Metabolism in vivo of 3,4,3',4'-tetrachlorobiphenyl and toxicological assessment of the metabolites in rats.
1. Metabolism in vivo of 3,4,3',4'-tetrachlorobiphenyl (TCB) and toxicological assessment of the metabolites were investigated in the rat. 2. Four metabolites were isolated from faeces of rats dosed with 3,4,3',4'-TCB. Two were identified as 5-hydroxy-3,4,3',4'-TCB and a chlorine-shift metabolite, 4-hydroxy-3,5,3',4'-TCB, by comparison of melting points, chromatographic mobilities and spectral features with those of the synthetic samples. A dihydroxy-TCB and monohydroxy-trichlorobiphenyl were also indicated by mass spectrometry to be excreted in faeces as minor metabolites. 3. Faecal excretion of unchanged 3,4,3',4'-TCB, 5-hydroxy-3,4,3',4'-TCB and 4-hydroxy-3,5,3',4'-TCB was 0.8%, 19.6% and 11.6% of dose, respectively, in 5 days after i.p. injection of 3,4,3',4'-TCB at a dose of 50 mg/kg. 4. From the inability to cause the liver hypertrophy and thymus atrophy, both monohydroxy-metabolites of 3,4,3',4'-TCB are much less toxic than the parent 3,4,3',4'-TCB. In addition, these phenolic metabolites did not induce the activities of benzo[a]pyrene hydroxylase and DT-diaphorase, whereas 3,4,3',4'-TCB greatly induced these activities. These results indicated that unlike PCB congeners with phenobarbital-type inducing ability, 3,4,3',4'-TCB, a prototype of 3-methylcholanthrene-type inducers, is detoxified by metabolic hydroxylation.
D000818:Animals; D001711:Biotransformation; D002849:Chromatography, Gas; D002855:Chromatography, Thin Layer; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D009929:Organ Size / Q000187:drug effects; D011078:Polychlorinated Biphenyls / Q000378:metabolism* / Q000633:toxicity; D051381:Rats
D011078:Polychlorinated Biphenyls; C028451:3,4,3',4'-tetrachlorobiphenyl