Precursor characteristics of mono-HAAs during chlorination and cytotoxicity of mono-HAAs on HEK-293T cells

Abstract

Monohaloacetic acids (mono-HAAs), a class of disinfection by-products widely occurred in drinking water, receives significant attention due to their extremely high toxicity. Many studies on the biological toxicity of mono-HAAs have been reported, yet the toxic effects of mono-HAAs on human renal cells (kidney is one of the target organs for disinfection by-products) has not been involved. Studies on organic precursors for mono-HAAs formation were also very limited due to their lower levels as compared to di-HAAs and tri-HAAs. Based on this, the formation of mono-HAAs after chlorination of some typical source water samples and their relationship with water quality parameters were investigated. Meanwhile, the cytotoxicity of monochloroacetic acid (MCAA), monobromoacetic acid (MBAA), and monoiodoacetic acid (MIAA) were tested using human embryonic kidney cells (HEK-293 T cells). The results showed that the levels of mono-HAAs formed during chlorination of source water samples were between 0.44 and 0.87 μg/L. Formation of MBAA positively (p < 0.05) correlated with bromide ion and dissolved organic carbon, but negatively (p < 0.01) correlated with SUVA₂₅₄ (specific UV absorbance at 254 nm), while formation of MCAA was only positively (p < 0.05) related with SUVA₂₅₄. These results suggested that although MCAA and MBAA both belong to the mono-HAAs, the characteristics of their organic precursors differ significantly. MCAA precursors have high aromaticity and are more hydrophobic, yet MBAA precursors have low aromaticity and are more hydrophilic. The half-lethal concentrations (LC₅₀) of MCAA, MBAA, and MIAA on HEK293T cells were 1196-1211 μM, 16.07-18.96 μM, and 6.08-6.17 μM, respectively. An in-depth analysis showed that the cytotoxicity of mono-HAAs on HEK 293 T cells could not be explained by the parameters concerning cellular uptake (e.g., logP and pKa), but the S_N2 reaction of C-X bond with cellular molecules (e.g., glyceraldehyde-3-phosphate dehydrogenase, etc) may be the relevant cause for the cytotoxicity of mono-HAAs on HEK 293 T cells.

Keywords: Cytotoxicity; Mechanism of toxicity; Monohaloacetic acid; Precursor.