Environmental Fate of Selected Anticancer Drugs: Photodegradation, Biodegradation and Toxicity of Cyclophosphamide, 5-Fluorouracil, Methotrexate and Imatinib

Umweltverhalten von ausgewählten Medikamenten gegen Krebs: Fotoabbau, Bioabbau und Giftigkeit von Cyclophosphamide, 5-Fluorouracil, Methotrexate and Imatinib

  • In the discourse on pharmaceuticals in the environment, hardly any attention has been paid to anticancer drugs. Because of their none-selective modes of action, that is, because they affect both cancerous and healthy cells, these drugs are regarded as potentially carcinogenic, genotoxic, mutagenic, and teratogenic substances. It is, however, not known how and to what extent these substances affect organisms and the environment in the long run. For this reason, this dissertation evaluated, addressing several endpoints and using organisms from different trophic levels and in silico predictions, the fate (bio- and photo degradation) and ecotoxicity of these substances. Four anticancer drugs (cyclophosphamide (CP), 5-fluorouracil (5-FU), methotrexate (MTX), and imatinib (IM) were selected. None of these anticancer compounds can be classified as ´readily biodegradable,´ a classification that indicates that biodegradation will only play a minor role in the elimination of these compounds and that they cannot be removed by the conventional processes used in sewage treatment plants and will most likely remain in the water cycle. Despite the high degrees of mineralization achieved in advanced (photo)oxidation processes, it was not possible to fully mineralize the compounds, a result that indicates that transformation products were created during these reactions. The ecotoxicity assays performed with V. fischeri indicated that 5-FU was, of all the substances tested, likely to be the most toxic (very toxic), followed by MTX (toxic) and IM (toxic/harmful), whereas CP was nontoxic. MTX presented the highest phytoxicity activity in the Lactuca sativa assay, followed by 5-FU, IM, and CP. The results of the tests performed with A. cepa showed cytotoxic (5-FU, MTX, and CP) and genotoxic effects (5-FU, CP, and IM) and mutagenic activity (5-FU, MTX, CP, and IM) of the compounds. Photo transformation products (PTPs) of CP, MTX, and 5-FU were nontoxic towards V. fischeri. However, some PTPs formed during the photodegradation of 5-FU led to positive mutagenic and genotoxic alerts in several in silico models. Not one of the compounds examined in this dissertation is likely to be fully eliminated from the water cycle by (natural) photolysis and/or advanced oxidation. Moreover, some of the treatments resulted in the formation of stable intermediates that were even less biodegradable than parent compounds. This finding shows that it is not enough to focus on primary elimination because TPs are not necessarily better biodegradable than their respective parent compounds. As indicated by the genotoxic and mutagenic positive alerts presented by different in silico models, the PTPs observed here are likely to require, despite their lower toxicity in comparison to the parent compounds, screening after treatments.
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Author:Carlos Alexandre Lutterbeck
URL: https://pub-data.leuphana.de/frontdoor/index/index/docId/742
Advisor:Klaus Kümmerer (Prof. Dr.)
Document Type:Doctoral Thesis
Year of Completion:2015
Date of Publication (online):2015/12/03
Publishing Institution:Leuphana Universität Lüneburg
Granting Institution:Leuphana Universität Lüneburg, Nachhaltigkeit
Date of final exam:2015/10/22
Release Date:2015/12/03
Tag:Anticancer Drug; Biodegradation; Photodegradation; Toxicity
GND Keyword:Cytostatikum; Biologischer Abbau; Toxizität
Institutes:Fak 3 - Umwelt und Technik (alt) / Chemie
Dewey Decimal Classification:3 Sozialwissenschaften / 33 Wirtschaft / 333.7 Natürliche Ressourcen, Energie und Umwelt