Person: Kolossa-Gehring, Marike
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Kolossa-Gehring
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Marike
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Veröffentlichung N-methylmalonamic acid (NMMA) as metabolite of methylisothiazolinone and methylchloroisothiazolinone in 24-h urine samples of the German Environmental Specimen Bank from 2000 to 2017(2020) Schettgen, Thomas; Kolossa-Gehring, Marike; Rüther, Maria; Weber, TillMethylisothiazolinone (MI) and the mixture of methylchloroisothiazolinone/methylisothiazolinone (MCI/MI, 3:1) are widespread biocides used in cosmetics, household products, paints or as disinfectant in air-conditioning systems. Exposure to these compounds has raised concerns due to their sensitizing potential, as rates of skin sensitization were reported to increase in the last decade. We have analyzed N-methylmalonamic acid (NMMA), a common metabolite of MI and MCI in 24-h urine samples of the German Environmental Specimen Bank collected from 480 participants (240 male/240 female) between the years 2000 and 2017. Using these data, we were able to calculate the overall daily intake of MI and/or MCI/MI (3:1) of the study participants and point out time trends. NMMA was determined in all urine samples investigated above the LOQ of 0.5 (my)g/L urine. Median and 95th percentile level of NMMA in all 24-h urine samples was 4.1 (my)g/g creatinine and 8.5 (my)g/g creatinine, respectively. This would correspond to a median and 95th percentile daily intake of 0.35 (my)g/kg bw and 0.71 (my)g/kg bw for exclusive uptake of MI and 0.64 (my)g/kg bw and 1.28 (my)g/kg bw for exclusive uptake of MCI/MI (3:1). We noted only slight variations over time for median exposures, but an increasing time trend in the 95th percentile exposure between 2006 and 2011 with a decrease in recent years, probably reflecting regulatory measures on MI and MCI/MI (3:1) in cosmetic products. Increasing knowledge on determinants of exposure to MI and/or MCI/MI (3:1) would be necessary to further lower exposure to these sensitizing compounds. © 2019 Elsevier Ltd. All rights reserved.Veröffentlichung Trends of exposure to acrylamide as measured by urinary biomarkers levels within the HBM4EU Biomonitoring Aligned Studies (2000-2021)(2022) Poteser, Michael; Kolossa-Gehring, Marike; Laguzzi, Federica; Schettgen, Thomas; Murawski, Aline; Rüther, Maria; Schmidt, Phillipp; Vogel, Nina; Weber, TillAcrylamide, a substance potentially carcinogenic in humans, represents a very prevalent contaminant in food and is also contained in tobacco smoke. Occupational exposure to higher concentrations of acrylamide was shown to induce neurotoxicity in humans. To minimize related risks for public health, it is vital to obtain data on the actual level of exposure in differently affected segments of the population. To achieve this aim, acrylamide has been added to the list of substances of concern to be investigated in the HBM4EU project, a European initiative to obtain biomonitoring data for a number of pollutants highly relevant for public health. This report summarizes the results obtained for acrylamide, with a focus on time-trends and recent exposure levels, obtained by HBM4EU as well as by associated studies in a total of seven European countries. Mean biomarker levels were compared by sampling year and time-trends were analyzed using linear regression models and an adequate statistical test. An increasing trend of acrylamide biomarker concentrations was found in children for the years 2014-2017, while in adults an overall increase in exposure was found to be not significant for the time period of observation (2000-2021). For smokers, represented by two studies and sampling for, over a total three years, no clear tendency was observed. In conclusion, samples from European countries indicate that average acrylamide exposure still exceeds suggested benchmark levels and may be of specific concern in children. More research is required to confirm trends of declining values observed in most recent years. © 2022 by the authorsVeröffentlichung Time trends of acrylamide exposure in Europe: combined analysis of published reports and current HBM4EU Studies(2022) Poteser, Michael; Hahn, Domenica; Laguzzi, Federica; Kolossa-Gehring, Marike; Schettgen, Thomas; Vogel, Nina; Weber, Till; Zimmermann, PhilippMore than 20 years ago, acrylamide was added to the list of potential carcinogens found in many common dietary products and tobacco smoke. Consequently, human biomonitoring studies investigating exposure to acrylamide in the form of adducts in blood and metabolites in urine have been performed to obtain data on the actual burden in different populations of the world and in Europe. Recognizing the related health risk, the European Commission responded with measures to curb the acrylamide content in food products. In 2017, a trans-European human biomonitoring project (HBM4EU) was started with the aim to investigate exposure to several chemicals, including acrylamide. Here we set out to provide a combined analysis of previous and current European acrylamide biomonitoring study results by harmonizing and integrating different data sources, including HBM4EU aligned studies, with the aim to resolve overall and current time trends of acrylamide exposure in Europe. Data from 10 European countries were included in the analysis, comprising more than 5500 individual samples (3214 children and teenagers, 2293 adults). We utilized linear models as well as a non-linear fit and breakpoint analysis to investigate trends in temporal acrylamide exposure as well as descriptive statistics and statistical tests to validate findings. Our results indicate an overall increase in acrylamide exposure between the years 2001 and 2017. Studies with samples collected after 2018 focusing on adults do not indicate increasing exposure but show declining values. Regional differences appear to affect absolute values, but not the overall time-trend of exposure. As benchmark levels for acrylamide content in food have been adopted in Europe in 2018, our results may imply the effects of these measures, but only indicated for adults, as corresponding data are still missing for children. © 2022 by the authorsVeröffentlichung Quantification of a mercapturate metabolite of the biocides methylisothiazolinone and chloromethylisothiazolinone ("M-12") in human urine using online-SPE-LC/MS/MS(2021) Schettgen, Thomas; Bertram, Jens; Kolossa-Gehring, Marike; Weber, TillMethylisothiazolinone and the reaction mixture of chloromethylisothiazolinone/methylisothiazolinone (MCI/MI, 3:1) are broadly used biocides that are contained in many products of everyday life (e.g. cosmetics, wet wipes, etc.). As MI and MCI are able to sensitize (and penetrate) the skin, their application in cosmetic products is of concern. In previous work, we have revealed a background exposure of the general population to MI and/or MCI/MI (3:1) by the determination of urinary N-methylmalonamic acid (NMMA) as the main human metabolite. To corroborate these findings, we have now developed a two-dimensional LC/MS/MS method for the quantification of a mercapturic acid metabolite of MI and MCI ((acetylamino){[3-(methylamino)-1-(methylthio)-3-oxopropyl]thio}acetic acid or shortly "M-12") in human urine. This analyte is enriched online using a Strata-X-column and stripped from the urinary matrix. Then, the analyte is back flushed to the analytical column (Phenomenex C18(2), 150 * 4.6 mm) and finally quantified by tandem mass spectrometry with the use of isotopically labelled M-12 as the internal standard. The LOQ for M-12 was 0.2 ng mL-1 urine and sufficient to quantify urinary background levels. Precision within and between series for M-12 in urine at concentrations varying from 0.2 to 5 ng mL-1 ranged from 2.1 to 23.9% and accuracy ranged from 86.3 to 101.8%. Mean accuracy for M-12 in individual urine samples was 94.3% (range: 89.7-102.9%). We applied this method to previously collected 24 h urine samples of 60 persons with no specific exposure to MI and/or MCI/MI (3:1). The metabolite M-12 could be quantified in each urine sample. The median and 95th percentile levels for urinary M-12 were determined to be 0.62 and 2.26 ng mL-1, respectively. In these urine samples, the concentrations of the previously determined metabolite NMMA and M-12 correlated well. In the future, we will apply this method to urine samples of a previously conducted human exposure study to explore the additional value of M-12 as a biomarker of exposure to MI and MCI. Quelle: https://pubs.rsc.org