Halogenated Nucleosides: Highly Toxic Biogenic Disinfection Byproducts Prevalent in Drinking Water

Abstract Five decades of research on disinfection byproducts (DBPs) reveals only the tip of the iceberg, with humus as their primary precursor. Here, we identified 15 halogenated nucleosides (HNSs) as new DBPs originating from biological materials in drinking water. A nationwide survey across China revealed that their individual detection frequencies ranged from 87% to 100%, with the maximum concentration reaching 141 ng/L. Two quantitative structure–activity relationship (QSAR) models were developed based on the cytotoxicity and genotoxicity data, with dipole moment (μ) and sum of the degree of valence (SVDe) as key cytotoxicity descriptors, and molar refractivity (R) together with number of H-bond donors (NHD) for genotoxicity. Integrated concentration and toxicity data revealed that halogenated (deoxy)cytidines and halogenated (deoxy)adenosines warrant priority regulatory consideration. The concentrations of HNSs were positively correlated with both pH (r = 0.6, P = 0.0005) and residual chlorine (r = 0.5, P = 0.0095) of drinking water samples, which may be related to local precipitation, temperature, and economic development. This study expands the scope of DBP research beyond humus-derived DBPs to biomolecule-derived ones.