Toxicity of 3,3',4,4'- and 2,2',5,5'-tetrabromobiphenyl: correlation of activity with aryl hydrocarbon hydroxylase induction and lack of protection by antioxidants.
3,3',4,4'-Tetrabromobiphenyl is a minor component of commercial polybrominated biphenyl (PBB) mixture fireMaster BP-6 and is a potent inducer of aryl hydrocarbon hydroxylase (AHH). A single ip dose of 3,3',4,4'-tetrabromobiphenyl (150 mumol/kg) caused significant reduction in the growth rate in the immature male Wistar rat, as well as pale enlarged livers and marked reduction in thymus size. Under light microscopy, hepatocytes were enlarged and vacuolated. The vacuoles, which were most prominent in the midzonal region of the lobule, corresponded to fat droplets in oil-red-O-stained sections. The thymus, especially the cortex, was markedly depleted of lymphocytes. Neither the reduced growth, altered organ weights nor the histopathology was reversed for the duration of the study by the coadministration of the antioxidants butylated hydroxy anisole (BHA), butylated hydroxy toluene (BHT), or vitamin E. Vitamin E did, however counter the negative effect of 3,3',4,4'-tetrabromobiphenyl on growth during the first 5 d of the study. 2,2',5,5'-Tetrabromobiphenyl, also a minor component of fireMaster BP-6, is a weak phenobarbital-type inducer of cytochrome P-450. When administered at the same dose, 2,2',5,5'-tetrabromobiphenyl did not elicit any observed toxic effects. These data confirm the correlation between AHH induction and toxicity for these PBBs and suggest that 3,3',4,4'-tetrabromobiphenyl may significantly contribute to the toxicity of fireMaster BP-6. Although there is evidence that polychlorinated biphenyls, and perhaps 2,3,7,8-tetrachlorodibenzo-p-dioxin, exert certain toxic effects via a lipid peroxidation mechanism, the toxic changes measured during this study were not reversed by the administration of the antioxidants.
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001189:Aryl Hydrocarbon Hydroxylases / Q000096:biosynthesis / Q000378:metabolism*; D001713:Biphenyl Compounds / Q000633:toxicity*; D004790:Enzyme Induction / Q000187:drug effects; D008099:Liver / Q000254:growth & development / Q000473:pathology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011075:Polybrominated Biphenyls / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D013154:Spleen / Q000254:growth & development; D013950:Thymus Gland / Q000254:growth & development
D000975:Antioxidants; D001713:Biphenyl Compounds; D011075:Polybrominated Biphenyls; D001189:Aryl Hydrocarbon Hydroxylases; C036685:3,3',4,4'-tetrabromobiphenyl; C028966:2,2',5,5'-tetrabromobiphenyl