有机磷酸酯阻燃剂的母婴传递特征及其对子代神经发育的影响研究

Organophosphate esters (OPEs) flame retardant has obvious neurodevelopmental toxicity, and their exposure may cause irreversible damage to the offspring with the susceptible nervous system. In this study,some OPEs flame retardants with high detection rate and obvious toxicity were chosen as the research objects. Based on Tongji birth cohort, a prospective cohort study will be developed to investigate the adverse effects of the OPEs exposure in the embryonic period and lactation on the neurodevelopment of offspring. The transfer characteristics will be clarified by detecting the OPEs exposure levels of the maternal-infant paired samples (maternal urine-breast milk-placenta-cord blood); The neurobehavioral development scale will be used to assess the neurodevelopment of 0-3 years old infants; According to these results, the association between the early exposure of OPEs and the neurodevelopment of offspring will be studied, and then the possible toxicological mechanism of OPEs will be discussed together with the related biomarkers, and the health risk assessment of OPEs exposure will be evaluated. The results will provide the basic data for investigating the exposure characteristics and the scientific basis for the environmental health reference doses of OPEs flame retardant.

有机磷酸酯 (organophosphate esters, OPEs) 阻燃剂具有明显的神经发育毒性。对于处于神经系统发育敏感期的胎儿和婴幼儿，OPEs暴露可能会对其造成不可逆转的损害。本研究以检出率高、毒性效应明显的OPEs阻燃剂为研究对象，将实验室分析检测与流行病学调查相结合，利用出生队列研究OPEs阻燃剂早期（胚胎期和哺乳期）暴露对子代神经发育的影响。通过检测母婴配对样本（母尿-母乳-胎盘-脐血）中OPEs阻燃剂的暴露水平，阐明OPEs阻燃剂的母婴传递特征；利用神经行为发育量表评估0-3岁婴幼儿的神经发育情况，开展OPEs阻燃剂早期暴露与子代神经行为发育的关联性研究，并结合相关的生物标志物，探讨OPEs阻燃剂可能的神经发育毒性作用机制，评估其早期暴露的健康风险。本项目将为我国掌握敏感人群OPEs阻燃剂的暴露特征提供基础数据，对制定OPEs阻燃剂的环境健康基准提供科学依据。

本项目建立了一种简便、快速、高通量的SIPTE-UPLC-MS/MS检测方法用于尿液中16种OPEs代谢产物的定量检测；基于健康宝贝出生队列评估了孕妇不同妊娠期OPEs的暴露特征及其浓度预测因子，结果表明我国孕妇人群普遍暴露于OPEs污染，孕妇尿液中OPEs代谢产物浓度在孕早、中和晚期的变异程度较大，提示孕期OPEs暴露的单次检测可能导致整个孕期孕妇暴露水平的错误分级；利用前瞻性队列研究设计分析了孕妇不同孕期OPEs暴露对子代体格发育和神经发育的影响，研究发现孕期多种OPEs暴露可降低子代年龄别体重和身高，且孕早期和孕晚期可能是子代OPEs宫内暴露的关键窗口期，同时孕期多种OPEs暴露与子代神经发育得分的降低有关，且孕早期和孕中期可能是子代OPEs宫内暴露的关键窗口期。此外，利用巢式病例对照研究探讨了孕妇孕期OPEs暴露与新生儿低出生体重和早产等不良妊娠结局的关系，结果显示，孕妇尿中DPHP浓度与新生儿低出生体重的发生风险存在明显的关联，经性别分层后该关联仅在女婴中显著；孕妇尿中BDCIPP和BCIPHIPP浓度则与新生儿早产的发生呈现显著的正关联。本项目研究结果为开展孕期OPEs暴露与子代生长发育的关联研究提供重要的基础数据，对制定OPEs阻燃剂的环境健康基准和确定孕期OPEs暴露的关键窗口期提供科学依据。