Using metabolic information for categorization and read-across in the OECD QSAR Toolbox

Metabolism is a critical aspect of toxicokinetics. It is crucial to take it into account when evaluating similarity among the chemicals participating in a read-across prediction. Lack of considerations on metabolism represents a major source of uncertainty in a read-across justification. To better assist users in applying metabolic considerations during data gap filling, the metabolism/transformations functionality in the OECD QSAR Toolbox has been upgraded in version 4. Analyses of metabolic similarity are specific to a toxic endpoint and dependent on data availability. By using optimized features, the metabolic simulators available in Toolbox can predict the generation of possible metabolites and take them into account for read-across. In the traditional downstream approach, metabolic information in the Toolbox is used to identify the formation of (a)biotic products of known toxicity and read-across their toxicity to the parent chemical. By a stepwise protocol the user may explore knowledge embedded in the Toolbox to identify source analogues that have the same pattern of metabolic activation as the target. Furthermore, following the upstream approach, precursors of the chemicals could be also searched in the Toolbox databases. Five scenarios, highlighting the applications of the metabolism in chemical assessment within the Toolbox, are illustrated. © 2019 Elsevier B.V.