A comparison of a commercial polybrominated biphenyl mixture, 2,4,5,2',4',5'-hexabromobiphenyl and 2,3,6,7-tetrabromonaphthalene as inducers of liver microsomal drug-metabolizing enzymes

Abstract

The commercial polybrominated biphenyl (PBB) mixture, Firemaster BP-6, is a mixed inducer of hepatic drug-metabolizing enzymes in the rat. Its effects resemble those of a combination of the phenobarbital and 3-methylcholanthrene classes of inducers. 2,3,6,7-Tetrabromonaphthalene (TBN) was studied as a prototype of the brominated naphthalenes which are present as minor contaminants of Firemaster BP-6. TBN is an isostere of 2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD), the most potent known inducer of the 3-methylcholanthrene class. TBN is a 3-methylcholanthrene-type inducer; however, it is 10 4 times less potent than TCDD and it is only slightly more potent than Firemaster. The relatively low potency of TBN does not appear to be due to metabolism, since comparable amounts of TBN and Piremaster were found in the liver at equivalent doses. In contrast to TBN, the predominant component, 2,4,5,2',4',5'-hexabromobiphenyl (HBB), is a pure phenobarbital-type inducer. The no effect level for the effects of a single dose of Firemaster or 2,4,5,2',4',5'-HBB on hepatic microsomal enzymes was 8 μmoles/kg (4.7 mg/kg of Firemaster). When Firemaster was given chronically 5 days a week for 15–30 days, changes in hepatic enzymes occurred with doses as low as 0.3 mg/kg/day. Using liver enzyme activities as an index of hepatic change, a 30-day recovery study showed that the liver does recover partially after exposure ceases. The degree of recovery correlates with a decrease in the concentration of PBBs in the liver as PBBs are redistributed from the liver to the fat. Porphyria was not observed during the chronic experiment, but gross hepatic porphyria developed in the Firemaster-treated rats during the recovery period.