新兴溴代阻燃剂的水环境暴露、毒性效应及分子机制

The toxicity and environmental health risks of persistent toxic substances (PTS) have been a great concern in China, and also in other countries. Novel brominated flame retardants (NBFRs) (also called as emerging BFRs) are widely used and distributed in the environment and organisms in China, however, their toxic effects and environmental health risks are not well-known. In this project, the cultured cells will be performed for rapid screening their potential endocrine disruption, neurotoxicity of selected NBFRs; the zebrafish will be used as in vivo model for investigation on the bioavailability of selected typical NBFRs and the potential target organs will be determined; The effects on growth, development, thyroid endocrine disruption, neurotioxicity and lipid metabolism in zebrafish embryos/larvae will be explored upon acute exposure to selected NBFRs. We will examine the endocrine disruption and reproductive effects on the fish after long-term exposure to lower concentrations, and the transgenerational toxicity in offspring via maternal bioaccumulation of selected NBFRs or the alterations of epigenetic modifications. Based on the results, adverse outcome pathways (AOPs) of typical NBFRs on growth/development or reproduction will be developed. The overall study will be contributed to understanding the toxicity and environmental health risk assessment, as well as for regulation and management of these emerging toxicants.

持久性有毒物质(PTS)的毒性效应和健康风险是我国重点关注的环境问题，也是国际环境领域重点科学前沿。新兴溴代阻燃剂（NBFRs）是广泛存在于我国环境和生物体内的有机污染物，但对其毒性效应和环境健康风险了解的甚少。本项目拟以典型NBFRs为研究对象，基于离体细胞快速筛查内分泌干扰和神经毒性效应；基于受试生物斑马鱼，研究其生物可利用性并确定积累的主要组织器官；测试急性暴露对斑马鱼胚胎/仔鱼的生长发育、甲状腺内分泌干扰、神经毒性效应和脂质代谢异常的影响；探究长期低剂量暴露对斑马鱼内分泌干扰和繁殖毒性效应的环境风险；揭示鱼类吸收积累传递污染物并引起子代健康危害的基本规律；阐明表观遗传学改变而引起跨代毒性效应的机制；发展和完善典型NBFRs对斑马鱼生长发育、繁殖的有害结局通路（AOP）。研究结果为评估新兴溴代阻燃剂类污染物的环境风险和管理控制提供科学数据。

新溴代阻燃剂（NBFRs）是广泛存在于环境和生物介质中的新污染物，但对其毒性效应和生态环境风险了解的甚少。本项目监测了NBFRs在浙江台州路桥区和广东汕头贵屿镇的暴露水平、环境行为以及风险，构建了水生态微宇宙系统，并研究了典型NBFRs在生物体内的积累和代谢；以斑马鱼为对象，重点研究典型NBFRs急性暴露引起的甲状腺内分泌干扰、神经发育毒性、脂质代谢的影响及机制、对成年期的影响，长期低剂量暴露的繁殖毒性、母体传递效应、对子代的健康危害以及表观遗传学机制。主要研究成果包括：（1）解析了水、沉积物、土壤和鱼类中NBFRs的分布特征，发现十溴二苯乙烷（DBDPE）是NBFRs中最主要的污染物；在有机溶剂和水生微宇宙体系中，DBDPE和四溴邻苯二甲酸双(2-乙基己基)酯（TBPH）通过逐级脱溴反应，产生多种脱溴降解产物；（2）发现DBDPE对斑马鱼仔鱼具有很强的甲状腺内分泌干扰效应，毒代动力学显示，斑马鱼大脑是DBDPE积累的主要靶器官，大脑定量蛋白组学以及平行反应监测技术表明，DBDPE影响雌激素以及肌肉收缩相关的生物学过程，扰乱胞内钙离子稳态，抑制脑-肝-性腺（HPGL）轴相关基因的表达，进而导致卵泡发育不良和生殖障碍；发现母代（F0）暴露DBDPE对斑马鱼F2代仔鱼表现出更严重的发育损伤和疾病的易感性，并揭示了跨代神经毒性和发育毒性效应的表观遗传学机制；（3）发现TBPH与血脑屏障紧密连接蛋白发生作用，影响其结构完整性，增加血脑屏障的通透性，揭示了TBPH对血脑屏障结构和功能的影响机制；TBPH急性暴露影响斑马鱼仔鱼脂质代谢、引起脂质代谢紊乱，并阐明了表观修饰DNA去甲基化的作用；发现长期低剂量暴露TBPH引起斑马鱼非酒精性脂肪肝发生、肠道微生物群落改变与斑马鱼肥胖；（4）揭示了典型新溴代阻燃剂作用的潜在分子靶点并构建了引起毒性效应的有害结局通路（AOP）。