Read-across-based intelligent learning: development of a global q-RASAR model for the efficient quantitative predictions of skin sensitization potential of diverse organic chemicals†

Abstract

Environmental chemicals and contaminants cause a wide array of harmful implications to terrestrial and aquatic life which ranges from skin sensitization to acute oral toxicity. The current study aims to assess the quantitative skin sensitization potential of a large set of industrial and environmental chemicals acting through different mechanisms using the novel quantitative Read-Across Structure–Activity Relationship (q-RASAR) approach. Based on the identified important set of structural and physicochemical features, Read-Across-based hyperparameters were optimized using the training set compounds followed by the calculation of similarity and error-based RASAR descriptors. Data fusion, further feature selection, and removal of prediction confidence outliers were performed to generate a partial least squares (PLS) q-RASAR model, followed by the application of various Machine Learning (ML) tools to check the quality of predictions. The PLS model was found to be the best among different models. A simple user-friendly Java-based software tool was developed based on the PLS model, which efficiently predicts the toxicity value(s) of query compound(s) along with their status of Applicability Domain (AD) in terms of leverage values. This model has been developed using structurally diverse compounds and is expected to predict efficiently and quantitatively the skin sensitization potential of environmental chemicals to estimate their occupational and health hazards.