Chlorination of antiviral drug ribavirin: kinetics, nontargeted identification, and concomitant toxicity evolution

Residual antiviral drugs in wastewater may increase the risk of generating transformation products (TPs) during wastewater treatment. Therefore, chlorination behavior and toxicity evolution are essential to understand the secondary ecological risk associated with their TPs. Herein, chlorination kinetics, transformation pathways, and secondary risks of ribavirin (RBV), one of the most commonly used broad-spectrum antivirals, were investigated. The pH-dependent second-order rate constants k increased from 0.18 M-1·s-1 (pH 5.8) to 1.53 M-1·s-1 (pH 8.0) due to neutral RBV and ClO- as dominant species. 12 TPs were identified using high-resolution mass spectrometry in a nontargeted approach, of which 6 TPs were reported for the first time, and their chlorination pathways were elucidated. The luminescence inhibition rate of Vibrio fischeri exposed to chlorinated RBV solution was positively correlated with initial free active chlorine, probably due to the accumulation of toxic TPs. Quantitative structure–activity relationship prediction identified 7 TPs with elevated toxicity, concentrating on developmental toxicity and bioconcentration factors, which explained the increased toxicity of chlorinated RBV. Overall, this study highlights the urgent need to minimize the discharge of toxic chlorinated TPs into aquatic environments and contributes to environmental risk control in future pandemics and regions with high consumption of antivirals. Wastewater treatment (including chlorination disinfection) cannot completely remove antivirals and may generate additional transformation products, making WWTPs a major source of hazardous antivirals in aquatic environments and posing unknown ecological risks. Current work revealed the chlorination kinetics and pathways of RBV for the first time, and the acute toxicity of chlorinated RBV increased due to the accumulation of 7 TPs with higher toxicity. These first findings on chlorination interaction and toxicity evolution of antiviral RBV provided theoretical support for environmental risk control in future pandemics and areas with high antiviral consumption.