Metabolic Studies on Polychlorinated Biphenyls. II. Metabolic Fate of 2, 4, 3', 4'-Tetrachlorobiphenyl in Rats

Abstract

In order to understand the toxic nature of Kanechlor-400 (KC-400, a commercial preparation of polychlorinated biphenyls) and establish the treatment of the patients of this KC-400 intoxication (so-called Yusho), metabolic fate of 2, 4, 3', 4'-tetrachlorobiphenyl (2, 4, 3', 4'-TCB), a major component of KC-400, was investigated using rats. It was found that at least four metabolites having phenolic nature were excreted exclusively into the feces together with a large amount of unchanged 2, 4, 3', 4'-TCB. Among these, a major metabolite (M-A2), mp 155-156°, and a minor metabolite (M-A1), mp 92-98°, were isolated from the feces and characterized to be monohydroxylated TCB by ultraviolet, infrared, nuclear magnetic resonance, and mass spectral analyses. After 2, 4, 3', 4'-TCB was orally administered at a single dose of 25 mg/body to the rat, a little less than one half of the dose was excreted as unchanged 2, 4, 3', 4'-TCB during 12 days, most of which were eliminated in the first day. The excretion of major metabolite reached maximum at the second day, and total M-A2 was accounted for about 10% of dose during 12 days. Both 2, 4, 3', 4'-TCB and its major metabolite were still excreted in a small but significant amount on 12th day.