Halogen substituents at the 4- and 4′-positions of biphenyl: Influence on hepatic function in the rat

Isomerically pure biphenyl substituted at the 4- and 4′-positions by fluorine, chlorine, bromine, or iodine were administered ip (0.2 mmol/kg) to weanling rats for 3 consecutive days and the animals were killed 4 days after the last injection. The influence of the halogen on hepatic function was assessed by measuring hepatic p-nitroanisole O-demethylase and aniline hydroxylase activities in the 12,000g, 20-min supernatant of 20% (w/v) liver homogenate, by examining the tissue by light and electron microscopy following fixation, and by quantitating the hepatic residues of halogenated biphenyls by gas-liquid chromatography. No effect was observed with 4,4′-difluorobiphenyl, whereas 4,4′-dichloro- and 4,4′-dibromobiphenyl caused marked induction of hepatic mono-oxygenases and proliferation of the hepatic smooth endoplasmic reticulum, the effect being more pronounced with the latter compound. In contrast to expectation, no morphological or biochemical alterations were observed following treatment with 4,4′-diiodobiphenyl despite the high hepatic residues detected. Biological influence does not appear to be related to the pathway of biotransformation or to the size of the halogen in the 4- and 4′-positions.