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- Time Trends of Acrylamide Exposure in Europe: Combined Analysis of Published Reports and Current HBM4EU StudiesPublication . Poteser, Michael; Laguzzi, Federica; Schettgen, Thomas; Vogel, Nina; Weber, Till; Zimmermann, Philipp; Hahn, Domenica; Kolossa-Gehring, Marike; Namorado, Sónia; Van Nieuwenhuyse, An; Appenzeller, Brice; Halldorsson, Thorhallur; Eiríksdóttir, Ása; Haug, Line Småstuen; Thomsen, Cathrine; Barbone, Fabio; Rosolen, Valentina; RAMBAUD, Loic; RIOU, Margaux; Göen, Thomas; Nübler, Stefanie; Schäfer, Moritz; Haji-Abbas-Zarrabi, Karin; Gilles, Liese; Rodriguez Martin, Laura; Schoeters, Greta; Sepai, Ovnair; Govarts, Eva; Moshammer, HannsMore 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.
- Cadmium exposure in adults across Europe: Results from the HBM4EU Aligned Studies survey 2014-2020Publication . Snoj Tratnik, Janja; Kocman, David; Horvat, Milena; Andersson, Anna-Maria; Juul, Anders; Jacobsen, Eva; Olafsdottir, Kristin; Klanova, Jana; Andryskova, Lenka; Janasik, Beata; Wasowicz, Wojciech; Janev Holcer, Natasa; Namorado, Sónia; Coelho, Inês; Rambaud, Loic; Riou, Margaux; Van Nieuwenhuyse, An; Appenzeller, Brice; Kolossa-Gehring, Marike; Weber, Till; Esteban, Marta; Castano, Argelia; Gilles, Liese; Rodriguez Martin, Laura; Schoeters, Greta; Sepai, Ovnair; Govarts, EvaThe 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.
- HBM4EU-MOM: Prenatal methylmercury-exposure control in five countries through suitable dietary advice for pregnancy – Study design and characteristics of participantsPublication . Katsonouri, Andromachi; Gabriel, Catherine; Esteban López, Marta; Namorado, Sónia; Halldorsson, Thorhallur; Snoj Tratnik, Janja; Rodriguez Martin, Laura; Karakoltzidis, Achilleas; Chatzimpaloglou, Anthoula; Giannadaki, Despina; Anastasi, Elena; Thoma, Anthi; Domínguez-Morueco, Noelia; Cañas, Ana; Jacobsen, Eva; Assunção, Ricardo; Peres, Maria; Santiago, Susana; Nunes, Carla; Pedraza-Diaz, Susana; Iavicoli, Ivo; Leso, Veruscka; Lacasaña, Marina; González-Alzaga, Beatriz; Horvat, Milena; Sepai, Ovnair; Castano, Argelia; Kolossa-Gehring, Marike; Karakitsios, Spyros; Sarigiannis, DimosthenisBackground: Seafood is a major source of vital nutrients for optimal fetal growth, but at the same time is the main source of exposure to methylmercury (MeHg), an established neurodevelopmental toxicant. Pregnant women must be provided with dietary advice so as to include safely fish in their diet for nutrition and mercury control. The aim of this work is to present the design of a multicentre randomized control trial (RCT), which combines human biomonitoring (HBM) with dietary interventions using seafood consumption advice to pregnant women for MeHg control, and to collect information about other possible sources of exposure to mercury. It also presents the materials developed for the implementation of the study and the characteristics of the study participants, which were self-reported in the first trimester of pregnancy. Methods: The "HBM4EU-MOM" RCT was performed in the frame of the European Human Biomonitoring Initiative (HBM4EU) in five coastal, high fish-consuming European countries (Cyprus, Greece, Spain, Portugal and Iceland). According to the study design, pregnant women (≥120/country, ≤20 weeks gestational age) provided a hair sample for total mercury assessment (THg) and personal information relevant to the study (e.g., lifestyle, pregnancy status, diet before and during the pregnancy, information on seafood and factors related to possible non-dietary exposures to mercury) during the first trimester of pregnancy. After sampling, participants were randomly assigned to "control" (habitual practices) or "intervention" (received the harmonized HBM4EU-MOM dietary advice for fish consumption during the pregnancy and were encouraged to follow it). Around child delivery, participants provided a second hair sample and completed another tailored questionnaire. Results: A total of 654 women aged 18-45 years were recruited in 2021 in the five countries, primarily through their health-care providers. The pre-pregnancy BMI of the participants ranged from underweight to obese, but was on average within the healthy range. For 73% of the women, the pregnancy was planned. 26% of the women were active smokers before the pregnancy and 8% continued to smoke during the pregnancy, while 33% were passive smokers before pregnancy and 23% remained passively exposed during the pregnancy. 53% of the women self-reported making dietary changes for their pregnancy, with 74% of these women reporting making the changes upon learning of their pregnancy. Of the 43% who did not change their diet for the pregnancy, 74% reported that their diet was already balanced, 6% found it difficult to make changes and 2% were unsure of what changes to make. Seafood consumption did not change significantly before and during the first trimester of pregnancy (overall average ∼8 times per month), with the highest frequency reported in Portugal (≥15 times per month), followed by Spain (≥7 times per month). During the first-trimester of pregnancy, 89% of the Portuguese women, 85% of the Spanish women and <50% of Greek, Cypriot and Icelandic women reported that they had consumed big oily fish. Relevant to non-dietary exposure sources, most participants (>90%) were unaware of safe procedures for handling spillage from broken thermometers and energy-saving lamps, though >22% experienced such an incident (>1 year ago). 26% of the women had dental amalgams. ∼1% had amalgams placed and ∼2% had amalgams removed during peri-pregnancy. 28% had their hair dyed in the past 3 months and 40% had body tattoos. 8% engaged with gardening involving fertilizers/pesticides and 19% with hobbies involving paints/pigments/dyes. Conclusions: The study design materials were fit for the purposes of harmonization and quality-assurance. The harmonized information collected from pregnant women suggests that it is important to raise the awareness of women of reproductive age and pregnant women about how to safely include fish in their diet and to empower them to make proper decisions for nutrition and control of MeHg, as well as other chemical exposures.
- Harmonization of Human Biomonitoring Studies in Europe: Characteristics of the HBM4EU-Aligned Studies ParticipantsPublication . Gilles, Liese; Govarts, Eva; Rodriguez Martin, Laura; Andersson, Anna-Maria; Appenzeller, Brice M.R.; Barbone, Fabio; Castano, Argelia; Coertjens, Dries; Den Hond, Elly; Dzhedzheia, Vazha; Eržen, Ivan; Esteban, Marta; Fábelová, Lucia; Fillol, Clémence; Franken, Carmen; Frederiksen, Hanne; Gabriel, Catherine; Haug, Line Småstuen; Horvat, Milena; Halldórsson, Thórhallur Ingi; Janasik, Beata; Holcer, Nataša Janev; Kakucs, Réka; Karakitsios, Spyros; Katsonouri, Andromachi; Klánová, Jana; Kold-Jensen, Tina; Kolossa-Gehring, Marike; Konstantinou, Corina; Koponen, Jani; Lignell, Sanna; Lindroos, Anna Karin; Makris, Konstantinos C.; Mazej, Darja; Morrens, Bert; Murínová, Ľubica Palkovičová; Namorado, Sónia; Pedraza-Diaz, Susana; Peisker, Jasmin; Probst-Hensch, Nicole; Rambaud, Loïc; Rosolen, Valentina; Rucic, Enrico; Rüther, Maria; Sarigiannis, Dimosthenis; Tratnik, Janja Snoj; Standaert, Arnout; Stewart, Lorraine; Szigeti, Tamás; Thomsen, Cathrine; Tolonen, Hanna; Eiríksdóttir, Ása; Van Nieuwenhuyse, An; Verheyen, Veerle J.; Vlaanderen, Jelle; Vogel, Nina; Wasowicz, Wojciech; Weber, Till; Zock, Jan-Paul; Sepai, Ovnair; Schoeters, GreetHuman 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 sociodemographics, 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 under represented. 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.
- 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)Publication . Govarts, Eva; Gilles, Liese; Rodriguez Martin, Laura; Santonen, Tiina; Apel, Petra; Alvito, Paula; Anastasi, Elena; Andersen, Helle Raun; Andersson, Anna-Maria; Andryskova, Lenka; ANTIGNAC, Jean-Philippe; Rüther, Maria; Sarigiannis, Denis; Silva, Maria João; Šlejkovec, Zdenka; Snoj Tratnik, Janja; Stajnko, Anja; Szigeti, Tamas; Tarazona, Jose; Thomsen, Cathrine; Tkalec, Žiga; Trnovec, Tomas; Tolonen, Hanna; Uhl, Maria; Van Nieuwenhuyse, An; Vasco, Elsa; Verheyen, Veerle J.; Viegas, Susana; Vinggaard, Anne Marie; Vogel, Nina; Vorkamp, Katrin; Wasowicz, Wojciech; Wimmerova, Sona; Weber, Till; Woutersen, Marjolijn; Zimmermann, Philipp; Zvonar, Martin; Koch, Holger; Kolossa-Gehring, Marike; Esteban López, Marta; Castano, Argelia; Stewart, Lorraine; Sepai, Ovnair; Appenzeller, Brice; Schoeters, Greta; Barbone, Fabio; Barnett-Itzhaki, Zohar; Barouki, Robert; Berman, Tamar; Bil, Wieneke; Borges, Teresa; Buekers, Jurgen; Cañas-Portilla, Ana; Covaci, Adrian; Csako, Zsofia; Den Hond, Elly; Dvorakova, Darina; Fabelova, Lucia; Fletcher, Tony; Frederiksen, Hanne; Gabriel, Catherine; Ganzleben, Catherine; Göen, Thomas; Halldorsson, Thorhallur; Haug, Line Småstuen; Horvat, Milena; Huuskonen, Pasi; Imboden, Medea; Jagodic Hudobivnik, Marta; Janasik, Beata; Janev Holcer, Natasa; Karakitsios, Spyros; Katsonouri, Andromachi; Klanova, Jana; Kokaraki, Venetia; Kold Jensen, Tina; Koponen, Jani; Laeremans, Michelle; Laguzzi, Federica; Lange, Rosa; Lemke, Nora; Lignell, Sanna; Lindroos, Anna Karin; Lobo Vicente, Joana; Luijten, Mirjam; Makris, Konstantinos C.; Mazej, Darja; Melymuk, Lisa; Meslin, Matthieu; Mol, Hans; Montazeri, Parisa; Murawski, Aline; Namorado, Sónia; Niemann, Lars; Nübler, Stefanie; Nunes, Baltazar; Olafsdottir, Kristin; Palkovicova Murinova, Lubica; Papaioannou, Nafsika; Pedraza-Diaz, Susana; Piler, Pavel; Plichta, Veronika; Poteser, Michael; Probst-Hensch, Nicole; Rambaud, Loic; Rauscher-Gabernig, Elke; Rausova, Katarina; Remy, Sylvie; Riou, Margaux; Rosolen, Valentina; Rousselle, ChristopheAbstract: 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.
- Trends of Exposure to Acrylamide as Measured by Urinary Biomarkers Levels within the HBM4EU Biomonitoring Aligned Studies (2000–2021)Publication . Poteser, Michael; Laguzzi, Federica; Schettgen, Thomas; Vogel, Nina; Weber, Till; Murawski, Aline; Schmidt, Phillipp; Rüther, Maria; Kolossa-Gehring, Marike; Namorado, Sónia; Van Nieuwenhuyse, An; Appenzeller, Brice; Dufthaksdóttir, Edda; Olafsdottir, Kristin; Haug, Line Småstuen; Thomsen, Cathrine; Barbone, Fabio; Rosolen, Valentina; RAMBAUD, Loic; RIOU, Margaux; Göen, Thomas; Nübler, Stefanie; Schäfer, Moritz; Zarrabi, Karin H.A.; Gilles, Liese; Rodriguez Martin, Laura; Schoeters, Greta; Sepai, Ovnair; Govarts, Eva; Moshammer, HannsAcrylamide, 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.
