Metabolism in vivo of 3, 4, 5, 3', 4'-pentachorobiphenyl and toxicological assessment of the metabolite in rats.

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Abstract
Metabolism in vivo of 3,4,5,3'',4''-pentachlorobiphenyl (PenCB) and toxicological assessment of the metabolite were investigated using male Wistar rats. Only one metabolite was isolated from the feces of rats administered 3,4,5,3'',4''-PenCB. By gas chromatography-mass spectrometry, the methylated metabolite was identified with the synthesized authentic sample, 4''-methoxy-3,4,5,3'',5''-PenCB. This indicated that the metabolite was 4''-hydroxy-3,4,5,3'',5''-PenCB, which was produced via a 4'',5''-expoixde formation and subsequent NIH-shift of the 4''-chlorine to the 5''-position. Administration of the metabolite at either single i.p. dose of 3 or 10 mg/kg to rats did not cause any toxic and biological effects such as body weight loss, atrophy of thymus and spleen, liver hypertrophy, increase of liver lipids, or 3-methylcholanthrene-type induction of liver enzymes. These changes were observed in rats adminstered with 3,4,5,3'',4''-PenCB at a single dose of 3 mg/kg. In addition, a trace amount of 4''-hydroxy-3,4,5,3'',5''-PenCB could be detected in rat liver 5 d after treatment with 3,4,5,3'',4''-PenCB or 4''-hydroxy-3,4,5,3'',5''-PenCB. The amount of this metabolite excreted in feces during 5 d after treatment with 3,4,5,3'',4''-PenCB accounted for only 1.3% of dose. In 4''-hydroxy-3,4,5,3'',5''-PenCB-treated rats, about 60% of dose was excreted as unchanged in feces for 5 d. These results suggest that this metabolite is a detoxified product and has no longer the higher affinity for the liver, being excreted rapidly into the feces.