饮用水中地西泮氯消毒副产物形成机制及神经发育毒性研究

The disinfection by-products in drinking water has always been one of the hot issues in water supply. As key factors of control and reduction of disinfection by-products, the natural and environmental organics are the most concerns by environmental scientists. As a central nervous system inhibitor, diazepam has the characteristics of quick absorption, long half-life, accumulation in the fetus, it also easily crosses the blood-brain barrier and placental barrier. The preliminary research indicated that diazepam and its chlorine disinfection by-products existed in drinking water in Beijing and the highest concentration was 100ng/L. Considering the fetus is sensitive to chemical pollutants and the nervous development can be influenced by the disinfection by-products in drinking water through placental transfer of pregnant women, we will investigate the transformation mechanism of diazepam chlorine disinfection by-products, synthesize and characterize the corresponding disinfection by-products, detect the concentration of diazepam and the disinfection by-product in drinking water of Beijing area, and further study the potential toxicity on central nervous of offspring by the way of animal experiment and population-based cohort study. This study can provide more theoretical basis for risk management.

饮用水消毒副产物一直是供水安全中关注的热点问题之一，水源水中的天然有机污染物和环境污染物作为消毒副产物控制和削减的关键是当前环境学家最为关注的对象物质。地西泮是一种中枢神经抑制剂，口服吸收快, 半衰期长，容易穿透血脑屏障和胎盘屏障在胎儿体内富集，前期研究发现地西泮及其氯消毒副产物普遍存在北京饮用水中最高浓度达到100ng/L。胎儿期是对各种化学污染物最敏感时期，母体可通过摄入饮用水中的消毒副产物再通过胎盘的传递作用影响胎儿的神经系统发育。研究地西泮氯消毒副产物的转化机制，合成表征相应的消毒副产物，分析北京地区饮用水中地西泮及其消毒副产物存在水平，并从模式动物暴露实验和人群队列研究两个层面阐明地西泮消毒副产物可能对子代中枢神经发育的影响，从而为相关部门进行风险管理提供理论依据。

饮用水消毒副产物一直是供水安全中关注的热点问题之一。本项目模拟地西泮的氯消毒转化机制，制备合成相应的氯消毒副产物。利用超高效液相色谱-串联质谱（UPLC-MS/MS）建立饮用水中地西泮及氯消毒副产物的检测方法，对不同季节的氯消毒饮用水进行监测。氯消毒副产物BP246，BP271，BP304(1)和，BP304(2)在饮用水中均有不同程度的检出。在毒性研究中发现BP246和BP304(1)能促进斑马鱼早期的神经元分化和发育，干扰细胞代谢，最终导致斑马鱼的神经行为异常。另外，建立DESI-MS成像技术快速检测出氯消毒副产物BP246在斑马鱼体内的分布及代谢。结果发现BP246主要富集于斑马鱼的肌肉组织和神经系统，并导致脊髓内胶质细胞对神经元的吞噬。采集了100余份孕产妇的血清样品及脐带血样品，对其中地西泮及消毒副产物的存在水平进行了初步分析，为人群健康风险评估提供参考数据。