Hepatotoxicity of monobromobenzene and hexabromobenzene: effects of repeated dosage in rats

The aim of the study was to determine whether monobromobenzene (BB) and hexabromobenzene (HBB) administered repeatedly (for 28 days) to female rats resulted in disturbances of heme synthesis. 5-Aminolevulinate dehydratase (ALA-D) and 5-aminolevulinate synthase (ALA-S) activities were slightly changed and the concentration of glutathione increased. The excretion of 5-aminolevulinic acid (ALA-U) in urine after all doses of BB and HBB increased already in the first week. After BB administration, increased excretion of coproporphyrins was detected only at the highest dose. The increased excretion of coproporphyrins following the administration of HBB could be observed already at the lowest dose (15 mg/kg). The excretion of uroporphyrins increased after two higher doses (75 and 375 mg/kg) in the fourth week of exposure. HBB also caused elevation of microsomal P450 level. The data suggest porphyrogenic activity of HBB; whereas in the case of BB we cannot exclude that elevated excretion of ALA-U resulted from kidney impairment.