Predicting cytotoxicity of binary pollutants towards a human cell panel in environmental water by experimentation and deep learning methods

Biological assays are useful in water quality evaluation by providing the overall toxicity of chemical mixtures in environmental waters. However, it is impossible to elucidate the source of toxicity and some lethal combination of pollutants simply using biological assays. As facile and cost-effective methods, computation model-based toxicity assessments are complementary technologies. Herein, we predicted the human health risk of binary pollutant mixtures (i.e., binary combinations of As(III), Cd(II), Cr(VI), Pb(II) and F(I)) in water using in vitro biological assays and deep learning methods. By employing a human cell panel containing human stomach, colon, liver, and kidney cell lines, we assessed the human health risk mimicking cellular responses after oral exposures of environmental water containing pollutants. Based on the experimental cytotoxicity data in pure water, multi-task deep learning was applied to predict cellular response of binary pollutant mixtures in environmental water. Using additive descriptors and single pollutant toxicity data in pure water, the established deep learning model could predict the toxicity of most binary mixtures in environmental water, with coefficient of determination (R2) > 0.65 and root mean squared error (RMSE) < 0.22. Further combining the experimental data on synergistic and antagonistic effects of pollutant mixtures, deep learning helped improve the predictive ability of the model (R2 > 0.74 and RMSE <0.17). Moreover, predictive models allowed us identify a number of toxicity source-related physiochemical properties. This study illustrates the combination of experimental findings and deep learning methods in the water quality evaluation.