典型的中长链全氟酸类(PFAAs)具有很强的生物富集能力，其中全氟辛基磺酸(PFOS)在人体内半衰期可达5年以上。虽然PFAAs碳链异构体均不易发生I相转化，但PFAAs碳链异构体在人体富集消除特征存在显著差异，遗憾的是其差异化效应的分子机制仍不清晰。鉴于PFAAs的富集消除对其体负荷乃至健康效应具有重要的影响，本项目拟采用PFAAs污染区域人群负荷和相关健康指标监控与实验室生物测试与分子模拟相结合的手段，重点对典型碳链异构PFAAs人体富集和消除机制进行研究。在暴露评价中，血液、尿液等生物样本用于估算体负荷和清除能力。分子模拟与生物测试探明PFAAs与人血清白蛋白、肝脂肪酸结合蛋白、有机阴离子转运蛋白等体内储库和转运分子选择性作用模式和效应，结合必要的人群调查数据建立涵盖体内转运、分布积累和跨越组织屏障等因素的富集清除模型，揭示碳链异构PFAAs人体内差异化富集消除的分子机理和结构基础。

Medium and long chain perfluoroalkyl acids(PFAAs) are of high bioaccumulation capacity, and the half-life of perfluorooctane sulfonate (PFOS) in human was reported to be even more than 5 years. Carbon-chain isomerism and chain length have been observed to contribute to the diverse bioaccumulation and elimination profiles of different PFAA isomers and congeners even though phase I biotransformation make no significant difference. Unfortunately, the underlying mechanisms for such differentiation in human are not clear at a molecular basis until now. This project will focus on the effect of carbon-chain isomerism on the bioaccumulation and elimination behavior of PFAAs in human since it result in different level of body burden and health risk. Integrated research methods will be adopted to couple biomonitoring technique and cohort analysis with in vitro bioassays and in silico prediction. On one hand, we will collect human samples such as serum and urine the sampled population to calculate the body burden and renal clearance. On the other hand, we will apply both in vitro bioassays and in silico simulation to explore the binding affinity and interaction mode of PFAAs with related proteins prevalent in storage, transport, and delivery of PFAAs such as human serum albumin, liver fatty acid binding protein, and organic anion transporter proteins. Consequently, models of PFAAs bioaccumulation and elimination will be established by determining the key parameters controlling how PFAAs may transport, distribute, deliver and even cross various barriers in human body. Such will help to reveal the differential accumulation and elimination mechanism of PFAA isomers in human. The achievement of this project will offer scientific evidence and technical support for health risk assessment of PFAAs.