Degradation of cyclophosphamide and 5-fluorouracil by UV and simulated sunlight treatments: Assessment of the enhancement of the biodegradability and toxicity.

Degradation of cyclophosphamide and 5-fluorouracil by UV and simulated sunlight treatments: Assessment of the enhancement of the biodegradability and toxicity.
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紫外线和模拟日光处理对环磷酰胺和 5-氟尿嘧啶的降解:评估生物降解性和毒性的增强

DOI:
10.1016/j.envpol.2015.10.016
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发表时间:
2016
影响因子:
8.9
通讯作者:
Kümmerer
Kümmerer
中科院分区:
环境科学与生态学2区
文献类型:
--
作者:
Carlos Alexandre Lutterbeck Wilde;Baginska;Machado;Kümmerer

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近年来,环境中的药物引起了公众的关注,并受到科学界的极大关注。然而,只有少数出版物关注抗癌药物,这是一类可表现出细胞毒性、遗传毒性、致突变、致癌和致畸作用的药物。本文研究了环磷酰胺(CP)和5-氟尿嘧啶(5-FU)的光降解、生物降解、细菌毒性、致突变和遗传毒性。在中性至轻微pH范围(7-7.8)下,使用两种不同的灯(中压汞灯和氙灯)进行光降解实验。通过液相色谱串联质谱法(LC-IT-MS/MS)监测母体化合物的主要消除。进行NPOC(不可净化的有机碳)分析,以评估矿化率。闭瓶试验(CBT)用于评估快速生物降解性。采用费氏弧菌(Vibrio fischeri)作为评价毒力的新方法。CP没有被任何灯降解,而5-FU被完全消除的照射与汞灯,但只有部分由氙灯。用紫外灯进行的实验没有观察到矿化,使用紫外灯256分钟后,5-FU的NPOC去除率仅为18%。没有一种母体化合物在CBT中容易生物降解。光解产生的光转化产物(PTPs)既不具有更好的生物降解性,也不具有比母体化合物5-FU更低的毒性。相比之下,用UV灯进行的测试的结果表明,产生了更多的可生物降解和无毒的5-FU PTP。在光降解实验过程中形成了三个PTP,并进行了鉴定。计算机模拟QSAR预测结果显示5-FU的致突变性和遗传毒性警报阳性,而形成的PTP中只有一个显示遗传毒性终点的阳性警报。
The presence of pharmaceuticals in the environment has triggered concern among the general population and received considerable attention from the scientific community in recent years. However, only a few publications have focused on anticancer drugs, a class of pharmaceuticals that can exhibit cytotoxic, genotoxic, mutagenic, carcinogenic and teratogenic effects. The present study investigated the photodegradation, biodegradation, bacterial toxicity, mutagenicity and genotoxicity of cyclophosphamide (CP) and 5-fluorouracil (5-FU). The photodegradation experiments were performed at a neutral to slight pH range (7–7.8) using two different lamps (medium-pressure mercury lamp and a xenon lamp). The primary elimination of the parent compounds was monitored by means of liquid chromatography tandem mass spectrometry (LC-IT-MS/MS). NPOC (non-purgeable organic carbon) analyses were carried out in order to assess mineralization rates. The Closed Bottle Test (CBT) was used to assess ready biodegradability. A new method usingVibrio fischeriwas adopted to evaluate toxicity. CP was not degraded by any lamp, whereas 5-FU was completely eliminated by irradiation with the mercury lamp but only partially by the Xe lamp. No mineralization was observed for the experiments performed with the Xe lamp, and a NPOC removal of only 18% was registered for 5-FU after 256 min using the UV lamp. Not one of the parent compounds was readily biodegradable in the CBT. Photo transformation products (PTPs) resulting from photolysis were neither better biodegradable nor less toxic than the parent compound 5-FU. In contrast, the results of the tests carried out with the UV lamp indicated that more biodegradable and non-toxic PTPs of 5-FU were generated. Three PTPs were formed during the photodegradation experiments and were identified. The results of thein silicoQSAR predictions showed positive mutagenic and genotoxic alerts for 5-FU, whereas only one of the formed PTPs presented positive alerts for the genotoxicity endpoint.
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