随着长链PFASs的限制生产和使用，多种替代品已被投入市场，其中PFECA是一类结构复杂的新型PFOA替代品，其生物可利用性和毒性评估亟需开展。本项目拟以PFASs与蛋白相互作用为突破口，通过体内暴露、体外细胞过表达、蛋白表达纯化、蛋白相互作用分析及计算机模拟等技术手段，（1）探究代表性PFECAs在小鼠血清、肝脏、肾脏及肌肉组织中的分布水平与PFOA异同，阐明其在小鼠体内的分布机制；（2）鉴定不同组织中与PFECAs结合的主要蛋白；（3）阐明PFECAs与关键蛋白的作用模式及关键氨基酸残基，揭示PFECAs链长、支链数目、氧原子数目和原子比例等在结合中扮演的角色，探讨PFECAs链长、结构等对其在不同组织中分布水平的影响。研究结果将为新型替代品生物有效性和毒性效应的评估提供新思路，为低蓄积性替代品的研发提供科学依据。

Driven by increasingly stringent restrictions on long-chain Per- and polyfluoroalkyl substances (PFASs), novel fluorinated compounds have emerged and replaced legacy PFASs in many industrial applications. Perfluoroalkyl ether carboxylic acids (PFECAs) are a series of PFOA alternatives with several oxygen atoms inserted into the carbon skeleton. As PFECA alternatives have been put into usage with limited information publicly available, their environmental and biological effects need to be carried out urgently. As has been reported, the interaction between PFOA and various proteins plays an important role in the distribution of PFOA in organisms. In this proposed project, we hypothesized that the distribution of PFECA alternatives is similar with that of PFOA, which may be a result of interactions of PFECA with proteins..Taking the interaction between PFASs and protein as a breakthrough, this project aims to to explore the mechanism of PFOA/PFECAs distribution with in vivo, in vitro and in sillico methods. Our proposed project is (1) to investigate the distribution of PFOA and PFECAs in serum, liver, kidney and muscle of mice and then elucidate the distribution mechanism of PFOA and PFECAs in mice. (2) to identify the main proteins that can interact with PFOA/PFECAs in different tissues. (3) to understand the effect of PFECAs structure (such as number of oxygen atoms, ratio of carbon atoms and oxygen atoms) on their protein binding capacity and distribution level in organisms..The research results will provide data support for the safety assessment of emerging PFAS alternatives, and provide scientific evidences for the formulation of management strategies and the development of low-accumulative PFAS alternatives.