Halogenated disinfection by-products in aquatic environments: Ecotoxicity patterns, mechanistic evidence, and emerging risk assessment challenges

Halogenated disinfection by-products (DBPs) have been assessed primarily through drinking-water-centered human health frameworks, whereas their ecotoxicity in natural aquatic environments remains insufficiently integrated with mechanistic evidence. This critical review synthesizes 780 aquatic toxicity records and recent mechanistic studies to evaluate ecotoxicity patterns, molecular initiating events, adverse outcome pathways (AOPs), and emerging risk-assessment challenges for halogenated DBPs. The compiled data reveal pronounced taxon- and endpoint-dependent sensitivity across phytoplankton, zooplankton, fish, and benthic organisms. Highly toxic aliphatic DBPs, especially haloacetonitriles (HANs) and selected monohalogenated haloacetic acids, can affect pelagic organisms at submicromolar or lower concentrations, whereas emerging aromatic and heterocyclic DBPs, including halobenzoquinones (HBQs), halonitrophenols (HNPs), halogenated salicylaldehydes (HSALs), halopyridines, and chlorobenzenediols, show high potency in early-life-stage and benthic-relevant endpoints. Putative upstream initiating processes include electrophilic interactions with DNA or proteins, redox-active chemical interactions, and specific receptor or enzyme interactions, while membrane partitioning and metabolic activation can modify internal exposure and downstream toxicity. We organize current mechanistic evidence into a qualitative DBP-relevant AOP-oriented framework that links putative molecular initiating events with reported key events and organism-level outcomes, while highlighting uncertainties in ecological translation. Future work should prioritize chronic mixture testing, early-life-stage and benthic endpoints, and quantitative key-event relationships for highly potent emerging DBPs.