Jiangsu Key Laboratory of Chemical Pollution Control and Resources Reuse, School of Environmental and Biological Engineering , Nanjing University of Science and Technology , Nanjing 210094 , People's Republic of China.
State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment , Nanjing University , Nanjing 210023 , China.
Environ Sci Technol. 2019 Feb 19;53(4):2151-2160. doi: 10.1021/acs.est.8b06246. Epub 2019 Feb 1.
The effects of 2-ethylhexyl diphenyl phosphate (EHDPP) on cytotoxicity and mRNA expression, as well as its metabolism, were investigated using a chicken embryonic hepatocyte (CEH) assay. After incubation for 36 h, the lethal concentration 50 (LC) was 50 ± 11 μM, suggesting that EHDPP is one of a small cohort of highly toxic organophosphate esters (OPEs). By use of a ToxChip polymerase chain reaction (PCR) array, we report modulation of 6, 11, or 16/43 genes in CEH following exposure to 0.1, 1, or 10 μM EHDPP, respectively. The altered genes were from all nine biological pathways represented on the ToxChip including bile acids/cholesterol regulation, glucose metabolism, lipid homeostasis, and the thyroid hormone pathway. After incubation for 36 h, 92.5% of EHDPP was transformed, and one of its presumed metabolites, diphenyl phosphate (DPHP), only accounted for 12% of the original EHDPP concentration. Further screening by use of high-resolution mass spectrometry revealed a novel EHDPP metabolite, hydroxylated 2-ethylhexyl monophenyl phosphate (OH-EHMPP), which was also detected in a human blood pool. Additional EHDPP metabolites detected in the human blood pool included EHMPP and DPHP. Overall, this study provided novel information regarding the toxicity of EHDPP and identified a potential EHDPP metabolite, OH-EHMPP, in both avian species and humans.
采用鸡胚肝细胞（CEH）测定法，研究了 2-乙基己基二苯磷酸酯（EHDPP）对细胞毒性、mRNA 表达及其代谢的影响。孵育 36 h 后，半数致死浓度（LC）为 50±11 μM，表明 EHDPP 是少数高度毒性有机磷酸酯（OPEs）之一。通过 ToxChip 聚合酶链反应（PCR）阵列，我们报告了在分别暴露于 0.1、1 或 10 μM EHDPP 后，CEH 中有 6、11 或 16/43 个基因被调节。受影响的基因来自 ToxChip 上代表的所有 9 个生物途径，包括胆汁酸/胆固醇调节、葡萄糖代谢、脂质稳态和甲状腺激素途径。孵育 36 h 后，92.5%的 EHDPP 发生转化，其一种假定代谢物二苯磷酸酯（DPHP）仅占原始 EHDPP 浓度的 12%。通过使用高分辨率质谱进一步筛选，发现了一种新型 EHDPP 代谢物，羟基化 2-乙基己基单苯磷酸酯（OH-EHMPP），也在人类血液库中检测到。在人类血液库中还检测到其他 EHDPP 代谢物，包括 EHMPP 和 DPHP。总体而言，本研究提供了有关 EHDPP 毒性的新信息，并在禽类和人类中鉴定了一种潜在的 EHDPP 代谢物 OH-EHMPP。
