内分泌干扰物（EDCs）因具有相似的作用终点，低剂量下混合暴露可能产生大于单一暴露的联合效应，已成为影响食品安全的一类重要风险因子，国际上已开始关注低剂量下混合暴露所引起的联合效应问题。本项目基于食用农产品中EDCs残留调查结果，选择γ-六氯环己烷（有机氯类农药）、邻苯二甲酸二(2-乙基)己酯（邻苯二甲酸酯类）和PCB153（多氯联苯）等3种具有雌激素效应的内分泌干扰物作为实验对象，依据食用农产品中实际残留水平和毒性效应水平设置暴露浓度，基于析因设计方法设计浓度组合，研究不同种类、不同浓度、不同时间处理后对人乳腺癌细胞MCF-7和乳腺上皮细胞MCF-10A的联合效应及变化规律，分析浓度相加、独立作用和联合指数等模型在联合效应预测中的适用性；对雌激素受体介导的典型信号通路中关键蛋白、化合物及基因表达进行对应分析，探索联合效应产生的分子机制。项目的实施将为科学评价EDCs联合效应，制定安全限量标准提供科学依据。

Endocrine disrupting chemicals (EDCs) have become one of the most important risk factors for food safety. It is known that EDCs have the same end point that human beings can be simultaneously exposed to several chemicals that might potentially contribute to combined adverse effects even when each compound was present below the concentration at which no effect was observed. Thus, exposure to EDCs becomes an important issue garnering wide attention among the international scientific and legislative communities. Here we selected three kinds of EDCs that had estrogen-like effects based on the survey of residue results, such as γ-hexachlorocyclohexane (organochlorine pesticides), Di(2-ethylhexyl) phthalate (PAEs) and PCB153. According to the factorial design method， various combinations will be set base on the actual residue levels in agro-products and different toxic effect levels. Therefore, the combined effects and signaling pathway induced by EDCs at lower concentrations on cell growth of MCF-7 human breast cancer cell and MCF-10A human mammary epithelial cell will be investigated. Moreover, prediction model (concentration addition method, independent action method and median-effect/combination index) will be assessed by comparing the measured effects. Furthermore, key proteins and compounds in estrogen receptor–mediated signaling pathway will be analysed to study the molecular mechamism of combined effects. This study will give valuable information for assessing the combined effects of EDCs， as well as benefit to formulate maximum residue limits scientifically.