Zitieren Sie bitte immer diesen URN: urn:nbn:de:kobv:b43-386016
Instrumental analysis, metabolism and toxicity of cis- and trans-zearalenone and their biotransformation products
- Trans-Zearalenone(ZEN)is a non-steroidal estrogenic mycotoxin which frequently contaminates cereal grains worldwide. Ingestion of food and feed containing ZEN causes numerous mycotoxicoses in animals and possibly humans with pronounced estrogenic effects. Due to the trans-configurated double bond, ZEN isomerizes to the cis-configuration upon the influence of light. This work investigates the instrumental analysis, metabolism and toxicity of ZEN and cis- ZEN. The first part focused on the determination of ZEN in edible oils. Due to a maximum level of 400 µg/kg ZEN in the European Union (EU), reliable analytical methods are needed. A comprehensive method comparison proved dynamic covalent hydrazine chemistry (DCHC) to be the most suitable approach. Thus, an automated solid phase extraction (SPE) coupled online to high performance liquid chromatography (HPLC) was developed with the novelty of a covalent SPE step comprising the DCHC principle. The automated online system allows anTrans-Zearalenone(ZEN)is a non-steroidal estrogenic mycotoxin which frequently contaminates cereal grains worldwide. Ingestion of food and feed containing ZEN causes numerous mycotoxicoses in animals and possibly humans with pronounced estrogenic effects. Due to the trans-configurated double bond, ZEN isomerizes to the cis-configuration upon the influence of light. This work investigates the instrumental analysis, metabolism and toxicity of ZEN and cis- ZEN. The first part focused on the determination of ZEN in edible oils. Due to a maximum level of 400 µg/kg ZEN in the European Union (EU), reliable analytical methods are needed. A comprehensive method comparison proved dynamic covalent hydrazine chemistry (DCHC) to be the most suitable approach. Thus, an automated solid phase extraction (SPE) coupled online to high performance liquid chromatography (HPLC) was developed with the novelty of a covalent SPE step comprising the DCHC principle. The automated online system allows an accurate, selective and reliable quantification of ZEN in edible oils in compliance with EU performance criteria while significantly reducing workload and thereby personnel costs. In contrast to ZEN, reference standards and analytical methods are missing for cis- ZEN which causes a lack of data on the occurrence, fate and risks of cis-ZEN. Therefore, a native and an isotopically labeled cis-ZEN standard were synthesized and implemented in an existing stable isotope dilution analysis HPLC tandem mass spectrometry (HPLC-MS/MS) method. Using this method, a large extent of cis-ZEN formation was observed for ZEN contaminated maize germ oils when exposed to daylight which confirms that cis-ZEN can be a relevant food contaminant and should be considered in the analysis of food and feed. Furthermore, this work investigated the in vitro phase I metabolism of ZEN and cis-ZEN in rat and human liver microsomes by using HPLC-MS and -MS/MS analyses. The metabolic pathways of cis-ZEN were found to be essentially similar to ZEN including reduction and oxidation reactions generating α- and β-cis- zearalenol as well as 13- and 15-OH-cis-ZEN. A previously unidentified oxidative metabolic pathway for both isomers of ZEN results in the formation of cis-ZEN-11,12-oxide and ZEN-11,12-oxide in human liver microsomes. The estrogenicity of cis-ZEN and its reductive metabolites was assessed using the E-Screen assay. cis-ZEN proved to be slightly more estrogenic than ZEN. Biotransformation of cis-ZEN to β-cis-ZEL corresponds to a detoxification, whereas metabolism to α-cis-ZEL resembles a metabolic activation as its estrogenicity considerably exceeds that of cis-ZEN. The catecholic metabolites can be expected to show a decreased estrogenicity as demonstrated for 15-OH- ZEN. Independent of the estrogenic effects, the catecholic and epoxidic metabolites identified in this work can be expected to act genotoxic and carcinogenic. The epoxides in particular could fundamentally change the widely accepted view of ZEN causing adverse effects exclusively through endocrine disrupting actions.…
Autor*innen: | Sarah Drzymala |
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Dokumenttyp: | Dissertation |
Veröffentlichungsform: | Eigenverlag BAM |
Schriftenreihe (Bandnummer): | BAM Dissertationsreihe (152) |
Sprache: | Englisch |
Jahr der Erstveröffentlichung: | 2016 |
Veröffentlichende Institution: | Bundesanstalt für Materialforschung und -prüfung (BAM) |
Titel verleihende Institution: | Technische Universität Berlin, Fakultät III − Prozesswissenschaften |
Gutachter*innen: | Juri Rappsilber, Leif-Alexander Garbe, Matthias KochORCiD, Roland Lauster |
Datum der Abschlussprüfung: | 10.07.2015 |
Verlag: | Bundesanstalt für Materialforschung und -prüfung (BAM) |
Verlagsort: | Berlin |
Jahrgang/Band: | 152 |
Erste Seite: | 1 |
Letzte Seite: | 160 |
DDC-Klassifikation: | Naturwissenschaften und Mathematik / Chemie / Analytische Chemie |
Technik, Medizin, angewandte Wissenschaften / Ingenieurwissenschaften / Ingenieurwissenschaften und zugeordnete Tätigkeiten | |
Technik, Medizin, angewandte Wissenschaften / Ingenieurwissenschaften / Angewandte Physik | |
Technik, Medizin, angewandte Wissenschaften / Ingenieurwissenschaften / Ingenieurbau | |
Technik, Medizin, angewandte Wissenschaften / Ingenieurwissenschaften / Sanitär- und Kommunaltechnik; Umwelttechnik | |
Freie Schlagwörter: | Hydrazinchemie; Isomerisierung; Isotopenstandard; SPE-HPLC Automatisierung Zearalenon |
URN: | urn:nbn:de:kobv:b43-386016 |
ISSN: | 1613-4249 |
ISBN: | 978-3-9817853-9-5 |
Verfügbarkeit des Dokuments: | Datei für die Öffentlichkeit verfügbar ("Open Access") |
Lizenz (Deutsch): | Creative Commons - Namensnennung-Nicht kommerziell-Keine Bearbeitung |
Datum der Freischaltung: | 08.12.2016 |
Referierte Publikation: | Nein |