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Relevance and Application of Read-Across - Mini Review of European Consensus Platform for Alternatives and Scandinavian Society for Cell Toxicology 2017 Workshop Session.
Basic & Clinical Pharmacology & Toxicology 2018 March 11
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.
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