The Procter & Gamble Company, Mason, OH, USA.
FICAM University of Tampere, Tampere, Finland.
Basic Clin Pharmacol Toxicol. 2018 Sep;123 Suppl 5:37-41. doi: 10.1111/bcpt.13006. Epub 2018 Apr 24.
Structure activity relationship (SAR)-based read-across is an effective approach for addressing data gaps in human health risk assessment for 'data-poor' chemicals. In read-across, available data on chemical structural analogues are used to predict the toxicity potential of the data-poor chemical. This approach has long been recognized by regulatory agencies and used by industry to evaluate the hazards of chemicals for which there are limited direct data. Construction of a scientifically robust SAR-based read-across hazard assessment is a complex and iterative process involving multiple considerations in each step. Traditional in vivo data generated using regulatory guideline compliant study designs typically forms the basis for read-across assessments. Recently, however, new data streams have been explored and incorporated to enhance read-across predictivity. These in vitro and omics data streams may be used in different ways involving identification of hazards or to provide insight into modes of action for observed toxicological responses. These 'new approach methods' can also enable comparison of biological responses across analogues or a category of structurally related chemicals in order to establish a pattern of biological similarity in addition chemical similarity and/or to help address potency differences across a category. The purpose of this workshop session was to inform on practical considerations in conducting SAR-based read-across assessments and to review recent activities related to application of new approach methods to the practice of read-across.
基于结构-活性关系(SAR)的类推是解决人类健康风险评估中“数据匮乏”化学品数据缺口的有效方法。在类推中,使用化学结构类似物的可用数据来预测数据匮乏化学品的毒性潜力。这种方法长期以来一直受到监管机构的认可,并被行业用于评估那些直接数据有限的化学品的危害。构建基于科学的 SAR 类推危害评估是一个复杂且迭代的过程,在每个步骤中都需要考虑多个因素。传统的使用监管指南合规研究设计生成的体内数据通常是类推评估的基础。然而,最近已经探索并纳入了新的数据流,以提高类推预测能力。这些体外和组学数据流可以以不同的方式使用,涉及识别危害或提供对观察到的毒理学反应作用模式的深入了解。这些“新方法”还可以使同类物或结构相关化学品类别中的生物学反应进行比较,以建立除化学相似性之外的生物学相似性模式,和/或帮助解决类别内的效力差异。本次研讨会的目的是告知基于 SAR 的类推评估中需要考虑的实际问题,并回顾与将新方法应用于类推实践相关的最新活动。