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Background: Bisphenol A (BPA; or 4,4′-isopropylidenediphenol) is an endocrine disrupting chemical. It was widely used in a variety of plastic-based manufactured products for several years. The European Food Safety Authority (EFSA) recently reduced the Tolerable Daily Intake (TDI) for BPA by 20,000 times due to concerns about immune-toxicity. Objective: We used human biomonitoring (HBM) data to investigate the general level of BPA exposure from 2007 to 2014 of European women aged 18–73 years (n = 4,226) and its determinants. Methods: Fifteen studies from 12 countries (Austria, Belgium, Denmark, France, Germany, Greece, Israel, Luxembourg, Slovenia, Spain, Sweden, and the United Kingdom) were included in the BPA Study protocol developed within the European Joint Programme HBM4EU. Seventy variables related to the BPA exposure were collected through a rigorous post-harmonization process. Linear mixed regression models were used to investigate the determinants of total urine BPA in the combined population. Results: Total BPA was quantified in 85–100 % of women in 14 out of 15 contributing studies. Only the Austrian PBAT study (Western Europe), which had a limit of quantification 2.5 to 25-fold higher than the other studies (LOQ=2.5 µg/L), found total BPA in less than 5 % of the urine samples analyzed. The geometric mean (GM) of total urine BPA ranged from 0.77 to 2.47 µg/L among the contributing studies. The lowest GM of total BPA was observed in France (Western Europe) from the ELFE subset (GM=0.77 µg/L (0.98 µg/g creatinine), n = 1741), and the highest levels were found in Belgium (Western Europe) and Greece (Southern Europe), from DEMOCOPHES (GM=2.47 µg/L (2.26 µg/g creatinine), n = 129) and HELIX-RHEA (GM=2.47 µg/L (2.44 µg/g creatinine), n = 194) subsets, respectively. One hundred percent of women in 14 out of 15 data collections in this study exceeded the health-based human biomonitoring guidance value for the general population (HBM-GVGenPop) of 0.0115 µg total BPA/L urine derived from the updated EFSA’s BPA TDI. Variables related to the measurement of total urine BPA and those related to the main socio-demographic characteristics (age, height, weight, education, smoking status) were collected in almost all studies, while several variables related to BPA exposure factors were not gathered in most of the original studies (consumption of beverages contained in plastic bottles, consumption of canned food or beverages, consumption of food in contact with plastic packaging, use of plastic film or plastic containers for food, having a plastic floor covering in the house, use of thermal paper…). No clear determinants of total urine BPA concentrations among European women were found. A broader range of data planned for collection in the original questionnaires of the contributing studies would have resulted in a more thorough investigation of the determinants of BPA exposure in European women. Conclusion: This study highlights the urgent need for action to further reduce exposure to BPA to protect the population, as is already the case in the European Union. The study also underscores the importance of pre-harmonizing HBM design and data for producing comparable data and interpretable results at a European-wide level, and to increase HBM uptake by regulatory agencies.

Based on toxicological evidence, children’s exposure to phthalates may contribute to altered neurodevelopment and abnormal regulation of brain-derived neurotrophic factor (BDNF). We analyzed data from five aligned studies of the Human Biomonitoring for Europe (HBM4EU) project. Ten phthalate metabolites and protein BDNF levels were measured in the urine samples of 1148 children aged 6–12 years from Italy (NACII-IT cohort), Slovakia (PCB-SK cohort), Hungary (InAirQ-HU cohort) and Norway (NEBII-NO). Serum BDNF was also available in 124 Slovenian children (CRP-SLO cohort). Children’s total, externalizing and internalizing behavioral problems were assessed using the Child Behavior Checklist at 7 years of age (only available in the NACII-IT cohort). Adjusted linear and negative binomial regression models were fitted, together with weighted quantile sum (WQS) regression models to assess phthalate mixture associations. Results showed that, in boys but not girls of the NACII-IT cohort, each natural-log-unit increase in mono-n-butyl phthalate (MnBP) and Mono(2-ethyl-5-oxohexyl) phthalate (MEOHP) was cross-sectionally associated with higher externalizing problems [incidence rate ratio (IRR): 1.20; 95% CI: 1.02, 1.42 and 1.26; 95% CI: 1.03, 1.55, respectively]. A suggestive mixture association with externalizing problems was also observed per each tertile mixture increase in the whole population (WQS—IRR = 1.15; 95% CI: 0.97, 1.36) and boys (IRR = 1.20; 95% CI: 0.96, 1.49). In NACII-IT, PCB-SK, InAirQ-HU and NEBII-NO cohorts together, urinary phthalate metabolites were strongly associated with higher urinary BDNF levels, with WQS regression confirming a mixture association in the whole population (percent change (PC) = 25.9%; 95% CI: 17.6, 34.7), in girls (PC = 18.6%; 95% CI: 7.92, 30.5) and mainly among boys (PC = 36.0%; 95% CI: 24.3, 48.9). Among CRP-SLO boys, each natural-log-unit increase in ∑DINCH concentration was associated with lower serum BDNF levels (PC: −8.8%; 95% CI: −16.7, −0.3). In the NACII-IT cohort, each natural-log-unit increase in urinary BDNF levels predicted worse internalizing scores among all children (IRR: 1.15; 95% CI: 1.00, 1.32). Results suggest that (1) children’s exposure to di-n-butyl phthalate (DnBP) and di(2-ethylhexyl) phthalate (DEHP) metabolites is associated with more externalizing problems in boys, (2) higher exposure to DINCH may associate with lower systemic BDNF levels in boys, (3) higher phthalate exposure is associated with higher urinary BDNF concentrations (although caution is needed since the possibility of a “urine concentration bias” that could also explain these associations in noncausal terms was identified) and (4) higher urinary BDNF concentrations may predict internalizing problems. Given this is the first study to examine the relationship between phthalate metabolite exposure and BDNF biomarkers, future studies are needed to validate the observed associations.

Human exposure to mercury can have serious health effects, especially in vulnerable groups such as children and fetuses. The use of dried blood spot (DBS) samples to collect capillary blood greatly facilitates sample collection and fieldwork, being a less invasive alternative to blood collection by venipuncture, needing a small volume of sample, and does not require specialized medical staff. Moreover, DBS sampling reduces logistical and financial barriers related to transport and storage of blood samples. We propose here a novel method to analyze total mercury in DBS samples in a Direct Mercury Analyzer (DMA) that allow the control of the volume of the DBS samples. This method has shown good results in terms of precision (

The knowledge of the effects of organophosphate flame retardants on children’s neurodevelopment is limited. The purpose of the present research is to evaluate the association between exposure to organophosphate flame retardants and children’s neurodevelopment in two European cohorts involved in the Human Biomonitoring Initiative Aligned Studies. The participants were school-aged children belonging to the Odense Child Cohort (Denmark) and the PCB cohort (Slovakia). In each cohort, the children’s neurodevelopment was assessed through the Full-Scale Intelligence Quotient score of the Wechsler Intelligence Scale for Children, using two different editions. The children’s urine samples, collected at one point in time, were analyzed for several metabolites of organophosphate flame retardants. The association between neurodevelopment and each organophosphate flame retardant metabolite was explored by applying separate multiple linear regressions based on the approach of MM-estimation in each cohort. In the Danish cohort, the mean ± standard deviation for the neurodevelopment score was 98 ± 12; the geometric mean (95% confidence interval (95% CI)) of bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) standardized by creatinine (crt) was 0.52 µg/g crt (95% CI = 0.49; 0.60), while that of diphenyl phosphate (DPHP) standardized by crt was 1.44 µg/g crt (95% CI = 1.31; 1.58). The neurodevelopment score showed a small, negative, statistically imprecise trend with BDCIPP standardized by crt (β = −1.30; 95%CI = −2.72; 0.11; p-value = 0.07) and no clear association with DPHP standardized by crt (β = −0.98; 95%CI = −2.96; 0.99; p-value = 0.33). The neurodevelopment score showed a negative trend with BDCIPP (β = −1.42; 95% CI = −2.70; −0.06; p-value = 0.04) and no clear association with DPHP (β = −1.09; 95% CI = −2.87; 0.68; p-value = 0.23). In the Slovakian cohort, the mean ± standard deviation for the neurodevelopment score was 81 ± 15; the geometric mean of BDCIPP standardized by crt was 0.18 µg/g crt (95% CI = 0.16; 0.20), while that of DPHP standardized by crt was 2.24 µg/g crt (95% CI = 2.00; 3.52). The association of the neurodevelopment score with BDCIPP standardized by crt was −0.49 (95%CI = −1.85; 0.87; p-value = 0.48), and with DPHP standardized by crt it was −0.35 (95%CI = −1.90; 1.20; p-value = 0.66). No clear associations were observed between the neurodevelopment score and BDCIPP/DPHP concentrations that were not standardized by crt. No clear associations were observed with bis(1-chloro-2-propyl) phosphate (BCIPP) in either cohort, due to the low detection frequency of this compound. In conclusion, this study provides only limited evidence of an inverse association between neurodevelopment and exposure to BDCIPP and DPHP. The timing of exposure and effect modification of other organophosphate flame retardant metabolites and other substances should be the subject of further investigations that address this scientific hypothesis.

Human biomonitoring (HBM) data in Europe are often fragmented and collected in different EU countries and sampling periods. Exposure levels for children and adult women in Europe were evaluated over time. For the period 2000–2010, literature and aggregated data were collected in a harmonized way across studies. Between 2011–2012, biobanked samples from the DEMOCOPHES project were used. For 2014–2021, HBM data were generated within the HBM4EU Aligned Studies. Time patterns on internal exposure were evaluated visually and statistically using the 50th and 90th percentiles (P50/P90) for phthalates/DINCH and organophosphorus flame retardants (OPFRs) in children (5–12 years), and cadmium, bisphenols and polycyclic aromatic hydrocarbons (PAHs) in women (24–52 years). Restricted phthalate metabolites show decreasing patterns for children. Phthalate substitute, DINCH, shows a non-significant increasing pattern. For OPFRs, no trends were statistically significant. For women, BPA shows a clear decreasing pattern, while substitutes BPF and BPS show an increasing pattern coinciding with the BPA restrictions introduced. No clear patterns are observed for PAHs or cadmium. Although the causal relations were not studied as such, exposure levels to chemicals restricted at EU level visually decreased, while the levels for some of their substitutes increased. The results support policy efficacy monitoring and the policy-supportive role played by HBM.

Humans are potentially exposed to a large amount of chemicals present in the environment and in the workplace. In the European Human Biomonitoring initiative (Human Biomonitoring for the European Union = HBM4EU), acrylamide, mycotoxins (aflatoxin B1, deoxynivalenol, fumonisin B1), diisocyanates (4,4′-methylenediphenyl diisocyanate, 2,4- and 2,6-toluene diisocyanate), and pyrethroids were included among the prioritized chemicals of concern for human health. For the present literature review, the analytical methods used in worldwide biomonitoring studies for these compounds were collected and presented in comprehensive tables, including the following parameter: determined biomarker, matrix, sample amount, work-up procedure, available laboratory quality assurance and quality assessment information, analytical techniques, and limit of detection. Based on the data presented in these tables, the most suitable methods were recommended. According to the paradigm of biomonitoring, the information about two different biomarkers of exposure was evaluated: a) internal dose = parent compounds and metabolites in urine and blood; and b) the biologically effective = dose measured as blood protein adducts. Urine was the preferred matrix used for deoxynivalenol, fumonisin B1, and pyrethroids (biomarkers of internal dose). Markers of the biological effective dose were determined as hemoglobin adducts for diisocyanates and acrylamide, and as serum-albumin-adducts of aflatoxin B1 and diisocyanates. The analyses and quantitation of the protein adducts in blood or the metabolites in urine were mostly performed with LC-MS/MS or GC-MS in the presence of isotope-labeled internal standards. This review also addresses the critical aspects of the application, use and selection of biomarkers. For future biomonitoring studies, a more comprehensive approach is discussed to broaden the selection of compounds.

Introduction: Chronic obstructive pulmonary disease (COPD) is a respiratory pathology with high prevalence, morbidity and mortality. The Spanish COPD guideline (GesEPOC) recommends individualizing treatment according to phenotypes. The phenotype classification was updated in 2021. This study aimed to determine the survival of patients by this new classification and compare the predictive capacity of mortality compared to the previous version. Methods: This observational study of COPD patients involved prospective follow-up for 6 years. Demographic and clinical data were collected at the beginning and evolutionary data at the end of the study. Patients were classified according to GesEPOC 2017 and GesEPOC 2021. Univariate survival analysis and multivariate analysis identified mortality risk factors. Results: Of the 273 patients, 243 (89.0%) were male. Ninety-three patients (34.1%) died during follow-up. Regarding phenotypes, 190 patients (69.6%) were non-exacerbators, 69 (25.3%) belonged to the non-eosinophilic exacerbator phenotype and 14 (5.1%) were of the eosinophilic exacerbator phenotype. Compared with non-exacerbator patients, those with the non-eosinophilic exacerbator phenotype had lower survival (p = 0.009). Risk factors independently associated with mortality were older age (p

Phthalates are mainly used as plasticizers and are associated inter alia with adverse effects on reproductive functions. While more and more national programs in Europe have started monitoring internal exposure to phthalates and its substitute 1,2-Cyclohexanedicarboxylic acid (DINCH), the comparability of results from such existing human biomonitoring (HBM) studies across Europe is challenging. They differ widely in time periods, study samples, degree of geographical coverage, design, analytical methodology, biomarker selection, and analytical quality assurance level. The HBM4EU initiative has gathered existing HBM data of 29 studies from participating countries, covering all European regions and Israel. The data were prepared and aggregated by a harmonized procedure with the aim to describe—as comparably as possible—the EU-wide general population’s internal exposure to phthalates from the years 2005 to 2019. Most data were available from Northern (up to 6 studies and up to 13 time points), Western (11; 19), and Eastern Europe (9; 12), e.g., allowing for the investigation of time patterns. While the bandwidth of exposure was generally similar, we still observed regional differences for Butyl benzyl phthalate (BBzP), Di(2-ethylhexyl) phthalate (DEHP), Di-isononyl phthalate (DiNP), and Di-isobutyl phthalate (DiBP) with pronounced decreases over time in Northern and Western Europe, and to a lesser degree in Eastern Europe. Differences between age groups were visible for Di-n-butyl phthalate (DnBP), where children (3 to 5-year olds and 6 to 11-year olds) had lower urinary concentrations than adolescents (12 to 19-year-olds), who in turn had lower urinary concentrations than adults (20 to 39-year-olds). This study is a step towards making internal exposures to phthalates comparable across countries, although standardized data were not available, targeting European data sets harmonized with respect to data formatting and calculation of aggregated data (such as developed within HBM4EU), and highlights further suggestions for improved harmonization in future studies.

Abstract Background During the last decade, the European Union initiated several projects in the domains of public and environmental health. Within this framework, BRIDGE Health (Bridging Information and Data Generation for Evidence-based Health policy and Research) and HBM4EU (European human biomonitoring initiative) have been implemented. Whereas, the focus of BRIDGE Health was towards a sustainable and integrated health information system (HIS), the aim of HBM4EU is to improve evidence of the internal exposure of European citizens to environmental chemicals by human biomonitoring (HBM) and the impact of internal exposure on health. As both, environmental and public health determinants are important for health promotion, disease prevention and policy, BRIDGE Health and HBM4EU have overlapping aims and outcomes. In order to improve health information regarding public health and environmental health issues, best use and exchange of respective networks and project results is necessary. Methods Both projects have implemented health information (HI) and HBM tasks in order to provide adequate environmental and public health information of the European population. Synergies of the projects were identified in the working progress and because of overlapping networks and experts a focused analysis of both projects was envisaged. This paper elaborates on the aims and outcomes of both projects and the benefit of merging and channelling research results for the use of better health information and policy making that may be of relevance for any other project in these research fields. Results The need for focused exchanges and collaborations between the projects were identified and benefits of exchanges were highlighted for the specific areas of indicator development, linkage of data repositories and the combination of HBM studies and health examination surveys (HES). Further recommendations for a European wide harmonisation among different tasks in the fields of public health and environmental health are being developed. Conclusions Lessons learned from HBM4EU and BRIDGE Health show that continuous efforts must be undertaken, also by succeeding projects, to guarantee the exchange between public health and environmental health issues. Networks covering both are essential to provide better evidence of knowledge. The experiences from BRIDGE Health and HBM4EU give a valuable input for any future activity in these domains. Avoiding overlaps and streamlining further exchange of public health and environmental health contributes to best use of research results and allows to develop new strategies and tools for improvement of health information and thus enhances people’s health and well-being.

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 µg/L). The 95th percentiles (P95) ranged between 0.24 and 0.37 µg/L urine for Gly and between 0.21 and 0.38 µg/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.

Information about the effects of phthalates and non-phthalate substitute cyclohexane-1,2-dicarboxylic acid diisononyl ester (HEXAMOLL® DINCH) on children’s neurodevelopment is limited. The aim of the present research is to evaluate the association between phthalate/HEXAMOLL® DINCH exposure and child neurodevelopment in three European cohorts involved in HBM4EU Aligned Studies. Participating subjects were school-aged children belonging to the Northern Adriatic cohort II (NAC-II), Italy, Odense Child Cohort (OCC), Denmark, and PCB cohort, Slovakia. In each cohort, children’s neurodevelopment was assessed through the Full-Scale Intelligence Quotient score (FSIQ) of the Wechsler Intelligence Scale of Children test using three different editions. The children’s urine samples, collected for one point in time concurrently with the neurodevelopmental evaluation, were analyzed for several phthalates/HEXAMOLL® DINCH biomarkers. The relation between phthalates/HEXAMOLL® DINCH and FSIQ was explored by applying separate multiple linear regressions in each cohort. The means and standard deviations of FSIQ were 109 ± 11 (NAC-II), 98 ± 12 (OCC), and 81 ± 15 (PCB cohort). In NAC-II, direct associations between FSIQ and DEHP’s biomarkers were found: 5OH-MEHP+5oxo-MEHP (β = 2.56; 95% CI 0.58–4.55; N = 270), 5OH-MEHP+5cx-MEPP (β = 2.48; 95% CI 0.47–4.49; N = 270) and 5OH-MEHP (β = 2.58; 95% CI 0.65–4.51; N = 270). On the contrary, in the OCC the relation between DEHP’s biomarkers and FSIQ tended to be inverse but imprecise (p-value ≥ 0.10). No associations were found in the PCB cohort. FSIQ was not associated with HEXAMOLL® DINCH in any cohort. In conclusion, these results do not provide evidence of an association between concurrent phthalate/DINCHHEXAMOLLR DINCH exposure and IQ in children.

Hyperuricemia is becoming a serious public health issue, which is highly influenced by environmental factors, although there is still controversial information on the potential influence of the exposure to Persistent Toxic Substances (PTSs) in the general population. In this study we aimed to assess the association. PTS exposure with uric acid homeostasis in a sample of the Spanish population.Participants were recruited during 2009–2010 in all the main geographical areas of Spain. Exposure to 34 PTSs was estimated by chemical analyses of serum levels of 6 Polychlorinated Biphenyls (PCBs, n = 950), 13 Organochlorine Pesticides (OCPs, n = 453), 6 Perfluoroalkyl Substances (PFAs, n = 755), 7 Polybrominated Diphenyl Ethers (PBDEs, n = 365), urinary Cadmium (n = 926), and Lead in whole blood (n = 882). The two study outcomes were defined as the prevalence of hyperuricemia in the study population and uric acid levels, the latter only in individuals with no previous diagnosis of hyperuricemia. Statistical analyses were performed by means of binomial logistic regression and linear regression, and mixture effects were screened using Weighted Quantile Sum Regression (WQS).Serum concentrations of γ-HCH, o,p´-DDE, PCB-138, PCB-153, PFOA, and urinary Cadmium were associated with an increased risk of hyperuricemia, while PBDE-153 showed an inverse association with the effect. Furthermore, exposure to Cadmium, PCB-138, and to PCB-153 was positively associated with uric acid levels. Results were consistent after lipid adjustment or standardization. WQS analyses revealed a major contribution of PCB-153 within the PCB mixture on both the risk of hyperuricemia and uric acid levels. Sensitivity analyses were performed by adjusting for dietary habits, fasting glucose and estimated glomerular filtration rate.Overall, we found novel associations between human exposure to mixtures of PTSs and disturbances in uric acid homeostasis. However, we cannot completely rule out potential residual confounding effect or reversed-causality related to the cross-sectional design. Keywords: Persistent toxic substances, Uric acid, Hyperuricemia, Metabolic disruption, Human biomonitoring, Spain

Pyrethroids are a major insecticide class, suitable for biomonitoring in humans. Due to similarities in structure and metabolic pathways, urinary metabolites are common to various active substances. A tiered approach is proposed for risk assessment. Tier I was a conservative screening for overall pyrethroid exposure, based on phenoxybenzoic acid metabolites. Subsequently, probabilistic approaches and more specific metabolites were used for refining the risk estimates. Exposure was based on 95th percentiles from HBM4EU aligned studies (2014–2021) covering children in Belgium, Cyprus, France, Israel, Slovenia, and The Netherlands and adults in France, Germany, Israel, and Switzerland. In all children populations, the 95th percentiles for 3-phenoxybenzoic acid (3-PBA) exceeded the screening value. The probabilistic refinement quantified the risk level of the most exposed population (Belgium) at 2% or between 1–0.1% depending on the assumptions. In the substance specific assessments, the 95th percentiles of urinary concentrations in the aligned studies were well below the respective human biomonitoring guidance values (HBM-GVs). Both information sets were combined for refining the combined risk. Overall, the HBM data suggest a low health concern, at population level, related to pyrethroid exposure for the populations covered by the studies, even though a potential risk for highly exposed children cannot be completely excluded. The proposed tiered approach, including a screening step and several refinement options, seems to be a promising tool of scientific and regulatory value in future.

Few data are available on the exposure of children to glyphosate (Gly) in Europe. Within HBM4EU, new HBM exposure data were collected from aligned studies at five sampling sites distributed over Europe (studies: SLO CRP (SI); ORGANIKO (CY); GerES V-sub (DE); 3XG (BE); ESTEBAN (FR)). Median Gly concentrations in urine were below or around the detection limit (0.1 µg/L). The 95th percentiles ranged between 0.18 and 1.03 µg Gly/L. The ratio of AMPA (aminomethylphosphonic acid; main metabolite of Gly) to Gly at molar basis was on average 2.2 and the ratio decreased with higher Gly concentrations, suggesting that other sources of AMPA, independent of metabolism of Gly to AMPA in the monitored participants, may concurrently operate. Using reverse dosimetry and HBM exposure data from five European countries (east, west and south Europe) combined with the proposed ADI (acceptable daily intake) of EFSA for Gly of 0.1 mg/kg bw/day (based on histopathological findings in the salivary gland of rats) indicated no human health risks for Gly in the studied populations at the moment. However, the absence of a group ADI for Gly+AMPA and ongoing discussions on e.g., endocrine disrupting effects cast some uncertainty in relation to the current single substance ADI for Gly. The carcinogenic effects of Gly are still debated in the scientific community. These outcomes would influence the risk conclusions presented here. Finally, regression analyses did not find clear associations between urinary exposure biomarkers and analyzed potential exposure determinants. More information from questionnaires targeting exposure-related behavior just before the sampling is needed.

A risk assessment (RA) was conducted to estimate the risk associated with methylmercury (MeHg) exposure of vulnerable European populations, using Human Biomonitoring (HBM) data. This RA was performed integrating published data from European HBM surveys and earlier EFSA approaches (EFSA 2012). Children/adolescents (3 to 17 years old) and women of childbearing age (18 to 50 years old) were selected as relevant study population groups for this RA. Two types of HBM datasets were selected: HBM studies (n = 18) with mercury (Hg) levels (blood and hair, total Hg and/or MeHg) in the general population in different EU countries and the DEMOCOPHES harmonized study in child–mother pairs (hair, total Hg) in 17 EU countries as a reference. Two approaches were included in the RA strategy: the first one was based on estimations of the fraction of children/adolescents and women of childbearing age, respectively, from the EU general population exceeding the HBM-I value established by the German Human Biomonitoring Commission, measured as Hazard Quotients (HQ); and the second approach was based on estimations of the fraction of the two population groups exceeding the Tolerable Weekly Intake (TWI) (or their equivalent to Tolerable Daily Intake (TDI)) defined by EFSA in 2012. The HQ approach showed that for both groups, the risk varies across EU countries and that some EU areas are close to or exceeding the exposure guidance values. This is the case of Spain and Portugal, which showed the highest HQ (GM and/or P95), probably due to their higher fish consumption. Results from the EFSA approach show that hair values of children/adolescents and women of childbearing age (both in selected HBM studies and in DEMOCOPHES study) are below the TDI of 1.9 µg/g; therefore, in general, the European population does not exceed the daily average/intake dose for MeHg and/or Hg. A possible risk underestimation was identified in our assessment since for many studies no data on P95 were available, causing loss of relevant information for risk characterization on the upper bound. In addition, data from other European countries also with high seafood consumption, such as France, Greece or Iceland, were not available. For this reason, further RA refinement is needed with harmonized and more widespread HBM data to account for differences in European exposure and associated risks, so that interventions to protect vulnerable citizens, can be applied.

The risk assessment of pesticide residues in food is a key priority in the area of food safety. Most jurisdictions have implemented pre-marketing authorization processes, which are supported by prospective risk assessments. These prospective assessments estimate the expected residue levels in food combining results from residue trials, resembling the pesticide use patterns, with food consumption patterns, according to internationally agreed procedures. In addition, jurisdictions such as the European Union (EU) have implemented large monitoring programs, measuring actual pesticide residue levels in food, and are supporting large-scale human biomonitoring programs for confirming the actual exposure levels and potential risk for consumers. The organophosphate insecticide chlorpyrifos offers an interesting case study, as in the last decade, its acceptable daily intake (ADI) has been reduced several times following risk assessments by the European Food Safety Authority (EFSA). This process has been linked to significant reductions in the use authorized in the EU, reducing consumers’ exposure progressively, until the final ban in 2020, accompanied by setting all EU maximum residue levels (MRL) in food at the default value of 0.01 mg/kg. We present a comparison of estimates of the consumer’s internal exposure to chlorpyrifos based on the urinary marker 3,5,6-trichloro-2-pyridinol (TCPy), using two sources of monitoring data: monitoring of the food chain from the EU program and biomonitoring of European citizens from the HB4EU project, supported by a literature search. Both methods confirmed a drastic reduction in exposure levels from 2016 onwards. The margin of exposure approach is then used for conducting retrospective risk assessments at different time points, considering the evolution of our understanding of chlorpyrifos toxicity, as well as of exposure levels in EU consumers following the regulatory decisions. Concerns are presented using a color code, and have been identified for almost all studies, particularly for the highest exposed group, but at different levels, reaching the maximum level, red code, for children in Cyprus and Israel. The assessment uncertainties are highlighted and integrated in the identification of levels of concern.

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, per- and 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 chromatography-tandem 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.

A quality assurance/quality control program was implemented in the framework of the EU project HBM4EU to assess and improve the comparability of biomarker analysis and to build a network of competent laboratories. Four rounds of proficiency tests were organized for 15 phthalate and two DINCH urinary biomarkers (0.2–138 ng/mL) over a period of 18 months, with the involvement of 28 laboratories. A substantial improvement in performance was observed after the first round in particular, and by the end of the program, an average satisfactory performance rate of 90% was achieved. The interlaboratory reproducibility as derived from the participants’ results varied for the various biomarkers and rounds, with an average of 24% for the biomarkers of eight single-isomer phthalates (e.g., DnBP and DEHP) and 43% for the more challenging biomarkers of the mixed-isomer phthalates (DiNP, DiDP) and DINCH. When the reproducibility was based only on the laboratories that consistently achieved a satisfactory performance, this improved to 17% and 26%, respectively, clearly demonstrating the success of the QA/QC efforts. The program thus aided in building capacity and the establishment of a network of competent laboratories able to generate comparable and accurate HBM data for phthalate and DINCH biomarkers in 14 EU countries. In addition, global comparability was ensured by including external expert laboratories.

Abstract Background To date Health information (HI) in the European Union does not comprise indicators or other information related to impacts of hazardous chemicals in consumer products, food, drinking water or air on the health status of the population. Therefore, we inventorised and evaluated the potential of environmental health surveillance and research data sources in the European population to provide HBM-based indicators of internal human exposure and health impact of relevant chemicals. Methods We established an up-dated inventory of European cross-sectional Human Biomonitoring (HBM) surveys and of birth cohorts, and compared chemicals and chemical groups addressed by HBM with indicators and health end points collected via European Core Health Indicators (ECHI), in birth registries, as well as in environmental and food data bases and health registries to see on how data collection could be aligned. Finally, we investigated study designs of HBM survey and health examination surveys for potential synergies. Results The inventory covers a total of 11 European cross-sectional national programmes and a large number of birth cohorts and includes information on study population, age groups, covered substances, sampled matrices, and frequency. The comparison of data collections shows that there are many overlaps between environmental chemicals with environmental and health reporting. HBM data could be linked with ECHI indicators for work-related risks, body mass index (BMI), and low birth weight, with perinatal disease, neurologic disorders, and some chronic diseases, or with data bases for e.g. indoor air, food, or consumer products. Existing initiatives to link data collections at European Environment Agency (EEA) and Joint Research Center (JRC) or at World Health Organization (WHO) are good options to further develop linkage of HBM with exposures sources and health end points. Conclusions There is potential to use HBM based information in a number of public health policies, and this would help to align reporting to international commitments. Environmental health surveillance based on HBM and HBM-based indicators, is an excellent tool to inform public health policies about risks from environmental chemicals, and the EU health information system would benefit from additional HBM-based indicators for monitoring exposure burden from environmental chemicals. Considerable efforts are needed to align and establish routine data collections and to develop a surveillance system and indicators which may inform public health policies.

Entre marzo de 2009 y julio de 2010 se desarrolló el trabajo de campo de BIOAMBIENT.ES, un estudio de biovigilancia de contaminantes ambientales en humanos de cobertura nacional. Esta nota pretende mostrar las tareas desarrolladas antes del comienzo del trabajo de campo con el fin de asegurar la calidad de las muestras recogidas, y consecuentemente de los resultados obtenidos. Se recogieron 1936 muestras de sangre, suero y orina, y 604 muestras de pelo, de trabajadores que acudían al reconocimiento anual de salud laboral en 38 centros de la Península, Ceuta y Canarias. Previamente se identificó el material idóneo para la recogida y el transporte de las muestras, y se entrenó al personal de campo. La planificación y la organización de la fase preanalítica hizo posible que menos del 1% de las muestras recogidas tuvieran que rechazarse por problemas de derrames, conservación, etc. Asimismo, los análisis no reflejan la presencia de interferencias preanalíticas.The fieldwork of BIOAMBIENT.ES was developed from March 2009 to July 2010. BIOAMBIENT.ES is a human biomonitoring study of environmental pollutants performed in Spain at the national level. This article aims to show the tasks performed before starting the fieldwork to ensure the quality of the samples and consequently the quality of the results. A total of 1,936 whole blood, serum and first-morning urine samples and 604 hair samples were collected from workers who attended the annual occupational health examination in 38 centers in the Peninsula, Ceuta and the Canary Islands. Before the fieldwork was started, the optimal sampling material and sample shipment was identified and fieldworkers were trained in their tasks. Due to the planning and organization of the pre-analytical phase, only 1% of the collected samples had to be rejected due to problem with spills, conservation, etc. In addition, the analyses conducted showed no pre-analytical interferences.