Adverse outcome pathway for the neurotoxicity of per-and polyfluoroalkyl substances:A systematic review  

作　　者：Shenpan Li Shuangjian Qin Huixian Zeng Weichun Chou Anna Oudin Katja M.Kanninen Pasi Jalava Guanghui Dong Xiaowen Zeng 

机构地区：[1]Joint International Research Laboratory of Envirorment and Health,Ministry of Education,Guangdong Provincial Engineering Technology Research Center of Ernvironmental,Plluion and Health Risk Assen,Department of Ocupational and Enirormental Healh,School of Public Health,Sun Yat-sen University,Guangzhou 510080,China [2]Department of Envirormental Sciences,College of Natural and Agrculural Sciences,University of California,Riverside,CA,United States [3]Department of Public Health and Clinical Medicine,Umed University,Umed,Sweden [4]A.I.Virtanen Institute for Molecular Sciences,Univesity of Eastern Finland,Kuopio,Pinland [5]Department of Environmental and Biological Science,University of Eastern Finland,Kuopio,Finland

出　　处：《Eco-Environment & Health》2024年第4期476-493,共18页生态环境与健康(英文)

基　　金：supported by the National Natural Science Foundation of China (No.82073503);the Natural Science Foundation of Guangdong Province (No.2021B1515020015);the Guangzhou Science and Technology Project (No.2024A04J6476).

摘　　要：Per-and polyfluoroalkyl substances(PFAS)are endocrine disruptors with unambiguous neurotoxic effects.However,due to variability in experimental models,population characteristics,and molecular endpoints,the elucidation of mechanisms underlying PFAS-induced neurotoxicity remains incomplete.In this review,we utilized the adverse outcome pathway(AOP)framework,a comprehensive tool for evaluating toxicity across multiple biological levels(molecular,cellular,tissue and organ,individual,and population),to elucidate the mechanisms of neurotoxicity induced by PFAS.Based on 271 studies,the reactive oxygen species(ROS)generation emerged as the molecular initiating event 1(MIE1).Subsequent key events(KEs)at the cellular level include oxidative stress,neuroinflammation,apoptosis,altered Ca2+signal transduction,glutamate and dopamine signaling dyshomeostasis,and reduction of cholinergic and serotonin.These KEs culminate in synaptic dysfunction at organ and tissue levels.Further insights were offered into MIE2 and upstream KEs associated with altered thyroid hormone levels,contributing to synaptic dysfunction and hypomyelination at the organ and tissue levels.The inhibition of Nat/l symporter(NIS)was identified as the MIE2,initiating a cascade of KEs at the cellular level,including altered thyroid hormone synthesis,thyroid hormone transporters,thyroid hormone metabolism,and binding with thyroid hormone receptors.All KEs ultimately result in adverse outcomes(AOs),including cognition and memory impairment,autism spectrum disorders,attention deficit hyperactivity disorders,and neuromotor development impairment.To our knowledge,this review represents the first comprehensive and systematic AOP analysis delineating the intricate mechanisms responsible for PFAS-induced neurotoxic effects,providing valuable insights for risk assessments and mitigation strategies against PFAS-related health hazards.

关 键 词：PFAS Adverse outcome pathway NEUROTOXICITY Thyroid hormones Risk assessment 

分 类 号：TP3[自动化与计算机技术—计算机科学与技术]