New Species and\nCytotoxicity Mechanism of Halohydroxybenzonitrile\nDisinfection Byproducts in Drinking Water

Recently, seven dihalohydroxybenzonitriles (diHHBNs)\nhave been\ndetermined as concerning nitrogenous aromatic disinfection byproducts\n(DBPs) in drinking water. Herein, eight new monohalohydroxybenzonitriles\n(monoHHBNs), including 3-chloro-2-hydroxybenzonitrile, 5-chloro-2-hydroxybenzonitrile,\n3-chloro-4-hydroxybenzonitrile, 3-bromo-2-hydroxybenzonitrile, 5-bromo-2-hydroxybenzonitrile,\n3-bromo-4-hydroxybenzonitrile, 5-iodo-2-hydroxybenzonitrile, and 3-iodo-4-hydroxybenzonitrile,\nwere detected and identified in drinking water for the first time.\nThereafter, the relative concentration–cytotoxicity contribution\nof each HHBN was calculated based on the acquired occurrence level\nand cytotoxicity data in this study, the genome-scale cytotoxicity\nmechanism was explored, and a quantitative structure–activity\nrelationship (QSAR) model was developed. Results indicated that new\nmonoHHBNs were present in drinking water at concentrations of 0.04–1.83\nng/L and exhibited higher cytotoxicity than some other monohalogenated\naromatic DBPs. Notably, monoHHBNs showed concentration<b>–</b>cytotoxicity contribution comparable to diHHBNs, which have been\npreviously identified as potential toxicity drivers in drinking water.\nTranscriptomic analysis revealed immunotoxicity and genotoxicity as\ndominant cytotoxicity mechanisms for HHBNs in Chinese hamster ovary\n(CHO-K1) cells, with potential carcinogenic effects. The QSAR model\nsuggested oxidative stress and cellular uptake efficiency as important\nfactors for their cytotoxicity, highlighting the importance of potential\niodinated HHBNs in drinking water, such as 3,5-diiodo-2-hydroxybenzonitrile,\nfor future studies. These findings are meaningful for better understanding\nthe health risk and toxicological significance of HHBNs in drinking\nwater.