基于毒理学数据库整合有害结局路径(AOP)分析的有机磷酸酯毒性及机制研究  

Study on Toxicity and Mechanisms of Organophosphates Based on Adverse Outcome Pathway(AOP)Analysis Integrated with Toxicological Databases

作　　者：王丝丝 赵菁蕾 王桥 刘言 李敬光 吴永宁 柳鑫 Wang Sisi;Zhao Jinglei;Wang Qiao;Liu Yan;Li Jingguang;Wu Yongning;Liu Xin(College of Food Science and Engineering,Wuhan Polytechnic University,Wuhan 430023,China;China National Center for Food Safety Risk Assessment,Beijing 100022,China)

机构地区：[1]武汉轻工大学食品科学与工程学院,武汉430023 [2]国家食品安全风险评估中心,北京100022

出　　处：《生态毒理学报》2024年第5期1-12,共12页Asian Journal of Ecotoxicology

基　　金：国家重点研发计划青年科学家项目(2022YFF1102500)。

摘　　要：有机磷酸酯(organophosphate esters,OPEs)作为新型阻燃剂被广泛应用,然而其环境迁移导致的潜在毒性引起了广泛关注。已有研究表明,OPEs对神经系统和肝脏功能具有毒性。本研究系统回顾了近年来关于OPEs的毒理学研究,全面分析了OPEs诱导的神经、心脏、肝脏、内分泌干扰及生殖发育毒性通路,并构建了OPEs的有害结局路径(AOP)框架。研究结果表明,OPEs暴露可引起乙酰胆碱酯酶和多巴胺等神经发育关键酶活性的改变,进而导致神经递质系统紊乱。此外,OPEs诱导的氧化应激和线粒体功能障碍可导致细胞凋亡及肝脏代谢功能损伤。这些机制突出显示了发育期生物体对OPEs暴露的高度敏感性,长期暴露可能导致发育和代谢紊乱。本研究通过整合现有毒理学数据并构建AOP框架,为OPEs的毒性机制提供了新的见解,为未来新型OPEs的生态风险评估奠定了理论基础。Organophosphate esters(OPEs),widely used as novel flame retardants,have raised increasing concern due to their potential toxicity resulting from environmental migration.Previous studies have demonstrated that OPEs can exert toxic effects on the nervous system and liver function.This study provides a systematic review of recent toxicological reports on OPEs,comprehensively analyzing the toxic pathways involved in OPE-induced neurotoxicity,cardiotoxicity,hepatotoxicity,endocrine disruption,and reproductive developmental toxicity,and constructing an adverse outcome pathway(AOP)framework for OPEs toxicity.The results indicate that OPEs exposure alters the activity of key neurodevelopmental enzymes,such as acetylcholinesterase and dopamine,leading to neurotransmitter system disruption.Additionally,OPEs induce oxidative stress and mitochondrial dysfunction,resulting in apoptosis and hepatic metabolic impairment.These mechanisms underscore the heightened sensitivity of developing organisms to OPE exposure,and prolonged exposure may lead to developmental and metabolic disorders.By integrating existing toxicological data and constructing an AOP framework,this study provides new insights into the toxic mechanisms of OPEs,offering a theoretical foundation for the ecological risk assessment of emerging OPE compounds.

关 键 词：有机磷酸酯 有害结局路径 风险评估 毒理学信号通路 

分 类 号：X171.5[环境科学与工程—环境科学]