Data fusion quantitative read-across structure-activity-activity relationships (q-RASAARs) for the prediction of toxicities of binary and ternary antibiotic mixtures toward three bacterial species

Antibiotics are often found in the environment as pollutants. They are usually found as mixtures in the environment and may produce toxicity against different ecological species due to joint exposure in the sub-optimal range. Sometimes the degradation products of parent chemicals also interact with it and cause mixture toxicity. In this study, we have developed three different mixture-Quantitative Structure-Activity Relationship (mixtureQSAR) models for three different bacterial species (Vibrio fischeri, Escherichia coli, and Bacillus subtilis). The toxicity data were collected from a previous experimental report in the literature, which comprised binary and ternary mixtures of sulfonamides (SAs), sulfonamide potentiators (SAPs), and tetracyclines (TCs). We have also explored the interspecies modeling to find inter-correlation among the toxicity of these studied organisms and have developed quantitative structure activity-activity relationship (QSAAR) models by employing the data fusion quantitative read-across structure-activity-activity relationship (q-RASAAR) and partial least squares (PLS) regression algorithms. All the models are strictly validated using both internal and external validation tests as suggested in the OECD guidelines. Three different mixing rules have been used in this study for descriptor computations to incorporate the additive and interaction effects among the mixture components. To the best of our knowledge, this is the first report of interspecies mixture toxicity models which can predict the cellular toxicity of binary and ternary mixtures against any of the three above-mentioned organisms.

Automated summary

This study developed three different mixture-Quantitative Structure-Activity Relationship (mixture-QSAR) models for three different bacterial species. Interspecies modeling was explored to find inter-correlation among the toxicity of the studied organisms, and quantitative structure activity-activity relationship (QSAAR) models were developed. All the models were validated using internal and external validation tests as suggested in the OECD guidelines.