Auflistung nach Autor:in "Brüning, Thomas"

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Daily intake and hazard index of parabens based upon 24 h urine samples of the German Environmental Specimen Bank from 1995 to 2012
(2016) Moos, Rebecca K.; Apel, Petra; Schröter-Kermani, Christa; Kolossa-Gehring, Marike; Brüning, Thomas; Koch, Holger M.
In recent years, exposure to parabens has become more of a concern because of evidence of ubiquitous exposure in the general population, combined with evidence of their potency as endocrine disruptors. New human metabolism data from oral exposure experiments enable us to back calculate daily paraben intakes from urinary paraben levels. We report daily intakes (DIs) for six parabens based on 660 24h urine samples from the German Environmental Specimen Bank collected between 1995 and 2012. Median DI values ranged between 1.1Ţg/kg bw/day for iso-butyl paraben and 47.5Ţg/kg bw/day for methyl paraben. The calculated DIs were compared with acceptable levels of exposure to evaluate the hazard quotients (HQs) that indicate that acceptable exposure is exceeded for values of >1. Approximately 5% of our study population exceeded this threshold for individual paraben exposure. The hazard index (HI) that takes into account the cumulative risk of adverse estrogenic effects was 1.3 at the 95th percentile and 4.4 at maximum intakes, mainly driven by n-propyl paraben exposure. HI values of >1 indicate some level of concern. However, we have to point out that we applied most conservative assumptions in the HQ/HI calculations. Also, major exposure reduction measures were enacted in the European Union after 2012. Quelle: www.nature.com
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
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/
Parabens and other phenols in urine samples of the German Environmental Specimen Bank (ESBHum) from 1995 to 2012
(2013) Moos, Rebecca K.; Kolossa-Gehring, Marike; Apel, Petra; Angerer, Jürgen; Brüning, Thomas; Koch, Holger M.
Because of the ubiquitous presence and the extensive use of parabensand other phenolic substances (like triclosan, triclocarban or benzophenones) in personal care and consumer products, food and beverage processing, pharmaceuticals and disinfectants humans are constantly exposed to these substances. Some of these substances are suspected to affect the endocrine system of humans. The German Environmental Specimen Bank (ESBHum) - supervised and scientifically coordinated by the German Federal Environment Agency (UBA) - archives human specimens since 1985 and thus allows assessing trends of human exposure. We quantified the body burden to these substances (9 parabens and 6 other phenolic substances) by analyzing 660 urine samples of the ESBHum (24h-urines) from the years 1995, 1997, 1999, 2001, 2003, 2005-2009 and 2012; 60 samples per year, from 30 male and 30 female volunteers (age: 21-29 years). We applied a newly developed highly sensitive on-line HPLC-MS/MS method, for the determination of these substances in urine. Analytical limits of quantification were in the range from 0.5 to 2 Ţg/L. The total concentration of the analytes (free and conjugated species) was measured. All samples were blinded before analysis. In nearly all samples parabens could be quantified.Median concentrations over the different years were around 40 Ţg/L for methyl-, 2 Ţg/L for ethyl- and 5 Ţg/L for n-propyl paraben. For the parabens this mainly reflects their consumption volume being highest for methyl paraben, followed by ethyl-, propyl- and butyl paraben. Triclosan was detected in around 60% of all samples analyzed. Median benzophenone-3 levels fell from around 2.5 Ţg/L (1995-2003) to < LOQ (2005-2012). For all other analytes medians are below the LOQ. Over the years we observed rather constant levels of exposures, except for the decrease in benzophenone-3. This retrospective study provides first data on internal exposures to the above substances in Germany from 1995 till 2012. Quelle: http://ehp.niehs.nih.gov
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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