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定量有害结局路径的构建方法及在毒理学中的应用研究进展OA北大核心CSTPCD

Advances in construction and applications of quantitative adverse outcome pathways in toxicology

中文摘要英文摘要

美国国家研究咨询委员会提出的"21世纪毒性测试——愿景与策略"对毒性评价和风险评估提出了新的要求和愿景,推动了新一代毒性测试方法和新一代风险评估方法学的发展.有害结局路径(AOP)作为一种先进的方法,具有较大应用潜力,近年来逐渐成为毒理学家关注的重点和新兴研究热点.定量AOP(qAOP)是在AOP理论上发展的新策略,其将定性AOP作为初始概念模型,通过数理模型描述剂量-响应和(或)响应-响应关系,提供了一种可定量预测体内毒性和风险的策略.本文就qAOP的概念和进展进行综述,介绍了2种构建qAOP的常用方法,贝叶斯网络模型和回归模型,并以实际案例展示qAOP在毒理学中的不同应用方向.

"Toxicity Testing in the 21st Century—A Vision and Strategy"proposed by the National Research Council of US has brought innovative directives and objectives for toxicity evaluation and risk assessment,pushing forward the next generation of toxicity testing and risk assessment.In this initiative,the concept of adverse outcome pathways(AOPs)has emerged as a prominent methodology,capturing the attention of toxicologists and researchers due to its promising applications in recent years.The quantitative AOP(qAOP)is an extension of the adverse outcome pathway,which is built upon the foundational qualitative adverse outcome pathway model and leverages mathematical frame-works to depict dose-response and/or response-response relationships.This article reviews the princi-ples and advancement surrounding qAOP,introduceds two prevalent methodologies for constructing qAOP,Bayesian network models and regression models,and demonstrates diverse applications of qAOP.Actual cases are used to underscore the transformative role of qAOP in contemporary toxicology and risk assessment practices.

李旻涛;陈锦瑶;练雪梅;霍娇;陈佳辉;姜蓓蓓;高杰;邹家丽;周倩如;严晓峰;罗书全;张华东

重庆市疾病预防控制中心,重庆 400042||重庆医科大学公共卫生学院,重庆 400016四川大学华西公共卫生学院,四川成都 610041重庆医科大学公共卫生学院,重庆 400016重庆市公共卫生医疗救治中心,重庆 400016||重庆市疾病预防控制中心,重庆 400042||重庆医科大学公共卫生学院,重庆 400016重庆市疾病预防控制中心,重庆 400042重庆市公共卫生医疗救治中心,重庆 400016

药学

定量有害结局路径毒性预测风险评估剂量响应关系

quantitative adverse outcome pathwaytoxicity predictionrisk assessmentdose-response relationship

《中国药理学与毒理学杂志》 2024 (006)

473-480 / 8

中国博士后科学基金(2022M710549);重庆市自然科学基金(cstc2021jcyj~msxmX0479);重庆市博士后特别资助项目(2022CQBSHTB2065) China Postdoctoral Science Foundation(2022M710549);Natural Science Foundation of Chongqing(cstc2021jcyj-msxmX0479);and Special Foundation of Chongqing Postdoctoral Program(2022CQBSHTB2065)

10.3867/j.issn.1000-3002.2024.06.009

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