Comparative cytotoxicity of halogenated aromatic DBPs and implications of the corresponding developed QSAR model to toxicity mechanisms of those DBPs: Binding interactions between aromatic DBPs and catalase play an important role

Halogenated aromatic disinfection byproducts (DBPs) are a new group of emerging DBPs identified recently. They have been detected in disinfected drinking water, wastewater effluents, recreational water and oil/gas produced water, at concentrations of ng/L to μg/L in general. Previously studies have demonstrated that most of them can induce developmental toxicity and growth inhibition in aquatic organisms based on in vivo bioassays. In this study, to further understand the adverse effects of aromatic DBPs to human health, the comparative cytotoxicity of 15 halogenated aromatic DBPs belonging to four subgroups (i.e., halophenols, halonitrophenols, halohydroxybenzaldehydes and halohydroxybenzoic acids) was evaluated with mammalian Chinese Hamster Ovary cells. The results indicated that the selected aromatic DBPs exhibited an in vitro toxicity rank order of halonitrophenols > halophenols > halohydroxybenzaldehydes > halohydroxybenzoic acids. The potential toxicity mechanisms involved with the antioxidant system were investigated by using molecular docking analysis between key antioxidant enzymes (i.e., catalase, superoxide dismutase, and glutathione S-transferase) and aromatic DBPs. Based on the observed cytotoxicity data and screening the candidate descriptors (including binding energies between the aromatic DBPs and key antioxidant enzymes as well as physical-chemical/quantum-chemical/topological descriptors), a QSAR model was developed as log (LC50) -1 = - 1.050ECAT + 0.300EHOMO - 0.238ELUMO- 0.164, indicating the importance of the interactions of aromatic DBPs towards catalase and the electrophilic/nucleophilic reactivity of aromatic DBPs in the toxicity mechanisms. In addition, the occurrence of the aromatic DBPs in tap water and finished water was studied in a mega city Shenzhen located in South China. Results showed that halogenated aromatic DBPs commonly existed in Shenzhen drinking water at ng/L levels, and three nitrogenous aromatic DBPs were detected in real drinking water for the first time. The major toxicity drivers among the target aromatic DBPs were identified through the integration of the measured concentrations and observed cytotoxicity; notably, DBPs with the highest concentrations may not contribute the highest proportions of overall toxicity.