3,3',4,4'-tetrachlorobiphenyl: metabolism by the chick embryo in ovo and toxicity of hydroxylated metabolites.
The metabolism of 3,3',4,4'-tetrachlorobiphenyl (TCB) has been studied in the chicken in ovo by analysis of bile from chick embryos. Four percent of the [14C]TCB dose injected into the air sac on day 13 of incubation was detected in the bile by day 19. An increase of more lipophilic TCB metabolites was observed by HPLC analysis after hydrolysis of the bile. TCB and three phenolic TCB metabolites were identified and quantified in the hydrolyzed bile: TCB (14 ng/gall bladder), 5-hydroxy-3,3',4,4'-tetrachlorobiphenyl (234 ng/gall bladder), 4-hydroxy-3,3',4',5-tetrachlorobiphenyl (45 ng/gall bladder) and 2-hydroxy-3,3',4,4'-tetrachlorobiphenyl (3 ng/gall bladder). The presence of two other TCB metabolites in the bile, a dihydroxy-tetrachlorobiphenyl and a dihydroxy-trichlorobiphenyl was also indicated. The method used in the present study is well suited for studies of metabolism in avian embryos in ovo. The three TCB metabolites identified all proved to be at least two orders of magnitude less toxic than TCB in a chick embryo test. These metabolites were also shown to bind with significantly lower affinity than TCB to the Ah receptor. TCB, 5-hydroxy-3,3',4,4'-tetrachlorobiphenyl, 4-hydroxy-3,3',4',5-tetrachlorobiphenyl and 2-hydroxy-3,3',4,4'-tetrachlorobiphenyl gave Kd values of 16, 33, 45 and 37 nM, respectively, in the Ah receptor test.
Wehler
E K
EK
Environmental Chemistry, Wallenberg Laboratory, Stockholm University, Sweden.
Brunström
B
B
Rannug
U
U
Bergman
A
A
D000818:Animals; D001646:Bile / Q000378:metabolism; D002642:Chick Embryo / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D005704:Gallbladder / Q000196:embryology / Q000378:metabolism; D008401:Gas Chromatography-Mass Spectrometry; D006900:Hydroxylation; D007700:Kinetics; D051379:Mice; D015394:Molecular Structure; D011078:Polychlorinated Biphenyls / Q000378:metabolism* / Q000633:toxicity; D018336:Receptors, Aryl Hydrocarbon; D011955:Receptors, Drug / Q000378:metabolism
D018336:Receptors, Aryl Hydrocarbon; D011955:Receptors, Drug; D011078:Polychlorinated Biphenyls; C028451:3,4,3',4'-tetrachlorobiphenyl