Tetrachlorobiphenyl, metabolization

Yoshimura, H.,Y. Yonemoto, H. Yamada, N. Koga, K. Oguri, S. Saeki. 1987. Metabolism in vivo of 3,4,3, 4 -tetrachlorobiphenyl and toxicological assessment of the metabolites in rats. Xenobiotica 17 897-910. 

Along with degree of chlorination another determinant of PCB metabolism in fish is species. Green sunfish and goldfish rapidly metabolize 2,2, 5-trichlorobiphenyl whereas bullheads and rainbow trout metabolize it slowly (26,29). There is little evidence for PCB metabolism in brook trout fed 4-chloro-, 4,4 -dichloro-, 2,2, 5,5 -tetrachloro- or 2,2, 4,4, 5,5 -hexachloro-biphenyl (31) and this was confirmed in rainbow trout by less than 1% of 2,2, 5,5 -tetrachlorobiphenyl accumulated being recovered as polar metabolites (25). 

Preston BD, Miller JA, Miller EC. 1983. Non-arene oxide aromatic ring hydroxylation of 2,2,5,5 -tetrachlorobiphenyl as the major metabolic pathway catalyzed by phenobarbital-induced rat liver microsomes. J Biol Chem 258 8304-8311. 

A comprehensive review of the metabolism of PCBs was published in 1976 by Sundstrom et al. (ref. 139a) confirming the importance of degree of substitution and location of halogens on toxicity. The lesser chlorinated biphenyls are more readily metabolized. The presence of at least two adjacent hydrogens—preferably in positions 3. 4, 5 or 3, 4, 5 —is required for the rapid metabolism of PCBs. This requirement is satisfied by all mono-, di- and trichlorobiphenyls, and by the tetrachlorobiphenyls with the exception of the 3. 3. 5. 5 -chlorinated PCB. This compound was reported particularly toxic to monkeys, and the intermediate formation of chlorinated dibenzofuran was postulated to account for this toxicity (ref. 139c). 

White, R.D., D. Shea and J.J. Stegeman. Metabolism of the aryl hydrocarbon receptor agonist 3,3, 4, 4 tetrachlorobiphenyl by the marine fish scup (Stenotomus chrysops) in vivo and in vitro. Drug Metab. Dispos. 25 564-572, 1997. 

Heinrich-Hirsch B, Beck H, Chahoud 1, et al. 1997. Tissue distribution, toxicokinetics and induction of hepatic drug metabolizing enzymes in male rats after a single s.c. dose of 3,4,3, 4 -tetrachlorobiphenyl (PCB-77). Chemosphere 34(5-7) 1523-1534. 

Klasson-Wehler E, Bergman A, Kowalski B, et al. 1987. Metabolism of 2,3,4, 6-tetrachlorobiphenyl Eormation and tissue localization of mercapturic acid pathway metabolites in mice. Xenobiotica 17 477-486. 

Klasson-Wehler E, Jonsson J, Bergman A, et al. 1989b. 3,3, 4,4 -tetrachlorobiphenyl and 3,3, 4,4, 5-pentachlorobiphenyl-tissue-localization and metabolic fate in the mouse. Chemosphere 19 809-812. 

Koga N, Beppu M, Ishida C, et al. 1989. Further studies on metabolism in vivo of 3,4,3, 4 -tetrachlorobiphenyl in rats identification of minor metabolites in rat feces. Xenobiotica... 

Studies of the anaerobic metabolism of 2,3,4,6-tetrachlorobiphenyl by freshwater sediments have demonstrated that temperature not only influences rate but may also influence metabolic pathways. The metabolism of this PCB congener was monitored for 1 year in sediments (exposed or not exposed to PCBs) under anaerobic conditions at temperatures ranging from 4 to 66°C. Dechlorination steps are summarized in Figure 9.11 with the black arrows indicating reactions observed in the nonexposed sediment. All reactions were observed with the exposed sediment. Little if any reaction was detected at 4°C and at the higher temperatures (37°C and above in the nonexposed sediment and 37-45°C with the exposed sediment). However, from 50-60°C almost 90% conversion to the 2,4,6-CB was observed. An example of the differences reported is provided in Figure 9.12. At 15 and 20°C, the first step was the loss of m-chlorine to produce the 2,4,6-CB. However, at 15°C the production of the 2,4-CB is favored along with the 4-CB in contrast... 

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