title: Degradation of cyclophosphamide and 5-fluorouracil by UV and simulated sunlight treatments: Assessment of the enhancement of the biodegradability and toxicity.
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.
authors.affiliation: Sustainable Chemistry and Material Resources, Institute of Sustainable and Environmental Chemistry, Faculty of Sustainability, Leuphana University of Lüneburg, Scharnhorststraße 1/C13, DE-21335 Lüneburg, Germany; Graduate Program in Environmental Technology, Universidade de Santa Cruz do Sul - UNISC, Av. Independência, 2293, CEP 96815-900, Santa Cruz do Sul, Rio Grande do Sul, Brazil. Electronic address: lutterbeck@leuphana.de.
authors.forename: Carlos Alexandre
authors.initials: CA
authors.lastname: Lutterbeck
authors.affiliation: Sustainable Chemistry and Material Resources, Institute of Sustainable and Environmental Chemistry, Faculty of Sustainability, Leuphana University of Lüneburg, Scharnhorststraße 1/C13, DE-21335 Lüneburg, Germany. Electronic address: wilde@leuphana.de.
authors.forename: Marcelo Luís
authors.initials: ML
authors.lastname: Wilde
authors.affiliation: Sustainable Chemistry and Material Resources, Institute of Sustainable and Environmental Chemistry, Faculty of Sustainability, Leuphana University of Lüneburg, Scharnhorststraße 1/C13, DE-21335 Lüneburg, Germany. Electronic address: ewelina.baginska@leuphana.de.
authors.forename: Ewelina
authors.initials: E
authors.lastname: Baginska
authors.affiliation: Sustainable Chemistry and Material Resources, Institute of Sustainable and Environmental Chemistry, Faculty of Sustainability, Leuphana University of Lüneburg, Scharnhorststraße 1/C13, DE-21335 Lüneburg, Germany. Electronic address: cleder@leuphana.de.
authors.forename: Christoph
authors.initials: C
authors.lastname: Leder
authors.affiliation: Graduate Program in Environmental Technology, Universidade de Santa Cruz do Sul - UNISC, Av. Independência, 2293, CEP 96815-900, Santa Cruz do Sul, Rio Grande do Sul, Brazil. Electronic address: enio@unisc.br.
authors.forename: Ênio Leandro
authors.initials: ÊL
authors.lastname: Machado
authors.affiliation: Sustainable Chemistry and Material Resources, Institute of Sustainable and Environmental Chemistry, Faculty of Sustainability, Leuphana University of Lüneburg, Scharnhorststraße 1/C13, DE-21335 Lüneburg, Germany. Electronic address: klaus.kuemmerer@uni.leuphana.de.
authors.forename: Klaus
authors.initials: K
authors.lastname: Kümmerer
mesh_terms: D048908:Aliivibrio fischeri / Q000187:drug effects / Q000378:metabolism; D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism / Q000528:radiation effects / Q000633:toxicity; D001673:Biodegradation, Environmental; D002853:Chromatography, Liquid; D003520:Cyclophosphamide / Q000737:chemistry / Q000378:metabolism / Q000528:radiation effects / Q000633:toxicity; D005472:Fluorouracil / Q000737:chemistry / Q000378:metabolism / Q000528:radiation effects / Q000633:toxicity; D007166:Immunosuppressive Agents / Q000737:chemistry / Q000378:metabolism / Q000528:radiation effects / Q000633:toxicity; D010782:Photolysis; D021281:Quantitative Structure-Activity Relationship; D013472:Sunlight; D053719:Tandem Mass Spectrometry
chemical_list: D000970:Antineoplastic Agents; D007166:Immunosuppressive Agents; D003520:Cyclophosphamide; D005472:Fluorouracil
keywords: 5-Fluorouracil; Biodegradation; Cyclophosphamide; Photodegradation; Toxicity