溴系阻燃剂的母婴暴露评估及母体孕期/哺乳期暴露对子代神经发育的影响

Brominated Flame Retardants (BFRs) are persistent organic pollutants which were found to be neurotoxic. In our former study we found that the 95% intake of BFRs was from food intake, and the exposure level of nursing infant was much higher than that of the adult (7 to 10 fold). However, the exposure characteristic of BFRs and health effect of BFRs for mother/infant were still unknown. In this project, dietary exposure of pregnant/delivery woman to BFRs will be assessed by a duplicate diet study. Based on cohort study, BFRs will be detected in paired cord blood, maternal blood, and breast milk samples. And the internal exposure level of BFRs for the pregnant/delivery woman, the exposure level of BFRs for the fetus and the estimated daily intake via human milk for infants, could be calculated. On the basis of all these results, the body burden, exposure estimation and health effect of BFRs for pregnant/delivery woman and infant would be evaluated. In addition, in order to evaluate the toxic effect of pregnant/lactational exposure to BFRs on the neurodevelopment of offspring, a experimental animal model will be developed to simulate the exposure mode of maternal BFRs exposure. In the study, the female mice got BFRs by intragastric administration immediately after pregnancy, and BFRs will be administered to the mice from pregnancy to ablactation, and the mice offspring gets the BFRs by cord blood in pregnancy and by breast feeding in lactation. The neurodevelopment of mice offspring will be evaluated by neurobehavioral test, neurotransmitter analysis and metabonomics. The result of this project will benefit the pollution abatement of BFRs.

溴系阻燃剂（BFRs）是具有神经发育毒性的持久性有机污染物。本课题组前期研究发现经膳食摄入占人群BFRs摄入的95%以上，且婴儿的外暴露水平是成人的7至10倍。但目前母婴等易感人群的BFRs暴露状况及健康风险尚未明确。本课题拟通过双份饭法精确测定孕产妇经膳食的BFRs外暴露水平，并通过测定配对的母亲静脉血、脐带血和哺乳期不同阶段母乳中BFRs含量，明确孕产妇孕期/哺乳期BFRs内暴露水平、孕期胎儿宫内BFRs暴露水平及婴儿在哺乳期经母乳的BFRs外暴露水平，以此评估孕产妇及婴儿在孕期/哺乳期的BFRs内外暴露水平及健康风险；在此基础上应用小鼠染毒模型模拟婴儿在孕期/哺乳期的BFRs暴露模式，对母鼠进行孕期至哺乳期全程染毒后，通过对仔鼠的神经行为测试、神经递质分析和脑匀浆液、血清的代谢组学分析，评估母体孕期/哺乳期BFRs暴露对子代神经发育的影响。本课题将为BFRs暴露健康风险评价提供依据。

溴系阻燃剂（BFRs）是备受关注的环境污染物，本课题开展了北京地区多溴联苯（PBDEs）和六溴环十二烷（HBCD）等BFRs的母婴暴露评估及母体孕期/哺乳期BFRs暴露对仔代的毒性效应。在建立了多种基质中多种BFRs测定方法的基础上。通过双份饭研究探索了孕产妇的BFRs外暴露水平，发现孕产妇经膳食的PBDEs和HBCD摄入量分别是3.69 ng/kg bw/day和1.23 ng/kg bw/day，采用暴露边界比评估法确认北京产妇经膳食摄入的BFRs暴露边界比远高于阈值，不会产生明显健康风险。通过对配对的脐带血和母乳的监测发现母血和母乳中∑PBDEs的中值分别是133 pg/mL和98.6 pg/mL，母血和母乳中∑HBCD的中值分别是124 pg/mL和160 pg/mL，这一含量高于国外诸多研究，显示北京市孕产妇仍处在较高的BFRs暴露之中。通过脐带血及哺乳期不同阶段的母乳的监测明确了胎儿经脐带血的暴露及婴儿经母乳的暴露。配对的母血、母乳和脐带血监测同时发现多数BFRs的母乳浓度>母血浓度>脐带血浓度。显然BFRs能通过胎盘屏障和血乳屏障，且更易通过血乳屏障通过母乳传递给婴儿，即婴儿产后经母乳暴露可能高于宫内暴露。通过对产后不同阶段母乳的监测发现其中∑PBDEs和∑HBCD的中值分别是2.75 ng/g lw和5.8 ng/g lw。但哺乳期不同阶段母乳中大多数BFRs的污染水平随着哺乳时间的延长未呈现有统计学意义的变化，推测孕产妇处在经母乳排出BFRs和经膳食摄入BFRs的动态平衡之中。通过母乳监测估算婴儿经母乳的PBDEs和HBCD摄入量分别是26.8 ng/kg bw/day和42.4 ng/kg bw/day。暴露边界比计算结果同样显示婴儿经母乳摄入BFRs引起健康风险较低，但母-婴比较发现婴儿的BFRs机体负荷水平远高于成年人，亟需在后续评估中继续监测婴儿的BFRs暴露与健康风险。本研究还通过大鼠染毒实验探索了母体孕期/哺乳期暴露对仔代的毒性效应，发现十溴联苯醚暴露可提高血清TSH水平但降低T4或T3水平，并观察到甲状腺组织结构和超微结构损伤，提示母体BFRs暴露会干扰仔代甲状腺激素的体内平衡。本研究结果将为BFRs的污染管控提供基础数据和科学依据。