Further studies on metabolism in vivo of 3,4,3',4'-tetrachlorobiphenyl in rats: identification of minor metabolites in rat faeces.
1. Metabolism in vivo of 3,4,3',4'-tetrachlorobiphenyl (TCB) was investigated in male Wistar rats. 2. Five new minor metabolites in addition to two previously identified major metabolites (5-hydroxy-3,4,3',4'-TCB and 4-hydroxy-3,5,3',4'-TCB) were isolated as methylated derivatives from faeces of rats treated with 3,4,3',4'-TCB, by silica gel column chromatography and subsequent preparative t.l.c. 3. Among these methylated metabolites, three were identified as dimethoxy-TCB, and one as monomethoxy-trichlorobiphenyl (TriCB), by g.l.c.-mass spectrometry. By comparison with synthetic standards they were fully identified as 2,5-dimethoxy-3,4,3',4'-TCB, 4,4'-dimethoxy-3,5,3',5'-TCB, 5,6-dimethoxy-3,4,3',4'-TCB, and 4-methoxy-3,3',4'-TriCB, respectively. The structures of these metabolites in rat faeces should therefore be 2,5-dihydroxy-3,4,3',4'-TCB, 4,4'-dihydroxy-3,5,3',5'-TCB, 5,6-dihydroxy-3,4,3',4'-TCB, and 4-hydroxy-3,3',4'-TriCB. 4. One further metabolite was isolated, which was shown to be an oxepin, existing in a state of equilibration with the 4',5'-oxide of the major metabolite, 4-hydroxy-3,5,3',4'-TCB, by mass and 1H-n.m.r. spectra. On standing for several months, this metabolite isomerized to a new compound with a different g.l.c. retention time, which on methylation yielded a product identical with synthetic 4,4'-dimethoxy-3,5,3',5'-TCB by g.l.c.-mass spectrometry. From these results this metabolite was assumed to be an oxepin, equilibrated with 4-hydroxy-4',5'-epoxy-3,5,3',4'-TCB.
Koga
N
N
Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Beppu
M
M
Ishida
C
C
Yoshimura
H
H
D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D002849:Chromatography, Gas; D002855:Chromatography, Thin Layer; D005243:Feces / Q000032:analysis; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008745:Methylation; D011078:Polychlorinated Biphenyls / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D011078:Polychlorinated Biphenyls; C028451:3,4,3',4'-tetrachlorobiphenyl