In Vitro Metabolism of the Brominated Flame Retardants 2-Ethylhexyl-2,3,4,5-Tetrabromobenzoate (TBB) and Bis(2-ethylhexyl) 2,3,4,5-Tetrabromophthalate (TBPH) in Human and Rat Tissues

Due to the phaseout of polybrominated diphenyl ether (PBDE) flame retardants, new chemicals, such as 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (TBB) and bis(2-ethylhexyl) 2,3,4,5-tetrabromophthalate (TBPH), have been used as replacements in some commercial flame retardant mixtures. Both chemicals have been detected in indoor dust at concentrations approaching the concentrations of PBDEs; however, little is known about their fate, metabolism, or toxicity. The goal of this study was to investigate the potential metabolism of these two brominated flame retardants in human and rat tissues by conducting in vitro experiments with liver and intestinal subcellular fractions. In all the experiments, TBB was consistently metabolized to 2,3,4,5-tetrabromobenzoic acid (TBBA) via cleavage of the 2-ethylhexyl chain without requiring any added cofactors. TBBA was also formed in purified porcine carboxylesterase but at a much faster rate of 6.29 ± 0.58 nmol min–1 mg protein–1. The estimated Km and Vmax values for TBB metab...