Humans are exposed to disinfection by-products (DBPs) mainly through drinking water ingestion and dermal contact. As an emerging class of nitrogenous DBPs (N-DBPs), haloacetamides (HAcAms) have been found to have significantly higher cytotoxicity than regulated DBPs. In this study, we investigated the cytotoxicity of HAcAms on two exposure pathway-related cell lines: human gastric epithelial GES-1 cells and immortalized keratinocytes HaCaT. Our results showed that the ranking order of cytotoxicity of 13 HAcAms was different between HaCaT and GES-1 cells. In addition, the 50% inhibitive concentration in HaCaT was 1.01-3.29 times that in GES-1. Further comparison among GES-1, HaCaT and CHO cell lines confirmed that different cell lines exhibited different sensitivity to the same compound. Importantly, HAcAms showed 5.83-7.13 × 104 times higher toxicity than the well-clarified DBP chloroform, clearly demonstrating the increased toxicity of HAcAms. Finally, using a novel high-content screening (HCS) analysis, we found that 39.29% of chlorinated HAcAms, 42.86% of brominated HAcAms and 16.07% of iodinated HAcAms significantly affected at least one of the cell-health parameters, such as nuclear size, membrane permeability, mitochondrial membrane potential, or cytochrome c release, in GES-1 or HaCaT cells. Thus, brominated HAcAms appear to have stronger effects under the sublethal exposure dose, possibly causing cytotoxicity via apoptosis. Together, our study provides new insights to the toxicity of HAcAms and a comprehensive toxicology dataset for health risk assessment.
Keywords: Apoptosis; Cytotoxicity; Disinfection by-product; Haloacetamides.
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