34 research outputs found
Human urinary arsenic species, associated exposure determinants and potential health risks assessed in the HBM4EU Aligned Studies
The European Joint Programme HBM4EU coordinated and advanced human biomonitoring (HBM) in Europe in order to provide science-based evidence for chemical policy development and improve chemical management. Arsenic (As) was selected as a priority substance under the HBM4EU initiative for which open, policy relevant questions like the status of exposure had to be answered. Internal exposure to inorganic arsenic (iAs), measured as Toxic Relevant Arsenic (TRA) (the sum of As(III), As(V), MMA, DMA) in urine samples of teenagers differed among the sampling sites (BEA (Spain) > Riksmaten adolescents (Sweden), ESTEBAN (France) > FLEHS IV (Belgium), SLO CRP (Slovenia)) with geometric means between 3.84 and 8.47 μg/L. The ratio TRA to TRA + arsenobetaine or the ratio TRA to total arsenic varied between 0.22 and 0.49. Main exposure determinants for TRA were the consumption of rice and seafood. When all studies were combined, Pearson correlation analysis showed significant associations between all considered As species. Higher concentrations of DMA, quantitatively a major constituent of TRA, were found with increasing arsenobetaine concentrations, a marker for organic As intake, e.g. through seafood, indicating that other sources of DMA than metabolism of inorganic As exist, e.g. direct intake of DMA or via the intake of arsenosugars or -lipids. Given the lower toxicity of DMA(V) versus iAs, estimating the amount of DMA not originating from iAs, or normalizing TRA for arsenobetaine intake could be useful for estimating iAs exposure and risk. Comparing urinary TRA concentrations with formerly derived biomonitoring equivalent (BE) for non-carcinogenic effects (6.4 μg/L) clearly shows that all 95th percentile exposure values in the different studies exceeded this BE. This together with the fact that cancer risk may not be excluded even at lower iAs levels, suggests a possible health concern for the general population of Europe.HBM4EU is co-financed under Horizon 2020 (grant agreement No 733032). The authors thank all investigators of the contributing studies for their participation and contribution to the joint HBM4EU survey and the national programme owners for their financial support. Also thanks to the participating teenagers and their families, the field workers that collected the samples. The FLEHS IV study was conducted within the framework of the Flemish Center of Expertise on Environment and Health (FLEHS 2016–2020) and funded by the Flemish Government, Department of Environment & Spatial Development. We thank the teenagers and their families that participated in the study, the field workers from the Pro vincial Institute of Hygiene and VITO for the sample and data collection. All collaborators of the scientific teams of the Flemish Center of Expertise on Environment and Health (https://www.milieu-en-gezondheid.be/en/about-the-center-0) and Karen Van Campenhout and Caroline Teughels from the Flemish Department of Environment & Spatial Development for their valuable input in the field work committee. The funding of the German Ministry for the Environment, Nature Conservation, Nuclear Safety and Consumer Protection is gratefully acknowledged. BEA study was co-funded by the Spanish Ministry of Agriculture, Fisheries and Food and the Insituto de Salud Carlos III (SEG 1321/15). In Slovenia the work was cofounded by the Slovenian Research Funding Agency – ARRS through a research programme P-0143. ESTEBAN was Funded by Sant´e Publique France and the French ministries of Health and the Environment. The study of RIKSMATEN was conducted and mainly financed by the Swedish Food Agency. Financial support was provided from the Swedish Civil Contingencies Agency and from the Swedish Environmental Pro tection Agency (SEPA).S
Cadmium exposure in adults across Europe: Results from the HBM4EU Aligned Studies survey 2014-2020
ReviewThe objectives of the study were to estimate the current exposure to cadmium (Cd) in Europe, potential differences between the countries and geographic regions, determinants of exposure and to derive European exposure levels. The basis for this work was provided by the European Human Biomonitoring Initiative (HBM4EU) which established a framework for alignment of national or regional HBM studies. For the purpose of Cd exposure assessment, studies from 9 European countries (Iceland, Denmark, Poland, Czech Republic, Croatia, Portugal, Germany, France, Luxembourg) were included and urine of 20–39 years old adults sampled in the years 2014–2021 (n = 2510). The measurements in urine were quality assured by the HBM4EU quality assurance/quality control scheme, study participants' questionnaire data were post-harmonized. Spatially resolved external data, namely Cd concentrations in soil, agricultural areas, phosphate fertilizer application, traffic density and point source Cd release were collected for the respective statistical territorial unit (NUTS). There were no distinct geographic patterns observed in Cd levels in urine, although the data revealed some differences between the specific study sites. The levels of exposure were otherwise similar between two time periods within the last decade (DEMOCOPHES - 2011–2012 vs. HBM4EU Aligned Studies, 2014–2020). The age-dependent alert values for Cd in urine were exceeded by 16% of the study participants. Exceedances in the different studies and locations ranged from 1.4% up to 42%. The studies with largest extent of exceedance were from France and Poland. Association analysis with individual food consumption data available from participants’ questionnaires showed an important contribution of vegetarian diet to the overall exposure, with 35% higher levels in vegetarians as opposed to non-vegetarians. For comparison, increase in Cd levels due to smoking was 25%. Using NUTS2-level external data, positive associations between HBM data and percentage of cropland and consumption of Cd-containing mineral phosphate fertilizer were revealed, which indicates a significant contribution of mineral phosphate fertilizers to human Cd exposure through diet. In addition to diet, traffic and point source release were identified as significant sources of exposure in the study population. The findings of the study support the recommendation by EFSA to reduce Cd exposure as also the estimated mean dietary exposure of adults in the EU is close or slightly exceeding the tolerable weekly intake. It also indicates that regulations are not protecting the population sufficiently.The HBM4EU project has received funding from the European
Union’s Horizon 2020 research and innovation programme under grant
agreement No. 733032. Co-funding for the HBM4EU Aligned Studies has
been provided by the national programs: Sant´e Publique France and the
French ministries of Health and the Environment (ESTEBAN, France);
MEYS (No. LM2018121), and Cetocoen Plus project (CZ.02.1.01/0.0/
0.0/15_003/0000469) (CELSPAC:YA, Czech Republic); the Ministry of
Science and Higher Education of Poland (contract no.3764/H2020/
2017/2) (POALES, Poland); Public Health Fund (Diet_HBM, Iceland);
Croatian Institute of Public Health (HBM survey in Croatia); National
Institute of Health Dr Ricardo Jorge (INSEF_ExpoQuim, Portugal);
German Ministry for the Environment, Nature Conservation, Nuclear
Safety and Consumer Protection (BMUV) (ESB, Germany); Luxembourg
Institute of Health (LIH), the Laboratoire national de sant´e (human
biomonitoring part), the Ministry of Higher Education and Research of
Luxembourg and the Ministry of Health of Luxembourg (Oriscav-Lux2,
Luxembourg); Candy Foundation (Nos. 2017–224 and 2020–344),
Absalon Foundation (No. F-23653-01), The Danish Environmental Protection Agency (Miljøstyrelsen: MST-621-00012 Center on Endocrine
Disrupters), The Research council of Capital Region of Denmark (No.
E− 22717-11), Research council of Rigshospitalet (Nos. E− 22717-12,
E− 22717-07, E− 22717-08), Aase og Ejnar Danielsens Fond (No.
10–001874), International Research and Research Training Centre for
Male Reproduction and Child Health (EDMaRC, No. 1500321/1604357)
(CPHMINIPUB (parents) and DYMS, Denmark). J.Kl. and L.A. thank the
CETOCOEN EXCELLENCE project No. CZ.02.1.01/0.0/0.0/17_043/
0009632 financed by MEYS for supportive background, and supported
from the European Union’s Horizon 2020 research and innovation
program under grant agreement No. 857560.info:eu-repo/semantics/publishedVersio
Trends of Exposure to Acrylamide as Measured by Urinary Biomarkers Levels within the HBM4EU Biomonitoring Aligned Studies (2000–2021)
This article belongs to the Special Issue Analysis of Human Biomonitoring Data and Risk Assessment of Human Exposure to Environmental Chemicals: What Do We Learn for Prevention?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.This work received external funding from the European Union’s Horizon 2020 research and
innovation program under grant agreement No. 733032 and received co-funding from the author’s
organizations. The Norwegian Institute of Public Health (NIPH) contributed to the funding of the
Norwegian Environmental Biobank (NEB). The laboratory measurements were partly funded by the
Research Council of Norway through research projects (275903 and 268465).info:eu-repo/semantics/publishedVersio
Time Trends of Acrylamide Exposure in Europe: Combined Analysis of Published Reports and Current HBM4EU Studies
This article belongs to the Special Issue Analysis of Human Biomonitoring Data and Risk Assessment of Human Exposure to Environmental Chemicals: What Do We Learn for Prevention?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.This work has received external funding from the European Union’s Horizon 2020 research
and innovation program under grant agreement No. 733032 and received co-funding from the
author’s organizations. The Norwegian Institute of Public Health (NIPH) has contributed to the
funding of the Norwegian Environmental Biobank (NEB). The laboratory measurements have partly been funded by the
Research Council of Norway through research projects (275903 and 268465).info:eu-repo/semantics/publishedVersio
EU-wide exposure data of 11 chemical substance groups from the HBM4EU Aligned Studies (2014–2021)
Funding Information: The authors would like to thank everybody who contributed to the HBM4EU Aligned Studies: the participating children, teenagers, adults and their families, the fieldworkers that collected the samples and database managers that made the information available to HBM4EU, the HBM4EU project partners, especially those from WP7 for developing all materials supporting the fieldwork, WP9 for organizing the QA/QC scheme under HBM4EU and all laboratories who performed the analytical measurements. We would like to acknowledge Sun Kyoung Jung from the National Institute of Environmental Research of South-Korea for providing the KoNEHS Cycle III results (crt adjusted). HBM4EU is co-financed under Horizon 2020 (grant agreement No 733032). The authors thank all principal investigators of the contributing studies for their participation and contribution to the HBM4EU Aligned Studies and the national program owners for their financial support. Further details on funding for all the participating studies can be found in the Supplemental Material, Table S12.As 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, Σ (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.publishersversionpublishe
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)
HBM4EU is co-financed under Horizon 2020 (grant agreement No 733032).As 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 from 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, and 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 the highest exceedance rates for toxicologically relevant arsenic in teenagers (40%), 3-PBA in children (36%), and between 11 and 14% for total DON, Σ (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 policymakers for the implementation of targeted measures.info:eu-repo/semantics/publishedVersio
From science to policy: How European HBM indicators help to answer policy questions related to phthalates and DINCH exposure
Within the European Human Biomonitoring (HBM) Initiative HBM4EU we derived HBM indicators that were designed to help answering key policy questions and support chemical policies. The result indicators convey information on chemicals exposure of different age groups, sexes, geographical regions and time points by comparing median exposure values. If differences are observed for one group or the other, policy measures or risk management options can be implemented. Impact indicators support health risk assessment by comparing exposure values with health-based guidance values, such as human biomonitoring guidance values (HBM-GVs). In general, the indicators should be designed to translate complex scientific information into short and clear messages and make it accessible to policy makers but also to a broader audience such as stakeholders (e.g. NGO's), other scientists and the general public. Based on harmonized data from the HBM4EU Aligned Studies (2014-2021), the usefulness of our indicators was demonstrated for the age group children (6-11 years), using two case examples: one phthalate (Diisobutyl phthalate: DiBP) and one non-phthalate substitute (Di-isononyl cyclohexane-1,2- dicarboxylate: DINCH). For the comparison of age groups, these were compared to data for teenagers (12-18 years), and time periods were compared using data from the DEMOCOPHES project (2011-2012). Our result indicators proved to be suitable for demonstrating the effectiveness of policy measures for DiBP and the need of continuous monitoring for DINCH. They showed similar exposure for boys and girls, indicating that there is no need for gender focused interventions and/or no indication of sex-specific exposure patterns. They created a basis for a targeted approach by highlighting relevant geographical differences in internal exposure. An adequate data basis is essential for revealing differences for all indicators. This was particularly evident in our studies on the indicators on age differences. The impact indicator revealed that health risks based on exposure to DiBP cannot be excluded. This is an indication or flag for risk managers and policy makers that exposure to DiBP still is a relevant health issue. HBM indicators derived within HBM4EU are a valuable and important complement to existing indicator lists in the context of environment and health. Their applicability, current shortcomings and solution strategies are outlined
Exposure Levels of Pyrethroids, Chlorpyrifos and Glyphosate in EU—An Overview of Human Biomonitoring Studies Published since 2000
Currently used pesticides are rapidly metabolised and excreted, primarily in urine, and urinary concentrations of pesticides/metabolites are therefore useful biomarkers for the integrated exposure from all sources. Pyrethroid insecticides, the organophosphate insecticide chlorpyrifos, and the herbicide glyphosate, were among the prioritised substances in the HBM4EU project and comparable human biomonitoring (HBM)-data were obtained from the HBM4EU Aligned Studies. The aim of this review was to supplement these data by presenting additional HBM studies of the priority pesticides across the HBM4EU partner countries published since 2000. We identified relevant studies (44 for pyrethroids, 23 for chlorpyrifos, 24 for glyphosate) by literature search using PubMed and Web of Science. Most studies were from the Western and Southern part of the EU and data were lacking from more than half of the HBM4EU-partner countries. Many studies were regional with relatively small sample size and few studies address residential and occupational exposure. Variation in urine sampling, analytical methods, and reporting of the HBM-data hampered the comparability of the results across studies. Despite these shortcomings, a widespread exposure to these substances in the general EU population with marked geographical differences was indicated. The findings emphasise the need for harmonisation of methods and reporting in future studies as initiated during HBM4EU
Literature review and evaluation of biomarkers, matrices and analytical methods for chemicals selected in the research program Human Biomonitoring for the European Union (HBM4EU)
Humans are potentially exposed to a large amount of chemicals present in the environment and in the workplace. In the European Human Biomonitoring initiative (Human Biomonitoring for the European Union = HBM4EU), acrylamide, mycotoxins (aflatoxin B1, deoxynivalenol, fumonisin B1), diisocyanates (4,4′-methylenediphenyl diisocyanate, 2,4- and 2,6-toluene diisocyanate), and pyrethroids were included among the prioritized chemicals of concern for human health. For the present literature review, the analytical methods used in worldwide biomonitoring studies for these compounds were collected and presented in comprehensive tables, including the following parameter: determined biomarker, matrix, sample amount, work-up procedure, available laboratory quality assurance and quality assessment information, analytical techniques, and limit of detection. Based on the data presented in these tables, the most suitable methods were recommended. According to the paradigm of biomonitoring, the information about two different biomarkers of exposure was evaluated: a) internal dose = parent compounds and metabolites in urine and blood; and b) the biologically effective = dose measured as blood protein adducts. Urine was the preferred matrix used for deoxynivalenol, fumonisin B1, and pyrethroids (biomarkers of internal dose). Markers of the biological effective dose were determined as hemoglobin adducts for diisocyanates and acrylamide, and as serum-albumin-adducts of aflatoxin B1 and diisocyanates. The analyses and quantitation of the protein adducts in blood or the metabolites in urine were mostly performed with LC-MS/MS or GC-MS in the presence of isotope-labeled internal standards. This review also addresses the critical aspects of the application, use and selection of biomarkers. For future biomonitoring studies, a more comprehensive approach is discussed to broaden the selection of compounds
Congenital mirror movements are associated with defective polymerization of RAD51
International audienceBackground. Mirror movements are involuntary movements of one hand that mirror intentional movements of the other hand. Congenital mirror movements (CMM) is a rare genetic disorder with autosomal dominant inheritance, in which mirror movements are the main neurological manifestation. CMM is associated with an abnormal decussation of the corticospinal tract, a major motor tract for voluntary movements. RAD51 is known to play a key role in homologous recombination with a critical function in DNA repair. While RAD51 haploinsufficiency was first proposed to explain CMM, other mechanisms could be involved. Methods. We performed Sanger sequencing of RAD51 in five newly identified CMM families to identify new pathogenic variants. We further investigated the expression of wild-type and mutant RAD51 in the patients' lymphoblasts at mRNA and protein levels. We then characterized the functions of RAD51 altered by non-truncating variants using biochemical approaches. Results. The level of wild-type RAD51 protein was lower in all the CMM patients' cells compared with their non-carrier relatives. The reduction was less pronounced in asymptomatic carriers. In vitro, mutant RAD51 proteins showed loss-of-function for polymerization, DNA binding, and strand exchange activity. Conclusion. Our study demonstrates that RAD51 haploinsufficiency, including loss-offunction of non-truncating variants, results in CMM. The incomplete penetrance likely results from post-transcriptional compensation. Changes in RAD51 levels and/or polymerization properties could influence guidance of the corticospinal axons during development. Our findings open up new perspectives to understand the role of RAD51 in neurodevelopment