2,2',4,4',5,5'-HEXABROMOBIPHENYL - ITS TOXICOKINETICS, BIOTRANSFORMATION AND PORPHYRINOGENIC ACTION IN RATS

The porphyrinogenic action of 2,2',4,4',5,5'-hexabromobiphenyl and its toxicokinetics were studied in female Wistar rats that were treated e very other day for 6 wk with oral doses of 112 mg/kg body weight. Subs equently, the animals were kept for a further period of 22.5 months bu t without supply of the brominated biphenyl. 10.5 months after cessati on of treatment the compound reached a maximum concentration in the ad ipose tissue followed by a gradual decline of its content. In the live r the concentration of the substance started to decrease 3 months afte r cessation of treatment. In the excreta, hexabromobiphenylol and two pentabromobiphenyls were detected as metabolites. The rate of biotrans formation amounted to about 5%. At the end of the dosing period no alt erations in the content and profile of the hepatic porphyrins were obs erved. Urinary porphyrins and their precursors delta-aminolaevulinic a cid and porphobilinogen were slightly elevated. The urinary porphyrin pattern and faecal porphyrin content and pattern did not differ from t hose of the controls. 15 and 18 months after cessation of treatment (1 6.5 and 19.5 months after the start of treatment) two animals were fou nd to have marked alterations in the content and profile of hepatic po rphyrins with uro- and heptacarboxyporphyrin predominating. It was con cluded that there is an extreme delayed individual porphyric response to 2,2',4,4',5,5'-hexabromobiphenyl in female rats.