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.