Degradation of cyclophosphamide and 5-fluorouracil by UV and simulated sunlight treatments: Assessment of the enhancement of the biodegradability and toxicity. (January 2016)

• Record Type: Journal Article
• Authors: Lutterbeck, Carlos Alexandre; Wilde, Marcelo Luís; Baginska, Ewelina; Leder, Christoph; Machado, Ênio Leandro; Kümmerer, Klaus
• Is Part Of: Environmental pollution. Volume 208:Part B(2016)
• Page Start: 467
• Page End: 476
• Publication Date: 2016-01
• Subjects: Cyclophosphamide -- 5-Fluorouracil -- Photodegradation -- Biodegradation -- Toxicity; 5-FU 5-fluorouracil -- AI acute luminescence inhibition -- CBT closed bottle test -- CFU colony forming units -- CI chronic luminescence inhibition -- CP cyclophosphamide -- DNA deoxyribonucleic acid -- DOC dissolved organic carbon -- EC effective concentration -- GI growth inhibition -- HPLC high performance liquid chromatography -- LC liquid chromatography -- LOEC lowest observed effect concentration -- LSSTP laboratory-scale sewage treatment plant -- MS mass spectrometry -- NPOC non purgeable organic carbon -- OECD organization for economic co-operation and development -- PTPs photo-transformation products -- QSAR quantitative structure–activity relationship -- TOC total organic carbon -- ThOD theoretical oxygen demand -- UV ultraviolet; Pollution -- Periodicals; Pollution -- Environmental aspects -- Periodicals; Environmental Pollution -- Periodicals; Pollution -- Périodiques; Pollution -- Aspect de l'environnement -- Périodiques; Pollution -- Effets physiologiques -- Périodiques; Pollution; Pollution -- Environmental aspects; Periodicals; Electronic journals; 363.73
• DOI: 10.1016/j.envpol.2015.10.016
• Languages: English
• ISSNs: 0269-7491

Abstract

Abstract: 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 using Vibrio fischeri was 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 the in silico QSAR predictions showed positive mutagenic and genotoxic alerts for 5-FU, whereas only one of the formed PTPs presented positive alerts for the genotoxicity endpoint. Highlights: CP was not degraded, and 5-FU was completely eliminated by irradiation by Hg lamp and partially with Xe lamp. 5-FU was only little mineralized by Hg-lamp photolysis. According to the CBT results, not one of the compounds is readily biodegradable. UV photolysis improved the biodegradability and reduced the toxicity of 5-FU. Xe-photolysis did neither change biodegradability nor toxicity. Abstract : Our study showed that the combination of suitable experimental and in silico tools can give valuable insights regarding the environmental risks that anticancer drugs and TPs can pose.