TY - JOUR A1 - Kittler, Katrin A1 - Hurtaud-Pessel, D. A1 - Maul, Ronald A1 - Kolrep, F. A1 - Fessard, V. T1 - In vitro metabolism of the cyanotoxin cylindrospermopsin in HepaRG cells and liver tissue fractions N2 - No evidence for phase I metabolites of the cyanotoxin cylindrospermopsin (CYN) was given using HepaRG cells and different liver tissue fractions when studying metabolic conversion. Although the application of ketoconazole, a CYP3A4 inhibitor, led to a decreased cytotoxicity of CYN, no metabolites were detected applying high resolution mass spectrometry. Quantification of non-modified CYN led to recovery rates of almost 100%. Consequently, reduction of CYN toxicity in the presence of metabolism inhibiting agents must be attributed to alternative pathways. KW - Cylindrospermopsin KW - Metabolism KW - Liver tissue fractions KW - HepaRG cells KW - LC-HRMS KW - Quantification KW - Cyanotoxin PY - 2016 DO - https://doi.org/10.1016/j.toxicon.2015.11.007 SN - 0041-0101 SN - 1879-3150 VL - 110 SP - 47 EP - 50 PB - Elsevier CY - Oxford [u.a.] AN - OPUS4-35222 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Kittler, Katrin A1 - Fessard, V. A1 - Maul, Ronald A1 - Hurtaud-Pessel, D. T1 - CYP3A4 activity reduces the cytotoxic effects of okadaic acid in HepaRG cells N2 - The biotoxin okadaic acid (OA), produced by dinoflagellates in marine environment, can accumulate in sponges and shellfish. Consumption of contaminated shellfish induces acute toxic effects such as diarrhea, nausea, vomiting, and abdominal pain. CYP3A4, one of the most important human xenobiotic metabolizing enzymes, is supposed to be involved in the metabolism of OA. Aim of our study was to evaluate the role of CYP3A4 in OA in vitro metabolism as well as in cell cytotoxicity in parallel. Therefore, a metabolic competent HepaRG cell line was exposed to OA with and without addition of the CYP3A4 inhibitor ketoconazole. Without the inhibitor, two mono-hydroxylated metabolites could be identified, whereas in its presence, no metabolites could be detected. Confirmation of the formed metabolites was accomplished by measuring the exact masses and investigating the fragmentation pattern. Data obtained from cytotoxicity assays showed that OA cytotoxicity is reduced when CYP3A4 is active. Thus, hydroxylation appears to be a crucial step for metabolic OA detoxification. KW - Okadaic acid KW - Cytochrome P-450 KW - Hydroxylation KW - Stability KW - Detoxification KW - Phase I metabolism PY - 2014 DO - https://doi.org/10.1007/s00204-014-1206-x SN - 0340-5761 SN - 1432-0738 VL - 88 IS - 8 SP - 1519 EP - 1526 PB - Springer CY - Berlin ; Heidelberg [u.a.] AN - OPUS4-31567 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Maul, Ronald A1 - Schwake-Anduschus, C. T1 - Darstellung des Verteilungsprofils von Fusarientoxinen im Weizenkorn T2 - 65. Tagung für Müllerei-Technologie CY - Detmold DA - 2014-09-09 PY - 2014 AN - OPUS4-32438 LA - deu AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Esslinger, Susanne A1 - Becker, Roland A1 - Maul, Ronald A1 - Nehls, Irene T1 - Hexabromcyclododecan - Untersuchungen zum Phase I Metabolismus PY - 2010 SN - 0934-3504 SN - 1865-5084 VL - 22 IS - 4 SP - 364 PB - Springer CY - Heidelberg AN - OPUS4-22907 LA - deu AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Maul, Ronald T1 - Target-Analytik mittels LC-MS/MS als Königsweg in der (Myko-)Toxinanalytik? T2 - Lebensmittelchemisches Seminar, Universität Hamburg, Institut für Lebensmittelchemie CY - Hamburg, Germany DA - 2010-11-26 PY - 2010 AN - OPUS4-22372 LA - deu AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Esslinger, Susanne A1 - Becker, Roland A1 - Maul, Ronald A1 - Nehls, Irene T1 - Hexabromocyclododecane enantiomers: microsomal degradation and patterns of hydroxylated metabolites N2 - The degradation of the enantiomers of α-, β-, and γ-hexabromocyclododecane (HBCD) by phase I metabolism was investigated using induced rat liver microsomes. HBCD isomers were quantified using HPLC-MS/MS (ESI-) after separation on a combination of a reversed phase and a chiral analytical column. The degradation of all six isomers followed first-order kinetics and the estimated half-lives ranged from 6.3 min for both β-HBCD enantiomers to 32.3 min in case of (+)-γ-HBCD. (+)-α- and (–)-γ-HBCD displayed significantly shorter half-lives than their corresponding antipodes. It could be shown that this degradation led to a significant enrichment of the first eluting enantiomers (–)-α- and (+)-γ-HBCD. Individual patterns of mono- and dihydroxylated derivatives obtained from each α- and γ-HBCD enantiomer were seen to be distinctly characteristic. The patterns of monohydroxylated HBCD derivatives detected in liver and muscle tissues of pollack, mackerel and in herring gull eggs were largely similar to those observed in the in vitro experiments with rat liver microsomes. This enabled individual hydroxy-HBCDs to be assigned to their respective parent HBCD enantiomers. KW - Brominated flame retardant KW - Cytochromes KW - Phase I metabolism KW - Hydroxylation KW - HPLC-MS/MS PY - 2011 DO - https://doi.org/10.1021/es1039584 SN - 0013-936X SN - 1520-5851 VL - 45 IS - 9 SP - 3938 EP - 3944 PB - ACS Publ. CY - Washington, DC AN - OPUS4-23837 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Dahmen-Levison, U. A1 - Maul, Ronald T1 - Mykotoxin-Bestimmung - jetzt auch vollautomatisch N2 - Überall, wo sich Schimmel bildet, können hochgiftige Mykotoxine entstehen, besorgniserregende Gifte für Mensch und Tier. Ungefähr ein Viertel der Weltnahrungsproduktion ist mit diesen schädlichen Stoffen infizier!, so die Ernährung- und Landwirtschaftsorganisation FAQ. Lebensmittel wie Getreide, Mais und Nüsse, die in grollen Mengen verarbeitet werden, sind ein idealer Nährboden für die Bildung von Mykotoxinen und können bereits vor der eigentlichen Verarbeitung kontaminiert sein. Eine Kontrolle der Lebensmittellieferungen ist also aus Sicherheitsgründen unerlässlich, denn schon geringe Mengen infizierter Lebensmittel können ganze Bestände vergiften. Aufwendige Laborverfahren, die extern von geschultem Fachpersonal durchgeführt werden und daher mehrere Tage dauern, bedeuten hohe Kosten für die verarbeitende Industrie. Die Aokin AG aus Berlin hat mit der Automatisierung des „aokinmycontrol-Systems den Analyseprozess industrietauglich gemacht. PY - 2011 SN - 0027-2949 VL - 148 IS - 12 SP - 386 EP - 390 PB - Schäfer CY - Detmold AN - OPUS4-25734 LA - deu AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Maul, Ronald T1 - Metabolic investigations, biomarker identification and impact on toxin risk assessment T2 - Institutsseminar am Analytikzentrum des Departments IFA-Tulln CY - Tulln an der Donau, Austria DA - 2012-06-05 PY - 2012 AN - OPUS4-26044 LA - deu AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Maul, Ronald A1 - Schwake-Anduschus, C. T1 - Minimisation of Fusarium Toxins Deoxynivalenol and Zearalenone after Harvest T2 - 4th MoniQA International Conference CY - Budapest, Hungary DA - 2013-02-26 PY - 2013 AN - OPUS4-27837 LA - deu AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Maul, Ronald T1 - Maskierte Mykotoxine - Relevanz in Lebens- und Futtermitteln T2 - BfR-Seminar CY - Berlin, Germany DA - 2013-06-05 PY - 2013 AN - OPUS4-28709 LA - deu AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER -