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The European Joint Programme HBM4EU coordinated and advanced human biomonitoring (HBM) in Europe in order to provide science-based evidence for chemical policy development and improve chemical management. Arsenic (As) was selected as a priority substance under the HBM4EU initiative for which open, policy relevant questions like the status of exposure had to be answered. Internal exposure to inorganic arsenic (iAs), measured as Toxic Relevant Arsenic (TRA) (the sum of As(III), As(V), MMA, DMA) in urine samples of teenagers differed among the sampling sites (BEA (Spain) > Riksmaten adolescents (Sweden), ESTEBAN (France) > FLEHS IV (Belgium), SLO CRP (Slovenia)) with geometric means between 3.84 and 8.47 μg/L. The ratio TRA to TRA + arsenobetaine or the ratio TRA to total arsenic varied between 0.22 and 0.49. Main exposure determinants for TRA were the consumption of rice and seafood. When all studies were combined, Pearson correlation analysis showed significant associations between all considered As species. Higher concentrations of DMA, quantitatively a major constituent of TRA, were found with increasing arsenobetaine concentrations, a marker for organic As intake, e.g. through seafood, indicating that other sources of DMA than metabolism of inorganic As exist, e.g. direct intake of DMA or via the intake of arsenosugars or -lipids. Given the lower toxicity of DMA(V) versus iAs, estimating the amount of DMA not originating from iAs, or normalizing TRA for arsenobetaine intake could be useful for estimating iAs exposure and risk. Comparing urinary TRA concentrations with formerly derived biomonitoring equivalent (BE) for non-carcinogenic effects (6.4 μg/L) clearly shows that all 95th percentile exposure values in the different studies exceeded this BE. This together with the fact that cancer risk may not be excluded even at lower iAs levels, suggests a possible health concern for the general population of Europe. HBM4EU is co-financed under Horizon 2020 (grant agreement No 733032). The authors thank all investigators of the contributing studies for their participation and contribution to the joint HBM4EU survey and the national programme owners for their financial support. Also thanks to the participating teenagers and their families, the field workers that collected the samples. The FLEHS IV study was conducted within the framework of the Flemish Center of Expertise on Environment and Health (FLEHS 2016–2020) and funded by the Flemish Government, Department of Environment & Spatial Development. We thank the teenagers and their families that participated in the study, the field workers from the Pro vincial Institute of Hygiene and VITO for the sample and data collection. All collaborators of the scientific teams of the Flemish Center of Expertise on Environment and Health (https://www.milieu-en-gezondheid.be/en/about-the-center-0) and Karen Van Campenhout and Caroline Teughels from the Flemish Department of Environment & Spatial Development for their valuable input in the field work committee. The funding of the German Ministry for the Environment, Nature Conservation, Nuclear Safety and Consumer Protection is gratefully acknowledged. BEA study was co-funded by the Spanish Ministry of Agriculture, Fisheries and Food and the Insituto de Salud Carlos III (SEG 1321/15). In Slovenia the work was cofounded by the Slovenian Research Funding Agency – ARRS through a research programme P-0143. ESTEBAN was Funded by Sant´e Publique France and the French ministries of Health and the Environment. The study of RIKSMATEN was conducted and mainly financed by the Swedish Food Agency. Financial support was provided from the Swedish Civil Contingencies Agency and from the Swedish Environmental Pro tection Agency (SEPA). Sí

Per-and polyfluoroalkyl substances (PFAS) are widespread pollutants that may impact youth adiposity patterns. We investigated cross-sectional associations between PFAS and body mass index (BMI) in teenagers/adolescents across nine European countries within the Human Biomonitoring for Europe (HBM4EU) initiative. We used data from 1957 teenagers (12-18 yrs) that were part of the HBM4EU aligned studies, consisting of nine HBM studies (NEBII, Norway; Riksmaten Adolescents 2016-17, Sweden; PCB cohort (follow-up), Slovakia; SLO CRP, Slovenia; CROME, Greece; BEA, Spain; ESTEBAN, France; FLEHS IV, Belgium; GerES V-sub, Germany). Twelve PFAS were measured in blood, whilst weight and height were measured by field nurse/physician or self-reported in ques-tionnaires. We assessed associations between PFAS and age-and sex-adjusted BMI z-scores using linear and logistic regression adjusted for potential confounders. Random-effects meta-analysis and mixed effects models were used to pool studies. We assessed mixture effects using molar sums of exposure biomarkers with toxicological/structural similarities and quantile g-computation. In all studies, the highest concentrations of PFAS were PFOS (medians ranging from 1.34 to 2.79 mu g/L). There was a tendency for negative associations with BMI z-scores for all PFAS (except for PFHxS and PFHpS), which was borderline significant for the molar sum of [PFOA and PFNA] and significant for single PFOA [beta-coefficient (95% CI) per interquartile range fold change =-0.06 (-0.17, 0.00) and-0.08 (-0.15,-0.01), respectively]. Mixture assessment indicated similar negative associations of the total mixture of [PFOA, PFNA, PFHxS and PFOS] with BMI z-score, but not all compounds showed associations in the same direction: whilst [PFOA, PFNA and PFOS] were negatively associated, [PFHxS] associated positively with BMI z-score. Our results indicated a tendency for associations of relatively low PFAS concentrations with lower BMI in European teenagers. More prospective research is needed to investigate this potential relationship and its implications for health later in life., European Commission 733032, Swedish Research Council European Commission 2017-00822

Human biomonitoring (HBM) data measured in specific contexts or populations provide information for comparing population exposures. There are numerous health-based biomonitoring guidance values, but to locate these values, interested parties need to seek them out individually from publications, governmental reports, websites and other sources. Until now, there has been no central, international repository for this information. Thus, a tool is needed to help researchers, public health professionals, risk assessors, and regulatory decision makers to quickly locate relevant values on numerous environmental chemicals. A free, on-line repository for international health-based guidance values to facilitate the interpretation of HBM data is now available. The repository is referred to as the "Human Biomonitoring Health-Based Guidance Value (HB2GV) Dashboard". The Dashboard represents the efforts of the International Human Biomonitoring Working Group (i-HBM), affiliated with the International Society of Exposure Science. The i-HBM's mission is to promote the use of population-level HBM data to inform public health decision-making by developing harmonized resources to facilitate the interpretation of HBM data in a health-based context. This paper describes the methods used to compile the human biomonitoring health-based guidance values, how the values can be accessed and used, and caveats with using the Dashboard for interpreting HBM data. To our knowledge, the HB2GV Dashboard is the first open-access, curated database of HBM guidance values developed for use in interpreting HBM data. This new resource can assist global HBM data users such as risk assessors, risk managers and biomonitoring programs with a readily available compilation of guidance values. Highlights: An international Human Biomonitoring Working Group (i-HBM) was formed in 2020; i-HBM working group is affiliated with the International Society of Exposure Science (ISES); i-HBM has developed the first curated database of HBM Health-Based Guidance Values or HB2GVs, The guidance values are freely available in the online HB2GV Dashboard. info:eu-repo/semantics/publishedVersion

© 2022 The Author(s). Published by Elsevier GmbH. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)., Obtaining holistic information about health and health determinants at the population level should also include data on environmental risk factors of health. So far, only a few countries have combined, at the national level, health and human biomonitoring (HBM) surveys to collect extensive information on health, lifestyles, biological health determinants and environmental exposures. This paper will provide guidelines on how to combine health and HBM surveys and what is the added value of doing so. Health and HBM surveys utilize similar infrastructure and data collection methods including questionnaires, collection and analysis of biological samples, and objective health measurements. There are many overlapping or comparable steps in these two survey types. At the European level, detailed protocols for conducting a health examination survey or HBM study exists separately but there is no protocol for a combined survey available by now. Our recommendations for combined health and HBM surveys focus on a cross-sectional survey on general population aged 6-79 years. To avoid unnecessary participant burden, for the selection of included measurements basic principle would be to ensure that results of the measurements have a public health relevance and clear interpretation. Combining health and HBM surveys into one survey would produce an extensive database for research to support policy decisions in many fields such as public health and chemical regulations. Combined surveys are cost-effective as only one infrastructure is needed to collect information and recruit participants., This project has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 733032.

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 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. The HBM4EU initiative is co-financed under Horizon 2020 (grant agreement No 733032). Additional financial support for the conduct of the studies is provided by each participating country. More information on co-funding of the individual studies is provided in Supplementary Materials, Table S14. info:eu-repo/semantics/publishedVersion

The European Human Biomonitoring Initiative (HBM4EU) assessed human biomonitoring data on phthalates in children and adolescents, that were sampled between 2014 and 2021, in a harmonised way. These so-called “HBM4EU Aligned Studies” revealed that almost all children and adolescents were exposed to multiple phthalates concurrently. Some phthalates have been shown to act in a dose-additive manner, thus, a mixture risk assessment is warranted. In our study, we determine the risk from combined exposure to five anti-androgenic phthalates, namely DEHP, DiBP, DnBP, BBzP and DiNP by making use of the hazard index (HI) approach. Toxicologically-based human biomonitoring guidance values (HBM-GVs) derived within the framework of HBM4EU served as basis. Our results show that exposures of 17% of children and adolescents from twelve European countries resulted in hazard indices (HI) > 1 with an HI of 1.77 at the 95th percentile (geometric mean, GM = 0.44). Main drivers for the mixture risk are DnBP and DiBP. Generalized Linear Model (GLM) analysis including four major exposure determinants (age, sex, European region, sampling year) simultaneously reveal differences for the European regions and between sampling years. Children and adolescents living in the Eastern region of Europe have on average, higher HIs (GM=0.58) than in the Southern region (GM = 0.36) and Western region (GM = 0.42). Moreover, participants from which urine samples were taken in the earlier years (2014–2016) seem to have higher average HI levels than participants from studies with later sampling periods. Strikingly, the majority (63%) of participants with HIs > 1 would have gone unnoticed in single substance risk assessments as individual phthalates levels were below corresponding HBM-GVs. Thus, our results underline the importance of mixture risk assessment approaches to adequately address risks from concurrent chemical exposure. The HBM4EU project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No 733032 and received co-funding from the author’s organizations. GerES V received funding by the German Ministry for the Environment, Nature Conservation, Nuclear Safety and Consumer Protection. The Norwegian Institute of Public Health (NIPH) has contributed to funding of the NEB II. The laboratory measurements have partly been funded by the Research Council of Norway through research projects (275903 and 268465). The Slovenian SLO-CRP study was cofinanced 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). BEA study was co-funded by the Spanish Ministry of Agriculture, Fisheries and Food and the Insituto de Salud Carlos III (SEG 1321/15). CROME study is co-funded by the European Commission research funds of Horizon 2020 (LIFE12 ENV/GR/001040). InAirQ is cofunded by Interreg CENTRAL EUROPE and the National Public Health Center, Hungary. ESTEBAN received funding by the Santé Public France and the French ministries of Health and the Environment. PCB cohort follow-up was funded by the Slovak Ministry of Health and the Slovak Research and Development Agency (project no PVV-0571-1). SPECIMEn-NL study was funded under the HBM4EU project. 3xG received cofunding from NIRAS, STORA and MONA. FLEHS IV was co-financed dby the Government of Flanders, Department of Environment & Spatial development. The CELSPAC studies are supported by the MEYS (LM2018121, CZ.02.1.01/0.0/0.0/17_043/0009632 and CZ.02.1.01/0.0/0.0/15_003/0000469) and from the European Union’s Horizon 2020 research and innovation programme under grant agreement (857560). The OCC studies was supported by Odense University Hospital, Denmark, the Region of Southern Denmark, The Municipality of Odense, Denmark, The University of Southern Denmark, Odense Patient data Exploratory Network (OPEN), Denmark, The Danish Center for Hormone Disrupting Chemicals (MST-611-00012), The Danish Research Council (4004-00352B_FSS), Novo Nordisk Foundation, Denmark (grant no. NNF19OC0058266 and NNF17OC0029404), HBM4EU, EU Horizon 2020 (grant no. 733032). Sí

© 2021 The Authors. Published by Elsevier GmbH. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)., Data generated by the rapidly evolving human biomonitoring (HBM) programmes are providing invaluable opportunities to support and advance regulatory risk assessment and management of chemicals in occupational and environmental health domains. However, heterogeneity across studies, in terms of design, terminology, biomarker nomenclature, and data formats, limits our capacity to compare and integrate data sets retrospectively (reuse). Registration of HBM studies is common for clinical trials; however, the study designs and resulting data collections cannot be traced easily. We argue that an HBM Global Registry Framework (HBM GRF) could be the solution to several of challenges hampering the (re)use of HBM (meta)data. The aim is to develop a global, host-independent HBM registry framework based on the use of harmonised open-access protocol templates from designing, undertaking of an HBM study to the use and possible reuse of the resulting HBM (meta)data. This framework should apply FAIR (Findable, Accessible, Interoperable and Reusable) principles as a core data management strategy to enable the (re)use of HBM (meta)data to its full potential through the data value chain. Moreover, we believe that implementation of FAIR principles is a fundamental enabler for digital transformation within environmental health. The HBM GRF would encompass internationally harmonised and agreed open access templates for HBM study protocols, structured web-based functionalities to deposit, find, and access harmonised protocols of HBM studies. Registration of HBM studies using the HBM GRF is anticipated to increase FAIRness of the resulting (meta)data. It is also considered that harmonisation of existing data sets could be performed retrospectively. As a consequence, data wrangling activities to make data ready for analysis will be minimised. In addition, this framework would enable the HBM (inter)national community to trace new HBM studies already in the planning phase and their results once finalised. The HBM GRF could also serve as a platform enhancing communication between scientists, risk assessors, and risk managers/policy makers. The planned European Partnership for the Assessment of Risk from Chemicals (PARC) work along these lines, based on the experience obtained in previous joint European initiatives. Therefore, PARC could very well bring a first demonstration of first essential functionalities within the development of the HBM GRF.

The 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. This publication reflects only the author’s view, and the European Commission is not responsible for any use that may be made of the information it contains. The authors would like to thank also the participants in the HBM4EU Aligned Studies, the fieldworkers that collected the samples and database managers that made the information available to HBM4EU, the laboratories who performed the analytical measurements and the HBM4EU project partners for the supporting material and organization of the QA/QC scheme. Sí

E-mail addresses: kvo@envs.au.dk (K. Vorkamp), Castano@isciii.es (A. Castaño), Jean-Philippe.Antignac@oniris-nantes.fr (J.-P. Antignac), Luis.Boada@ulpgc.es (L.D. Boada), ECequier@quimica.udl.cat (E. Cequier), Adrian.Covaci@uantwerpen.be (A. Covaci), M.Esteban@isciii.es (M. Esteban López), LineSmastuen.Haug@fhi.no (L.S. Haug), Kasper@ipa-dguv.de (M. Kasper-Sonnenberg), Koch@ipa-dguv.de (H.M. Koch), Octavio.Perez@ulpgc.es (O. Pérez Luzardo), Agnese.Osite@lu.lv (A. Osīte), Loic.Rambaud@santepubliquefrance.fr (L. Rambaud), mtpin@ticino.com (M.-T. Pinorini), Gabriele.Sabbioni@bluewin.ch (G. Sabbioni), Cathrine.Thomsen@fhi.no (C. Thomsen).; International audience; The major purpose of human biomonitoring is the mapping and assessment of human exposure to chemicals. The European initiative HBM4EU has prioritized seven substance groups and two metals relevant for human exposure: Phthalates and substitutes (1,2-cyclohexane dicarboxylic acid diisononyl ester, DINCH), bisphenols, perand polyfluoroalkyl substances (PFASs), halogenated and organophosphorous flame retardants (HFRs and OPFRs), polycyclic aromatic hydrocarbons (PAHs), arylamines, cadmium and chromium. As a first step towards comparable European-wide data, the most suitable biomarkers, human matrices and analytical methods for each substance group or metal were selected from the scientific literature, based on a set of selection criteria. The biomarkers included parent compounds of PFASs and HFRs in serum, of bisphenols and arylamines in urine, metabolites of phthalates, DINCH, OPFRs and PAHs in urine as well as metals in blood and urine, with a preference to measure Cr in erythrocytes representing Cr (VI) exposure. High performance liquid chromatographytandem mass spectrometry (LC-MS/MS) was the method of choice for bisphenols, PFASs, the HFR hexabromocyclododecane (HBCDD), phenolic HFRs as well as the metabolites of phthalates, DINCH, OPFRs and PAHs in urine. Gas chromatographic (GC) methods were selected for the remaining compounds, e.g. GC-low resolution MS with electron capture negative ionization (ECNI) for HFRs. Both GC-MS and LC-MS/MS were suitable for arylamines. New developments towards increased applications of GC-MS/MS may offer alternatives to GC-MS or LC-MS/MS approaches, e.g. for bisphenols. The metals were best determined by inductively coupled plasma (ICP)-MS, with the particular challenge of avoiding interferences in the Cd determination in urine. The evaluation process revealed research needs towards higher sensitivity and non-invasive sampling as well as a need for more stringent quality assurance/quality control applications and assessments.

As part of the Human Biomonitoring for Europe (HBM4EU) initiative a human biomonitoring (HBM) survey is conducted in 21 countries. This survey builds on existing HBM capacity in Europe by aligning national or regional HBM studies. The survey targets 3 age groups (i) children aged 6-11 years, (ii) teenagers aged 12-19 years and (iii) young adults aged 20-39 years and includes a total of 9493 participants (3151 children, 2953 teenagers and 3389 young adults). Depending on the age group, internal exposure to phthalates and substitute Hexamoll® DINCH, brominated and organophosphorus flame retardants, per-/poly-fluorinated compounds, cadmium, bisphenols and/or polycyclic aromatic hydrocarbons are assessed. The main goal of the programme is to obtain quality controlled and comparable HBM data of exposure to chemicals, prioritized under HBM4EU, with European wide coverage to inform the development of environment and health policies. This paper describes the framework of the HBM4EU survey and the approach that has been applied to align European HBM initiatives across Europe. HBM4EU is co-financed under Horizon 2020 (grant agreement No 733032). The authors thank all principle investigators of the contributing studies for their participation and contribution to the joint HBM4EU survey and the national programme owners for their financial support. In addition we want to thank Dr. Liesbeth Bruckers and Dr. Michael Schümann. Sí

The European Joint Programme HBM4EU is the backbone for knowledge on human exposure to environmental chemicals in the EU. It will inform European and national policy makers to take science based de...

The French biomonitoring program consists now of two distinct cross-sectional national biomonitoring surveys: a perinatal component based on a selection of pregnant women enrolled in the French Lon...

La surveillance du risque d’origine fecale porte par l’eau du robinet se focalise traditionnellement sur les epidemies. Une etude pilote a ete menee pour apprehender le potentiel des donnees de remboursement des medicaments de l’Assurance maladie pour la detection automatisee des agregats (DAA) de cas de gastro-enterite aigue medicalisee (GEAm) d’origine hydrique. Le nombre hebdomadaire de cas de GEAm a ete derive de cette base de donnees pour les 1 541 communes de trois departements a dominante rurale pendant la periode 2009-2012. Nous avons developpe une methode de DAA combinant deux methodes fondees sur la comparaison spatiale des taux d’incidence (methode A) et de l’evolution temporelle de ces taux d’incidence (methode B) entre la commune ciblee et les communes du departement. Pour chaque departement, nous avons ainsi teste chaque commune, semaine par semaine, durant la periode d’etude. 210 agregats « commune × semaine » impliquant plus de cinq cas de GEAm ont ete identifies par les methodes A et B, formant 193 agregats consolides de 1 a 3 semaines. 10% des communes ont eprouve un agregat et 1,5% en ont eprouve plusieurs. L’inference a la France entiere indique que 1000 agregats (soit 30000 cas de GEAm au total) pourraient etre detectes annuellement. Cet impact ne represente qu’une faible part du total des cas de GEAm d’origine hydrique.La finalite de la DAA est d’orienter les investi gations de terrain vers les situations les plus a risque par le signalement en routine aux autorites locales des agregats trouves par DAA, de stimuler la prevention du risque en coordination avec la mise en place des Water safety plans et d’encourager la remontee d’information pour alimenter la surveillance des facteurs de risque au niveau national. La discussion porte sur cette perspective de sante publique ainsi que sur l’amelioration possible de la methode.

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.

Resume Objectifs La stimulation medullaire (SM) est une technique antalgique indiquee dans le traitement des douleurs chroniques neuropathiques irreductibles. Elle beneficie d’une prise en charge par l’assurance maladie depuis 2002. Ce travail a pour objectif de presenter un mode original de collaboration public–prive et d’en evaluer l’efficience. Methodes Depuis 2004, trois structures douleur francaises du secteur public collaborent avec un neurochirurgien installe en etablissement de sante prive, selon une procedure organisationnelle bien etablie. Un registre prospectif a ete mis en place pour evaluer l’efficacite et la securite de nos pratiques. Resultats Notre serie porte sur 141 patients ayant beneficie d’une phase test de SM ; 75 % ont ete implantes definitivement. Parmi les patients non perdus de vue, 81,7 % beneficient d’un soulagement superieur a 80 % de la douleur a long terme (12 mois) : ces resultats sont nettement superieurs a ceux de la litterature. Le taux de complications est quant a lui inferieur a celui des series publiees, la grande majorite des complications etant mineures et reversibles. Conclusions Notre mode original de collaboration public–prive a permis de simplifier et de decloisonner les filieres de mise en place de la SM dans notre territoire de sante, au benefice direct des patients. Les resultats de notre serie en termes d’efficacite et de securite viennent confirmer la pertinence d’une telle organisation.

An 11-year-old boy's epileptic seizures started with a feeling of impending crisis, dizziness, headache, and a bad taste in the mouth. This was followed by swallowing and a burning sensation in the left hand. At the same time, other parts of the body experienced allodynia. MRI and CT scans showed a right anteromesial temporal lesion which proved at neuropathology to be a ganglioglioma. Lesionectomy resulted in complete cessation of seizures. Seizures were absent at an 18-month follow-up. Allodynia is discussed in relation to the locality of the lesion.

In the Nantes area, 410,000 inhabitants are supplied with water pumped from the Loire River. The treatment of this water is carried out through a process of complete clarification and disinfection. During the study period (2002–07), the quality of drinking water complied with European microbial standards and mean turbidity in finished water was 0.05 NTU (nephelometric turbidity units). We aimed to characterize the link between produced water turbidity and other operational data and the incidence of acute gastroenteritis (AGE) in the Nantes area. The daily number of medical prescriptions for AGE was drawn from the French national health insurance system’s drug reimbursement data. We modeled this time series using Poisson regression within the framework of a Generalized Additive Model. We showed that an interquartile range turbidity degradation (0.042–0.056 NTU) was connected to a 4.2% (CI95=(1.5%; 6.9%)) increase in the risk of AGE in children and a 2.9% (CI95=(0.5%; 5.4%)) increase in adults. The slope of the turbidity risk function was higher during both high- and low-water conditions of the river. High values of daily flow of produced water were also associated with higher endemic levels of AGE.

Objective. Ostreopsis ovata and Ostreopsis siamensis are tropical unicellular algae that have been found recently in the Mediterranean. Both of these dinoflagellates produce palytoxin (PTX)-like toxins that are powerful vasoconstrictors in mammals. Since 2003, Ostreopsis blooms in Italy and Spain have been accompanied by reports of respiratory problems and skin/mucosa irritation in persons in contact with toxic microalgal cells (epiphytes, plankton, or sea spray) or associated toxins. Methods. In France, a surveillance network has been set up to monitor water conditions and to protect swimmers from contamination due to Ostreopsis. Results. Between 2006 and 2009, a total of nine blooms were observed on the French Mediterranean coast including five that led to manifestations in divers, swimmers, and shoreline inhabitants. A total of 47 patients presented symptoms of involving benign or mild skin, mucosal, and/or respiratory irritation that regressed spontaneously without treatment within 12-72 h (4-12 h with nonsteroidal anti-inflammatory drugs). During the study period, five beaches were temporarily closed. Discussion. In the Mediterranean, Ostreopsis blooms induce skin and respiratory disorders when human beings are exposed to saltwater with a high concentration of algal cells. However, palytoxin dosages carried out on the food chain (urchins, mussels) indicate that this risk of toxins accumulation in seafood must be taken into account and that the surveillance network should be upgraded accordingly.

BACKGROUND Regimens combining oxaliplatin with fluorouracil and folinic acid are standard therapeutic options for patients with metastatic colorectal carcinoma. Oxaliplatin has a good safety profile, although it is responsible for dose-limiting neurotoxicity typically consisting of two distinct clusters of symptoms. Cold-induced distal paresthesiae occur during or shortly after infusion in most patients and are usually transient and mild. A persistent sensory peripheral neuropathy may develop with prolonged treatment, eventually causing superficial and deep sensory loss, sensory ataxia and functional impairment. METHODS The authors report four cases of atypical neurotoxicity induced by oxaliplatin in patients treated for metastatic colorectal carcinoma. Two patients were male and two were female, with an age range of 52–59 years. RESULTS Three patients experienced Lhermitte sign and two experienced urinary retention. In all cases, the cumulative dose of oxaliplatin was higher than 1000 mg (range, 1248–2040 mg). Brain and spinal magnetic resonance imaging was performed in two patients and was normal. Somatosensory evoked potentials were recorded in two patients and suggested cervical dorsal column dysfunction. Symptoms resolved a few weeks after discontinuation of oxaliplatin. CONCLUSIONS Lhermitte sign may be induced via a neurotoxic effect on the ascending axons of these T-shaped neurons. An atonic bladder may be the result of damage to the sensory portion of the sacral reflex arc, either in the dorsal roots, as for example in diabetic neuropathy, or in the posterior columns, as in tabes dorsalis. Alternatively, it may result from a paralysis of the parasympathetic fibers that control the bladder musculature. It is unclear at present whether the micturition difficulties observed in patients in the current series are due to sensory neuropathy or to autonomic neuropathy, event if the former hypothesis seems more likely, as autonomic neuropathy has not been previously observed with oxaliplatin, and its association with cisplatin is exceedingly rare and controversial. Cancer 2002;94:2434–40. © 2002 American Cancer Society. DOI 10.1002/cncr.10500