The GEMAS Project: Geochemistry of European agricultural and grazing land soils.

Viene illustrato il progetto GEMAS che ha interessato la campionatura e le analisi di suoli dell'ntero continente Europeo da parte dei Servizi Geologici d'Europa, nell'ìambito delle attività dell'EuroGeoSurvey

Transcriptome Analysis in Peripheral Blood of Humans Exposed to Environmental Carcinogens: A Promising New Biomarker in Environmental Health Studies

BACKGROUND: Human carcinogenesis is known to be initiated and/or promoted by exposure to chemicals that occur in the environment. Molecular cancer epidemiology is used to identify human environmental cancer risks by applying a range of effect biomarkers, which tend to be nonspecific and do not generate insights into underlying modes of action. Toxicogenomic technologies may improve on this by providing the opportunity to identify, molecular biomarkers consisting of altered gene expression profiles. OBJECTIVES: The aim of the present study, was to monitor the expression of selected genes in a random sample of adults in Flanders selected from specific regions with (presumably,) different environmental burdens. Furthermore, associations of gene expression with blood and urinary, measures of biomarkers of exposure, early, phenotypic effects, and tumor markers were investigated. RESULTS: Individual gene expression of cytochrome p450 1B1, activating transcription factor 4, mitogen-activated protein kinase K superoxide dismutase 2 (Mn), chemokine (C-X-C motif) ligand 1 (melanoma growth stimulating activity, alpha), diacylglycerol 0 acyltransferase homolog 2 (mouse), tigger transposable element derived 3, and PTEN-induced putative kinasel were measured by means of quantitative polymerase chain reaction in peripheral blood cells of 398 individuals. After correction for the confounding effect of tobacco smoking, inhabitants of the Olen region showed the highest differences in gene expression levels compared with inhabitants from the Gent and fruit cultivation regions. Importantly, we observed multiple significant correlations of particular gene expressions with blood and urinary, measures of various environmental carcinogens. CONCLUSIONS: Considering the observed significant differences between gene expression levels in inhabitants of various regions in Flanders and the associations of gene expression with blood or urinary measures of environmental carcinogens, we conclude that gene expression profiling appears promising as a tool for biological monitoring in relation to environmental exposures in humans

Glyphosate and AMPA in human urine of HBM4EU-aligned studies: part B adults

Within HBM4EU, human biomonitoring (HBM) studies measuring glyphosate (Gly) and aminomethylphosphonic acid (AMPA) in urine samples from the general adult population were aligned and quality-controlled/assured. Data from four studies (ESB Germany (2015-2020); Swiss HBM4EU study (2020); DIET-HBM Iceland (2019-2020); ESTEBAN France (2014-2016)) were included representing Northern and Western Europe. Overall, median values were below the reported quantification limits (LOQs) (0.05-0.1 microg/L). The 95th percentiles (P95) ranged between 0.24 and 0.37 microg/L urine for Gly and between 0.21 and 0.38 microg/L for AMPA. Lower values were observed in adults compared to children. Indications exist for autonomous sources of AMPA in the environment. As for children, reversed dosimetry calculations based on HBM data in adults did not lead to exceedances of the ADI (proposed acceptable daily intake of EFSA for Gly 0.1 mg/kg bw/day based on histopathological findings in the salivary gland of rats) indicating no human health risks in the studied populations at the moment. However, the controversy on carcinogenicity, potential endocrine effects and the absence of a group ADI for Gly and AMPA induce uncertainty to the risk assessment. Exposure determinant analysis showed few significant associations. More data on specific subgroups, such as those occupationally exposed or living close to agricultural fields or with certain consumption patterns (vegetarian, vegan, organic food, high cereal consumer), are needed to evaluate major exposure sources

Prenatal and postnatal exposure to persistent organic pollutants and Infant growth: A pooled analysis of seven european birth cohorts

Background: Infant exposure to persistent organic pollutants (POPs) may contribute to obesity. However, many studies so far have been small, focused on transplacental exposure, used an inappropriate measure to assess postnatal exposure through breastfeeding if any, or did not discern between prenatal and postnatal effects. Objectives: We investigated prenatal and postnatal exposure to POPs and infant growth (a predictor of obesity). Methods: We pooled data from seven European birth cohorts with biomarker concentrations of polychlorinated biphenyl 153 (PCB-153) (n = 2,487), and p,p´-dichlorodiphenyldichloroethylene (p,p´-DDE) (n = 1,864), estimating prenatal and postnatal POPs exposure using a validated pharmacokinetic model. Growth was change in weight-for-age z-score between birth and 24 months. Per compound, multilevel models were fitted with either POPs total exposure from conception to 24 months or prenatal or postnatal exposure. Results: We found a significant increase in growth associated with p,p´-DDE, seemingly due to prenatal exposure (per interquartile increase in exposure, adjusted β = 0.12; 95% CI: 0.03, 0.22). Due to heterogeneity across cohorts, this estimate cannot be considered precise, but does indicate that an association with infant growth is present on average. In contrast, a significant decrease in growth was associated with postnatal PCB-153 exposure (β = –0.10; 95% CI: –0.19, –0.01). Conclusion: To our knowledge, this is the largest study to date of POPs exposure and infant growth, and it contains state-of-the-art exposure modeling. Prenatal p,p´-DDE was associated with increased infant growth, and postnatal PCB-153 with decreased growth at European exposure levels

Approaches to mixture risk assessment of PFASs in the European population based on human hazard and biomonitoring data

Per- and polyfluoroalkyl substances (PFASs) are a highly persistent, mobile, and bioaccumulative class of chemicals, of which emissions into the environment result in long-lasting contamination with high probability for causing adverse effects to human health and the environment. Within the European Biomonitoring Initiative HBM4EU, samples and data were collected in a harmonized way from human biomonitoring (HBM) studies in Europe to derive current exposure data across a geographic spread. We performed mixture risk assessments based on recent internal exposure data of PFASs in European teenagers generated in the HBM4EU Aligned Studies (dataset with N = 1957, sampling years 2014-2021). Mixture risk assessments were performed based on three hazard-based approaches: the Hazard Index (HI) approach, the sum value approach as used by the European Food Safety Authority (EFSA) and the Relative Potency Factor (RPF) approach. The HI approach resulted in the highest risk estimates, followed by the RPF approach and the sum value approach. The assessments indicate that PFAS exposure may result in a health risk in a considerable fraction of individuals in the HBM4EU teenager study sample, thereby confirming the conclusion drawn in the recent EFSA scientific opinion. This study underlines that HBM data are of added value in assessing the health risks of aggregate and cumulative exposure to PFASs, as such data are able to reflect exposure from different sources and via different routes.This work was supported by the European Union’s Horizon 2020 research and innovation programme under Grant agreement No 733032 HBM4EU (www.HBM4EU.eu), and received co-funding from the au thors’ organizations. The Norwegian Institute of Public Health (NIPH) has contributed to funding of the Norwegian Environmental Biobank (NEB), and the laboratory measurements have partly been funded by the Research Council of Norway through research projects (275903 and 268465). The PCB cohort (follow-up) received additional funding from the Ministry of Health of the Slovak Republic (program 07B0103).S

Time Trends of Acrylamide Exposure in Europe: Combined Analysis of Published Reports and Current HBM4EU Studies

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

Birth Weight and Prenatal Exposure to Polychlorinated Biphenyls (PCBs) and Dichlorodiphenyldichloroethylene (DDE): A Meta-analysis within 12 European Birth Cohorts

Objectives: Exposure to high concentrations of persistent organochlorines may cause fetal toxicity, but the evidence at low exposure levels is limited. Large studies with substantial exposure contrasts and appropriate exposure assessment are warranted. Within the framework of the EU (European Union) ENRIECO (ENvironmental Health RIsks in European Birth Cohorts) and EU OBELIX (OBesogenic Endocrine disrupting chemicals: LInking prenatal eXposure to the development of obesity later in life) projects, we examined the hypothesis that the combination of polychlorinated biphenyls (PCBs) and dichlorodiphenyldichloroethylene (DDE) adversely affects birth weight

PFAS levels and determinants of variability in exposure in European teenagers - Results from the HBM4EU aligned studies (2014-2021)

Background: Perfluoroalkyl substances (PFAS) are man-made fluorinated chemicals, widely used in various types of consumer products, resulting in their omnipresence in human populations. The aim of this study was to describe current PFAS levels in European teenagers and to investigate the determinants of serum/plasma concentrations in this specific age group. Methods: PFAS concentrations were determined in serum or plasma samples from 1957 teenagers (12-18 years) from 9 European countries as part of the HBM4EU aligned studies (2014-2021). Questionnaire data were post-harmonized by each study and quality checked centrally. Only PFAS with an overall quantification frequency of at least 60% (PFOS, PFOA, PFHxS and PFNA) were included in the analyses. Sociodemographic and lifestyle factors were analysed together with food consumption frequencies to identify determinants of PFAS exposure. The variables study, sex and the highest educational level of household were included as fixed factors in the multivariable linear regression models for all PFAS and each dietary variable was added to the fixed model one by one and for each PFAS separately. Results: The European exposure values for PFAS were reported as geometric means with 95% confidence intervals (CI): PFOS [2.13 μg/L (1.63-2.78)], PFOA ([0.97 μg/L (0.75-1.26)]), PFNA [0.30 μg/L (0.19-0.45)] and PFHxS [0.41 μg/L (0.33-0.52)]. The estimated geometric mean exposure levels were significantly higher in the North and West versus the South and East of Europe. Boys had significantly higher concentrations of the four PFAS compared to girls and significantly higher PFASs concentrations were found in teenagers from households with a higher education level. Consumption of seafood and fish at least 2 times per week was significantly associated with 21% (95% CI: 12-31%) increase in PFOS concentrations and 20% (95% CI: 10-31%) increase in PFNA concentrations as compared to less frequent consumption of seafood and fish. The same trend was observed for PFOA and PFHxS but not statistically significant. Consumption of eggs at least 2 times per week was associated with 11% (95% CI: 2-22%) and 14% (95% CI: 2-27%) increase in PFOS and PFNA concentrations, respectively, as compared to less frequent consumption of eggs. Significantly higher PFOS concentrations were observed for participants consuming offal (14% (95% CI: 3-26%)), the same trend was observed for the other PFAS but not statistically significant. Local food consumption at least 2 times per week was associated with 40% (95% CI: 19-64%) increase in PFOS levels as compared to those consuming local food less frequently. Conclusion: This work provides information about current levels of PFAS in European teenagers and potential dietary sources of exposure to PFAS in European teenagers. These results can be of use for targeted monitoring of PFAS in food.This work was supported by the European Union’s Horizon 2020 research and innovation programme under Grant agreement No 733032 HBM4EU (www.HBM4EU.eu), and received co-funding from the authors’ organizations: Riksmaten Adolescents: Riksmaten Adolescents was performed by the Swedish Food Agency with financial support from the Swedish Environmental Protection Agency and the Swedish Civil Contingencies Agency. NEB II: The Norwegian Institute of Public Health (NIPH) has contributed to 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) PCB cohort follow-up: PCB cohort follow-up received additional funding from the Ministry of Health of the Slovak Republic, program 07B0103. BEA: BEA study was funded by the Spanish Ministry of Agriculture, Fisheries and Food and the Instituto de Salud Carlos III (SEG 1321/15) SLO-CRP: The Slovenian SLO-CRP study was co-financed by the Jozef Stefan Institute program P1- 0143, and a national project “Exposure of children and adolescents to selected chemicals through their habitat environment” (grant agreement No. C2715-16-634802). CROME: CROME study was co-funded by the European Commission research funds of Horizon 2020. ESTEBAN: ESTEBAN study was funded by Santé Publique France and the French ministries of Health and the Environment. GerES V-sub: The funding of the German Ministry for the Environment, Nature Conservation, Nuclear Safety and Consumer Protection is gratefully acknowledged. FLEHS IV: The Flemish Center of Expertise on Environment and Health is funded by the Government of Flanders, Department of Environment & Spatial Development.S

Prenatal Stress Exposure Related to Maternal Bereavement and Risk of Childhood Overweight

BACKGROUND: It has been suggested that prenatal stress contributes to the risk of obesity later in life. In a population-based cohort study, we examined whether prenatal stress related to maternal bereavement during pregnancy was associated with the risk of overweight in offspring during school age. METHODOLOGY/PRINCIPAL FINDINGS: We followed 65,212 children born in Denmark from 1970-1989 who underwent health examinations from 7 to 13 years of age in public or private schools in Copenhagen. We identified 459 children as exposed to prenatal stress, defined by being born to mothers who were bereaved by death of a close family member from one year before pregnancy until birth of the child. We compared the prevalence of overweight between the exposed and the unexposed. Body mass index (BMI) values and prevalence of overweight were higher in the exposed children, but not significantly so until from 10 years of age and onwards, as compared with the unexposed children. For example, the adjusted odds ratio (OR) for overweight was 1.68 (95% confidence interval [CI] 1.08-2.61) at 12 years of age and 1.63 (95% CI 1.00-2.61) at 13 years of age. The highest ORs were observed when the death occurred in the period from 6 to 0 month before pregnancy (OR 3.31, 95% CI 1.71-6.42 at age 12, and OR 2.31, 95% CI 1.08-4.97 at age 13). CONCLUSIONS/SIGNIFICANCE: Our results suggest that severe pre-pregnancy stress is associated with an increased risk of overweight in the offspring in later childhood

Harmonization of human biomonitoring studies in Europe: characteristics of the HBM4EU-aligned studies participants

Human 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 socio-demographics, 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((R)) DINCH, and flame retardants. Samples from 2950 teenagers aged 12-18 years are collected for the analysis of biomarkers for phthalates, Hexamoll((R)) 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 underrepresented. 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