Grouping of chemicals for safety assessment: the importance of toxicokinetic properties of salicylate esters.

Grouping of chemicals has been proposed as a strategy to speed up the screening and identification of potential substances of concern among the broad chemical universe under REACH. Such grouping is usually based on shared structural features and should only be used for the prioritization objectives. However, additional considerations (as well as structural similarity) are needed, e.

Identifying chemicals based on receptor binding/bioactivation/mechanistic explanation associated with potential to elicit hepatotoxicity and to support structure activity relationship-based read-across.

The liver is the most common target organ in toxicology studies. The development of chemical structural alerts for identifying hepatotoxicity will play an important role in model prediction and help strengthen the identification of analogs used in structure activity relationship (SAR)- based read-across. The aim of the current study is development of an SAR-based expert-system decision tree for screening of hepatotoxicants across a wide range of chemistry space and proposed modes of action for clustering of chemicals using defined core chemical categories based on receptor-binding or bioactivation.

Structure activity relationship (SAR) toxicological assessments: The role of expert judgment.

Structure activity relationships (SAR) and read-across are widely used animal alternative approaches for filling toxicological data gaps. A framework describing the use of expert judgment in evaluating analogs for SAR has been published and widely cited, however, reliance on expert judgment can introduce inconsistent results across experts and hinder transparency. Here we explore the use of a quantitative similarity score between an analog and a Structure of Interest (SOI) to see if these scores correlate with the expert judgement-based suitability rankings.