| 1. |
- Kupers, LK, et al.
(författare)
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Meta-analysis of epigenome-wide association studies in neonates reveals widespread differential DNA methylation associated with birthweight
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 1893-
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Tidskriftsartikel (refereegranskat)abstract
- Birthweight is associated with health outcomes across the life course, DNA methylation may be an underlying mechanism. In this meta-analysis of epigenome-wide association studies of 8,825 neonates from 24 birth cohorts in the Pregnancy And Childhood Epigenetics Consortium, we find that DNA methylation in neonatal blood is associated with birthweight at 914 sites, with a difference in birthweight ranging from −183 to 178 grams per 10% increase in methylation (PBonferroni < 1.06 x 10−7). In additional analyses in 7,278 participants, <1.3% of birthweight-associated differential methylation is also observed in childhood and adolescence, but not adulthood. Birthweight-related CpGs overlap with some Bonferroni-significant CpGs that were previously reported to be related to maternal smoking (55/914, p = 6.12 x 10−74) and BMI in pregnancy (3/914, p = 1.13x10−3), but not with those related to folate levels in pregnancy. Whether the associations that we observe are causal or explained by confounding or fetal growth influencing DNA methylation (i.e. reverse causality) requires further research.
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| 11. |
- Poteser, M, et al.
(författare)
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Trends of Exposure to Acrylamide as Measured by Urinary Biomarkers Levels within the HBM4EU Biomonitoring Aligned Studies (2000-2021)
- 2022
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Ingår i: Toxics. - : MDPI AG. - 2305-6304. ; 10:8
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Tidskriftsartikel (refereegranskat)abstract
- Acrylamide, 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.
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| 15. |
- Vogel, N, et al.
(författare)
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Exposure to Phthalates in European Children, Adolescents and Adults since 2005: A Harmonized Approach Based on Existing HBM Data in the HBM4EU Initiative
- 2023
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Ingår i: Toxics. - : MDPI AG. - 2305-6304. ; 11:3
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 16. |
- Vogel, N, et al.
(författare)
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Exposure to Phthalates in European Children, Adolescents and Adults since 2005: A Harmonized Approach Based on Existing HBM Data in the HBM4EU Initiative
- 2023
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Ingår i: Toxics. - : MDPI AG. - 2305-6304. ; 11:3
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 17. |
- Covaci, Adrian, et al.
(författare)
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Urinary BPA measurements in children and mothers from six European member states: Overall results and determinants of exposure.
- 2015
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Ingår i: Environmental Research. - : Elsevier BV. - 1096-0953 .- 0013-9351. ; 141:Oct 13, s. 77-85
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Tidskriftsartikel (refereegranskat)abstract
- For the first time in Europe, both European-wide and country-specific levels of urinary Bisphenol A (BPA) were obtained through a harmonized protocol for participant recruitment, sampling and quality controlled biomarker analysis in the frame of the twin projects COPHES and DEMOCOPHES. 674 child-mother pairs were recruited through schools or population registers from six European member states (Belgium, Denmark, Luxembourg, Slovenia, Spain and Sweden). Children (5-12y) and mothers donated a urine sample. Information on socio-demographic characteristics, life style, dietary habits, and educational level of the parents was provided by mothers. After exclusion of urine samples with creatinine values below 300mg/L or above 3000mg/L, 653 children and 639 mothers remained for which BPA was measured. The geometric mean (with 95% confidence intervals) and 90th percentile were calculated for BPA separately in children and in mothers and were named "European reference values". After adjustment for confounders (age and creatinine), average exposure values in each country were compared with the mean of the "European reference values" by means of a weighted analysis of variance. Overall geometric means of all countries (95% CI) adjusted for urinary creatinine, age and gender were 2.04 (1.87-2.24) µg/L and 1.88 (1.71-2.07) µg/L for children (n=653) and mothers (n=639), respectively. Multiple regression analysis was used to identify significant environmental, geographical, personal or life style related determinants. Consumption of canned food and social class (represented by the highest educational level of the family) were the most important predictors for the urinary levels of BPA in mothers and children. The individual BPA levels in children were significantly correlated with the levels in their mothers (r=0.265, p<0.001), which may suggest a possible common environmental/dietary factor that influences the biomarker level in each pair. Exposure of the general European population was well below the current health-based guidance values and no participant had BPA values higher than the health-based guidance values.
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| 20. |
- Poteser, M, et al.
(författare)
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Time Trends of Acrylamide Exposure in Europe: Combined Analysis of Published Reports and Current HBM4EU Studies
- 2022
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Ingår i: Toxics. - : MDPI AG. - 2305-6304. ; 10:8
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Tidskriftsartikel (refereegranskat)abstract
- More 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.
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| 22. |
- Socianu, S., et al.
(författare)
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Chemical Mixtures in the EU Population: Composition and Potential Risks
- 2022
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Ingår i: International Journal of Environmental Research and Public Health. - : MDPI AG. - 1660-4601. ; 19:10
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Tidskriftsartikel (refereegranskat)abstract
- Regulating chemical mixtures is a complex scientific and policy task. The aim of this study was to investigate typical mixtures and their potential risks based on internal exposure levels in the European population. Based on human biomonitoring (HBM) data made available via the HBM4EU project, we derived generic mixtures representative of a median (P50) and a worst-case scenario (P95) for adults and children. We performed a mixture risk assessment based on HBM concentrations, health-based guidance values (HBGVs) as internal thresholds of concern, and the conservative assumption of concentration addition applied across different toxicological endpoints. Maximum cumulative ratios (MCRs) were calculated to characterize the mixture risk. The mixtures comprise 136 biomarkers for adults and 84 for children, although concentration levels could be quantified only for a fraction of these. Due to limited availability of HBGVs, the mixture risk was assessed for a subset of 20 substance-biomarker pairs for adults and 17 for children. The mixture hazard index ranged from 2.8 (P50, children) to 9.2 (P95, adults). Six to seven substances contributed to over 95% of the total risk. MCR values ranged between 2.6 and 5.5, which is in a similar range as in previous studies based on human external exposures assessments. The limited coverage of substances included in the calculations and the application of a hazard index across toxicological endpoints argue for caution in the interpretation of the results. Nonetheless the analyses of MCR and MAF(ceiling) can help inform a possible mixture assessment factor (MAF) applicable to single substance risk assessment to account for exposure to unintentional mixtures.
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| 23. |
- Vorkamp, Katrin, et al.
(författare)
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Coordination of chemical analyses under the European Human Biomonitoring Initiative (HBM4EU) : Concepts, procedures and lessons learnt
- 2023
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Ingår i: International Journal of Hygiene and Environmental Health. - 1438-4639. ; 251
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Forskningsöversikt (refereegranskat)abstract
- The European Human Biomonitoring Initiative (HBM4EU) ran from 2017 to 2022 with the aim of advancing and harmonizing human biomonitoring in Europe. More than 40,000 analyses were performed on human samples in different human biomonitoring studies in HBM4EU, addressing the chemical exposure of the general population, temporal developments, occupational exposure and a public health intervention on mercury in populations with high fish consumption. The analyses covered 15 priority groups of organic chemicals and metals and were carried out by a network of laboratories meeting the requirements of a comprehensive quality assurance and control system. The coordination of the chemical analyses included establishing contacts between sample owners and qualified laboratories and monitoring the progress of the chemical analyses during the analytical phase, also addressing status and consequences of Covid-19 measures. Other challenges were related to the novelty and complexity of HBM4EU, including administrative and financial matters and implementation of standardized procedures. Many individual contacts were necessary in the initial phase of HBM4EU. However, there is a potential to develop more streamlined and standardized communication and coordination in the analytical phase of a consolidated European HBM programme.
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