Prediction and mechanism of combined toxicity of surfactants and antibiotics in aquatic environment based on in silico method

The coexistence of surfactants and antibiotics in aquatic environments can potentially trigger combined toxic effects on aquatic organisms. Unfortunately, the effects of these joint toxins and the corresponding mechanism remain unclear. In this study, we performed individual and combined toxicity experiments involving surfactants and antibiotics. Six quantitative structure-activity relationship (QSAR) models and two traditional mixture models were developed. Moreover, the toxic mechanisms were explored with molecular dynamics (MD) simulations and density functional theory (DFT) calculations. The results shown that synergistic toxicity effects were observed in the binary mixture of levofloxacin (LEV) and octylphenol ethoxylate (Triton X-100). In addition, the best QSAR model (RF-PLS), which included four mixture descriptors (RDF155i#3, MATS3e#2, ETA_BetaP_ns#6, MLFER_E#6) exhibited excellent performance (R2 = 0.921, R2adj = 0.875, Q2LOO = 0.820, Q2ext = 0.889, and CCC = 0.954). Further analysis revealed that the electrostatic potential of different target chemicals and their binding ability with enzymes affected the activity of AChE of Daphnia magna, resulting in different toxicity. Specifically, in the AChE + Triton X-100 + LEV system, the second pollutant enhances the ability of the overall system to bind pollutants, which exhibit a synergistic effect during the binding process.