Exposure of the general French population to metals and metalloids in 2014-2016: Results from the Esteban study.

BACKGROUND: The purpose of the Esteban study was to describe levels of various biomarkers of exposure to several environmental pollutants, including metals and metalloids, among the French population. This paper describes the distribution of concentrations of 28 metals and metalloids in two different populations, and estimates the main determinants of exposure to total arsenic, the sum of inorganic arsenic (iAs) and its two metabolites monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA), cadmium, chromium, copper, mercury and nickel. METHODS: Esteban is a cross-sectional study conducted between 2014 and 2016 on a random sample of 2503 adults (18-74 years old) and 1104 children (6-17 years old) from the general population. The data collected included biological samples (blood, hair, and urines), socio-demographic characteristics, environmental and occupational exposure, and information on dietary factors and lifestyle. The geometric mean and percentiles of the distribution were estimated for each metal. Multivariate analyses were performed to identify the determinants of exposure using a generalized linear model. RESULTS: Only four metals had a quantification rate below 90% in adults (beryllium, iridium, palladium, and platinum), and three metals in children (beryllium, iridium, and platinum). The concentrations of total arsenic, cadmium, chromium and mercury were higher than those found in most international studies. The determinants significantly associated with exposure were mainly diet and smoking. CONCLUSIONS: Esteban provided a nationwide description of 28 metal and metalloid exposure levels for adults (some never measured before) and for the first time in children. The study results highlighted widespread exposure to several metals and metalloids. These results could be used to advocate public health decisions for continued efforts to reduce harmful exposure to toxic metals. The Reference values (RV95) built from Esteban could also be used to support future government strategies.

Characterization of organic contaminants in hair for biomonitoring purposes.

Biological monitoring is one way to assess human exposure to contaminants. Blood and urine are often used as biological matrices, but hair is an innovative and effective tool for quantifying more biomarkers over a wider exposure window. In order to improve the use of hair in exposure assessment, this article identifies relevant compounds in the literature to investigate hair contamination. Statistical analysis was performed to correlate the physical-chemical properties of the relevant compounds and their concentration levels in hair. Phthalates, pyrethroids and organophosphate flame retardants were chosen for further study of the interpretation of hair measurements for exposure assessment. No significant correlation was found between the average concentration levels in the literature and the physical-chemical properties of the selected compounds. This work also explores the properties of hair and the analytical process that may impact the quantification of organic contaminants in hair. The sample preparation method (sampling, storage, washing) were also studied and adaptations were suggested to improve the existing methods.

Exposure of the general French population to herbicides, pyrethroids, organophosphates, organochlorines, and carbamate pesticides in 2014-2016: Results from the Esteban study.

Esteban is a nationwide cross-sectional study conducted in France in 2014-2016, including 2503 adults aged 18-74 years old and 1104 children aged 6-17 years old, as part of the French Human Biomonitoring programme. The present paper describes the biological levels of five families of pesticides analysed on random sub-samples of 900 adults and 500 children for urine concentrations, and 759 adults and 255 children for serum concentrations, and the determinants of exposure. Organophosphates, carbamates and herbicides were measured in urine by UPLC-MS/MS; chlorophenols and pyrethroids were measured in urine by GC-MS/MS; specific organochlorines were measured in serum by GC-HRMS. Multivariate analyses were performed to identify the determinants of exposure using a generalized linear model. Pyrethroid metabolites were quantified in 99% of adults and children, with the exeption of F-PBA, which was quantified in 31% of adults and 27% of children, respectively. Carbamates and some specific organophosphates were barely or not quantified. DMTP was quantified in 82% of adults and 93% of children, and γ-HCH (lindane) was quantified in almost 50% of adults and children. Concentration levels of pesticide biomarkers were consistent with comparable international studies, except for ß-HCH, DMTP, and the deltamethrin metabolite Br2CA, whose levels were sometimes higher in France. Household insecticide use and smoking were also associated with higher levels of pyrethroids. All pyrethroids concentration levels were below existing health-based HBM guidance values, HBM-GVsGenPop, except for 3-PBA, for which approximately 1% and 10% of children were above the lower and upper urine threshold values of 22 µg/L and 6.4 µg/L, respectively. Esteban provides a French nationwide description of 70 pesticide biomarkers for the first time in children. It also describes some pesticide biomarkers for the first time in adults, including glyphosate and AMPA. For the latter, urine concentration levels were overall higher in children than in adults. Our results highlight a possible beneficial impact of existing regulations on adult exposure to organochlorine and organophosphate pesticides between 2006 and 2016, as concentration levels decreased over this period.

FAIR environmental and health registry (FAIREHR)- supporting the science to policy interface and life science research, development and innovation.

The environmental impact on health is an inevitable by-product of human activity. Environmental health sciences is a multidisciplinary field addressing complex issues on how people are exposed to hazardous chemicals that can potentially affect adversely the health of present and future generations. Exposure sciences and environmental epidemiology are becoming increasingly data-driven and their efficiency and effectiveness can significantly improve by implementing the FAIR (findable, accessible, interoperable, reusable) principles for scientific data management and stewardship. This will enable data integration, interoperability and (re)use while also facilitating the use of new and powerful analytical tools such as artificial intelligence and machine learning in the benefit of public health policy, and research, development and innovation (RDI). Early research planning is critical to ensuring data is FAIR at the outset. This entails a well-informed and planned strategy concerning the identification of appropriate data and metadata to be gathered, along with established procedures for their collection, documentation, and management. Furthermore, suitable approaches must be implemented to evaluate and ensure the quality of the data. Therefore, the 'Europe Regional Chapter of the International Society of Exposure Science' (ISES Europe) human biomonitoring working group (ISES Europe HBM WG) proposes the development of a FAIR Environment and health registry (FAIREHR) (hereafter FAIREHR). FAIR Environment and health registry offers preregistration of studies on exposure sciences and environmental epidemiology using HBM (as a starting point) across all areas of environmental and occupational health globally. The registry is proposed to receive a dedicated web-based interface, to be electronically searchable and to be available to all relevant data providers, users and stakeholders. Planned Human biomonitoring studies would ideally be registered before formal recruitment of study participants. The resulting FAIREHR would contain public records of metadata such as study design, data management, an audit trail of major changes to planned methods, details of when the study will be completed, and links to resulting publications and data repositories when provided by the authors. The FAIREHR would function as an integrated platform designed to cater to the needs of scientists, companies, publishers, and policymakers by providing user-friendly features. The implementation of FAIREHR is expected to yield significant benefits in terms of enabling more effective utilization of human biomonitoring (HBM) data.

Relation of urinary bisphenol concentration and diabetes or prediabetes in French adults: A cross-sectional study.

BACKGROUND: International research has recently shown an association between exposure to bisphenol A (BPA) and the risk of diabetes, although limited results are available for exposure to bisphenol S (BPS) and bisphenol F (BPF). The aim of this study was to examine the relationships between impregnation with BPA, BPS, and BPF and the prevalence of diabetes or prediabetes in the French adult population. METHODS: Based on the Esteban cross-sectional study, 852 adults aged 18 to 74 years living in France were included. To assess the link between urinary concentration of BPA, BPS and BPF and a state of dysglycemia (diabetes or prediabetes), logistic regression multivariable models were performed and adjusted for known risk factors for diabetes and urine creatinine concentration. RESULTS: The percentage of included individuals with diabetes or prediabetes was 17.8% (95% CI = [15.3-20.4]). Urinary BPA concentration was significantly higher in people with diabetes or prediabetes, independent of the known risk factors for diabetes (OR for an increase of 0.1 units in log-transformed concentration of BPA (µg/L) = 1.12; 95%CI = [1.05-1.19], p < 0.001). However, we did not find any significant independent association between urinary BPS and BPF levels and the prevalence of diabetes or prediabetes. CONCLUSIONS: In this sample, considering the diabetes risk factors, diabetes or prediabetes was positively associated with higher urinary BPA concentration but not with urinary BPS and BPF concentrations. However, analysis of prospective longitudinal studies are still necessary to demonstrate a causal link between bisphenol exposure and the risk of diabetes or prediabetes.

Assessment of multi-chemical exposure using human biomonitoring data from the French Esteban study using exposure load method.

Exposure to chemical substances is common and comes from several sources (environmental, food, and occupational). It is often studied using a substance-by-substance approach. Although this method helps identify the determinants of exposure to a single chemical, it cannot accurately reflect exposure to multiple chemicals. In this study, we used the concept of exposure load (EL) to evaluate multi-chemical exposure in a representative sample of the general French population. EL corresponds to the number of substances (or metabolites) measured in body fluids above a defined concentration threshold. EL was calculated for adults and children separately for two groups of substances: those currently found in domestic environments (Group A) and pesticides (Group B). Although the EL does not assess the health impact linked to multi-chemical exposure, it does aid in the identification of particularly vulnerable populations. Accordingly, preventive actions specifically aimed at these subgroups could be useful. In Group A, we found that multi-chemical exposure was generalized since all the adults and children had an EL greater than or equal to 13 (out of 22 substances studied) when the LOQ (limit of quantification) was considered as the discretization threshold. In adults, men, smokers and people of working age (i.e., people under 60 years old) had a higher EL. In Group B, multi-chemical exposure was also generalized, since all the adults (15 substances studied) and children (13 substances studied) had a mean EL almost equal to 6 when the LOQ was considered as the discretization threshold. In adults, persons with occupational exposure to pesticide dust had a higher EL when the P90 was considered as the discretization threshold. This study highlights widespread multi-chemical exposure in adults and children in France, and the major impact of occupational exposure (Group B) and tobacco smoking (Group A) on EL.

Developing human biomonitoring as a 21st century toolbox within the European exposure science strategy 2020-2030.

Human biomonitoring (HBM) is a crucial approach for exposure assessment, as emphasised in the European Commission's Chemicals Strategy for Sustainability (CSS). HBM can help to improve chemical policies in five major key areas: (1) assessing internal and aggregate exposure in different target populations; 2) assessing exposure to chemicals across life stages; (3) assessing combined exposure to multiple chemicals (mixtures); (4) bridging regulatory silos on aggregate exposure; and (5) enhancing the effectiveness of risk management measures. In this strategy paper we propose a vision and a strategy for the use of HBM in chemical regulations and public health policy in Europe and beyond. We outline six strategic objectives and a roadmap to further strengthen HBM approaches and increase their implementation in the regulatory risk assessment of chemicals to enhance our understanding of exposure and health impacts, enabling timely and targeted policy interventions and risk management. These strategic objectives are: 1) further development of sampling strategies and sample preparation; 2) further development of chemical-analytical HBM methods; 3) improving harmonisation throughout the HBM research life cycle; 4) further development of quality control / quality assurance throughout the HBM research life cycle; 5) obtain sustained funding and reinforcement by legislation; and 6) extend target-specific communication with scientists, policymakers, citizens and other stakeholders. HBM approaches are essential in risk assessment to address scientific, regulatory and societal challenges. HBM requires full and strong support from the scientific and regulatory domain to reach its full potential in public and occupational health assessment and in regulatory decision-making.

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® 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 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.

Estimation of blood lead levels in the French population using two complementary approaches: Esteban (2014-2016) as part of the human biomonitoring program and the national surveillance system for childhood lead poisoning (2015-2018).

BACKGROUND: Used widely for centuries, lead is a common environmental pollutant. As a cumulative toxic, its presence in the body is always evidence of exposure, and health effects occur without threshold. Though regulated by European directives, lead requires close monitoring due to its environmental persistence and toxicity. METHODS: The first data source was the French surveillance system for monitoring childhood lead poisoning, which records the screening results of children (-18 years), providing data on their temporal and geographical distribution, characteristics, and risk factors. The second data source was Esteban, a cross-sectional study conducted in 2014-2016 on a random sample of the French population as part of the human biomonitoring program. The Esteban lead study concerns 904 children (6-17 years) and 999 adults (18-74 years), providing data on biological samples, sociodemographic characteristics, occupational exposure, environmental and dietary factors. RESULTS: The surveillance system highlighted that lead poisoning affected 10% of children screened between 2015 and 2018. The main risk factor remains housing. Esteban confirmed this observation, finding a general mean of blood lead level (BLL) at 9.9 and 18.5 µg/L for children and adults, respectively. In children, parents' occupation increased BLLs. In adults, the greatest exposure factors were smoking, age, place of residence, alcohol, bread-based products, and homegrown livestock products. In both, drinking tap water and year of housing construction increased BLLs. CONCLUSIONS: The surveillance system showed a high number of children with lead poisoning despite the implementation of prevention measures, which mainly concern lead paints in old and degraded homes. To help identify children at risk, healthcare providers need to know about exposure from housing and the emerging sources identified in the Esteban survey. Despite lower BLLs, the well-known risk factors of lead exposure persist, meaning prevention efforts must continue in order to limit their impact on the population.

Risk Assessment of Dietary Exposure to Organophosphorus Flame Retardants in Children by Using HBM-Data.

Due to their extensive usage, organophosphorus flame retardants (OPFRs) have been detected in humans and in the environment. Human are exposed to OPFRs via inhalation of indoor air, dust uptake or dietary uptake through contaminated food and drinking water. Only recently, few studies addressing dietary exposure to OPFRs were published. In this study, we used human biomonitoring (HBM) data of OPFRs to estimate how much the dietary intake may contribute to the total exposure. We estimated by reverse dosimetry, the daily intake of tris (2-chloroethyl) phosphate (TCEP), tris (1-chloro-2-propyl) phosphate (TCIPP), tris (1,3-dichloro-2-propyl) phosphate (TDCIPP) for children using HBM data from studies with sampling sites in Belgium, Denmark, France, Germany, Slovenia and Slovakia. For estimating the dietary exposure, a deterministic approach was chosen. The occurrence data of selected food categories were used from a published Belgium food basket study. Since the occurrence data were left-censored, the Lower bound (LB)-Upper bound (UB) approach was used. The estimated daily intake (EDI) calculated on the basis of urine metabolite concentrations ranged from 0.03 to 0.18 µg/kg bw/d for TDCIPP, from 0.05 to 0.17 µg/kg bw/d for TCIPP and from 0.02 to 0.2 µg/kg bw/d for TCEP. Based on national food consumption data and occurrence data, the estimated dietary intake for TDCIPP ranged from 0.005 to 0.09 µg/kg bw/d, for TCIPP ranged from 0.037 to 0.2 µg/kg bw/d and for TCEP ranged from 0.007 to 0.018 µg/kg bw/d (summarized for all countries). The estimated dietary intake of TDCIPP contributes 11-173% to the EDI, depending on country and LB-UB scenario. The estimated dietary uptake of TCIPP was in all calculations, except in Belgium and France, above 100%. In the case of TCEP, it is assumed that the dietary intake ranges from 6 to 57%. The EDI and the estimated dietary intake contribute less than 3% to the reference dose (RfD). Therefore, the estimated exposure to OPFRs indicates a minimal health risk based on the current knowledge of available exposure, kinetic and toxicity data. We were able to show that the dietary exposure can have an impact on the general exposure based on our underlying exposure scenarios.

Identification of pesticides exposure biomarkers for residents living close to vineyards in France.

Biomonitoring can be relevant for assessing pesticides exposure of residents living close to vineyards (LCTV). However, because xenobiotics are generally present at low levels in human biological matrices and the sources of pesticide exposure are multiple, several challenges need to be overcome to reliably assess exposure in residents LCTV. This includes particularly identifying the most appropriate exposure biomarkers, the biological matrices in which they should be measured, and analytical methods that are sufficiently sensitive and specific to quantify them. The aim of the present study was to develop a tiered approach to identify relevant biomarkers and matrices for assessing pesticide exposure in residents LCTV. We used samples from a biobank for 121 adults and children included in a national prevalence study conducted between 2014 and 2016 who lived near or far from vineyards. We analyzed five priority pesticides (folpet, mancozeb, tebuconazole, glyphosate, and copper) and their metabolites in urine and hair samples. We identified relevant biomarkers according to three criteria related to: i) the detection frequency of those pesticides and metabolites in urine and hair, ii) the difference in concentrations depending on residence proximity to vineyards and, iii) the influence of other environmental and occupational exposure sources on pesticide levels. This tiered approach helped us to identify three relevant metabolites (two metabolites of folpet and one of tebuconazole) that were quantified in urine, tended to be higher in residents LCTV than in controls, and were not significantly influenced by occupational, dietary, or household sources of pesticide exposure. Our approach also helped us to identify the most appropriate measurement strategies (biological matrices, analytical methods) to assess pesticide exposure in residents LCTV. The approach developed here was a prerequisite step for guiding a large-scale epidemiological study aimed at comprehensively measuring pesticides exposures in French residents LCTV with a view to developing appropriate prevention strategies.

Exposure of the French population to bisphenols, phthalates, parabens, glycol ethers, brominated flame retardants, and perfluorinated compounds in 2014-2016: Results from the Esteban study.

BACKGROUND: As part of the French Human Biomonitoring (HBM) programme, the Esteban study described, among other things, biomarkers levels of various chemicals in adults (18-74 years old) and children (6-17 years old). This paper describes the design of the study and provides, for the first time, data on the biological exposure of the general French population to a wide range of contaminants posing a threat to human health which are currently found in domestic environments. METHODS: Esteban is a cross-sectional study conducted on a nationwide sample of the French general population. Exposure biomarkers of six families of contaminants deemed detrimental to adults' and children's health were measured in biological samples collected either at participants' homes by a nurse, or brought to a National Health Insurance examination centre. All participants were randomly selected (2503 adults and 1104 children). The geometric mean and percentiles of the distribution of levels were estimated for each biomarker. Most of the descriptive statistical analyses were performed taking into account the sampling design. RESULTS: Results provided a nationwide description of biomarker levels. Bisphenols (A, S and F), and some metabolites of phthalates and perfluorinated compounds (PFCs) (specifically, PFOS and PFOA) were quantified in almost all the biological samples analysed. Higher levels were observed in children (except for PFCs). Levels were coherent with international studies, except for bisphenols S and F, brominated flame retardants (BFRs) and parabens (with higher levels reported in the USA than in France). CONCLUSION AND PERSPECTIVES: This study is the first to provide a representative assessment of biological exposure to domestic contaminants at the French population level. Our results show that the French general population was exposed to a wide variety of pollutants in 2014-2016, and identify the determinants of exposure. These findings will be useful to stakeholders who wish to advocate an overall reduction in the French population's exposure to harmful substances. Similar future studies in France will help to measure temporal trends, and enable public policies focused on the reduction of those chemicals in the environment to be evaluated.

Chlordecone and organochlorine compound levels in the French West Indies population in 2013-2014.

Agricultural activities in the Caribbean, especially banana cropping, are known for their significant use of pesticides. In particular is chlordecone, which was used between 1972 and 1993 against the banana root borer, Cosmopolites sordidus (Germar, 1824). In this context, "Kannari study: Health, Nutrition and Exposition to Chlordecone in French West Indies" was put in place in 2013-2014 to supplement knowledge about the exposure of the population to chlordecone and other organochlorine pollutants. The data collected comprised a dietary intake description, data from biological samples (blood sample), socioeconomic and demographic information, and data from complementary specific items relative to life habits. A total of 742 subjects (292 in Guadeloupe and 450 in Martinique) were included in the impregnation component of the Kannari study. In this study, chlordecone and organochlorine compounds were detected in almost all participants. This result suggests that exposure to chlordecone is widespread, but also to other organochlorine pesticides. Chlordecone impregnation of the majority of the population appears to have decreased between 2003 and 2013, but various subgroups of the population remain highly exposed. The levels of impregnation are determined by dietary exposure and environmental contamination. However, total consumption of fresh fish (all species combined), especially from informal channels, is the main source of exposure to chlordecone. The serum PCB concentrations measured in the French Caribbean Islands of Guadeloupe and Martinique are lower than those observed in metropolitan France in 2007 (French Nutrition and Health Survey (ENNS)). In contrast, the French West Indies population seems more exposed to lindane than the French mainland population, and this exposure also seems more recent.

Pesticide exposures for residents living close to agricultural lands: A review.

BACKGROUND: Residents living close to agricultural lands might be exposed to pesticides through non-occupational pathways including spray drift and volatilization of pesticides beyond the treated area. OBJECTIVE: This review aimed to identify and analyze scientific literature measuring pesticide exposure in non-farmworker residents living close to agricultural lands, and to suggest practical implications and needs for future studies. METHODS: A review was performed using inclusion criteria to identify original articles of interest published between 2003 and 2018. RESULTS: From the 29 articles selected in this review, 2 belonged to the same study and were grouped, resulting in a total of 27 studies. Seven studies assessed exposure to pesticides using environmental samples, 13 collected biological samples and 7 analyzed both. Nine studies included a reference group of residents living far from agricultural lands while 11 assessed the influence of the spraying season or spray events on pesticide exposures. Studies included in this review provide evidence that residents living near to agricultural lands are exposed to higher levels of pesticides than residents living further away. DISCUSSION AND CONCLUSION: This review highlights that the following study design characteristics may be more appropriate than others to measure pesticide spray drift exposure in non-farmworker residents living close to agricultural lands: inclusion of a non-agricultural control group, collection of both biological and environmental samples with repeated sampling, measurements at different periods of the year, selection of numerous study sites related to one specific crop group, and measurements of pesticides which are specific to agricultural use. However, few studies to date incorporate all these characteristics. Additional studies are needed to comprehensively measure non-occupational pesticide exposures in this population in order to evaluate health risks, and to develop appropriate prevention strategies.

Prenatal exposure to lead in France: Cord-blood levels and associated factors: Results from the perinatal component of the French Longitudinal Study since Childhood (Elfe).

BACKGROUND: As a result of the ban on lead in gasoline on 2nd January 2000, the French population's exposure to lead has decreased in recent years. However, because of the acknowledged harmful cognitive effects of lead even at low levels, lead exposure remains a major public health issue. In France, few biomonitoring data are available for exposure to lead in pregnant women and newborn. The purpose of the perinatal component of the French human biomonitoring (HBM) program was to describe levels of various biomarkers of exposure to several environmental pollutants, including lead, among mother-baby pairs. In this paper, we aimed to describe the distribution of cord blood lead levels (CBLL) in French mother-baby pairs, and to estimate the contribution of the main lead exposure risk factors to these levels. METHOD: A total of 1968 mother-baby pairs selected from the participants of the perinatal component of the French HBM program were included in the study on lead. Lead levels were analyzed in cord blood collected at child delivery by inductively coupled plasma-mass spectrometry (ICP-MS). The data collected included biological sample, socio-demographic characteristics, environmental and occupational exposure, and information on dietary factors. RESULTS: CBLL were quantified for 99.5% of the sample. The CBLL geometric mean was 8.30 µg/l (95% CI [7.94-8.68]) with a 95th percentile of 24.3 µg/l (95% CI [20.7-27.1]). Factors significantly associated with CBLL were tap water consumption, alcohol consumption, shellfish consumption, vegetable consumption, bread consumption, smoking, and the mother being born in countries where lead is often used. CONCLUSION: This study provides the first reference value for CBLL in a random sample of mother-baby pairs not particularly exposed to high levels of lead (24.3 µg/l). A substantial decrease in CBLL over time was observed, which confirms the decrease of exposure to lead among the general population. CBLL observed in this French study were in the range of those found in recent surveys conducted in other countries.

The French human biomonitoring program: First lessons from the perinatal component and future needs.

This paper presents a progress report of the French human biomonitoring (HBM) program established in 2010. This program has been designed to provide a national representative estimation of the French population's exposure to various environmental chemicals and to study the determinants of exposure. This program currently consists in two surveys: a perinatal component related to a selection of 4145 pregnant women who have been enrolled in the Elfe cohort (the French Longitudinal Study since Childhood) in 2011, and a general population survey related to adults aged 18-74 years and children as from 6 years (Esteban). The aim of this manuscript is to present highlights of the French human biomonitoring program with particular focus on the prioritization of biomarkers to be analyzed in the program and the selection of biomarkers applied to both program components. The Delphi method was used to establish a consensual list of prioritized biomarkers in 2011. First results of the perinatal component of the French HBM program have shown that the biomarkers prioritized were relevant, as almost all pregnant women were exposed to them. However, for some biomarkers, levels' decreases have been observed which may partly be explained by measures taken to prohibit some of these chemicals (e.g. atrazine) and by industrial processes evolutions leading to the substitution of others (e.g. bisphenol A, di-2-ethylhexyl phthalate/DEHP, dialkyl phosphates). Therefore, the list of biomarkers to be monitored in the French HBM program has been implemented to include some substitutes of biomarkers prioritized in the first instance (e.g. bisphenol S, F). Finally, this method combines rigor and flexibility and helped us to build a prioritized list that will be shared and supported by many if not all actors.

Arsenic urinary concentrations in children living in a naturally arsenic contaminated area.

A cross sectional study using environmental and biological samples was undertaken to assess the association between arsenic (As) soil concentrations and urinary As levels of children living in an area where the soil is naturally As rich, during summer and winter. Twenty-nine children aged between 2 and 7 years from 21 dwellings in the summer study, and 23 of the 29 previous children from 17 dwellings in the winter study, were recruited. Housing characteristics, living conditions and individual characteristics were collected by questionnaire, and urine samples were collected for iAs+MMA+DMA measurement. Soil total As content and bioaccessibility were measured. Urinary As concentrations revealed that the children were not overexposed. Low bioaccessibility combined with moderately high levels in soil could explain this result. The concentration of arsenic in soil and soil-related factors appeared to contribute to the children's impregnation in summer but not in winter, which could be related to the children's behavior. This study highlights the need for additional studies of children to better understand their behavior, and obtain reference values in this particular population.

Highlights of recent studies and future plans for the French human biomonitoring (HBM) programme.

This manuscript presents highlights of recent studies and perspectives from the French human biomonitoring (HBM) programme. Until recently, HBM studies focused on specific populations or pollutants to gain a better understanding of exposure to environmental chemicals, to help regulators reduce environmental exposure and to monitor existing policies on specific concerns. Highlights of recent multicentre biomonitoring studies with specific population or pollutant focus are given. These French HBM studies have been implemented to know: (1) the influence of living near an incinerator on serum dioxin and polychlorinated biphenyl (PCB) levels, (2) the influence of consuming river fish contaminated by PCBs on serum PCBs of fishermen, and (3) the evolution of blood lead levels in children from 1 to 6 years old since 1995. Special emphasis is placed on the use of an integrated (HBM coupled with nutrition and health studies), multipollutant approach. This approach has been initiated in France with a recent national population-based biomonitoring survey, the Etude Nationale Nutrition Santé (ENNS; French Nutrition and Health Survey). This survey will provide the first reference distribution for 42 biomarkers in the French population. The current national HBM strategy will build upon the ENNS and include a national survey of people aged between 6 and 74 years complemented for the neonatal period and childhood by the Etude Longitudinale Française depuis l'Enfance (ELFE; French longitudinal study of children). France also contributes to the harmonization of HBM activities in Europe through participation in European HBM projects.

Does arsenic in soil contribute to arsenic urinary concentrations in a French population living in a naturally arsenic contaminated area?

A cross sectional study using environmental and biological samples was implemented to assess the association between arsenic (As) concentrations in the environment and urinary As levels of residents living in an area where the soil is naturally As rich. As was measured in drinking water, atmospheric particulate matter, and soil and a geographic information system was used to assign environmental concentrations closest to the participants' dwellings and the sum of inorganic As and metabolites in urine samples. The only potential source of As environmental contamination was from soil with a range of 13-131 mg As/kg of dry matter. As(V) was the only species present among As extracted from the analyzed soil samples. The chemical extraction showed a poor mobility of As soil. There was no difference between child and teenager, and adult urinary As concentrations, though men had higher urinary As concentrations than women (p<0.001). Given the important differences in lifestyle between 7-18 year olds, men, and women, these groups were analyzed separately. Whilst we were unable to find a stable model for the 7-18 year old group, for the adult men group we found that seafood consumption in the 3 days prior to the investigation (p=0.02), and beer (p=0.03) and wine consumption in the 4 days before the study, were associated with As urinary levels (µg/L). In adult women, creatinine was the only variable significantly associated with As urinary concentration (µg/L). The concentrations we measured in soils were variable and although high, only moderately so and no link between As concentrations in the soil and urinary As concentrations could be found for either men or women. Some individual factors explained half of the variability of adult men urinary As levels. The unexplained part of the variability should be searched notably in As mobility in soil and uncharacterized human behavior.

Urinary arsenic concentrations and speciation in residents living in an area with naturally contaminated soils.

A cross sectional study was carried out to evaluate arsenic exposure of residents living in an area with a soil naturally rich in arsenic (As), through urinary measurements. During the summer of 2007, 322 people aged over 7 years and resident in the study area for at least 4 days prior to the investigation were recruited. The sum of urinary inorganic arsenic and metabolites (iAs+MMA+DMA) and speciation were determined by graphite furnace atomic absorption spectrometry and high performance liquid chromatography coupled to inductively coupled plasma mass spectrometry, respectively. Geometric means levels of iAs+MMA+DMA were 3.6 microg/L or 4.4 microg/g creatinine. The percent of DMA, As(III) and MMA contribution to urinary arsenic concentrations was respectively 84.2%, 12% and 3.7%. We found significant associations between urinary arsenic concentrations and the consumption of seafood (p=0.03), the consumption of wine (p=0.03) and beer (p=0.001), respectively 3 and 4 days before the investigation. When we focus on the various species, As(V) was rarely detected and DMA is the predominant metabolite composing the majority of measurable inorganic-related As in the urine. Considering the percent of DMA contribution to iAs+MMA+DMA urinary concentrations, almost half of the subjects had 100% of DMA contribution whatever the concentration of urinary As whereas the others had a lower DMA contribution, between 39 and 90%. Arsenic levels reported in this original study in France were between 2 and 4 times lower than in other studies dealing with iAs+MMA+DMA levels associated with soil arsenic exposure. Arsenic levels were similar to those observed in unexposed individuals in European countries, although 10% were above the French guideline values for the general population.