Identification of Tetrabromobisphenol A Diallyl Ether as an Emerging Neurotoxicant in Environmental Samples by Bioassay-Directed Fractionation and HPLC-APCI-MS/MS

Brominated flame retardants (BFRs) have been widely used as additives in products to reduce their flammability. Recent findings suggested that some BFRs exhibit neurotoxicity and thus might pose a threat to human health. In this work, a neurotoxicity assay-directed analysis was developed, combining sample cleanup, fractionation, chemical identification, and bioassay. Viability of primary cultured cerebellar granule neurons (CGNs) was used to evaluate the neurotoxicity of extracts or separated fractions from environmental samples. Tetrabromobisphenol A diallyl ether (TBBPA DAE) was identified as the causative toxicant in sediment samples collected from a river near a brominated flame retardant (BFR) manufacturing plant in South China. Liquid chromatography atmospheric pressure chemical ionization tandem mass spectrometry (LC-APCI-MS/MS) was optimized to determine TBBPA DAE levels in the potent fractions and to confirm TBBPA DAB as the key neurotoxicant. On the basis of comparison with the structure of other TBBPA derivatives, the 1-propenyl group in TBBPA DAB appears to be the cause for the neurotoxic potency. The levels of TBBPA DAB in samples along the river were found at up to 49 ng/L for river water, 10 183 ng/g dry weight (dw) in surface sediments, and 42 ng/g dw in soils. According to the distribution of TBBPA DAB in the environmental samples, the manufacturing plant was identified as the release source of TBBPA DAF.. To our knowledge, this study is the first to demonstrate potential neurotoxicity induced by TBBPA DAB in real environmental samples.