Metabolic Studies on Polychlorinated Biphenyls. III. Complete Structure and Acute Toxicity of the Metabolites of 2, 4, 3', 4'-Tetrachlorobiphenyl

The present investigation was undertaken to establish the structures of two metabolites which were isolated from the feces of rats administered with 2, 4, 3', 4'-tetrachlorobiphenyl (2, 4, 3', 4'-TCB), a major component of commercial preparation of polychlorinated biphenyls. For this purpose six possible isomers of monohydroxy-2, 4, 3', 4'-TCB were synthesized by condensation reactions between appropriate diazotized dichloroanilines and dichlorophenols. Among these isomers, 5-hydroxy-and 3-hydroxy-2, 4, 3', 4'-TCB were shown to be identical with a major metabolite (M-A2), mp 155-156°, and a minor metabolite (M-A1), mp 92-98°, respectively. Further study was made to know the acute lethal dose of 2, 4, 3', 4'-TCB and its major metabolite, 5-hydroxy-2, 4, 3', 4'-TCB, by i.p. injection using male mice of CF-1 strain. The results showed that LD50 of 2, 4, 3', 4'-TCB and 5-hydroxy-2, 4, 3', 4'-TCB were 2.15 g/kg and 0.43 g/kg, respectively, suggesting that acute toxicity of 2, 4, 3', 4'-TCB might be attributable to phenolic metabolites produced in vivo.