壬基酚膳食暴露致卵巢癌发生风险的定量评估

This project focuses on the relationship between nonylphenol, an endocrine disrupting chemical extensively existing in food, and ovarian cancer, a disease resulted from explicit toxic effect. Combining metabolic dynamic parameters from long term exposure with bioavailability from different food matrix, PBPK/PD models will be established to obtain risk assessment on long term dietary exposure to nonylphenol. Quantitative description was conducted to present the relationship between nonylphenol dietary intake(external exposure dose) and body absorption(internal exposure dose) as well as toxic effect which is quantified by CA125 in serum and specific metabolic marker in urine. Moreover, we can confirm high exposure population, analyse food contribution rate and define risk characteristic so as to predict risk arising from dietary exposure to nonylphenol as well as evaluate accuracy in practical application. This project will offer an universal platform for quantitative assessment on other dietary hazards. Our results will help promote disease control related to food safety and improve social health management scientifically and practically.

本项目选择食品污染广泛的模式危害因素（壬基酚）及其效应关系明确的毒性效应疾病（卵巢癌），以长期低剂量暴露的代谢动力学参数，及不同食品基质下的生物利用率共同作为调整参数，构建基于生理代谢/效应动力学（PBPK/PD）模型的、可准确描述壬基酚膳食实际暴露特点的健康风险定量评估技术，进行壬基酚膳食摄入量（外暴露剂量）与人体吸收利用量（内暴露剂量）及毒效应（卵巢癌发生风险，以尿中特异性代谢标志物水平结合血清CA125水平进行量化）之间的定量描述。在此基础上确定高端暴露人群、分析食物贡献率、明确风险特征，实现以人群壬基酚膳食摄入量定量评估发生毒效应的概率或/和严重程度。本项目预期获得生物学机制模型的构建及整合、以及模型校准及验证的方法，研究成果将可为其他膳食危害因素暴露风险的定量评估提供通用的方法学平台，对实现健康风险的预测预警，提升食品安全相关的疾病防控能力具有重要的科学价值和实际意义。

本项目掌握了壬基酚长期低剂量膳食暴露的代谢动力学行为；获得了适于描述壬基酚早期轻微毒性效应的最敏感的生物标志物，为定量表达壬基酚低剂量膳食暴露的毒性效应程度提供了更为科学严谨的新依据；掌握模型构建、整合和校正的方法，建立长期低剂量膳食壬基酚暴露的PBPK/PD模型；通过PBPK/PD模型拟合暴露剂量-毒效应反应曲线，获得了BMDL值，可定量判断壬基酚膳食暴露致卵巢癌发生风险程度；进行了PBPK/PD模型应用初探。本项目的研究结果已发表论文13篇，均为SCI收录，均已第一/唯一标注本项目批准号（81673171）.已申请发明专利2项。培养硕士和博士研究生8名。