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  • Veröffentlichung
    Einflüsse aus der Umwelt auf Kinder
    (2014) Kolossa-Gehring, Marike
  • Veröffentlichung
    Development of a multi-compartment pharmacokinetic model to characterize the exposure to Hexamoll® DINCH®
    (2015) Schütze, Andre; Apel, Petra; Lorber, Matthew; Gawrych, Katarzyna; Kolossa-Gehring, Marike; Brüning, Thomas; Koch, Holger Martin
    We developed and calibrated a multi compartment pharmacokinetic (PK) model to predict urinary concentrations after oral exposure of four specific DINCH metabolites: MINCH, OH-MINCH, cx-MINCH, and oxo-MINCH. This descriptive model has 4 compartments: a "stomachŁ (SC) compartment, a "holdingŁ (HC) compartment, a "bloodŁ (BC) compartment and a "bladderŁ (BLC) compartment. DINCH is assumed to first deposit into the SC, with transfer split between the HC and the BC. Unmetabolized DINCH from the HC then transfers to the BC. The DINCH metabolism is assumed to occur in the BC before excretion via the BLC. At each urination event, all the metabolite mass in the BLC is excreted. The model was calibrated using published urine metabolite data from 3 different male volunteers, each orally dosed with 50 mg DINCH. Full urine voids were taken for 48 h after dosage. The predicted values showed a good agreement with the observed urinary DINCH metabolite concentrations, with a Spearman correlation coefficient exceeding 0.7 for all oxidized metabolites. We showed the importance of a holding reservoir. Without it, a good agreement could not be found. We applied the model to a set of 24-h general population samples measured for DINCH metabolites. The model was unable to duplicate the ratio of metabolites seen in the 24-h samples. Two possibilities were offered to explain the difference: the exposure pattern in the general population did not match the oral exposure in the dosing experiments, or the long-term toxicokinetics of DINCH was not captured in the 48-h controlled dosing experiments.Quelle: http://www.sciencedirect.com
  • Veröffentlichung
    A pilot study on the feasibility of European harmonized Human Biomonitoring: Strategies towards a common approach, challenges and opportunities
    (2015) Casteleyn, Ludwine; Dumez, Birgit; Becker, Kerstin; Den Hond, Elly; Schoeters, Greet; Castaño, Argelia; Koch, Holger Martin; Angerer, Jürgen; Esteban, Marta; Exley, Karen; Sepai, Ovnair; Bloemen, Louis; Fiddicke, Ulrike; Horvath, Milena; Knudsen, Lisbeth E.; Joas, Anke; Joas, Reinhard; Biot, Pierre; Koppen, C.; Dewolf, M.-C.; Katsonouri, Andromachi; Hadjipanayis, Adamos; Cerna, Milena; Krskova, A.; Kolossa-Gehring, Marike; Nielsen, Jeanette K.S.; Jensen, J.F.; Rudnai, Peter; Közepesy, S.; Mulcahy, M.F.R.; Mannion, R.; Gutleb, Arno C.; Fischer, M.E.; Ligocka, Danuta; Jakubowski, M.; Reis, M.Fátima; Namorado, S.; Lupsa, Ioana-Rodica; Schwedler, Gerda; Gurzau, Anca Elena
    In 2004theEuropeanCommissionandMemberStatesinitiatedactivitiestowardsaharmonizedap-
    proach forHumanBiomonitoringsurveysthroughoutEurope.Themainobjectivewastosustainen-
    vironmental healthpolicybybuildingacoherentandsustainableframeworkandbyincreasingthe
    comparability ofdataacrosscountries.Apilotstudy totestcommonguidelinesforsettingupsurveys
    wasconsideredakeystepinthisprocess.Throughabottom-upapproachthatincludedallstakeholders,
    a jointstudyprotocolwaselaborated.
    FromSeptember2011tillFebruary2012,17Europeancountriescollecteddatafrom1844mother-
    child pairsintheframeofDEMOnstrationofastudytoCoordinateandPerformHumanBiomonitoring
    on aEuropeanScale(DEMOCOPHES). Mercury inhairandurinarycadmiumandcotininewereselected
    as biomarkersofexposurecoveredbysufficient analyticalexperience.PhthalatemetabolitesandBi-
    sphenol Ainurinewereaddedtotakeintoaccountincreasingpublicandpoliticalawarenessfor
    emerging typesofcontaminantsandtotestlessadvancedmarkers/markerscoveredbylessanalytical
    experience.Extensiveeffortstowardschemo-analyticalcomparabilitywereincluded.
    The pilotstudyshowed thatcommonapproachescanbefoundinacontextofconsiderablediffer-
    ences withrespecttoexperienceandexpertize,socio-culturalbackground,economicsituationandna-
    tional priorities.ItalsoevidencedthatcomparableHumanBiomonitoringresultscanbeobtainedinsuch
    context.AEuropeannetworkwasbuilt,exchanging information,expertise andexperiences,andpro-
    viding trainingonallaspectsofasurvey.Akeychallengewas finding therightbalancebetweenarigid
    structure allowingmaximalcomparabilityanda flexibleapproachincreasingfeasibilityandcapacity
    building. NextstepsinEuropeanharmonizationinHumanBiomonitoringsurveysincludetheestab-
    lishment ofajointprocessforprioritizationofsubstancestocoverandbiomarkerstodevelop,linking
    biomonitoring surveyswithhealthexaminationsurveysandwithresearch,andcopingwiththediverse
    implementations ofEUregulationsandinternationalguidelineswithrespecttoethicsandprivacy.
    ©2014ElsevierInc.Allrightsreserved.
  • Veröffentlichung
    Die Umweltprobenbank des Bundes
    (2016) Schröter-Kermani, Christa; Gies, Andreas; Kolossa-Gehring, Marike
    Die Umweltprobenbank des Bundes (UPB) hat das Ziel, biologische Proben aus der Umwelt und vom Menschen über lange Zeit veränderungsfrei zu lagern, um sie für zukünftige Forschung zu archivieren. Sie bietet die einzigartige Möglichkeit, die Belastung der Umwelt und des Menschen über einen langen Zeitraum zu verfolgen. Die UPB wurde parallel zur Erarbeitung des ersten deutschen Chemikaliengesetzes in den 1970er-Jahren konzipiert. Im Jahr 1979 begann sie ihren Probebetrieb. Nachdem 1982 das Chemikaliengesetz in Kraft trat, begann die UPB 1985 ihren dauerhaften Regelbetrieb. Mit der europäischen Chemikalienverordnung REACH wurde 2007 die Verantwortung für die Sicherheit der vermarkteten Chemikalien und die Aufgabe der Risikobewertung maßgeblich der Industrie übertragen. Seitdem ist die UPB noch wichtiger geworden, um die eigenverantwortliche Bewertung der Industrie zu überprüfen, den Erfolg von Minderungsmaßnahmen zu evaluieren und damit letztlich den Schutz von Mensch und Umwelt vor schädlichen Umwelteinflüssen sicherzustellen. Dies geschieht durch regelmäßige Beobachtung der Belastungen und Analyse zeitlicher Trends. Die Ergebnisse der UPB dienen heute der Beratung der politischen Entscheidungsträger über die Notwendigkeit, Maßnahmen zu ergreifen. Informationen zur Belastungsprävention werden für die Allgemeinbevölkerung und den öffentlichen Gesundheitsdienst zur Verfügung gestellt. Die UPB ist somit ein wichtiges Monitoringinstrument des Bundesministeriums für Umwelt, Naturschutz, Bau und Reaktorsicherheit und kooperiert mit namhaften Forschungs- und Universitätsinstituten. Das Umweltbundesamt konzeptioniert und steuert die Arbeit der UPB, leitet die wissenschaftliche Auswertung der Daten und bereitet diese für die Umweltpolitik und die Öffentlichkeit auf.
    Quelle: http://link.springer.com/
  • Veröffentlichung
    Phthalate metabolites in 24-h urine samples of the German Environmental Specimen Bank (ESB) from 1988 to 2015 and a comparison with US NHANES data from 1999 to 2012
    (2017) Koch, Holger M.; Apel, Petra; Schütze, Andre; Conrad, André; Pälmke, Claudia; Kolossa-Gehring, Marike; Brüning, Thomas; Rüther, Maria
    The German Environmental Specimen Bank (ESB) continuously collects 24-h urine samples since theearly 1980s in Germany. In this study we analyzed 300 urine samples from the years 2007 to 2015 for 21phthalate metabolites (representing exposure to 11 parent phthalates) and combined the data with twoprevious retrospective measurement campaigns (1988 to 2003 and 2002 to 2008). The combined datasetcomprised 1162 24-h urine samples spanning the years 1988 to 2015. With this detailed set of humanbiomonitoring data we describe the time course of phthalate exposure in Germany over a time frame of27 years. For the metabolites of the endocrine disrupting phthalates di(2-ethylhexyl) phthalate (DEHP),di-n-butyl phthalate (DnBP) and butylbenzyl phthalate (BBzP) we observed a roughly ten-fold decline inmedian metabolite levels from their peak levels in the late 1980s/early 1990s compared to most recentlevels from 2015. Probably, bans (first enacted in 1999) and classifications/labelings (enacted in 2001 and2004) in the European Union lead to this drop. A decline in di-isobutyl phthalate (DiBP) metabolite levelsset in only quite recently, possibly due to its later classification as a reproductive toxicant in the EU in 2009.In a considerable number of samples collected before 2002 health based guidance values (BE, HBM I) havebeen exceeded for DnBP (27.2%) and DEHP (2.3%) but also in recent samples some individual exceedancescan still be observed (DEHP 1.0%). A decrease in concentration for all low molecular weight phthalates,labelled or not, was seen in the most recent years of sampling. For the high molecular weight phthalates,DEHP seems to have been substituted in part by di-isononyl phthalate (DiNP), but DiNP metabolite levelshave also been declining in the last years. Probably, non-phthalate alternatives increasingly take overfor the phthalates in Germany. A comparison with NHANES (National Health and Nutrition ExaminationSurvey) data from the United States covering the years 1999 to 2012 revealed both similarities anddifferences in phthalate exposure between Germany and the US. Exposure to critical phthalates hasdecreased in both countries with metabolite levels more and more aligning with each other, but highmolecular weight phthalates substituting DEHP (such as DiNP) seem to become more important in theUS than in Germany.
    © 2016 Elsevier GmbH. All rights reserved
  • Veröffentlichung
    Glyphosate in German adults - Time trend (2001 to 2015) of human exposure to a widely used herbicide
    (2017) Conrad, André; Schröter-Kermani, Christa; Hoppe, Hans-Wolfgang; Kolossa-Gehring, Marike; Pieper, Silvia; Rüther, Maria
  • Veröffentlichung
    New human biomonitoring methods for chemicals of concern̶the German approach to enhance relevance
    (2017) Fiddicke, Ulrike; Leng, Gabriele; Kolossa-Gehring, Marike; Angerer, Jürgen; Wolz, Birgit
  • Veröffentlichung
    New specific and sensitive biomonitoring methods for chemicals of emerging health relevance
    (2017) Leng, Gabriele; Fiddicke, Ulrike; Gries, Wolfgang; Kolossa-Gehring, Marike
    In this publication the challenges to cope for the aim to obtain innovative biomonitoring methods in our laboratory are visualized for di(2-propylheptyl)phthalate, 2-mercaptobenzothiazole, 3,5-di-tert-butyl-4-hydroxytoluene, 4-nonylphenol, 4-tert-octylphenol, 3-(4-methylbenzylidene)camphor, 4,4'-methylene diphenyl diisocyanate, and Hexabromocyclododecane. For these substances new specific markers were explored based on animal or human kinetic data with urine being the preferred matrix compared to blood. The determination of these markers was complex in all cases, because the sample preparation as well as the detection by high performance liquid chromatography, capillary gas chromatography coupled to tandem mass spectrometers or high resolution mass spectrometry should enable the lowest possible detection limit by use of minimal biological sample volumes. To get a first hint of a possible background level, the analytical methods were applied to urine samples of about 40 persons for each chemical. For Di(2-propylheptyl)phthalate and 2-Mercaptobenzothiazole first results are presented from population biomonitoring. Quelle: http://www.sciencedirect.com