Disinfection Byproducts Confirmed over 50 Years: Systematic Curation, Modes of Toxic Action, and Toxicogenomics

Research on water disinfection byproducts (DBPs) over the past 50 years has unveiled more than 700 DBPs, many of which pose unrecognized risks to human health. Despite significant progress, systematic integration of the chemical curation of the confirmed DBPs with emerging toxicological paradigms is missing. This review systematically curates 716 confirmed DBPs reported from 1974 to 2024, offering a comprehensive resource to support risk identification and prioritization. We introduce a multiple classification framework based on molecular scaffolds, functional groups, and halogenation patterns, enabling researchers to map structural diversity to toxicological profiles. The modes of action applied in DBP research outlined here include nonspecific baseline toxicity, receptor- or enzyme-specific interactions, and reactive mechanisms such as oxidative stress and genotoxicity. Furthermore, we provide a system-level toxicogenomic view of DBP-induced toxicity, which has progressed from static single- and multiomics approaches to emerging time-resolved omics. These approaches reveal DBP-induced perturbations: the genome defines susceptibility, the transcriptome reflects expression levels, the proteome indicates functional execution, and the metabolome captures phenotypic outcomes. This review underscores critical knowledge gaps while charting future directions for DBP risk assessment and regulation and supports global efforts toward clean and safe drinking water.