BACKGROUND: Exposure to toxic trace elements, which include metals and metalloids, can induce adverse health effects, including life-threatening diseases. Conversely, essential trace elements are vital for bodily functions, yet their excessive (or inadequate) intake may pose health risks. Therefore, identifying levels and determinants of exposure to trace elements is crucial for safeguarding human health. METHODS: The present study analyzed urinary concentrations of 14 trace elements (arsenic, cadmium, cobalt, chromium, copper, mercury, manganese, molybdenum, nickel, lead, antimony, selenium, thallium, and zinc) and their exposure determinants in 711 individuals, spanning from children to young adults from a Central European population from the Czech Republic. Multivariate linear regression and non-parametric Kruskal-Wallis ANOVA were used to investigate exposure determinants. Estimates of 95th percentile concentrations and confidence intervals were carried out to establish reference values (RV95). The study also assessed the percentage of population exceeding health-based guidance values (GVs) to gauge health risks. RESULTS: Young adults showed elevated toxic element concentrations, whereas children exhibited higher concentrations of essential elements. Mercury concentrations were associated with both dental amalgam filling count and seafood intake; arsenic concentrations were associated with seafood, rice, and mushroom consumption. Mushroom consumption also influenced lead concentrations. Sex differences were found for cadmium, zinc, nickel, and cobalt. Between 17.9% and 25% of the participants exceeded recommended GV for arsenic, while 2.4% to 2.8% exceeded GV for cadmium. Only one participant exceeded the GV for mercury, and none exceeded GVs for chromium and thallium. Essential trace elements' GVs were surpassed by 38% to 68.5% participants for zinc, 1.3% to 1.8% for molybdenum, and 0.2% to 0.3% for selenium. IMPACT: The present study examines trace element exposure in a Central European population from the Czech Republic, unveiling elevated exposure levels of toxic elements in young adults and essential elements in children. It elucidates key determinants of trace element exposure, including dietary and lifestyle indicators as well as dental amalgam fillings. Additionally, the study establishes novel reference values and a comparison with established health-based human biomonitoring guidance values, which are crucial for public health decision-making. This comprehensive biomonitoring study provides essential data to inform public health policies and interventions.

• Keywords
• Heavy metals, Human biomonitoring, Human exposure, Trace elements, Urine,
• MeSH
• Biological Monitoring * MeSH
• Child MeSH
• Cohort Studies MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Metalloids * urine   MeSH
• Child, Preschool MeSH
• Trace Elements * urine   MeSH
• Metals, Heavy * urine   MeSH
• Environmental Exposure * analysis   MeSH
• Check Tag
• Child MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Male MeSH
• Child, Preschool MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Czech Republic MeSH
• Names of Substances
• Metalloids * MeSH
• Trace Elements * MeSH
• Metals, Heavy * MeSH

BACKGROUND: Temporal trends of chemicals in the population are key to identifying changing sources of chemicals and determining the effectiveness of various legislative measures. OBJECTIVE: The present study focused on time comparisons to explore a possible decrease in PAH metabolite levels in the Czech population. Legislative measures occurred between sampling periods, including restricting smoking and the Air Protection Act. METHODS: Ten metabolites of PAHs were measured in urine samples collected in 2011-2012 from mothers and children from DEMOCOPHES-CZ study (N = 235) and in 2019-2020 from children, teenagers, and young adults from CELSPAC studies (N = 809). Multivariate linear regression, Kruskal-Wallis ANOVA, and Mann-Whitney test (MW) were used to investigate differences in OH-PAHs between periods, age categories, and exposure determinants. RESULTS: Median concentrations significantly decreased between 2011-2020 by 30-35% for 1-OH-NAP, 2-and 3-OH-FLUO, 85% for 1-OH-PHE, and 44% for 2/3-OH-PHE, while 2-OH-NAP increased by 29% in non-smoking adults. In children, median concentrations of all metabolites decreased by 10-51%, with 2-OH-NAP rising by 49%. Smokers showed the largest differences, with significant decreases of 46-59% in the median concentrations of 2-OH-NAP, 2/3-OH-PHE, 9-OH-PHE, and 1-OH-PYR, and 76-91% in OH-FLUOs, 1-OH-NAP, and 1-OH-PHE. Fish and offal consumption, season, locality, and type of cooking were significant factors associated with levels of OH-PAHs, explaining 4-9% of the variability. Smoking was the main contributor in 2011, explaining up to 45% variability; no difference was found between smokers and non-smokers in 2019. New reference values of OH-PAHs in urine were calculated for the Czech population. IMPACT: This study analyses the temporal trends of OH-PAHs in the population in the context of introduced legislative measures. In addition, it examines OH-PAH exposure in children, adolescents, and young adults in relation to lifestyle factors and establishes new reference values for polycyclic aromatic hydrocarbons that are important for public health decision-making. Biomonitoring over time is an essential tool for establishing new measures to protect public health. Created in BioRender. Komprdova, K. (2025) https://BioRender.com/u10q831 .

• Keywords
• Biomonitoring, Chemical exposure, Legislation, Polycyclic aromatic hydrocarbons,
• Publication type
• Journal Article MeSH

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.

• Keywords
• HBM4EU Aligned Studies, WISC, children, human biomonitoring, neurodevelopment, organophosphate flame retardants,
• Publication type
• Journal Article MeSH

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.

• Keywords
• DINCH, OPFRs, PAHs, bisphenols, cadmium, hazardous chemical, human biomonitoring, phthalates,
• Publication type
• Journal Article MeSH

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.

• Keywords
• HBM4EU, exposure, human biomonitoring, phthalates, pollutants,
• Publication type
• Journal Article MeSH

Many legacy and emerging flame retardants (FRs) have adverse human and environmental health effects. This study reports legacy and emerging FRs in children from nine European countries from the HBM4EU aligned studies. Studies from Belgium, Czech Republic, Germany, Denmark, France, Greece, Slovenia, Slovakia, and Norway conducted between 2014 and 2021 provided data on FRs in blood and urine from 2136 children. All samples were collected and analyzed in alignment with the HBM4EU protocols. Ten halogenated FRs were quantified in blood, and four organophosphate flame retardants (OPFR) metabolites quantified in urine. Hexabromocyclododecane (HBCDD) and decabromodiphenyl ethane (DBDPE) were infrequently detected (<16% of samples). BDE-47 was quantified in blood from Greece, France, and Norway, with France (0.36 ng/g lipid) having the highest concentrations. BDE-153 and -209 were detected in <40% of samples. Dechlorane Plus (DP) was quantified in blood from four countries, with notably high median concentrations of 16 ng/g lipid in Slovenian children. OPFR metabolites had a higher detection frequency than other halogenated FRs. Diphenyl phosphate (DPHP) was quantified in 99% of samples across 8 countries at levels ∼5 times higher than other OPFR metabolites (highest median in Slovenia of 2.43 ng/g lipid). FR concentrations were associated with lifestyle factors such as cleaning frequency, employment status of the father of the household, and renovation status of the house, among others. The concentrations of BDE-47 in children from this study were similar to or lower than FRs found in adult matrices in previous studies, suggesting lower recent exposure and effectiveness of PBDE restrictions.

• Keywords
• Children, Europe, HBM4EU, Human biomonitoring, Organophosphate flame retardants, Polybrominated diphenyl ethers,
• MeSH
• Child MeSH
• Adult MeSH
• Halogenated Diphenyl Ethers MeSH
• Humans MeSH
• Lipids MeSH
• Flame Retardants * MeSH
• Check Tag
• Child MeSH
• Adult MeSH
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH
• Geographicals
• Europe MeSH
• Names of Substances
• 2,2',4,4'-tetrabromodiphenyl ether MeSH Browser
• Halogenated Diphenyl Ethers MeSH
• Lipids MeSH
• Flame Retardants * MeSH

Within the European Human Biomonitoring (HBM) Initiative HBM4EU we derived HBM indicators that were designed to help answering key policy questions and support chemical policies. The result indicators convey information on chemicals exposure of different age groups, sexes, geographical regions and time points by comparing median exposure values. If differences are observed for one group or the other, policy measures or risk management options can be implemented. Impact indicators support health risk assessment by comparing exposure values with health-based guidance values, such as human biomonitoring guidance values (HBM-GVs). In general, the indicators should be designed to translate complex scientific information into short and clear messages and make it accessible to policy makers but also to a broader audience such as stakeholders (e.g. NGO's), other scientists and the general public. Based on harmonized data from the HBM4EU Aligned Studies (2014-2021), the usefulness of our indicators was demonstrated for the age group children (6-11 years), using two case examples: one phthalate (Diisobutyl phthalate: DiBP) and one non-phthalate substitute (Di-isononyl cyclohexane-1,2- dicarboxylate: DINCH). For the comparison of age groups, these were compared to data for teenagers (12-18 years), and time periods were compared using data from the DEMOCOPHES project (2011-2012). Our result indicators proved to be suitable for demonstrating the effectiveness of policy measures for DiBP and the need of continuous monitoring for DINCH. They showed similar exposure for boys and girls, indicating that there is no need for gender focused interventions and/or no indication of sex-specific exposure patterns. They created a basis for a targeted approach by highlighting relevant geographical differences in internal exposure. An adequate data basis is essential for revealing differences for all indicators. This was particularly evident in our studies on the indicators on age differences. The impact indicator revealed that health risks based on exposure to DiBP cannot be excluded. This is an indication or flag for risk managers and policy makers that exposure to DiBP still is a relevant health issue. HBM indicators derived within HBM4EU are a valuable and important complement to existing indicator lists in the context of environment and health. Their applicability, current shortcomings and solution strategies are outlined.

• Keywords
• DINCH, HBM4EU, Human biomonitoring (HBM), Phthalates, Science-policy uptake, indicator,
• MeSH
• Biological Monitoring MeSH
• Child MeSH
• Phthalic Acids * MeSH
• Carboxylic Acids MeSH
• Humans MeSH
• Adolescent MeSH
• Policy MeSH
• Check Tag
• Child MeSH
• Humans MeSH
• Adolescent MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH
• Names of Substances
• Phthalic Acids * MeSH
• Carboxylic Acids MeSH
• phthalic acid MeSH Browser