职业高暴露人群血液中有机磷酸酯阻燃剂代谢产物的分析鉴定和蓄积特征研究

With the widespread usage of organophosphate flame retardants (OPFRs) in recent years, the potential adverse health effects caused by OPFRs are more and more concerned in the field of environmental science. Generally, researchers only focus on the parent compounds of OPFRs when they investigate the adverse health effects of OPFRs though human blood. However, in vitro metabolic studies have shown that OPFRs may also exist in the form of metabolites in human blood, which has not yet been proved by in vivo experiments. In our preliminary experiments, we used tris(1-chloro-2-propyl) phosphate (TCIPP) to try to explore whether the metabolites really exist in the blood sampling from the human body. We unexpectedly found that TCIPP metabolite was detected in all blood samples and the concentration of the metabolite was higher than the parent TCIPP. Thus, we propose the hypothesis that the metabolites rather than parent compounds are the major form in the human blood for some kinds of OPFRs. To verify this hypothesis, human blood samples will be collected from e-waste dismantling worker and analyzed to identify some potential OPFRs metabolites by liquid chromatography quadrupole time-of-flight mass spectrometry. Analytical method for simultaneously quantitative detection of OPFRs and their metabolites will be also established to reveal the relationships of the concentration levels and composition patterns between metabolites and parent compounds of OPFRs. After completing the research project, the issue that metabolites or parent compounds of OPFRs are the main existing form in human blood will be clarified. Accumulation characteristics of OPFRs in blood from the occupationally exposed population will be understood. The results of the project will provide data support for further study on metabolism, internal exposure and health effect of OPFRs.

随着有机磷酸酯阻燃剂（OPFRs）的广泛使用，其对人体的健康效应已成为环境科学领域研究的热点问题。目前，通过人体血液研究OPFRs健康效应的报道都只关注其原型化合物，而体外模拟代谢研究显示OPFRs在人体血液中还可能以代谢产物的形式存在，但尚未有体内研究进行证实。前期我们对磷酸三（1-氯-二丙基）酯（TCIPP）进行了预实验，发现在血液中不仅能检测到TCIPP的代谢产物，且浓度均高于TCIPP。我们推测“部分OPFRs可能主要以代谢产物的形式存在于人体血液中”。为证实该假设，本项目拟选取电子垃圾拆解工人血液为研究对象，采用高分辨质谱对血液中OPFRs潜在的代谢产物进行定向筛查，并建立定量方法分析血液中OPFRs代谢产物的浓度、构成以及与原型化合物的关系，明确OPFRs在人体血液中的存在形式，阐明该职业暴露人群血液中OPFRs的蓄积特征，为OPFRs的代谢、内暴露和健康效应研究提供数据支持。

随着有机磷酸酯阻燃剂（OPFRs）的广泛使用，其对人体的健康效应已成为环境科学领域研究的热点问题。本项目以OPFRs为研究对象，围绕它们在电子垃圾拆解区的外暴露和内暴露情况展开研究，重点探讨了有机磷酸三酯（tri-OPEs）在人体血液中的代谢和蓄积情况，获得如下重要结果：（1）采用液相色谱-四极杆飞行时间质谱在人体血液中鉴定出3种新的芳基tri-OPEs的羟基代谢产物，分别为羟基磷酸三苯酯（OH-TPHP）、羟基磷酸三甲苯酯（OH-TMPP）和羟基磷酸三（2-乙基己基）二苯酯（OH-EHDPP），这些代谢产物可作为血液暴露芳基tri-OPEs的标志物。（2）采用液相-色谱串联质谱建立了同时检测tri-OPEs和有机磷酸二酯（di-OPEs）的分析方法，特别地，针对目前多种新型芳基tri-OPEs在环境中不断地被报道但缺乏完善的分析方法，本项目建立了同时检测17中芳基tri-OPEs的分析方法，该方法在室内灰尘和人体血液中得到了很好的应用。（3）通过采集广东某电子垃圾集聚园区的灰尘样品，发现电子垃圾拆解不仅能释放出高浓度的传统tri-OPEs（总浓度：1120−40800 ng/g），还能释放出多种新型tri-OPEs（总浓度：568−86900 ng/g）和di-OPEs（总浓度：1630−40300 ng/g），说明新型tri-OPEs和di-OPEs对人体外暴露OPFRs的贡献不容忽略。（4）通过对电子垃圾拆解工人血液中tri-OPEs和di-OPEs浓度的测定，发现不仅14种tri-OPEs（总浓度：未检出−11.2 ng/g）能在血液中检出，7种di-OPEs（总浓度：未检出−9.9 ng/g）也能在血液中检出，说明tri-OPEs在人体血液中能进行代谢转化，且母体与代谢物在血液中共存。上述系列研究结果对于进一步理解OPFRs的代谢、内暴露和健康效应具有重要意义。