Toxicity assessment of verapamil and its photodegradation products
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RESEARCH ARTICLE
Toxicity assessment of verapamil and its photodegradation products Šárka Klementová 1 & Martina Poncarová 1 & David Kahoun 1 & Michal Šorf 1,2
&
Eliška Dokoupilová 1 & Pavla Fojtíková 1
Received: 29 February 2020 / Accepted: 22 June 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Pathways of photochemical degradation of a cardiovascular drug verapamil under conditions relevant to natural waters and the toxicity of the photoproducts to Daphnia magna were investigated. Photodegradation was shown to proceed via photocatalysed mechanism. Two main photodegradation pathways were recognised: the first leading to hydroxylation at the methylamino position followed by splitting of verapamil molecule into two fragments, and the second providing the main active metabolite of verapamil, norverapamil, and a series of norverapamil isomers, followed again by their splitting at the amino group position. Twenty-two products of photodegradation were identified. Toxicity assays in sublethal concentrations of the parental drug, of the photoproduct mixture, and of norverapamil revealed no direct negative response in Daphnia magna to verapamil. On the other hand, photochemical products significantly lowered the number of juveniles, number of clutches, and body size of Daphnia. The exposition of Daphnia to norverapamil showed the same but even more pronounced effects than its exposition to the mixture of photoproducts, which leads to the conclusion that norverapamil is mainly responsible for the toxicity of photoproduct mixture and represents a noteworthy threat to aquatic invertebrates. Keywords Cardiovascular drugs . Verapamil . Photocatalysed degradation in aqueous solution . Chronic toxicity . Daphnia magna
Introduction The earliest evidence of pharmaceuticals in the aquatic environment was reported in the 1970s; now, a few decades later, pharmacological products are considered as emerging contaminants of great environmental concern (e.g. Fent et al. 2006; Boxall et al. 2012; Bu et al. 2016; Sangion and Gramatica 2016; Biel-Maeso et al. 2018), since they have the potential to have considerable impact on entire ecosystems (e.g. Daughton 2004; Li 2014; Patel et al. 2019). Pharmaceuticals include an enormous group of compounds—more than 3000 frequently used pharmaceuticals are registered in the European Union market alone Responsible editor: Lotfi Aleya * Michal Šorf [email protected] 1
Faculty of Science, University of South Bohemia, Branišovská 1716/31c, 370 05 České Budějovice, Czech Republic
2
Faculty of AgriSciences, Department of Zoology, Fisheries, Hydrobiology and Apiculture, Mendel University in Brno, Zemědělská 1, 613 00 Brno, Czech Republic
(Taylor and Senac 2014). Wastewater treatment plants were designed to handle relatively easily and moderately degradable organics in the mg dm−3 range of concentration; they were not intended to remove micropollutants of very different solubilities, polarities, absorption abilities, and other properties that can be present and activ
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