Disposition of o‐benzyl‐p‐chlorophenol in male rats

Abstract

The disposition and metabolism of o‐benzyl‐p‐chlorophenol (BCP) were studied in male Fischer‐344 rats. Three days after oral administration of [¹⁴C]BCP at 10, 100, or 1000 mg/kg, more than 90% of each dose was excreted in urine and feces. Comparison of disposition after intravenous, dermal, or oral administration indicated that BCP was not completely absorbed from the gastrointestinal tract or skin. Biliary excretion of BCP was dose‐dependent, with proportionally less BCP‐derived radioactivity being excreted in the bile as the dose was raised. The results also indicated that enterohepatic circulation was involved in BCP disposition. The major in vivo metabolites were glucuronyl conjugates of BCP and hydroxy‐BCP. Clutathione conjugates were also present in urine. In vitro metabolism studies support the observation that microsomal oxidation and glutathione and glucuronyl conjugation play major roles in BCP metabolism. Spleen, kidney, and liver contained the highest tissue concentrations of BCP‐derived radioactivity. The presence of more nonextractable BCP‐derived radioactivity in kidney than in liver is compatible with the hypothesis that covalent binding of BCP to renal tissue may be associated with BCP‐induced nephrotoxicity.