Metabolism and disposition of ortho-benzyl-para-chlorophenol in male rats

The metabolism and disposition of ortho-benzyl-para-chlorophenol (BCP) has been investigated in the male rat following an oral dose of 69 mg/kg or 206 mg/kg. BCP was rapidly eliminated at both dose levels with 45-49% of the dose appearing in the urine and 44-49% in the feces during the 5-d period after dosing. After 5 d only 0.28-0.3% of the dose remained in the body, with almost half this value accounted for in the liver and kidney. The dynamics for the overall elimination of radioactivity from the body was biphasic at both dose levels. The initial rapid alpha phase had a well defined half-life of 8-9 h, and the slower beta phase had an estimated half-life of approximately 52-140 h. Analysis of the 12-24-h urine indicated that a majority of the radioactivity (41-61%) was present as sulfate and/or glucuronide conjugates. Treatment with purified aryl sulfatase suggested that sulfate esters were the predominate conjugate. Gas chromatography-mass spectroscopy (GC/MS) of the products isolated after enzymatic hydrolysis of the conjugates and purification by thin-layer chromatography (TLC) identified BCP, as well as two metabolites in which the benzyl ring was modified. One metabolite contained a hydroxyl substituent on the benzyl ring, and the other contained a hydroxyl and a methoxyl substituent. Preliminary analysis of the 12-24-h feces demonstrated the presence of BCP and two other components with chromatographic properties identical to the metabolites identified in the urine. A metabolic pathway for BCP has been proposed to account for the observed metabolites.