School of Environmental Science and Engineering, China-America CRC for Environment & Health, Shandong University, Qingdao 266237, China.
School of Environment, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310024, China.
Environ Sci Technol. 2024 Sep 3;58(35):15816-15826. doi: 10.1021/acs.est.4c06163. Epub 2024 Aug 21.
Recently, seven dihalohydroxybenzonitriles (diHHBNs) have been determined as concerning nitrogenous aromatic disinfection byproducts (DBPs) in drinking water. Herein, eight new monohalohydroxybenzonitriles (monoHHBNs), including 3-chloro-2-hydroxybenzonitrile, 5-chloro-2-hydroxybenzonitrile, 3-chloro-4-hydroxybenzonitrile, 3-bromo-2-hydroxybenzonitrile, 5-bromo-2-hydroxybenzonitrile, 3-bromo-4-hydroxybenzonitrile, 5-iodo-2-hydroxybenzonitrile, and 3-iodo-4-hydroxybenzonitrile, were detected and identified in drinking water for the first time. Thereafter, the relative concentration-cytotoxicity contribution of each HHBN was calculated based on the acquired occurrence level and cytotoxicity data in this study, the genome-scale cytotoxicity mechanism was explored, and a quantitative structure-activity relationship (QSAR) model was developed. Results indicated that new monoHHBNs were present in drinking water at concentrations of 0.04-1.83 ng/L and exhibited higher cytotoxicity than some other monohalogenated aromatic DBPs. Notably, monoHHBNs showed concentrationcytotoxicity contribution comparable to diHHBNs, which have been previously identified as potential toxicity drivers in drinking water. Transcriptomic analysis revealed immunotoxicity and genotoxicity as dominant cytotoxicity mechanisms for HHBNs in Chinese hamster ovary (CHO-K1) cells, with potential carcinogenic effects. The QSAR model suggested oxidative stress and cellular uptake efficiency as important factors for their cytotoxicity, highlighting the importance of potential iodinated HHBNs in drinking water, such as 3,5-diiodo-2-hydroxybenzonitrile, for future studies. These findings are meaningful for better understanding the health risk and toxicological significance of HHBNs in drinking water.
最近，有七种二卤羟基苯并腈（diHHBNs）被确定为饮用水中含氮芳香族消毒副产物（DBPs）。在此，首次在饮用水中检测并鉴定了八种新的单卤羟基苯并腈（monoHHBNs），包括 3-氯-2-羟基苯腈、5-氯-2-羟基苯腈、3-氯-4-羟基苯腈、3-溴-2-羟基苯腈、5-溴-2-羟基苯腈、3-溴-4-羟基苯腈、5-碘-2-羟基苯腈和 3-碘-4-羟基苯腈。此后，根据本研究中获得的出现水平和细胞毒性数据，计算了每种 HHBN 的相对浓度-细胞毒性贡献，探索了基于基因组规模的细胞毒性机制，并开发了定量构效关系（QSAR）模型。结果表明，新的单卤羟基苯并腈以 0.04-1.83ng/L 的浓度存在于饮用水中，且其细胞毒性高于其他一些单卤代芳香族 DBPs。值得注意的是，单卤羟基苯并腈的浓度-细胞毒性贡献可与已被确定为饮用水中潜在毒性驱动因素的二卤羟基苯并腈相媲美。转录组分析表明，HHBN 在 CHO-K1 细胞中具有免疫毒性和遗传毒性，是主要的细胞毒性机制，具有潜在的致癌作用。QSAR 模型表明氧化应激和细胞摄取效率是其细胞毒性的重要因素，突出了饮用水中潜在的碘代 HHBN（如 3,5-二碘-2-羟基苯腈）的重要性，值得未来进一步研究。这些发现对于更好地了解 HHBN 在饮用水中的健康风险和毒理学意义具有重要意义。
