The influence of pure polychlorinated biphenyl compounds on hepatic function in the rat |
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Authors: | G J Johnstone D J Ecobichon O Hutzinger |
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Affiliation: | 1. Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada;2. Atlantic Regional Laboratory, National Research Council, Halifax, Nova Scotia, Canada |
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Abstract: | Pure biphenyl and isomerically pure mono-, di-, tetra-, hexa-, and octachlorobiphenyls of known chemical composition were injected ip (50 mg/kg/day) into young male Wistar rats for 3 days; the animals were killed 96 hr after the last injection. The potency of the pure PCBs was compared to that of o,p′-DDT and p,p′-DDT and commercial Aroclors (1254, 1260) administered at the same concentrations. Hepatic function was assessed by pentobarbital sleeping times and in vitro assays of hepatic microsomal O-demethylase, N demethylase, aniline hydroxylase, nitroreductase, carboxylesterase and the cytoplasmic bromosulfophthalein-glutathione conjugating enzyme. Biphenyl and 4-monochlorobiphenyl did not cause induction of hepatic drug-metabolizing enzymes. Microsomal mono-oxygenases were induced by hexa- and octachlorobiphenyls and by di- and tetrachlorobiphenyls with chlorines substituted at the 3 and 4 positions. Nitroreductase and carboxylesterase activities were affected only by the highly chlorinated compounds whereas all agents, including biphenyl, caused a marked induction of the bromosulfophthalein-conjugating system. |
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