Target analysis, occurrence and cytotoxicity of halogenated polyhydroxyphenols as emerging disinfection byproducts in drinking water

Abstract

Halogenated aromatic disinfection byproducts (DBPs) in drinking water, such as halogenated phenols, have received widespread attention due to their high toxicity and ubiquitous occurrence in recent years. This study identified a group of emerging halogenated aromatic DBPs, known as halogenated polyhydroxyphenols (HPPs), and investigated their occurrence and cytotoxicity. We developed a highly sensitive solid-phase extraction ultra-performance liquid chromatography-tandem mass spectrometry (SPE-UPLC-MS/MS) method under multiple reaction monitoring (MRM) mode, with recoveries ranging from 86 to 115% and method detection limits (MDLs) ranging from 0.10 to 1.87 ng/L for the analysis of 15 HPPs. Eleven of these HPP DBPs were detected in collected drinking water samples using this method with detection frequencies ranging from 14 to 100% and a maximum concentration of 24 ng/L. The IC₅₀ of the 15 HPPs in Chinese hamster ovary (CHO-K1) cells were ranged from 15.13 µM to 6.08×10³ µM. The tested HPPs with -CHO substitution exhibited higher cytotoxicity compared to those with -COOH substitution. The TIC-Tox values of HPPs were calculated to be higher than those of HPs, indicating a potential necessity to pay attention to HPP DBPs. A quantitative structure-activity relationship (QSAR) model was developed for the cytotoxicity of HPPs, which was shown to be significantly associated with acid dissociation constant (pK_a) and total valence connectivity (TVCon). To the best of our knowledge, this study reported the analysis, occurrence, and cytotoxicity of HPP DBPs in drinking water for the first time.

Keywords: Cytotoxicity; Disinfection byproducts (DBPs); Drinking water; Halogenated polyhydroxyphenols (HPPs); QSAR model; UPLC-MS/MS.