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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.

Poorly metabolized polychlorinated biphenyl (PCB) congeners are bioaccumulated in the bodies of rodents and humans. Little is known about the continuing biological effects of these persistent chemicals. To determine whether a single high dose of a PCB mixture to mice would have long‐term effects on liver enzymes, Aroclor 1254 was given at a single dose of 500 mg/kg to (C57BL/6 × DBA/2)F1 female mice. Paired controls received olive oil. Mice were killed at intervals of 0.5 to 55 weeks after treatment and liver assessed for aminopyrine demethylase activity. At selected time points, blood and homogenates of liver and of whole carcass were analyzed for content of PCBs by gas chromatography with electron capture detection. Hepatic aminopyrine demethylase activity was significantly elevated in Aroclor‐treated mice, relative to controls, for 42 weeks after treatment. A three‐ to fourfold increase persisted for at least 14 weeks, with a convergence of treated and control values thereafter. Significant amounts of nine PCB congeners were detected in carcass, liver, and blood; total carcass PCB, estimated on the basis of these congeners, correlated significantly with liver aminopyrine demethylase elevation, and a similar trend was noted for liver. At 42 weeks after treatment, total PCB levels were 70 mg/kg for carcass, 2.4 mg/kg for liver and 0.28 mg/kg for blood. Congener profiles were similar in all three compartments, with the majority of the retained chemical being 2,3′,4,4′,5‐ and 2,3,3′,4,4′‐pentachlorobiphenyl and 2,2′,4,4′,5,5′‐and 2,2′,3,4,4′,5′‐hexachlorobiphenyl. These results suggest that congeners bioaccumulated after a high PCB dose retain biological activity in the body for nearly a year after treatment.