Chlorination, chloramination and ozonation of carbamazepine enhance cytotoxicity and genotoxicity: Multi-endpoint evaluation and identification of its genotoxic transformation products.

Investigations have focused on the removal and transformation of pharmaceuticals during drinking water and wastewater treatment. In the present study, we investigated for the first time the changes of the cytotoxicity and genotoxicity based on different modes of action (MoAs) during chlorination, chloramination and ozonation processes of the anti-epileptic drug carbamazepine (CBZ). The results illustrated that ozonation enhanced the cytotoxicity and the chromosome damage effects on CHO-K1 cells detected by cytokinesis-block micronucleus (CBMN) assay based on high-content screening technique, though ozonation showed the highest removal efficiency for CBZ. Non-target chemical analysis followed by quantitative structure-activity relationship (QSAR) analysis for the transformation products (TPs) suggested that the chromosomal damage effects could probably be attributed to 1-(2-benzaldehyde)-4-hydro-(1H,3H)-quinazoline-2-one (BQM) and 1-(2-benzaldehyde)-(1H,3H)-quinazoline-2,4-dione (BQD). In contrast to CBZ itself and the ozonated sample, the chlorinated and chloraminated samples caused DNA damage effects in SOS/ umu test. Acridine, 9 (10) H-acridone, chlorinated 9 (10) H-acridone and TP-237, which were first identified in the chlorination or chloramination processes, were predicted to be the DNA damaging agents. These genotoxic TPs were primarily generated from the oxidation of seven-membered N -heterocyclic in CBZ. This study highlighted the potential adverse effects generated in ozonation process and the oxidation of N -heterocyclic containing pollutants. [ABSTRACT FROM AUTHOR]