Hepatotoxicity of tetrabromobisphenol-A: effects of repeated dosage in rats

Tetrabromobisphenol-A (TBBP-A) is used as a reactive flame retardant and as an intermediate in the production of other flame-retardants. In our study, TBBP-A was administered intragastrically, daily for 7 or 7-28 days at three dose levels. Significant changes of biochemical indicators were noted with regard to glutathione (GSH), malondialdehyde (MDA) and 5-aminolevulinate dehydratase (ALA-D). The level of GSH was lowered by the two higher doses (female rats only) and MDA was elevated by the highest dose (male rats only). The ALA-D activity reacted in opposite directions for both sexes. Other indicators did not yield any conclusive results. The 28-day study was performed on female rats. For GSH and MDA the medium dose resulted in a systematic increase. Insignificant changes in ALA-D activity in the liver were observed throughout the experiment. The activity of 5-aminolevulinate synthase had a decreasing tendency at 250 mg/kg of TBBP-A during the whole time of observation. Other general indices such as the activity of gamma-glutamyltransferase, concentration of microsomal proteins and the level of cytochrome P-450 did not show any significant changes. The most pronounced changes were noted with regard to indicators of porphyrogenic action. The results suggest that TBBP-A is capable of disturbing the heme metabolism in rats.