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.

中文翻译：

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卡马西平的氯化，氯化和臭氧化可增强细胞毒性和遗传毒性：遗传毒性转化产物的多端点评估和鉴定

研究集中于饮用水和废水处理过程中药物的去除和转化。在本研究中，我们首次研究了抗癫痫药物卡马西平（CBZ）在氯化，氯化和臭氧化过程中基于不同作用方式（MoAs）的细胞毒性和遗传毒性的变化。结果表明，臭氧化增强了通过高含量筛选技术通过胞质分裂阻滞微核（CBMN）测定法检测到的CHO-K1细胞的细胞毒性和染色体损伤作用，尽管臭氧化显示出对CBZ的最高去除效率。非目标化学分析，然后对转化产物（TPs）进行定量构效关系（QSAR）分析，表明染色体损伤作用可能归因于1-（2-苯甲醛）-4-氢-（1H，3H ）-喹唑啉-2-酮（BQM）和1-（2-苯甲醛）-（1H，3H）-喹唑啉-2,4-二酮（BQD）。与CBZ本身和臭氧化样品相反，氯化和氯化样品在SOS /umu测试。cr啶，9（10）H-ac啶酮，氯化的9（10）H-ac啶酮和TP-237，是在氯化或氯化过程中最先发现的，预计它们是DNA的破坏剂。这些遗传毒性TPs主要是由CBZ中的七元N杂环氧化而产生的。这项研究强调了臭氧化过程中产生的潜在不利影响以及含有N-杂环的污染物的氧化。