Kasper-Sonnenberg, Monika; Pälmke, Claudia; Wrobel, Sonja; Brüning, Thomas; Murawski, Aline; Apel, Petra; Weber, Till; Kolossa-Gehring, Marike; Koch, Holger M. Environ Int 195 (2025), 109-190, online: 12. Dezember 2024 The German Environmental Specimen Bank (ESB) annually archives 24-h urine samples since the early 1980s. In this study, we analyzed 420 of these samples from the years 2014 to 2022 for metabolites of 18 phthalates and two substitutes. We merged the new data with the data from previous measurement campaigns to a combined dataset of 1825 samples covering a 35-year period from 1988 to 2022 to investigate time trends, calculate daily intakes and perform an anti-androgenic mixture risk assessment. With the extended set of 41 biomarkers, we are now able to monitor the exposure to all EU-labelled reprotoxic phthalates. Most phthalate exposures continued to decrease since first measurements in the 80s, with biggest drops for DnBP (96.6 %) and DEHP (90.9 %). DiNP and DiDP, seen on the rise in earlier campaigns, now declined. Exposures to the newly included, reprotoxic phthalates were generally negligible. Regarding mixture risk, 5 % of the highly exposed still exceeded the Hazard Index (HI) of 1 in 2009. In the current measurement campaign only three individuals (0.7 %) exceeded the HI of 1 (with exceedances still driven by DEHP and DnBP).In 2022, 20 % of the individuals still had an HI > 0.2, which we propose as a benchmark for interpreting phthalate mixture risk, considering concurrent exposures to other anti-androgens. Exposure to the substitutes DINCH and DEHTP continues to increase, with daily intakes of DEHTP exceeding those of DEHP since 2018. Compared with the United States (US) National Health and Nutrition Examination Survey (NHANES) phthalate exposures seem to align, except for DEHTP with up to ten times higher levels in the US. Human biomonitoring (HBM) is the ideal tool to capture actual mixture exposures per individual, integrating all external exposure sources and pathways, thus we will continue to use HBM in exposure and risk assessment of phthalates and other (anti-androgenic) chemicals. doi: 10.1016/j.envint.2024.109190
Over 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 Authors
Vogel, Nina; Frederiksen, Hanne; Lange, Rosa; Jorgensen, Niels; Koch, Holger M.; Weber, Till; Andersson, Anna-Maria; Kolossa-Gehring, Marike Int J Hyg Environ Health 248 (2023), 114080; online: 17 Januar 2023 Over 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 (mug/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 ( approximately 10-68% and approximately 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. doi: 10.1016/j.ijheh.2022.114080
Antje Gerofke, Rosa Lange, Nina Vogel, Phillipp Schmidt, Till Weber, Madlen David, Hanne Frederiksen, Kirsten Baken, Eva Govarts, Liese Gilles, Laura Rodriguez Martin, Žanna Martinsone, Tiina Santonen, Greet Schoeters, Martin Scheringer, Elena Domínguez-Romero, Marta Esteban López, Argelia Castaño Calvo, Holger M. Koch, Petra Apel, Marike Kolossa-Gehring Int J Hyg Environ Health; online : 16. April 2024 Phthalates and the substitute plasticizer DINCH belong to the first group of priority substances investigated by the European Human Biomonitoring Initiative (HBM4EU) to answer policy-relevant questions and safeguard an efficient science-to-policy transfer of results. Human internal exposure levels were assessed using two data sets from all European regions and Israel. The first collated existing human biomonitoring (HBM) data (2005–2019). The second consisted of new data generated in the harmonized “HBM4EU Aligned Studies” (2014–2021) on children and teenagers for the ten most relevant phthalates and DINCH , accompanied by a quality assurance/quality control (QA/QC) program for 17 urinary exposure biomarkers. Exposures differed between countries, European regions, age groups and educational levels. Toxicologically derived Human biomonitoring guidance values (HBM-GVs) were exceeded in up to 5% of the participants of the HBM4EU Aligned Studies. A mixture risk assessment (MRA) including five reprotoxic phthalates (DEHP, DnBP , DiBP, BBzP , DiNP) revealed that for about 17% of the children and teenagers, health risks cannot be excluded. Concern about male reproductive health emphasized the need to include other anti-androgenic substances for MRA. Contaminated food and the use of personal care products were identified as relevant exposure determinants paving the way for new regulatory measures. Time trend analyses verified the efficacy of regulations: especially for the highly regulated phthalates exposure dropped significantly, while levels of the substitutes DINCH and DEHTP increased. The HBM4EU e-waste study, however, suggests that workers involved in e-waste management may be exposed to higher levels of restricted phthalates. Exposure-effect association studies indicated the relevance of a range of endpoints. A set of HBM indicators was derived to facilitate and accelerate science-to-policy transfer. Result indicators allow different groups and regions to be easily compared. Impact indicators allow health risks to be directly interpreted. The presented results enable successful science-to-policy transfer and support timely and targeted policy measures. doi.org/10.1016/j.ijheh.2024.114378 Vergrößert anzeigen
Background European chemicals management aims to protect human health and the environment from legacy and emerging contaminants. The plasticizer market changed in response to the restriction of low molecular weight (LMW) phthalate plasticizers such as Di (2-ethylhexyl) phthalate (DEHP) due to their hazardous properties. We investigated patterns and trends of 19 regulated and emerging plasticizers in house dust from German homes and in suspended particulate matter (SPM) from major German rivers. The samples were used from the mid-2000s and late 2010s from two governmental long-term monitoring programs in Germany. Results While the sum of the respective plasticizer levels hardly changed over the study period, we observed a significant decrease of LMW phthalates in both house dust (2003/06, 80% of the (Sigma)plasticizer concentration; 2014/17, 31%) and SPM (2005, 48%; 2017, 28%). This was accompanied by their substitution with high molecular weight (HMW) phthalates and non-phthalates. HMW phthalates increased from 19% of the (Sigma)plasticizer concentration to 46% between the mid-2000s and the late 2010s in house dust, and from 50% to 63% in SPM samples. Diisononyl phthalate (DINP) replaced DEHP as the dominant plasticizer in both compartments. A significant tenfold increase (p<0.05) was observed in SPM samples for Di (2-propylheptyl) phthalate (DPHP) (1-13%), compared to low levels in house dust (2014/17, 1%). Non-phthalates increased to 23% of the (Sigma)plasticizer concentration in house dust but only to 9% in SPM (mid-2000s: house dust,<1%; SPM, 1.5%). In recent house dust samples, Di (2-ethylhexyl) terephthalate (DEHT) had the third highest concentration of all plasticizers and contributed 18% to the total load, whereas Tris (2-ethylhexyl) trimellitate (TOTM) was one of the major non-phthalates in SPM samples. Conclusions Unlike in the indoor environment, the substitution of LMW phthalates in the aquatic environment was characterized by a significant shift towards plasticizers with potentially hazardous properties. DPHP and TOTM were identified by European chemical regulation as potentially endocrine disrupting compounds and persistent, bioaccumulative and toxic compounds. Our data document the need for integrated chemicals management to safeguard the transition to a non-toxic environment. © The Author(s) 2022
Anzahl der Proben: 75 Gemessener Parameter: Mono(4-methyl-7-oxo-octyl)phthalat ist ein oxydierter Metabolit von DiNP mit funktioneller oxo-Gruppe. Probenart: 24h-Sammelurin Eine ideale Matrix für das Human-Biomonitoring, weil mit dem Urin Chemikalien und/oder deren Metabolite ausgeschiedenen werden, die zuvor in direktem Kontakt mit dem Organismus standen. Messungen im Urin können somit zuverlässige Aussagen über die interne Belastung des Menschen liefern. Probenahmegebiet: Münster Bedeutende Universitätsstadt sowie Dienstleistungs- und Verwaltungszentrum in Nordrhein-Westfalen.
Anzahl der Proben: 75 Gemessener Parameter: Mono(4-methyl-7-hydroxyoctyl)phthalat ist ein oxydierter Metabolit von DiNP mit funktioneller OH-Gruppe. Probenart: 24h-Sammelurin Eine ideale Matrix für das Human-Biomonitoring, weil mit dem Urin Chemikalien und/oder deren Metabolite ausgeschiedenen werden, die zuvor in direktem Kontakt mit dem Organismus standen. Messungen im Urin können somit zuverlässige Aussagen über die interne Belastung des Menschen liefern. Probenahmegebiet: Münster Bedeutende Universitätsstadt sowie Dienstleistungs- und Verwaltungszentrum in Nordrhein-Westfalen.
Anzahl der Proben: 48 Gemessener Parameter: Mono(4-methyl-7-carboxyheptyl)phthalat ist ein oxydierter Metabolit von DiNP mit funktioneller Carboxyl-Gruppe. Probenart: 24h-Sammelurin Eine ideale Matrix für das Human-Biomonitoring, weil mit dem Urin Chemikalien und/oder deren Metabolite ausgeschiedenen werden, die zuvor in direktem Kontakt mit dem Organismus standen. Messungen im Urin können somit zuverlässige Aussagen über die interne Belastung des Menschen liefern. Probenahmegebiet: Münster Bedeutende Universitätsstadt sowie Dienstleistungs- und Verwaltungszentrum in Nordrhein-Westfalen.
Phthalates are mainly used as plasticizers for polyvinyl chloride (PVC). Exposure to several phthalates is associated with different adverse effects most prominently on the development of reproductive functions. The HBM4EU Aligned Studies (2014-2021) have investigated current European exposure to ten phthalates (DEP, BBzP, DiBP, DnBP, DCHP, DnPeP, DEHP, DiNP, DiDP, DnOP) and the substitute DINCH to answer the open policy relevant questions which were defined by HBM4EU partner countries and EU institutions as the starting point of the programme. The exposure dataset includes ~5,600 children (6-11 years) and adolescents (12-18 years) from up to 12 countries per age group and covering the North, East, South and West European regions. Study data from participating studies were harmonised with respect to sample size and selection of participants, selection of biomarkers, and quality and comparability of analytical results to provide a comparable perspective of European exposure. Phthalate and DINCH exposure were deduced from urinary excretions of metabolites, where concentrations were expressed as their key descriptor geometric mean (GM) and 95th percentile (P95). This study aims at reporting current exposure levels and differences in these between European studies and regions, as well as comparisons to human biomonitoring guidance values (HBM-GVs). GMs for children were highest for total-DEHP metabolites (33.6 mikrog/L), MiBP (26.6 mikrog/L), and MEP (24.4 mikrog/L) and lowest for total-DiDP metabolites (1.91 mikrog/L) and total-DINCH metabolites (3.57 mikrog/L). In adolescents highest GMs were found for MEP (43.3 mikrog/L), total-DEHP metabolites (28.8 mikrog/L), and MiBP (25.6 mikrog/L) and lowest for total-DiDP metabolites (= 2.02 mikrog/L) and total-DINCH metabolites (2.51 mikrog/L). In addition, GMs and P95 stratified by European region, sex, household education level, and degree of urbanization are presented. Differences in average biomarker concentrations between sampling sites (data collections) ranged from factor 2 to 9. Compared to the European average, children in the sampling sites OCC (Denmark), InAirQ (Hungary), and SPECIMEn (The Netherlands) had the lowest concentrations across all metabolites and ESTEBAN (France), NAC II (Italy), and CROME (Greece) the highest. For adolescents, comparably higher metabolite concentrations were found in NEB II (Norway), PCB cohort (Slovakia), and ESTEBAN (France), and lower concentrations in POLAES (Poland), FLEHS IV (Belgium), and GerES V-sub (Germany). Multivariate analyses (Survey Generalized Linear Models) indicate compound-specific differences in average metabolite concentrations between the four European regions. Comparison of individual levels with HBM-GVs revealed highest rates of exceedances for DnBP and DiBP, with up to 3 and 5%, respectively, in children and adolescents. No exceedances were observed for DEP and DINCH. With our results we provide current, detailed, and comparable data on exposure to phthalates in children and - for the first time - in adolescents, and - for the first time - on DINCH in children and adolescents of all four regions of Europe which are particularly suited to inform exposure and risk assessment and answer open policy relevant questions. © 2023 The Authors.
Phthalates 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 authors
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