Studies on polychlorinated biphenyls, with emphasis on the role of 2,2',5,5'-tetrachlorobiphenyl 3,4-oxide in the metabolism of 2,2',5,5'-tetrachlorobiphenyl in the rat
The pathways of metabolism of 2,2',5,5'-tetrachlorobiphenyl (TCB), a major component of the polychlorinated biphenyl (PCB) mixture Aroclor 1254, were investigated in the rat and in rat liver microsomal systems. TCB was metabolized by phenobarbital-induced microsomes to 3-hydroxy-TCB and 3,4-dihydroxy-TCB, as major metabolites (> 95% of the metabolites), and to TCB 3,4-oxide (TCBO), 3,4-dihydro-3,4-dihydroxy-TCB and a presumed 3,3'-dihydroxy-TCB, as minor metabolites. Similar ratios of these ring-hydroxy metabolites (as conjugates) were also excreted in the bile of TCB-treated rats. Studies of the metabolic fates of synthetic TCBO, 3-hydroxy-TCB and 4-hydroxy-TCB showed that the majority (> 90%) of the primary oxidation of TCB occurred via 3-hydroxylation mechanisms not involving TCBO. These data provide the first example of an aromatic substrate which undergoes cytochrome P-450-mediated ring-hydroxylation almost exclusively by a non-arene oxide pathway. The hepatic tumor-promoting activity of the PCB mixture Aroclor 1254 was investigated in the rat. Aroclor 1254 and Aroclor 1254 freed of the intrinsic polychlorinated dibenzofuran impurities showed equal activity for promotion of diethylnitrosamine-initiated liver tumors. The promoting activity of the Aroclor was thus deduced to be a function of the PCB's.
- OSTI ID:
- 5929636
- Resource Relation:
- Other Information: Thesis (Ph. D.)
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
CHLORINATED AROMATIC HYDROCARBONS
METABOLISM
BIOCHEMISTRY
BIOLOGICAL PATHWAYS
LIVER
MICROSOMES
RATS
ANIMALS
AROMATICS
BODY
CELL CONSTITUENTS
CHEMISTRY
DIGESTIVE SYSTEM
GLANDS
HALOGENATED AROMATIC HYDROCARBONS
MAMMALS
ORGANIC CHLORINE COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANOIDS
ORGANS
RODENTS
VERTEBRATES
560305* - Chemicals Metabolism & Toxicology- Vertebrates- (-1987)