Nephrotoxic potential and toxicokinetics of tetrabromobisphenol A in rat for risk assessment.

Tetrabromobisphenol A (TBBPA), one of the most widely used global brominated flame retardants, is used to improve fire safety of laminates in electrical and electronic equipment. To investigate the nephrotoxic potential of TBBPA and its toxicokinetic profile in rats, single-dose and daily 14-d repeated-dose toxicity studies at 200, 500, or 1000 mg/kg were performed. Several biochemical parameters were analyzed to evaluate nephrotoxicity of TBBPA. High-dose 1000 mg/kg TBBPA significantly elevated renal thiobarbituric acid-reactive substance (TBARS) levels, and superoxide dismutase (SOD) activity was increased at all 3 doses administered. This was associated with no change in the activity of catalase (CAT). Our results suggest that acute 1-d high-dose administration of TBBPA produced transient renal changes at 5 h. Subsequently, TBBPA in serum, urine, and kidney was determined by liquid chromatography-mass spectroscopy (LC/MS). Toxicokinetic studies indicated that TBBPA shows relatively a short half-life (7-9 h) and was eliminated almost completely in feces by 2 d. Based on the results from the 14-d repeated-dose study, TBBPA did not accumulate in the rat, and was eliminated in feces. The present results suggested that TBBPA may not be toxic to kidney, as the chemical is not bioavailable and is not present in renal tissue.

Identification of glutathione conjugates of 1-bromopentane and its hepatotoxicity in female BALB/c mice.

Halogenated organic compounds, such as 1-bromopentane (1-BPT), are used as cleaning agents, synthesis agents, or extraction solvents in the workplace. In the present study, glutathione (GSH) conjugation and hepatotoxicity induced by 1-BPT were investigated in female BALB/c mice. S-Bromopentyl GSH, S-bromopentyl cysteine, and mono-hydroxypentyl mercapturic acid were identified in liver by liquid chromatography-electrospray ionization tandem mass spectrometry. Oral treatment of mice with 1-BPT at 1500 mg/kg produced maximum GSH conjugates at 6 h after treatment. For hepatotoxicity tests, the animals were treated orally with 1-BPT at 375, 750, or 1500 mg/kg in corn oil once for a dose response study or at 1500 mg/kg for 6, 12, 24, or 48 h for a time course study. 1-BPT dose-dependently increased serum activity of ALT and AST and decreased hepatic GSH levels, peaking at 6 and 12 h after treatment. 1-BPT (750 and 1500 mg/kg) also significantly increased the hepatic content of malondialdehyde. Thus, 1-BPT could cause hepatotoxicity and depletion of GSH content by forming GSH conjugates, presenting a toxicity mechanism and potential biomarkers for low molecular weight haloalkanes.