Person: Lange, Rosa
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Publication Deutsche Umweltstudie zur Gesundheit von Kindern und Jugendlichen 2014-2017 (GerES V)(Umweltbundesamt, 2023) Hahn, Domenica; Kolossa-Gehring, Marike; Lange, Rosa; Lemke, Nora; Murawski, Aline; Peisker, Jasmin; Debiak, Malgorzata; Rucic, Enrico; Zimmermann, Philipp; David, Madlen; Gerofke, Antje; Weber, Till; Pack, Kim LauraIn der Deutschen Umweltstudie zur Gesundheit (GerES) wird die Schadstoff-Belastung der Bevölkerung repräsentativ für die Menschen in Deutschland erhoben. In der fünften Erhebung, GerESV (2014-2017), wurden 2.294 Kinder und Jugendliche im Alter von 3 bis 17 Jahren aus 167 Orten in ganz Deutschland untersucht. GerES V ist eine bevölkerungsrepräsentative Querschnittstudie und wurde in enger Kooperation mit der "Studie zur Gesundheit von Kindern und Jugendlichen in Deutschland" (KiGGS Welle 2) des Robert-Koch-Instituts durchgeführt. Im Human-Biomonitoring (HBM) von GerESV wurden 107 verschiedene Substanzen im Blut bzw. Urin der Teilnehmenden gemessen. Der vorliegende Bericht fasst die HBM-Ergebnisse von GerESV zusammen. Bei Vorliegen entsprechender Beurteilungswerte wird eine gesundheitliche Bewertung vorgenommen. Der Bericht gibt einen Überblick über die Abläufe der Datenerhebung und die chemisch-analytischen und statistischen Methoden. Die wichtigsten Ergebnisse zu Belastungsquellen und -pfaden sowie besonders belasteten Bevölkerungsgruppen sind zusammengefasst und in aggregierter Form tabellarisch präsentiert. Für jede untersuchte Substanz werden außerdem die Quellen, die toxikologischen Eigenschaften und aktuellen Regulationen aufgeführt. Die bisherige Nutzung der Daten aus GerES V für Politik- und Öffentlichkeitsarbeit sowie in internationalen Kooperationen ist ebenfalls dargelegt. Quelle: ForschungsberichtPublication Time Patterns in Internal Human Exposure Data to Bisphenols, Phthalates, DINCH, Organophosphate Flame Retardants, Cadmium and Polyaromatic Hydrocarbons in Europe(2023) Martin, Laura Rodriguez; Gilles, Liese; Helte, Emilie; Kolossa-Gehring, Marike; Lange, Rosa; Pack, Kim Laura; Schmidt, Phillipp; Vogel, Nina; Weber, TillHuman biomonitoring (HBM) data in Europe are often fragmented and collected in different EU countries and sampling periods. Exposure levels for children and adult women in Europe were evaluated over time. For the period 2000-2010, literature and aggregated data were collected in a harmonized way across studies. Between 2011-2012, biobanked samples from the DEMOCOPHES project were used. For 2014-2021, HBM data were generated within the HBM4EU Aligned Studies. Time patterns on internal exposure were evaluated visually and statistically using the 50th and 90th percentiles (P50/P90) for phthalates/DINCH and organophosphorus flame retardants (OPFRs) in children (5-12 years), and cadmium, bisphenols and polycyclic aromatic hydrocarbons (PAHs) in women (24-52 years). Restricted phthalate metabolites show decreasing patterns for children. Phthalate substitute, DINCH, shows a non-significant increasing pattern. For OPFRs, no trends were statistically significant. For women, BPA shows a clear decreasing pattern, while substitutes BPF and BPS show an increasing pattern coinciding with the BPA restrictions introduced. No clear patterns are observed for PAHs or cadmium. Although the causal relations were not studied as such, exposure levels to chemicals restricted at EU level visually decreased, while the levels for some of their substitutes increased. The results support policy efficacy monitoring and the policy-supportive role played by HBM. © 2023 by the authorsPublication Concurrent assessment of Phthalates/HEXAMOLL ® DINCH Exposure and Wechsler intelligence scale for children performance in three European cohorts of the HBM4EU aligned studies(2022) Rosolen, Valentina; Apel, Petra; Giordani, Elisa; Mariuz, Marika; Kolossa-Gehring, Marike; Lange, RosaInformation about the effects of phthalates and non-phthalate substitute cyclohexane-1,2-dicarboxylic acid diisononyl ester (HEXAMOLL® DINCH) on children's neurodevelopment is limited. The aim of the present research is to evaluate the association between phthalate/HEXAMOLL® DINCH exposure and child neurodevelopment in three European cohorts involved in HBM4EU Aligned Studies. Participating subjects were school-aged children belonging to the Northern Adriatic cohort II (NAC-II), Italy, Odense Child Cohort (OCC), Denmark, and PCB cohort, Slovakia. In each cohort, children's neurodevelopment was assessed through the Full-Scale Intelligence Quotient score (FSIQ) of the Wechsler Intelligence Scale of Children test using three different editions. The children's urine samples, collected for one point in time concurrently with the neurodevelopmental evaluation, were analyzed for several phthalates/HEXAMOLL® DINCH biomarkers. The relation between phthalates/HEXAMOLL® DINCH and FSIQ was explored by applying separate multiple linear regressions in each cohort. The means and standard deviations of FSIQ were 109 +/- 11 (NAC-II), 98 +/- 12 (OCC), and 81 +/- 15 (PCB cohort). In NAC-II, direct associations between FSIQ and DEHP's biomarkers were found: 5OH-MEHP+5oxo-MEHP (beta=2.56; 95% CI 0.58-4.55; N=270), 5OH-MEHP+5cx-MEPP (beta=2.48; 95% CI 0.47-4.49; N=270) and 5OH-MEHP (beta=2.58; 95% CI 0.65-4.51; N=270). On the contrary, in the OCC the relation between DEHP's biomarkers and FSIQ tended to be inverse but imprecise (p-value >/= 0.10). No associations were found in the PCB cohort. FSIQ was not associated with HEXAMOLL® DINCH in any cohort. In conclusion, these results do not provide evidence of an association between concurrent phthalate/DINCHHEXAMOLLR DINCH exposure and IQ in children. © 2022 by the authorsPublication 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 authorsPublication Scoping Review - The Association between Asthma and Environmental Chemicals(2021) Mattila, Tiina; Santonen, Tiina; Kolossa-Gehring, Marike; Andersen, Helle Raun; Lange, RosaAsthma is one of the most common chronic diseases worldwide affecting all age groups from children to the elderly. In addition to other factors such as smoking, air pollution and atopy, some environmental chemicals are shown or suspected to increase the risk of asthma, exacerbate asthma symptoms and cause other respiratory symptoms. In this scoping review, we report environmental chemicals, prioritized for investigation in the European Human Biomonitoring Initiative (HBM4EU), which are associated or possibly associated with asthma. The substance groups considered to cause asthma through specific sensitization include: diisocyanates, hexavalent chromium Cr(VI) and possibly p-phenylenediamine (p-PDA). In epidemiological studies, polyaromatic hydrocarbons (PAHs) and organophosphate insecticides are associated with asthma, and phthalates, per- and polyfluoroalkyl substances (PFASs), pyrethroid insecticides, mercury, cadmium, arsenic and lead are only potentially associated with asthma. As a conclusion, exposure to PAHs and some pesticides are associated with increased risk of asthma. Diisocyanates and Cr(VI) cause asthma with specific sensitization. For many environmental chemicals, current studies have provided contradicting results in relation to increased risk of asthma. Therefore, more research about exposure to environmental chemicals and risk of asthma is needed. © 2021 by the authorsPublication Phthalate metabolites in urine of children and adolescents in Germany. Human biomonitoring results of the German Environmental Survey GerES V, 2014-2017(2020) Conrad, André; Daniels, Anja; Kolossa-Gehring, Marike; Lange, Rosa; Rucic, Enrico; Schmied-Tobies, Maria Irene Hilde; Schulz, Christine; Schwedler, GerdaDuring the population representative German Environmental Survey of Children and Adolescents (GerES V, 2014-2017) 2256 first-morning void urine samples from 3 to 17 years old children and adolescents were analysed for 21 metabolites of 11 different phthalates (di-methyl phthalate (DMP), di-ethyl phthalate (DEP), butylbenzyl phthalate (BBzP), di-iso-butyl phthalate (DiBP), di-n-butyl phthalate (DnBP), di-cyclohexyl phthalate (DCHP), di-n-pentyl phthalate (DnPeP), di-(2-ethylhexyl) phthalate (DEHP), di-iso-nonyl phthalate (DiNP), di-iso-decyl phthalate (DiDP) and di-n-octyl phthalate (DnOP)). Metabolites of DMP, DEP, BBzP, DiBP, DnBP, DEHP, DiNP and DiDP were found in 97-100% of the participants, DCHP and DnPeP in 6%, and DnOP in none of the urine samples. Geometric means (GM) were highest for metabolites of DiBP (MiBP: 26.1 my g/L), DEP (MEP: 25.8 my g/L), DnBP (MnBP: 20.9 my g/L), and DEHP (cx-MEPP: 11.9 my g/L). For all phthalates but DEP, GMs were consistently higher in the 3-5 years old children than in the 14-17 years old adolescents. For DEHP, the age differences were most pronounced. All detectable phthalate biomarker concentrations were positively associated with the levels of the respective phthalate in house dust. In GerES V we found considerably lower phthalate biomarker levels than in the preceding GerES IV (2003-2006). GMs of biomarker levels in GerES V were only 18% (BBzP), 23% (MnBP), 23% (DEHP), 29% (MiBP) and 57% (DiNP) of those measured a decade earlier in GerES IV. However, some children and adolescents still exceeded health-based guidance values in the current GerES V. 0.38% of the participants had levels of DnBP, 0.08% levels of DEHP and 0.007% levels of DiNP which were higher than the respective health-based guidance values. Accordingly, for these persons an impact on health cannot be excluded with sufficient certainty. The ongoing and substantial exposure of vulnerable children and adolescents to many phthalates confirms the need of a continued monitoring of established phthalates, whether regulated or not, as well as of potential substitutes. With this biomonitoring approach we provide a picture of current individual and cumulative exposure developments and body burdens to phthalates, thus providing support for timely and effective chemicals policies and legislation. © 2020 The Authors. Published by Elsevier GmbH.Publication The European Human Biomonitoring Initiative (HBM4EU): Human biomonitoring guidance values (HBM-GVs) for the aprotic solvents N-methyl-2-pyrrolidone (NMP) and N-ethyl-2-pyrrolidone (NEP)(2021) Apel, Petra; Gerofke, Antje; David, Madlen; Kolossa-Gehring, Marike; Lange, RosaToxicologically and/or epidemiologically derived guidance values referring to the internal exposure of humans are a prerequisite for an easy to use health-based interpretation of human biomonitoring (HBM) results. The European Joint Programme HBM4EU derives such values, named human biomonitoring guidance values (HBM-GVs), for priority substances which could be of regulatory relevance for policy makers and have been identified by experts of the participating countries, ministries, agencies and stakeholders at EU and national level. NMP and NEP are such substances for which unresolved policy relevant issues should be clarified by targeted research. Since widespread exposure of the general population in Germany to NMP and NEP was shown for the age groups 3-17 years and 20-29 years, further investigations on exposure to NMP and NEP in other European countries are warranted. The HBM-GVs derived for both solvents focus on developmental toxicity as decisive endpoint. They amount for the sum of the two specific urinary NMP metabolites 5-HNMP and 2-HMSI and likewise of the two specific urinary NEP metabolites 5-HNEP and 2-HESI to 10 mg/L for children and 15 mg/L for adolescents/adults. The values were determined following a consultation process on the value proposals within HBM4EU. A health-based risk assessment was performed using the newly derived HBM-GVGenPop and exposure data from two recent studies from Germany. The risk assessment revealed that even when considering the combined exposure to both substances by applying the Hazard Index approach, the measured concentrations are below the HBM-GVGenPop in all cases investigated (i.e., children, adolescents and young adults). © 2021 The Authors. Published by Elsevier GmbH.Publication Urinary excretion of phthalates and the substitutes DINCH and DEHTP in Danish young men and German young adults between 2000 and 2017 - a time trend analysis(2023) Frederiksen, Hanne; Kolossa-Gehring, Marike; Lange, Rosa; Vogel, Nina; Weber, TillOver the last twenty-five years it has become evident that exposure to several phthalates can have adverse effects on human health, such as endocrine disruption. This led to a series of EU regulations that resulted in a decrease in the production volumes of the restricted phthalates and an increased production of substitutes. The current study describes the impact of regulations and changes in production and use of phthalates and their substitutes on internal exposure patterns in two European populations since the beginning of the 2000'ies. Using harmonised data from young adults in Denmark (Danish Young Men Study, n = 1,063, spot urine) and Germany (Environmental Specimen Bank, n = 878, 24-h urine) with repeated cross-sectional design (3-11 cycles per biomarker) we applied Locally Estimated Scatterplot Smoothing (LOESS) and Generalized Linear Models (GLMs) to estimate time trends and the role of covariates on the trend (e.g. age, BMI). Time trends of daily excretion (mikrog/24h) are comparable between the two samples for the regulated (DEHP, BBzP, DiNP, DnBP, DiBP, DiDP/DPHP) as well as the non-regulated substances (DMP, DEP, DINCH, DEHTP) although the rate of change differ for some of the compounds. GLM results indicate that the daily excretion of the most regulated phthalates has decreased over time (DEHP yearly about 12-16%, BBzP 5%, DnBP 0.3-17%, and DiBP 4-12%). Interestingly, also the non-regulated phthalates DMP and DEP decreased by 6-18% per year. In sharp contrast, the phthalate substitutes DINCH and DEHTP show very steep annual increases (~10-68% and ~100%, respectively) between 2009 and 2017. We did not find an effect of age, sex, BMI, or education on the time trend. The present study provides comparable insights into how exposure to phthalates and two of their substitutes have changed over the last two decades in Germany and Denmark. © 2022 The AuthorsPublication Human biomonitoring initiative (HBM4EU): Human biomonitoring guidance values (HBM-GVs) derived for cadmium and its compounds(2021) Lamkarkach, Farida; Apel, Petra; Ougier, Eva; Garnier, Robert; Kolossa-Gehring, Marike; Lange, RosaAims The methodology agreed within the framework of the HBM4EU project is used in this work to derive HBM-GVs for the general population (HBM-GVGenPop) and for workers (HBM-GVWorker) exposed to cadmium (Cd) and its compounds. Methods For Cd, a significant number of epidemiological studies with doseââą Ìresponse relationships are available, in particular for kidney effects. These effects are described in terms of a relation between urinary Cd (U-Cd) or blood Cd (B-Cd) levels and low molecular weight proteinuria (LMWP) markers like beta-2-microglobulin (Î22M) and retinol-binding protein (RBP). In order to derive HBM-GVs for the general population and workers, an assessment of data from evaluations conducted by national or international organisations was undertaken. In this work, it appeared relevant to select renal effects as the critical effect for the both groups, however, differences between general population (including sensitive people) and workers (considered as an homogenous population of adults who should not be exposed to Cd if they suffer from renal diseases) required the selection of different key studies (i.e. conducted in general population for HBM-GVGenPop and at workplace for HBM-GVWorker). Results and conclusions For U-Cd, a HBM-GVGenPop of 1 (my)g/g creatinine (creat) is recommended for adults older than 50 years, based on a robust meta-analysis performed by EFSA (EFSA, 2009a). To take into account the accumulation of Cd in the human body throughout life, threshold or 'alert' values according to age were estimated for U-Cd. At workplace, a HBM-GVWorker of 2 (my)g/g creat is derived from the study of Chaumont et al., (2011) for U-Cd, and in addition to this recommendation a HBM-GVworker for B-Cd of 5 Ìg/L is also proposed. The HBM-GVWorker for U-Cd is similar to the biological limit value (BLV) set by the new amendment of the European Carcinogens and Mutagens Directive in June 2019 (2 (my)g/g creat for U-Cd). © 2021 The AuthorsPublication Environmental substances associated with osteoporosis - a scoping review(2021) Elonheimo, Hanna; Kolossa-Gehring, Marike; Tolonen, Hanna; Lange, RosaIntroduction: Osteoporosis is a disease having adverse effects on bone health and causing fragility fractures. Osteoporosis affects approximately 200 million people worldwide, and nearly 9 million fractures occur annually. Evidence exists that, in addition to traditional risk factors, certain environmental substances may increase the risk of osteoporosis. Methods: The European Human Biomonitoring Initiative (HBM4EU) is a joint program coordinating and advancing human biomonitoring in Europe. HBM4EU investigates citizens' exposure to several environmental substances and their plausible health effects aiming to contribute to policymaking. In HBM4EU, 18 priority substances or substance groups were selected. For each, a scoping document was prepared summarizing existing knowledge and health effects. This scoping review is based on these chemical-specific scoping documents and complementary literature review. Results: A possible link between osteoporosis and the body burden of heavy metals, such as cadmium (Cd) and lead (Pb), and industrial chemicals such as phthalates and per- and poly-fluoroalkyl substances (PFASs) was identified. Conclusions: Evidence shows that environmental substances may be related to osteoporosis as an adverse health effect. Nevertheless, more epidemiological research on the relationship between health effects and exposure to these chemicals is needed. Study results are incoherent, and pervasive epidemiological studies regarding the chemical exposure are lacking. © 2021 by the authors