GenoITS: Implementation of an Integrated Testing Strategy workflow for genotoxicity using QSAR-based tools

• Decisional workflow to assess the genotoxicity following REACH regulations. • Assessment performed using experimental data and QSAR predictions. • Output as a binary classification (genotoxic/non-genotoxic). • Assessment report and QPRFs for each prediction automatically delivered to the user. To assess the potential impact of chemical substances on human health and the environment, and to ensure the safety of chemicals, the EU's REACH regulation requires registrants of chemicals to undertake a battery of tests to fulfil Standard Information Requirements. These tests raise two main concerns, (1) the economic burden due to the resources needed to perform the tests, both in materials and time invested, and (2) the ethical considerations of using animal testing. For this reason, nowadays the regulatory agencies encourage registrants to minimize the number of experiments performed on animals (3Rs). In this work we have developed an exclusively computational Integrated Testing Strategy to assess the genotoxicity of chemicals. A complete set of data of assays for gene mutation and cytogenotoxicity (in bacteria, in vitro and in vivo ) are used. These assays are integrated into an automated workflow called GenoITS, which is part of the ProtoPRED Ⓡ prediction suite ( https://protopred.protoqsar.com/ ). This automated workflow is based on the schema proposed by REACH to assess the genotoxicity. The GenoITS workflow leads the user through this testing strategy, allowing to work with their own data and filling the gaps with our in-house QSAR (Quantitative Structure-Activity Relationship) models, and a binary classification result (genotoxic/not genotoxic) is delivered as a final output, by combining the results of the different tests required by different regulations to evaluate the genotoxicity. This workflow is presented as a commercial web-based technological platform that will provide significant benefit to the community using REACH and other regulations.