Metabolismin vivoof 3,4,3′,4′-tetrachlorobiphenyl and toxicological assessment of the metabolites in rats

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Abstract
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 50mg/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.

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