344 (F344) rats (4-12/group) by pretreatment (i.p.) with phenobarbital (PB, 75 mg/kg/day for 3 days), beta-naphthof lavone (BNF, 100 mg/kg/day for 4 days) or pyridine (PYR, 100 mg/kg/day for 4 days). P450 activity was inhibited by pretreatment with piperon yl butoxide (PiBx) 30 min prior to injection of 3,5-DCA. Upon completi on of a designated pretreatment regimen, 0.4 or 0.8 mmol/kg 3,5-DCA wa s injected into F344 rats. Pair-fed controls were injected with 25% et hanol solution or physiological saline (2.5 ml/kg). The renal changes monitored at 24 and 48 h following treatment with 0.8 mmol/kg 3,5-DCA were characterized by increased blood urea nitrogen (BUN) level and de creased renal cortical slice accumulation of p-aminohippurate (PAH). P lasma alanine transaminase activity (ALT/GPT) was increased 24 h after injection of 0.8 mmol/kg 3,5-DCA while liver wt. was unchanged. PB or PYR pretreatment did not alter the renal or hepatic effects of 3,5-DC A while BNF pretreatment slightly reduced toxicity. In contrast, PiBx pretreatment increased the renal and hepatic changes associated with 3 ,5-DCA. The results with PiBx suggest that either the parent compound possesses some direct cytotoxicity or that a toxic metabolite was gene rated through a biotransformation pathway not inhibited by PiBx.