水-沉积物体系中四溴双酚-A和镉复合污染的环境行为及其甲状腺激素干扰效应的研究

化学物质的复合污染研究一直备受关注，溴代阻燃剂四溴双酚-A(TBBPA)和重金属镉（Cd）是广泛存在的环境污染物，并具有典型的甲状腺激素干扰效应，但对其复合污染的环境行为及生物毒性效应还未见报道。本项目通过水-沉积物体系污染物的环境行为模拟实验，研究TBBPA和Cd复合污染的相互作用、迁移转化及环境归趋；利用大鼠模型，研究TBBPA和Cd在生物体内的负荷及代谢状况，结合细胞模型，从组织、细胞、分子等不同层次指标，研究TBBPA和Cd联合暴露引起的甲状腺激素干扰效应，并从甲状腺激素的合成、运输、代谢及细胞作用等角度探讨其生物学机制。该研究成果有助于揭示溴代阻燃剂和重金属复合污染的环境行为特征，并为甲状腺激素干扰物的复合污染效应研究提供借鉴，为复合污染的潜在生态危害和健康风险评估提供理论依据。

Tetrabromobisphenol（TBBPA）and Cadmium (Cd) are both very important environmental and occupational toxicants and are jointly present in environment, especially in natural water and surficial sediments. Cd may combine with TBBPA and affect the adsorption, desorption and degradation behaviors of each other in water and sediments. Therefore, it is necessary to study the different environmental behavior of Cd and TBBPA coexisting in natural water and sediments system. Thyroid hormone is essential for the normal physiological function of vertebrates, playing key roles in regulating metabolism, growth and development. In recent years, many studies about thyroid disruptors have been published. TBBPA and Cd are both known to disturb thyroid hormone function. Several reports have shown that TBBPA can bind to thyroid receptors (TR) and may produce complex effects on thyroid hormone signaling, while the suppression of hepatic deiodinase activity through lipid peroxidation was hypothesized to be the mechanism of Cd's thyroid disrupting effect. Coexposure to multiple substances, which have been shown to have different mechanisms of action in inducing thyroid disruption, is a reality in the human populations throughout the industralized world. As such, the possibility that the cumulative effects of the mixture could have greater impact in inducing thyroid dysfunction than would occur from exposure to comparable doses of the individual components alone has significant public health implications. However, there are limited studies in the literature that examine mixtures of thyroid disrupting chemicals. Like their combined environmental behavior, the combined toxic effects of TBBPA and Cd, which are often coexist in environmental media, have not been reported yet. In this project, water-sediment pollutants transport and transformation model will be developed to study various environmental behaviors and fate of TBBPA and Cd. Pubertal female rat assay will be used to detect the effect of TBBPA and Cd on thyroid function. Several thyroid endpoints will be selected as main indicators of thyroid disrupting effects, including serum hormone concentration, thyroid gland weights, thyroid histomorphology, etc. The underlying mechanism of the disturbance effect will be investigated by means of RT-PCR, ELISA and Western-blot, which are used to detect the changes of target genes and proteins. In addition to rat model, GH3 cell and FRTL-5 cell assay will be used to test the interfering effects of TR signaling and the ability to inhibit thyroglobulin synthesis respectively. This project not only will be benefit for understanding the environmental behavior and toxic effects of combination of brominated flame retardants and heavy metals, but also will provide scientific basis for environmental health risk assessment of combined pollution.