Halogenated disinfection byproducts (halo-DBPs) are drinking water contaminants of great public health concern. Nine haloaliphatic DBPs have been regulated by the U.S. Environmental Protection Agency and various halophenolic compounds have been identified as emerging DBPs. In this study, we evaluated the cytotoxic interactions of the regulated bromoacetic acid and three emerging bromophenolic DBPs, i.e., 2,4,6-tribromophenol, 3,5-dibromo-4-hydroxybenzoic acid, and 3,5-dibromo-4-hydroxybenzaldehyde. Cytotoxicity was measured for each DBP individually as well as each of their mixtures using in vitro human epithelial colorectal adenocarcinoma (Caco-2) and neuroblastoma (SH-SY5Y) cells. Concentration addition (CA) model and isobolographic analysis were employed to characterize the interactions among the DBPs. Bioassay of reactive oxidative species (ROS) production was conducted to further investigate the interactions of DBPs. Our results show that the cytotoxicity of four bromo-DBPs against both cell-types followed the descending rank order of bromoacetic acid &gt; 2,4,6-tribromophenol &gt; 3,5-dibromo-4-hydroxybenzaldehyde &gt; 3,5-dibromo-4-hydroxybenzoic acid. Compared with the toxicity data in literature, our finding that bromoacetic acid showed higher cytotoxicity than bromophenolic DBPs was consistent with the results from Chinese hamster ovary cells (a staple in vitro model of DBP toxicological studies); but different from the results obtained from in vivo biological models. With CA model prediction, mixtures of four bromo-DBPs exhibited synergistic cytotoxic effects. Isobolographic analysis of binary DBP mixtures revealed that, for Caco-2 cells, bromoacetic acid, 2,4,6-tribromophenol, and 3,5-dibromo-4-hydroxybenzoic acid induced synergism; for SH-SY5Y cells, bromoacetic acid induced synergism with all three bromophenolic DBPs. Generation of ROS played a significant role in the synergistic cytotoxicity.

Synergistic cytotoxicity of bromoacetic acid and three emerging bromophenolic disinfection byproducts against human intestinal and neuronal cells

ACS Fall 2021

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