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Female, 180–200 g Sprague-Dawley rats were used to determine if 3,4,3',4'-tetrabromobi-phenyl (34-TBB) is a promoter or initiator in a two-stage hepatocarcinogenesis assay. To test for promotion, rats were partially hepatectomized (PH) 24 hr before initiation (day 1) with 10 mg of diethylnitrosamine (DEN)/kg body weight given intraperitoneally (IP). Thirty days later, promotion was with 34-TBB (0.1,1 or 5 mg/kg) or phenobarbital (PB) (500 mg/kg) in diets for 180 days. To test for initiation, rats were PH and were initiated on day 1 with 34-TBB (1, 5, or 10 mg/kg) orally or DEN (10 mg/kg) IP. On day 31, promotion was with 500 mg of PB/kg of diet for 180 days. Noninitiated and non-PH rats were used to assess the histological and ultrastructural tissue changes associated with administration of 34-TBB in the diet for 180 days. Tumor promotion-initiation were assessed by counting and measuring hepatic enzyme-altered foci (EAF) with gamma-glutamyl transpeptidase (GGT) activity. Congener 34-TBB acts as a promoter in experimental hepatocarcinogenesis in rats, as evidenced by increased numbers of GGT-positive EAF. Also, 34-TBB may have initiation potential, as suggested by increased numbers of EAF in rats initiated with 34-TBB and promoted by PB. Dietary administration of 34-TBB for 180 days is not severely toxic in rats, as evidenced by mild histological and ultrastructural changes and minimal alterations in organ and body weights. Congener 34-TBB does not accumulate in liver and adipose tissue of rats.

Tumor-Promoting, Initiating, and Hepatotoxic Effects of 3,4,3',4'-Tetrabromobiphenyl (34-TBB) in Rats