Listen
3 Ergebnisse
Suchergebnisse
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 MartinWe 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.comVeröffentlichung Metabolites of the alkyl pyrrolidone solvents NMP and NEP in 24-h urine samples of the German Environmental Specimen Bank from 1991 to 2014(2018) Ulrich, Nadin; Bury, Daniel; Koch, Holger Martin; Kolossa-Gehring, Marike; Rüther, Maria; Weber, TillPurpose The aim of this study was to get a first overview of the exposure to the solvents and reproductive toxicants N-methyl-2-pyrrolidone (NMP) and N-ethyl-2-pyrrolidone (NEP) in Germany. NMP and NEP metabolite concentrations were determined in 540 24-h urine samples of the German Environmental Specimen Bank collected from 1991 to 2014. With these data we were able to investigate NMP/NEP exposures over time and to evaluate associated risks. Methods NMP metabolites 5-hydroxy-N-methyl-2-pyrrolidone (5-HNMP) and 2-hydroxy-N-methylsuccinimide (2-HMSI) and NEP metabolites 5-hydroxy-N-ethyl-2-pyrrolidone (5-HNEP) and 2-hydroxy-N-ethylsuccinimide (2-HESI) were determined by stable isotope dilution analysis using solid phase extraction followed by derivatization (silylation) and GCâ€ÌEIâ€ÌMS/MS. Results We were able to quantify 5-HNMP and 2-HMSI in 98.0 and 99.6% and 5-HNEP and 2-HESI in 34.8 and 75.7% of the samples. Metabolite concentrations were rather steady over the timeframe investigated, even for NEP which has been introduced as an NMP substitute only in the last decade. Calculated median daily intakes in 2014 were 2.7 Ìg/kg bw/day for NMP and 1.1 Ìg/kg bw/day for NEP. For the combined risk assessment of NMP and NEP exposure, the hazard index based on the human biomonitoring assessment I values (HBM I values) was less than 0.1. Conclusions Based on the investigated subpopulation of the German population, individual and combined NMP and NEP exposures were within acceptable ranges in the investigated timeframe. Sources of NEP exposure in the 90s and 00s remain elusive. © Springer-Verlag GmbH Germany, part of Springer Nature 2018Veröffentlichung A human biomonitoring study assessing glyphosate and Aminomethylphosphonic Acid (AMPA) exposures among farm and non-farm families(2022) Connolly, Alison; Koch, Holger Martin; Bury, Daniel; Conrad, André; Kolossa-Gehring, Marike; Murawski, AlineGlyphosate-based pesticides are the highest-volume used herbicides worldwide. International concerns regarding the potential human adverse effects of glyphosate exposures have heightened since IARC classified glyphosate as probably carcinogenic to humans. Human biomonitoring (HBM) studies have identified ubiquitous exposure to glyphosate and its main breakdown product, aminomethylphosphonic acid (AMPA), from environmental exposures. The IMAGE research project aimed to investigate farm and non-farm families' exposure to glyphosate while aligning with the Human Biomonitoring for Europe (HBM4EU) initiative. The study recruited non-farm and farm families (who use glyphosate on their farms). Each family member provided a urine sample that was analysed using gas chromatography coupled with tandem mass spectrometry, with a limit of quantification of 0.05 (micro)g/L for glyphosate and AMPA. In addition to general information on background exposures in farm and non-farm families, we investigated relationships in exposure between families and family members. We recruited 68 families, including 54 non-farm and 14 farm families (180 vs. 45 individuals). Some pesticide users (n = 14, all male farmers) had slightly elevated AMPA levels compared to other adult participants but, overall, we observed no significant differences between farm and non-farm families. The main metabolite, AMPA, was quantifiable in twice as many samples as glyphosate (61% vs. 32%), with a maximum concentration of 7.24 (micro)g/L vs. 3.21 (micro)g/L. Compared to previous studies, exposure levels were relatively low and far below current health-based guidance values (3% or less for glyphosate and AMPA). Study results suggest potential exposures from residential co-exposures or living with a pesticide user. This is the first study internationally to investigate glyphosate and AMPA across family members (farm and non-farm). We found comparably low glyphosate and AMPA exposures among these families. These results enhance our understanding of glyphosate exposures for different demographic groups and contribute to the scientific knowledge on exposures required for regulatory risk assessments and the re-evaluation of glyphosate in 2022 by the European Commission. © 2022 by the authors