左氧氟沙星氧化转化机制及毒性评价研究
文献类型：学位论文
| 作者 | 阴俊霞 |
| 学位类别 | 博士 |
| 答辩日期 | 2012-11 |
| 授予单位 | 中国科学院研究生院 |
| 授予地点 | 北京 |
| 导师 | 杜宇国 ; 魏东斌 |
| 关键词 | 左氧氟沙星 氯化消毒 高锰酸钾 Fenton 毒性 Levofloxacin Chlorination Potassium permanganate Fenton Toxicity |
| 其他题名 | Transformation Mechanism and Toxicity Assessment of Levofloxacin in Oxidation Process |
| 学位专业 | 环境科学 |
| 中文摘要 | 药物与个人护理品（Pharmaceuticals and Personal Care Products ，PPCPs）是一类与人们日常生活最为密切相关的化合物，因其具有环境“准持久性”和一定的毒性效应引起了研究者的关注。近年来由于抗生素的广泛使用甚至滥用，导致大量原药及其衍生物通过各种方式进入环境，诱导环境中抗药菌的产生，对人体健康和生态安全造成巨大威胁，引起了社会各界的广泛关注。氟喹诺酮类抗生素因其良好的抗菌作用占据了较大市场份额，其所带来的环境污染问题逐渐成为近年的研究热点。目前关于氟喹诺酮类抗生素在水处理过程中的转化机制及其潜在的毒性效应还鲜有报道。本文以用量最大的左氧氟沙星为研究对象，探讨了在不同氧化处理过程中的转化行为，具体工作如下： 以次氯酸钠为消毒剂，研究左氧氟沙星在氯化消毒过程中的转化机制。利用 UPLC、MS、NMR 等工具分离、识别转化产物，在氯化消毒体系中鉴定出14 种未见报道的新化合物；根据化学反应原理和模型试验推导出可能的转化路径， 主要包括四种反应类型：脱羧氯代反应，氧化酯化反应，水解反应（氨水解、酯 水解、F 原子水解）以及氧化脱烷基反应；同时，利用正交实验研究了不同pH 值、氯剂量对氯化转化的影响，发现酸性条件下反应最为复杂，反应类型和产物 种类最多，增加氯的剂量有利于转化反应的进行。通过搭建毒性测试平台，对左 氧氟沙星氯化转化过程的遗传毒性、急性毒性、内分泌干扰效应及抗菌活性进行 了研究。发现在酸、中、碱性三种pH 条件下毒性变化趋势相似，投加低剂量的 氯（小于3eq）导致遗传毒性明显升高，投加高剂量的氯（10eq 以上）时，体系的遗传毒性明显下降；抗菌活性随着氯剂量的增加而降低，说明在氯化消毒过程中破坏了药效官能团，失去了抗菌活性。 氯消毒体系中存在溴离子、碘离子往往因生成溴代、碘代消毒副产物而导致 健康风险的升高。本文分别探讨了溴、碘离子存在对左氧氟沙星氯化转化行为的 影响，结果发现：溴离子的存在导致左氧氟沙星的氯化反应发生改变，与无溴离 子存在的氯化反应相比，多生成了10 种含溴消毒副产物，体系的遗传毒性明显 升高；碘离子存在时消毒体系的遗传毒性比溴离子存在时更加显著，这可能与生 成碘代消毒副产物有关。 在此基础上，本文还研究了左氧氟沙星在其他氧化处理中的转化行为。首先 考察了高锰酸钾与左氧氟沙星的反应，初步鉴定出4 种主要的转化产物，并对其 转化过程的遗传毒性进行了检测，发现左氧氟沙星在高锰酸钾氧化体系中毒性明 显降低；其次，探讨了二氧化锰对左氧氟沙星的转化行为，发现其结果与高锰酸 钾体系相似。另外，还研究了Fenton 试剂对左氧氟沙星的氧化作用，初步鉴定 出3 种转化产物，其中有氧化酯化产物的存在。同时，利用正交实验研究了不同 pH 值、Fe2+初始浓度、H2O2 初始浓度对反应的影响，且对转化过程进行了动力学研究，综合准一级反应方程。 本文关于左氧氟沙星在不同氧化体系中的转化行为及毒性变化的研究结果，不仅可以为该类抗生素在环境中的转化行为及其潜在环境风险评价提供基础数据，还可以为该类废水处理技术的选择和工艺参数的优化提供技术支持。 |
| 英文摘要 | Pharmaceuticals and personal care products is a kind of compounds closely to people's daily life, and it has drawn researchers’ attention because of its environmental persistence and certain toxicity. A large volume of antibiotics and their derivatives have entered into environment in various ways due to their widespread use even abuse. It has been paid much attention on the potential harm to human health and ecological security due to the occurrence of drug resistant bacteria in the environment. Fluoroquinolones occupy a large share in antibiotics market because of their excellent antibacterrial activity. There are many studies on pollution characterization of fluoroquinolones in the past decade, while transformation mechanism and potential toxicity changes in the process of water treatment is rarely reported. In the present study, levoflocaxin is selected as a target compound to investigate its transformation behaviors in different oxidation processes. The specific work is as follows: Firstly, in the sodium hypochlorite oxidation system, 14 novel products were isolated and identified by UPLC, MS, NMR. The possible transformation pathways of levofloxacin in NaClO system was proposed based on chemical reaction principles and model reactions. There are four types of reactions: decarboxylation and chlorination, oxidative esterification, hydrolysis (amine hydrolysis, ester hydrolysis and F atoms hydrolysis), and dealkylation. Orthogonal experiments were conducted to explore the effect of pH value and chlorine dosage on the chlorination transformation. It was found that reaction types and transformation products were the most abundant under acidic condition, and the increasing dose of chlorine would promote the transformation of levofloxacin. At the same time, genetic toxicity, acute toxicity, endocrine disrupting effect and antibacterial activity were measured to evaluate the potential hazards in chlorination process. It was found that all four kinds of toxicities had similar tendency under the three pH conditions. Especially, genetic toxicity increased significantly at 3eq of chlorine dose, while it decreased significantly as increasing chlorine dose to 10eq. Antibacterial activity decreased with the increase of chlorine dosages which can be attributed to the destroy of pharmacophore in the chlorination process. Secondly, the effects of bromide and iodide ions on the chlorination of levofloxacin were explored. The results showed that the presence of bromide ion would change chlorination characteristics of levofloxacin and 10 of new brominated products were identified. The chlorination system containing bromide and iodide ions exhibited much higher genetic toxicity than that without bromide and iodide ions due to the formation of brominated and iodinated products. And the toxicity of chlorination system with iodide was higher than that with bromide ions. Thirdly, the transformation behaviors of levofloxacin in some other oxidation processes have also been studied. In potassium permanganate oxidation system, four major oxidation products were identified and the genetic toxicity of reaction mixture decreased significantly with the oxidation by potassium permanganate. The case with manganese dioxide oxidation was similar to that with potassium permanganate. In the Fenton oxidation system, three transformation products were identified. And orthogonal experiments were conducted to study the effects of the pH values, initial concentration of Fe2+ and H2O2 on the transformation kinetics. We expected that the results of transformation behaviors and toxicity tests in this study could not only provide a theoretical basis for evaluating the potential environmental risk of quinolones antibiotics, but also provide the technical support for selecting and optimizing operational parameters in wastewater treatment practice. |
| 公开日期 | 2014-05-12 |
| 源URL | [http://ir.rcees.ac.cn/handle/311016/7216]  |
| 专题 | 生态环境研究中心_中国科学院环境生物技术重点实验室 |
| 推荐引用方式 GB/T 7714 | 阴俊霞. 左氧氟沙星氧化转化机制及毒性评价研究[D]. 北京. 中国科学院研究生院. 2012. |
入库方式： OAI收割
来源：生态环境研究中心
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。