State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing, 210046, China.
Institute of Soil and Water Resources and Environmental Science, College of Environmental and Resource Sciences, Zhejiang University, Hangzhou, 310058, China.
Chemosphere. 2020 Aug;253:126653. doi: 10.1016/j.chemosphere.2020.126653. Epub 2020 Apr 3.
Novel brominated flame retardants (NBFRs) have been widely used and frequently detected in various environmental matrices. In this study, 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (TBB), bis-(2-ethylhexyl) tetrabromophthalate (TBPH) and their metabolites (namely 2,3,4,5-tetra-bromo benzoic acid (TBBA) and mono(2-ethylhexyl) tetrabromophthalate (TBMEHP)) were exposed to human umbilical vein endothelial cells (HUVECs). Metabolites can induce stronger cytotoxicity than parent compounds with EC50 at 47.3 (TBBA), 8.6 μg/ml (TBMEHP) vs > 200 μg/mL for parent compounds. Gene expression of platelet endothelial cell adhesion molecule-1, the gene associated with blood platelet kinetics, was significantly induced under TBBA and TBMEHP exposure. The in vivo test was consistent with gene expression result that the number of platelets in mouse blood was significantly increased after gavaged with 0.8 μg/mL TBBA and TBMEHP. In addition, TBB or TBPH were exposed to mice via gavage, and higher concentrations of TBBA (4 h, 60.8 ± 12.9 ng/mL, 8 h, 69.4 ± 2.24 ng/mL) in mouse blood were found than those of TBMEHP (4 h, 17.2 ± 4.01 ng/mL, 8 h, 12.8 ± 3.20 ng/mL), indicating that TBB was more readily in vivo metabolized than TBPH. The in vivo metabolism of TBB and TBPH and the stronger toxicity of their metabolites underscore the potential risk through NBFR exposure and the importance of understanding NBFR metabolism process.
新型溴化阻燃剂 (NBFRs) 已被广泛使用，并经常在各种环境基质中被检测到。在本研究中，2-乙基己基-2,3,4,5-四溴苯甲酸（TBB）、双（2-乙基己基）四溴邻苯二甲酸酯（TBPH）及其代谢物（即 2,3,4,5-四溴苯甲酸（TBBA）和单（2-乙基己基）四溴邻苯二甲酸酯（TBMEHP））被暴露于人脐静脉内皮细胞（HUVECs）中。代谢物的细胞毒性比母体化合物更强，其 EC50 分别为 47.3（TBBA）、8.6μg/ml（TBMEHP），而母体化合物的 EC50 则>200μg/ml。TBBA 和 TBMEHP 暴露后，与血小板动力学相关的基因血小板内皮细胞黏附分子-1 的基因表达显著增加。体内试验与基因表达结果一致，即经灌胃给予 0.8μg/ml TBBA 和 TBMEHP 后，小鼠血液中的血小板数量明显增加。此外，通过灌胃将 TBB 或 TBPH 暴露于小鼠体内，在小鼠血液中发现了更高浓度的 TBBA（4 小时，60.8±12.9ng/ml；8 小时，69.4±2.24ng/ml），而 TBMEHP 的浓度较低（4 小时，17.2±4.01ng/ml；8 小时，12.8±3.20ng/ml），表明 TBB 在体内比 TBPH 更容易代谢。TBB 和 TBPH 的体内代谢及其代谢物的更强毒性强调了通过 NBFR 暴露所带来的潜在风险，以及理解 NBFR 代谢过程的重要性。
