Advancing the identification of toxic by-products in disinfected water by integrating effect-directed analysis and nontarget screening.

The disinfection of drinking water inevitably generates disinfection by-products (DBPs), potentially jeopardizing human health. While previous research has mainly focused on risk from regulated DBPs, recent studies have indicated that these known compounds can only explain a small fraction of toxicity observed in disinfected water. Identifying toxic DBPs is therefore a critical step forward. Effect-directed analysis (EDA) has emerged as a promising tool for identifying the toxicity drivers in complex mixtures. Here, we examined the potential and challenges of applying EDA to identify toxic DBPs and proposed an integrative framework that combines EDA with nontarget screening to enable high-throughput analysis for DBPs. Standardizing sample preparation protocols for quenching and enrichment and prioritizing toxicity endpoints based on human health relevance are recommended for developing an effective EDA process. Furthermore, advancing non-target screening data processing techniques is essential for the confident identification and structural elucidation of unknown DBPs, enabling the tracking of their formation and transformation during disinfection processes. Collectively, these advances will support improved DBP regulation and disinfection practices, ultimately aiding the delivery of safer, higher-quality drinking water.