基于构效关系的交叉参照工作流程及应用  

The procedure and application of structure activity relationship (SAR)-based read-across

作　　者：王莹 Jane Rose ZHANG Xiao-ling 管娜 戎志毅 高仁君[3] 黄梅 马书霞 苏毅 张霞 WANG Ying;JANE Rose;ZHANG Xiao-ling;GUAN Na;RONG Zhi-yi;GAO Ren-jun;HUANG Mei;MA Shu-xia;SU Yi;ZHANG Xia(P&G Technology(Beijing)Co.Ltd.,Beijing 101312,China;Procter&Gamble Mason Business Center,Mason 0H 45040,USA;Dow Chemical(China)Investment Co.Ltd.,Shanghai 201203,China;Lubrizol Management(Shanghai)Co.Ltd.,Shanghai 200126,China;BASF(China)Co.Ltd.,Shanghai 200137,China;DuPont(China)Research&Development and Management Co.Ltd.,Shanghai 201203,China;Symrise.AG,Holzminden Lower Saxony 37603 Germany;Interteh Shanghai Testing Service Ltd.,Shanghai 200233,China)

机构地区：[1]北京宝洁技术有限公司,北京101312 [2]Procter&Gamble Mason Business Center,Mason 0H 45040 [3]陶氏化学中国投资有限公司,上海201203 [4]路博润管理上海有限公司,上海200126 [5]巴斯夫中国有限公司,上海200137 [6]杜邦中国研发管理有限公司,上海201203 [7]德国德之馨,德国霍尔茨明登37603 [8]上海天祥质量技术服务有限公司,上海200233

出　　处：《毒理学杂志》2022年第2期102-106,112,共6页Journal of Toxicology

摘　　要：动物试验的替代方法对于填补当今化学物危害评估中的毒理学数据空白非常重要,而基于构效关系的交叉参照(SAR-based Read-Across)方法是目前应用最广泛的替代方法之一,在过去约25年中已被全球多个监管机构接受并广泛使用。交叉参照方法的科学依据是化学物质的结构会影响其理化性质、代谢以及反应活性等,从而影响其生物学效应。当某化学物缺乏毒理学数据时,可利用其结构类似物的数据,通过交叉参照方法预测该化学物的毒性/生物活性。为了更好的应用交叉参照方法,国际上已有监管机构、学术组织和学者发表了相关的工作流程或框架。虽然针对该方法的应用背景不尽相同,但这些流程或框架所包含的流程和步骤都很相似,并包含相同的科学考量要素。Animal alternative approaches are very important to fill in the toxicological data gap for chemical hazard assessment currently. The structure activity relationship(SAR)-based read-across is one of the most widely used animal alternative method, which has been accepted and widely used by many regulatory agencies globally in the past 25 years. The scientific foundation of read-across is that the structure of a chemical will affect its physiochemical properties, metabolism, reactivity and etc, so that to affect the biological activity. When there’s data gap for a specific chemical(target chemical), the data of its structurally similar analog(s) can be used to predict the toxicity/biological activity of the target chemical by the read-across. To enable a better application, some global authorities, academic organizations, as well as toxicologists have published the framework or guidance on read-across. Although the purposes to use read-cross approach are different, the framework or working process on read-across contains the same key steps and the same key scientific elements.

关 键 词：构效关系 交叉参照 ADME 科学要素论证 不确定性分析 

分 类 号：R114[医药卫生—卫生毒理学] R99[医药卫生—公共卫生与预防医学]