Aromatic disinfection byproducts (DBPs) are a class of compounds that are of particular interest to environmental health scientists due to the induced detrimental effects when compared to exposure to regulated DBPs, all of which are aliphatic in nature. Drinking water, swimming pool water, and wastewater have all been shown to contain aromatic DBPs. Nitrogenous DBPs (N-DBPs) stand out among aromatic DBPs because of the presence of nitrogen-containing functional groups such as –NO2, –NH2, and –CN. Previous studies utilized an array of functional bioassays and have demonstrated that aromatic N-DBPs induce higher cytotoxicity and genotoxicity when compared to either the regulated DBPs or aromatic carbonaceous disinfection byproducts (C-DBPs). N-DBPs increased toxicity may be attributed to the combination of aromaticity and lipophilicity, due to the nitrogen moieties. However, the molecular mechanisms of N-DBPs toxicity are unclear. Halophenylacetonitriles (HPANs) and halonitrophenols (HNPs) are common aromatic N-DBPs which have been found in water sources. For this study, we employed our rapid enzymatic activity model (REAM) to assess 2-chlorophenylacetonitrile, 3,4-dichlorophenylacetonitrile, 2,6-dibromo-4-nitrophenol, 2-bromo-4-chloro-6-nitrophenol, 2,6-dichloro-4-nitrophenol, and 2,6-diiodo-4-nitrophenol alterations in the activity of multiple enzymes relating to antioxidant defense mechanisms (catalase and glutathione peroxidase) and cellular metabolism mechanisms (pyruvate dehydrogenase and lactate dehydrogenase). Preliminary results, which have been compared to the previously published literature, indicate that the N-DBPs interact with these enzymes, triggering a statistically significant change in activity. Our results demonstrate the utility of cell-free assays as a technique for pre-screening adverse health effects of N-DBPs, deciphering specific mechanisms of toxic action, and helping set a research agenda for this understudied class of contaminants.

Assessment of nitrogenous disinfection byproducts using enzymatic activity assays to elucidate potential mechanisms of toxic action

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