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 every other day for 6 wk with oral doses of 112 mg/kg body weight. Subsequently, the animals were kept for a further period of 22.5 months but without supply of the brominated biphenyl. 10.5 months after cessation of treatment the compound reached a maximum concentration in the adipose tissue followed by a gradual decline of its content. In the liver the concentration of the substance started to decrease 3 months after cessation of treatment. In the excreta, hexabromobiphenylol and two pentabromobiphenyls were detected as metabolites. The rate of biotransformation amounted to about 5%. At the end of the dosing period no alterations in the content and profile of the hepatic porphyrins were observed. Urinary porphyrins and their precursors delta-aminolaevulinic acid and porphobilinogen were slightly elevated. The urinary porphyrin pattern and faecal porphyrin content and pattern did not differ from those of the controls. 15 and 18 months after cessation of treatment (16.5 and 19.5 months after the start of treatment) two animals were found to have marked alterations in the content and profile of hepatic porphyrins with uro- and heptacarboxyporphyrin predominating. It was concluded that there is an extreme delayed individual porphyric response to 2,2',4,4',5,5'-hexabromobiphenyl in female rats.