首次深入了解斑马鱼体内 2-乙基己基二苯基磷酸酯转化产物的形成及其潜在毒性的预测,Environmental Science & Technology

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首次深入了解斑马鱼体内 2-乙基己基二苯基磷酸酯转化产物的形成及其潜在毒性的预测
Environmental Science & Technology ( IF 10.8 ) Pub Date : 2022-12-14 , DOI: 10.1021/acs.est.2c05506
Rongyan Yang ₁ , Yongxiu Ye ₁ , Ying Chen ₁ , Yi Yang ₁ , Liping Yang ₁ , Yiming Yao ₁ , Wenjue Zhong ₁ , Lingyan Zhu ₁

Affiliation

作为环境中经常检测到的有机磷阻燃剂，2-乙基己基二苯基磷酸酯（EHDPHP）容易发生生物转化，而其转化产物的转化机制和潜在毒性尚不清楚。在本研究中，体内通过疑似筛选分析暴露斑马鱼 21 天的 EHDPHP 转化产物，并通过质谱法鉴定。鉴定了 15 种代谢物，包括 10 种 I 期和 5 种 II 期产物，其中单羟基化产物为主要产物，其中 5-OH-EHDPHP 是最主要的。首次报道了 EHDPHP 的两种硫酸化产物和一种末端去饱和代谢产物。密度泛函计算与分子对接相结合表明，对接在蛋白质口袋中的 EHDPHP 的特定构象有利于 5-OH-EHDPHP 的初级形成，5-OH-EHDPHP 被强化为更合适的 EHDPHP 暴露生物标志物。体外_测试表明，EHDPHP 转化不仅发生在肝脏中，而且发生在肠道中，肠道微生物在其中发挥了重要作用。由于缺乏标准，计算机毒性预测结合分子对接表明，几种代谢物可能导致比 EHDPHP 更高的毒性。由于EHDPHP的特定体内转化，该结果提供了对潜在健康风险的深入洞察。

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First Insight into the Formation of In Vivo Transformation Products of 2-Ethylhexyl diphenyl phosphate in Zebrafish and Prediction of Their Potential Toxicities

As a frequently detected organophosphorus flame retardant in the environment, 2-ethylhexyl diphenyl phosphate (EHDPHP) is vulnerable to biotransformation, while the transformation mechanisms and potential toxicities of its transformation products remain unclear. In the present study, in vivo transformation products of EHDPHP in exposed zebrafish for 21d were analyzed by suspect screening and identified by mass spectrometry. Fifteen metabolites were identified, including 10 phase I and 5 phase II products with monohydroxylated products being primary, among which 5-OH-EHDPHP was the most predominant. Two sulfation products and one terminal desaturation metabolite of EHDPHP were reported for the first time. A density functional calculation coupled with molecular docking disclosed that the specific conformation of EHDPHP docked in the protein pockets favored the primary formation of 5-OH-EHDPHP, which was fortified to be a more suitable biomarker of EHDPHP exposure. The in vitro tests suggested that EHDPHP transformation took place not only in liver but also in intestine, where gut microbes played an important role. Due to lack of standards, in silico toxicity prediction combined with molecular docking indicated that several metabolites potentially cause higher toxicities than EHDPHP. The results provide deep insight into the potential health risks due to specific in vivo transformation of EHDPHP.

更新日期：2022-12-14

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