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Veröffentlichung Exposure to phthalates in European children, adolescents and adults since 2005: a harmonized approach based on existing HBM data in the HBM4EU Initiative(2023) Kolossa-Gehring, Marike; Lange, Rosa; Murawski, Aline; Rüther, Maria; Gerofke, Antje; Schmidt, Phillipp; Springer, Andrea; Vogel, Nina; Weber, TillPhthalates are mainly used as plasticizers and are associated inter alia with adverse effects on reproductive functions. While more and more national programs in Europe have started monitoring internal exposure to phthalates and its substitute 1,2-Cyclohexanedicarboxylic acid (DINCH), the comparability of results from such existing human biomonitoring (HBM) studies across Europe is challenging. They differ widely in time periods, study samples, degree of geographical coverage, design, analytical methodology, biomarker selection, and analytical quality assurance level. The HBM4EU initiative has gathered existing HBM data of 29 studies from participating countries, covering all European regions and Israel. The data were prepared and aggregated by a harmonized procedure with the aim to describe - as comparably as possible - the EU-wide general population's internal exposure to phthalates from the years 2005 to 2019. Most data were available from Northern (up to 6 studies and up to 13 time points), Western (11; 19), and Eastern Europe (9; 12), e.g., allowing for the investigation of time patterns. While the bandwidth of exposure was generally similar, we still observed regional differences for Butyl benzyl phthalate (BBzP), Di(2-ethylhexyl) phthalate (DEHP), Di-isononyl phthalate (DiNP), and Di-isobutyl phthalate (DiBP) with pronounced decreases over time in Northern and Western Europe, and to a lesser degree in Eastern Europe. Differences between age groups were visible for Di-n-butyl phthalate (DnBP), where children (3 to 5-year olds and 6 to 11-year olds) had lower urinary concentrations than adolescents (12 to 19-year-olds), who in turn had lower urinary concentrations than adults (20 to 39-year-olds). This study is a step towards making internal exposures to phthalates comparable across countries, although standardized data were not available, targeting European data sets harmonized with respect to data formatting and calculation of aggregated data (such as developed within HBM4EU), and highlights further suggestions for improved harmonization in future studies. © 2023 by the authorsVeröffentlichung Umweltprobenbank des Bundes(Umweltbundesamt, 2022) Badry, Alexander; Bandow, Nicole; Fettig, Ina; Körner, Andrea; Koschorreck, Jan; Künitzer, Anita; Nagorka, Regine; Rüther, Maria; Weber, Till; Wellmitz, Jörg; Deutschland. UmweltbundesamtDieser Bericht fasst die wesentlichen Arbeiten der Umweltprobenbank des Bundes im Jahr 2020 zusammen. Die Umweltprobenbank des Bundes unterstützt die Umsetzung des Vorsorgeprinzips mit einer wissenschaftlichen Infrastruktur, einer umfassende Datenbasis zur Bestimmung und Bewertung des Ist-Zustandes der Umwelt und einer langfristigen Beobachtung der in der Umwelt stattfindenden chemischen, physikalischen und biologischen Entwicklungsprozesse. Dafür sammeln Fachleute Humanproben ausgewählter Standorte gemeinsam mit ökologisch repräsentativen Umweltproben, archivieren sie bei tiefkalten Temperaturen und führen Untersuchungen auf gesundheits- und umweltrelevante Stoffe durch. Auf diese Weise wird auch eine Kontrolle der Wirksamkeit umweltpolitischer Maßnahmen möglich, beispielsweise bei Beschränkungen der Verwendung von Stoffen. Quelle: www.umweltbundesamt.deVeröffentlichung Die Umweltprobenbank des Bundes - Umwelt- und Humanproben(2020) Kolossa-Gehring, Marike; Körner, Andrea; Koschorreck, Jan; Rüther, Maria; Weber, TillVeröffentlichung Determinants of exposure to acrylamide in European children and adults based on urinary biomarkers: results from the "European Human Biomonitoring Initiative" HBM4EU participating studies(2023) Fernández, Sandra; Poteser, Michael; Govarts, Eva; Kolossa-Gehring, Marike; Murawski, Aline; Rüther, Maria; Schmidt, Phillipp; Vogel, Nina; Weber, TillLittle is known about exposure determinants of acrylamide (AA), a genotoxic food-processing contaminant, in Europe. We assessed determinants of AA exposure, measured by urinary mercapturic acids of AA (AAMA) and glycidamide (GAMA), its main metabolite, in 3157 children/adolescents and 1297 adults in the European Human Biomonitoring Initiative. Harmonized individual-level questionnaires data and quality assured measurements of AAMA and GAMA (urine collection: 2014-2021), the short-term validated biomarkers of AA exposure, were obtained from four studies (Italy, France, Germany, and Norway) in children/adolescents (age range: 3-18 years) and six studies (Portugal, Spain, France, Germany, Luxembourg, and Iceland) in adults (age range: 20-45 years). Multivariable-adjusted pooled quantile regressions were employed to assess median differences ((beta) coefficients) with 95% confidence intervals (95% CI) in AAMA and GAMA ((micro)g/g creatinine) in relation to exposure determinants. Southern European studies had higher AAMA than Northern studies. In children/adolescents, we observed significant lower AA associated with high socioeconomic status (AAMA: (beta) = -9.1 (micro)g/g creatinine, 95% CI -15.8, -2.4; GAMA: (beta) = -3.4 (micro)g/g creatinine, 95% CI-4.7, - 2.2), living in rural areas (AAMA: (beta) = - 4.7 (micro)g/g creatinine, 95% CI - 8.6, - 0.8; GAMA: (beta) = - 1.1 (micro)g/g creatinine, 95% CI -1.9, -0.4) and increasing age (AAMA: (beta)= -1.9 (micro)g/g creatinine, 95% CI -2.4, -1.4; GAMA: (beta) = -0.7 (micro)g/g creatinine, 95% CI -0.8, -0.6). In adults, higher AAMA was also associated with high consumption of fried potatoes whereas lower AAMA was associated with higher body-mass-index. Based on this large-scale study, several potential determinants of AA exposure were identified in children/adolescents and adults in European countries. © The Author(s) 2023Veröffentlichung 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 course of phthalate cumulative risks to male developmental health over a 27-year period: Biomonitoring samples of the German Environmental Specimen Bank(2020) Apel, Petra; Kortenkamp, Andreas; Conrad, André; Koch, Holger Martin; Kolossa-Gehring, Marike; Rüther, MariaIn several human biomonitoring surveys, changes in the usage patterns of phthalates have come to light, but their influence on the risks associated with combined exposures is insufficiently understood. Based on the largest study to date, the 27-year survey of urinary phthalate metabolite levels in 24-hour urine samples from the German Environmental Specimen Bank, we present a deep analysis of changing phthalate exposures on mixture risks. This analysis adopts the Hazard Index (HI) approach based on the five phthalates DBP, DIBP, BBP, DEHP and DINP. Calculations of the hazard index for each study participant included updated phthalate reference doses for anti-androgenicity (RfDAAs) that take account of new evidence of phthalates' developmental toxicity. The Maximum Cumulative Ratio (MCR) approach was used to establish whether a subjectâ€Ìs combined exposure was dominated by one phthalate or was influenced by several phthalates simultaneously. Generally, over the years there was a shift towards lower HIs and higher MCRs, reflecting an increased complexity of the combined exposures. The decade from 1988 to about 1999 was characterised by rather high HIs of between 3 and 7 (95th percentile) which were driven by exposure to DBP and DEHP, often exceeding their single acceptable exposures. Traditional single phthalate risk assessments would have underestimated these risks by up to 50%. From 2006 onwards, no study participant experienced exposures above acceptable levels for a single phthalate, but combined exposures were still in excess of HI = 1. From 2011 onwards most individuals stayed below HI = 1. In interpreting these results, we caution against the use of HI = 1 as an acceptable limit and develop proposals for improved and more realistic mixture risk assessments that take account of co-exposures to other anti-androgenic substances also capable of disrupting the male reproductive system. From this perspective, we regard HIs between 0.1 and 0.2 as more appropriate for evaluating combined phthalate exposures. Assessed against lowered HIs of 0.1 - 0.2, the combined phthalate exposures of most study participants exceeded acceptable levels in all study years, including 2015. Continued monitoring efforts for phthalate combinations are required to provide the basis for appropriate risk management measures. © 2020 The Authors.Veröffentlichung Umweltprobenbank des Bundes(Umweltbundesamt, 2023) Ahting, Maren; Badry, Alexander; Hoffmann, Gabriele; Körner, Andrea; Koschorreck, Jan; Meier, Christiane; Nagorka, Regine; Rüther, Maria; Schmidt, Susanne; Weber, Till; Wellmitz, Jörg; Ziegler, Korinna; Deutschland. UmweltbundesamtDieser Bericht fasst die wesentlichen Arbeiten der Umweltprobenbank des Bundes im Jahr 2021 zusammen. Die Umweltprobenbank des Bundes unterstützt die Umsetzung des Vorsorgeprinzips mit einer wissenschaftlichen Infrastruktur, einer umfassende Datenbasis zur Bestimmung und Bewertung des Ist-Zustandes der Umwelt und einer langfristigen Beobachtung der in der Umwelt stattfindenden chemischen, physikalischen und biologischen Entwicklungsprozesse. Dafür sammeln Fachleute Humanproben ausgewählter Standorte gemeinsam mit ökologisch repräsentativen Umweltproben, archivieren sie bei tiefkalten Temperaturen und führen Untersuchungen auf gesundheits- und umweltrelevante Stoffe durch. Auf diese Weise wird auch eine Kontrolle der Wirksamkeit umweltpolitischer Maßnahmen möglich, beispielsweise bei Beschränkungen der Verwendung von Stoffen. Quelle: www.umweltbundesamt.deVeröffentlichung Harmonized human biomonitoring in European children, teenagers and adults: EU-wide exposure data of 11 chemical substance groups from the HBM4EU Aligned Studies (2014-2021)(2023) Govarts, Eva; Apel, Petra; Gilles, Liese; Rodriguez Martin, Laura; Kolossa-Gehring, Marike; Lange, Rosa; Lemke, Nora; Murawski, Aline; Rüther, Maria; Vogel, Nina; Weber, Till; Zimmermann, PhilippAs one of the core elements of the European Human Biomonitoring Initiative (HBM4EU) a human biomonitoring (HBM) survey was conducted in 23 countries to generate EU-wide comparable HBM data. This survey has built on existing HBM capacity in Europe by aligning national or regional HBM studies, referred to as the HBM4EU Aligned Studies. The HBM4EU Aligned Studies included a total of 10,795 participants of three age groups: (i) 3,576 children aged 6-12 years, (ii) 3,117 teenagers aged 12-18 years and (iii) 4,102 young adults aged 20-39 years. The participants were recruited between 2014 and 2021 in 11-12 countries per age group, geographically distributed across Europe. Depending on the age group, internal exposure to phthalates and the substitute DINCH, halogenated and organophosphorus flame retardants, per- and polyfluoroalkyl substances (PFASs), cadmium, bisphenols, polycyclic aromatic hydrocarbons (PAHs), arsenic species, acrylamide, mycotoxins (deoxynivalenol (total DON)), benzophenones and selected pesticides was assessed by measuring substance specific biomarkers subjected to stringent quality control programs for chemical analysis. For substance groups analyzed in different age groups higher average exposure levels were observed in the youngest age group, i.e., phthalates/DINCH in children versus teenagers, acrylamide and pesticides in children versus adults, benzophenones in teenagers versus adults. Many biomarkers in teenagers and adults varied significantly according to educational attainment, with higher exposure levels of bisphenols, phthalates, benzophenones, PAHs and acrylamide in participants (from households) with lower educational attainment, while teenagers from households with higher educational attainment have higher exposure levels for PFASs and arsenic. In children, a social gradient was only observed for the non-specific pyrethroid metabolite 3-PBA and di-isodecyl phthalate (DiDP), with higher levels in children from households with higher educational attainment. Geographical variations were seen for all exposure biomarkers. For 15 biomarkers, the available health-based HBM guidance values were exceeded with highest exceedance rates for toxicologically relevant arsenic in teenagers (40%), 3-PBA in children (36%), and between 11 and 14% for total DON, Summe (PFOA + PFNA + PFHxS + PFOS), bisphenol S and cadmium. The infrastructure and harmonized approach succeeded in obtaining comparable European wide internal exposure data for a prioritized set of 11 chemical groups. These data serve as a reference for comparison at the global level, provide a baseline to compare the efficacy of the European Commission's chemical strategy for sustainability and will give leverage to national policy makers for the implementation of targeted measures. © 2023 The AuthorsVeröffentlichung Harmonization of Human Biomonitoring Studies in Europe: characteristics of the HBM4EU-aligned studies participants(2022) Gilles, Liese; Govarts, Eva; Rodriguez Martin, Laura; Kolossa-Gehring, Marike; Peisker, Jasmin; Rucic, Enrico; Rüther, Maria; Vogel, Nina; Weber, TillHuman biomonitoring has become a pivotal tool for supporting chemicals' policies. It provides information on real-life human exposures and is increasingly used to prioritize chemicals of health concern and to evaluate the success of chemical policies. Europe has launched the ambitious REACH program in 2007 to improve the protection of human health and the environment. In October 2020 the EU commission published its new chemicals strategy for sustainability towards a toxic-free environment. The European Parliament called upon the commission to collect human biomonitoring data to support chemical's risk assessment and risk management. This manuscript describes the organization of the first HBM4EU-aligned studies that obtain comparable human biomonitoring (HBM) data of European citizens to monitor their internal exposure to environmental chemicals. The HBM4EU-aligned studies build on existing HBM capacity in Europe by aligning national or regional HBM studies. The HBM4EU-aligned studies focus on three age groups: children, teenagers, and adults. The participants are recruited between 2014 and 2021 in 11 to 12 primary sampling units that are geographically distributed across Europe. Urine samples are collected in all age groups, and blood samples are collected in children and teenagers. Auxiliary information on socio-demographics, lifestyle, health status, environment, and diet is collected using questionnaires. In total, biological samples from 3137 children aged 6-12 years are collected for the analysis of biomarkers for phthalates, HEXAMOLL® DINCH, and flame retardants. Samples from 2950 teenagers aged 12-18 years are collected for the analysis of biomarkers for phthalates, Hexamoll® DINCH, and per- and polyfluoroalkyl substances (PFASs), and samples from 3522 adults aged 20-39 years are collected for the analysis of cadmium, bisphenols, and metabolites of polyaromatic hydrocarbons (PAHs). The children's group consists of 50.4% boys and 49.5% girls, of which 44.1% live in cities, 29.0% live in towns/suburbs, and 26.8% live in rural areas. The teenagers' group includes 50.6% girls and 49.4% boys, with 37.7% of residents in cities, 31.2% in towns/suburbs, and 30.2% in rural areas. The adult group consists of 52.6% women and 47.4% men, 71.9% live in cities, 14.2% in towns/suburbs, and only 13.4% live in rural areas. The study population approaches the characteristics of the general European population based on age-matched EUROSTAT EU-28, 2017 data; however, individuals who obtained no to lower educational level (ISCED 0-2) are underrepresented. The data on internal human exposure to priority chemicals from this unique cohort will provide a baseline for Europe's strategy towards a non-toxic environment and challenges and recommendations to improve the sampling frame for future EU-wide HBM surveys are discussed. © 2022 by the authors