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

HBM4EU-MOM: Prenatal methylmercury-exposure control in five countries through suitable dietary advice for pregnancy – Study design and characteristics of participants

Background: 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 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.We acknowledge funding for HBM4EU from the European Union’s Horizon 2020 research and innovation program under grant agreement #733032 and the national governments of the participating countries. This publication reflects only the authors’ views, and the European Commission is not responsible for any use that may be made of the in formation it contains.info:eu-repo/semantics/publishedVersio

Economic benefits of methylmercury exposure control in Europe : monetary value of neurotoxicity prevention

© 2013 Bellanger et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background: Due to global mercury pollution and the adverse health effects of prenatal exposure to methylmercury (MeHg), an assessment of the economic benefits of prevented developmental neurotoxicity is necessary for any cost-benefit analysis. Methods: Distributions of hair-Hg concentrations among women of reproductive age were obtained from the DEMOCOPHES project (1,875 subjects in 17 countries) and literature data (6,820 subjects from 8 countries). The exposures were assumed to comply with log-normal distributions. Neurotoxicity effects were estimated from a linear dose-response function with a slope of 0.465 Intelligence Quotient (IQ) point reduction per μg/g increase in the maternal hair-Hg concentration during pregnancy, assuming no deficits below a hair-Hg limit of 0.58 μg/g thought to be safe. A logarithmic IQ response was used in sensitivity analyses. The estimated IQ benefit cost was based on lifetime income, adjusted for purchasing power parity. Results: The hair-mercury concentrations were the highest in Southern Europe and lowest in Eastern Europe. The results suggest that, within the EU, more than 1.8 million children are born every year with MeHg exposures above the limit of 0.58 μg/g, and about 200,000 births exceed a higher limit of 2.5 μg/g proposed by the World Health Organization (WHO). The total annual benefits of exposure prevention within the EU were estimated at more than 600,000 IQ points per year, corresponding to a total economic benefit between €8,000 million and €9,000 million per year. About four-fold higher values were obtained when using the logarithmic response function, while adjustment for productivity resulted in slightly lower total benefits. These calculations do not include the less tangible advantages of protecting brain development against neurotoxicity or any other adverse effects. Conclusions: These estimates document that efforts to combat mercury pollution and to reduce MeHg exposures will have very substantial economic benefits in Europe, mainly in southern countries. Some data may not be entirely representative, some countries were not covered, and anticipated changes in mercury pollution all suggest a need for extended biomonitoring of human MeHg exposure.Exposure data were contributed from the DEMOCOPHES project (LIFE09 ENV/BE/000410) carried out thanks to joint financing of 50% from the European Commission programme LIFE + along with 50% from each participating country (see the national implementation websites accessible via http://www.eu-hbm.info/democophes/project-partners). Special thanks go to the national implementation teams. The COPHES project that provided the operational and scientific framework was funded by the European Community's Seventh Framework Programme - DG Research (Grant Agreement Number 244237). Additional exposure data were supported by the PHIME project (FOOD-CT-2006-016253) and ArcRisk (GA 226534). We are grateful to Yue Gao and colleagues for sharing Flanders exposure data from the Flemish Center of Expertise on Environment and Health, financed and steered by the Ministry of the Flemish Community. National exposure data from the 2006–2007 French national survey on nutrition and health (Etude Nationale Nutrition Santé) were made available by Nadine Fréry, French Institute for Public Health Surveillance. Data from the Norwegian Mother and Child Cohort Study (a validation sample) were kindly provided by Anne Lise Brantsæter, National Institute of Public Health, Oslo. The UK mercury data were obtained from the ALSPAC pregnancy blood analyses carried out at the Centers for Disease Control and Prevention with funding from NOAA (the US National Oceanographic and Atmospheric Administration). The studies in the Faroe Islands were supported by the US National Institutes of Health (ES009797 and ES012199). The contents of this paper are solely the responsibility of the authors and do not necessarily represent the official views of the funding agencies

Has the 3R's Concept a Future in Ecotoxicology?

The 3Rs approach as formulated by Russel and Birch in 1959 is outlining 3 strategies for reducing the number and the suffering of experimental animals used in research and testing through ¿Replacement, Reduction and Refinement¿. We here discuss if a 3R's based approach can be applied in testing of ecotoxicity of chemicals with the ambition to abolish the use of experimental animals in favour of a battery of alternative methods. The current status of alternatives in aquatic ecotoxicology is reviewed and how well they perform in comparison with current in vivo methods. We conclude that theoretically can alternative methods and approaches replace animal based testing but the way to reach this goal is long. A development of more sophisticated alternative methods is needed focusing on specific and physiologically/toxicologically representative endpoints. We underline the importance to gain more information on toxic mechanisms of chemicals and here will hopefully the rapid developments in the ¿omics¿ area give new possibilities. The issue is how to interpret results from highly refined in vitro systems to ¿ecological relevance¿. The leap is probably not as big as it seems in a first glance.We should not be blinded by ecological ¿fundamentalism¿. The ecosystem is built up by individuals. If the survival and fitness of individuals are compromised the whole system will suffer. The current in vitro methods and particularly and hopefully the future methods have the full potential to protect individuals, and by proper models and assumptions the ecosystem. Email Address for correspondence: [email protected]

Testing in Aquatic Ecotoxicology - What Are the Scientific Conditions for the '3R' Concept?

Europe is introducing a new regulatory system (REACH) for management of chemicals. The overriding objective is to ensure protection of human health and the environment and at the same time have a control of the flow of use of chemicals in the Society. An important component in REACH is extended hazard assessment for chemicals in use of more than 1 ton/year. Approximately 30.000 chemicals fall in this group. Information on toxicity and the biological behaviour of chemicals has therefore a central position in REACH. This need leads to an increasing demand on biological tests and test methods. However, already in the starting instructions of REACH (Commission White Paper on a new Chemical legislation, EC 2001) it was stated that REACH should not lead to an increased use of test animals. Instead, REACH should stimulate the development of alternative methods and approaches. These include in vitro methods, in silico methods (QSAR, SAR) and the optimal use of information from one method to another, so called ¿read across¿. An intensive development is currently going on, particularly in the industry, to meet the REACH testing requirements in a cost-effective manner. In this chapter, we will evaluate how and if a 3R based approach can be applied in testing of ecotoxicity of chemicals. The 3R approach (reduce-refine-replace) is a strategy to reduce or totally abolish the use of experimental animals in favour of alternative methods. We review the current status of alternatives in aquatic ecotoxicology and how well they perform in comparison with current in vivo methods. We will conclude that theoretically can alternative methods and approaches replace animal based testing but the way to reach this goal is long. A strong development of more sophisticated alternative methods is needed focusing on specific and physiologically/toxicologically representative endpoints. We underline the importance to gain more information on toxic mechanisms of chemicals. New exciting biochemical techniques are waiting around the corner, e.g. in the genomics area and they need to be integrated in future test paradigms.JRC.DDG.H.ADV01-Adviso

Harmonised human biomonitoring in Europe: Activities towards an EU HBM framework

Human biomonitoring (HBM) can be an effective tool to assess human exposure to environmental pollutants and potential health effects and is increasingly seen as an essential element in a strategy when integrating health and environment. HBM can be used (i) to prioritise actions and measures for policy making; (ii) to evaluate policy actions aimed at reducing exposure to potentially hazardous environmental stressors; and (iii) to promote more comprehensive health impact assessments of policy options. In support of the European Environment and Health Action Plan 2004-2010, European scientists, experts from authorities and other stakeholders joined forces to work towards developing a functional framework and standards for a coherent HBM in Europe. Within the European coordination action on human biomonitoring, 35 partners from 27 European countries in the COPHES consortium aggregated their experiences and expertise and developed harmonized approaches and recommendations for better comparability of HBM data in Europe via the elaboration of a harmonized study protocol. This protocol is the product of discussion and compromises on the selection of environmental exposures, national environmental health concerns, and political and health priorities. The harmonised approach includes sampling recruitment, and analytical procedures, communication strategies and biobanking initiatives. The protocols and the harmonised approach are a means to increase acceptance and policy support and to in the future to enable determination of time trends. The common pilot study protocol will shortly be tested, adapted and assessed in the framework of the DEMOCOPHES in 17 European countries, including 16 EU Member States. COPHES and DEMOCOPHES constitute important steps towards establishing human biomonitoring as a tool for EU environmental and health policy and to improve quantification of exposure of the general European population to existing and emerging pollutants.status: publishe

The Use of Fish Cells in Ecotoxicology. The Report and Recommendations of ECVAM Workshop No. 47.

Abstract not availableJRC.I-Institute for Health and Consumer Protection (Ispra