Isomerically pure bromobiphenyl congeners and hepatic mono-oxygenase activities in the rat: Influence of position and degree of bromination

Isomerically pure di-, tri-, tetra-, penta-, hexa-, and octabromobiphenyls were injected ip into weanling rats at a dosage of 0.2 mmol/kg/day for 3 consecutive days and the animals were killed 96 hr after the last injection. The influence of position and degree of bromination of the biphenyl nucleus on hepatic function was assessed by measuring changes in activities of hepatic p-nitroanisole O-demethylase (OD) and aniline hydroxylase (AH), by examining morphological changes by electron microscopy, and by comparing the results with those of animals treated with equivalent doses of Firemaster BP6. Bromobiphenyl residues were extracted from liver and analyzed by gas-liquid chromatography. Hepatic O-demethylase activities were increased proportionally as the degree of bromination increased, observations which correlated well with the increased tissue residues and changes in morphology. Marked increases in aniline hydroxylase were observed following treatment with certain di- and tribromobiphenyl congeners but, as the degree of bromination increased above four atoms per molecule, aniline hydroxylase activity was reduced to levels equal to or below those of control, vehicle-treated animals. In contrast, increases in both mono-oxygenases were observed following treatment with Firemaster BP6, fivefold increases for OD and twofold for AH. In vitro experiments with highly brominated congeners suggested that these influenced the AH assay by interacting with microsomal cytochrome P-450.