Auflistung nach Autor:in "Schütze, Andre"

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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
DPHP metabolites in urine samples of the German Environmental Specimen Bank from 1999 to 2012
(2014) Schütze, Andre; Gries, Wolfgang; Kolossa-Gehring, Marike; Apel, Petra; Schröter-Kermani, Christa; Brühning, Thomas; Leng, Gabriele; Koch, Holger Martin
The aim of this study was to investigate a possible time trend and status quo of
dipropylheptylphthalate (DPHP) exposure. DPHP is used as a substitute of other high molecular weightphthalates in high temperature applications (e.g cable wires, roofing membranes, etc.). DPHP was selected inthe cooperation project between the German Federal Ministry for Environment (BMU) and the German ChemicalIndustry Association (VCI) due to its listing as High Production Volume (HPV) chemical in the European Union.The BMU-VCI project establishes new human biomonitoring methods and biomarkers for fifty emergingsubstances. 300 urine samples (24-hour voids) from the German Environmental Specimen Bank were analyzedfor three specific, secondary oxidized DPHP metabolites (with hydroxyl, oxo and carboxy modifications of thealkyl side chain). Urine samples were collected in the years 1999, 2003, 2006, 2009 and 2012, 60 samples peryear, from 30 male and 30 female volunteers (age: 21-29 years). The samples were analyzed by liquid/liquidextraction followed by GC-HRMS, which enabled us to distinguish between DPHP and Di-iso-decyl phthalate(DiDP) metabolites. The limit of quantification was between 0.15 ìg/l and 0.3 ìg/l, depending on the metabolite.All samples were blinded before analysis. DPHP metabolites were not detected in the years 1999-2006.Thereafter, detection rates increased from 3.3% in 2009 to 21.7% in 2012. As expected, mono-oxo-propylheptylphthalate (oxo-MPHP) was the most abundant metabolite, with concentrations between Quelle: 24th Annual Meeting ofThe International Society of Exposure Science: Exposure Science Integration to Protect Ecological Systems,Human Well-Being, and Occupational Health; Abstrct Book ISES 2014 / International Society of Exposure Science, Cincinnati: 2014, S.128
New biomarkers of exposure for alternative plasticisers and sunscreens
(2015) Koch, Holger M.; Schütze, Andre; Leibold, Edgar; Otter, Rainer; Kolossa-Gehring, Marike; Brüning, Thomas
Hexamoll DINCH was one of the first substances selected in the BMUB-VCI cooperation project on human biomonitoring. DINCH, a "non-phthalateŁ and "non-aromaticŁ plasticizer intended to replace critical phthalates in sensitive applications has been introduced in the European market in 2002. We investigated human metabolism after oral dosage, identified specific urinary metabolites as biomarkers of exposure, and applied the new analytical method to sensitively determine these metabolites in urine samples annually collected by the German Environmental Specimen Bank. We observed the onset of exposure in 2006 (7% of the samples >LOQ) with steadily increasing metabolite levels and 98% of the samples >LOQ in 2012. Based upon metabolism/elimination and a TDI of 1 mg/kg/day, the German Human Biomionitoring Commission derived HBM values (similar to biomonitoring equivalents, BE) of 3 mg/L (sum OH- and cx-MINCH) for children and 4.5 mg/L for adults. Current 95th percentiles of urinary levels are approx. 1000-fold below these HBM values. DINCH biomonitoring is included in the ongoing German Environmental Survey (GerES5) enabling us to closely follow DINCH exposures and propose measures for reduction of exposure, if warranted. DEHTP (tere-phthalate) and DEHA/DINA (adipates) have also gained increasing importance as a phthalate substitutes and consequently been included in the BMUB-VCI project. We have already identified valuable biomarkers for DEHTP exposure. In recently collected urine samples, we could detect these DEHTP metabolites in 100% of the samples. For DEHTP and the adipates similar steps and measures are currently on the way, as described above for DINCH. As an additional substance class of interest, sunscreen agents have recently been included in the BMUB-VCI cooperation project.
Quelle: http://www.ises2015.org/
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.
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