Optimizing Analog Identification and Evaluation in the OECD QSAR Toolbox to Enable Robust Read-Across.

Read-across is one of the most widely used New Approach Methods (NAMs) for evaluating the safety of a chemical with insufficient toxicological data. However, the identification of analogs suitable for read-across is not always straightforward as it requires understanding of critical chemical and biological features that drive toxicity. The OECD QSAR Toolbox is recommended as a valuable tool to support analog identification. Here, a case study is presented on Benzenesulfonic acid, comparing two different analog identification approaches within the Toolbox. The suitability of analogs identified from each method was evaluated and the approach that retrieved the highest suitability analogs served as criteria for determining the best analog identification approach. The selected approach was then applied to a second case study to assess the systemic toxicity data that will predict the safety of Tropolone. A third case study on 5-Dodecanoylsalicylic acid analyzed analogs identified for skin sensitization using the Defined Approaches for Skin Sensitization (DASS) Automated Workflow (AW) and a new approach developed internally. Through these case studies, this paper aims to analyze and define the steps involved in analog identification and evaluation within the Toolbox as well as critically assessing the corresponding data supporting the read-across prediction of a target chemical toxicity potential.