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Per- and polyfluoroalkyl substances (PFASs) were one of the priority substance groups selected which have been investigated under the ambitious European Joint programme HBM4EU (2017-2022). In order to answer policy relevant questions concerning exposure and health effects of PFASs in Europe several activities were developed under HBM4EU namely i) synthesis of HBM data generated in Europe prior to HBM4EU by developing new platforms, ii) development of a Quality Assurance/Quality Control Program covering 12 biomarkers of PFASs, iii) aligned and harmonized human biomonitoring studies of PFASs. In addition, some cohort studies (on mother-child exposure, occupational exposure to hexavalent chromium) were initiated, and literature researches on risk assessment of mixtures of PFAS, health effects and effect biomarkers were performed. The HBM4EU Aligned Studies have generated internal exposure reference levels for 12 PFASs in 1957 European teenagers aged 12-18 years. The results showed that serum levels of 14.3% of the teenagers exceeded 6.9 μg/L PFASs, which corresponds to the EFSA guideline value for a tolerable weekly intake (TWI) of 4.4 ng/kg for some of the investigated PFASs (PFOA, PFOS, PFNA and PFHxS). In Northern and Western Europe, 24% of teenagers exceeded this level. The most relevant sources of exposure identified were drinking water and some foods (fish, eggs, offal and locally produced foods). HBM4EU occupational studies also revealed very high levels of PFASs exposure in workers (P95: 192 μg/L in chrome plating facilities), highlighting the importance of monitoring PFASs exposure in specific workplaces. In addition, environmental contaminated hotspots causing high exposure to the population were identified. In conclusion, the frequent and high PFASs exposure evidenced by HBM4EU strongly suggests the need to take all possible measures to prevent further contamination of the European population, in addition to adopting remediation measures in hotspot areas, to protect human health and the environment. HBM4EU findings also support the restriction of the whole group of PFASs. Further, research and definition for additional toxicological dose-effect relationship values for more PFASs compounds is needed., (Copyright © 2023 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Characterization of PCB exposure sources for vulnerable population groups is essential to minimize the health effects of PCB exposure. At the same time, it is important to consolidate the knowledge on threshold intakes of PCBs for infants and toddlers to prevent health effects. We estimated total PCB concentrations from birth to 2 years of age in children from Slovak and Czech populations, which continue to have high PCB concentrations in breast milk. Using a pharmacokinetic (PK) model, we characterized dominant PCB exposure sources and estimated new threshold estimated daily intakes (TEDI) (above which adverse effects cannot be excluded) for postnatal PCB exposure in infants and toddlers. In the PK model, concentrations of seven indicator PCBs in breast milk and cord blood samples from 291 mother-child pairs from the Slovak birth cohort, and 396 breast milk samples from Czech mothers we used, together with their physiological characteristics and PCB concentrations from other exposure sources (food, dust, air). The estimated total PCB concentrations in children's blood at different ages were compared with threshold PCB concentrations of 500, 700 and 1000 ng·g lipid -1 in serum proposed by the French Agency for Food, Environmental and Occupational Health & Safety (ANSES) and the German Environment Agency (UBA), above which possible adverse health effects may be expected. We estimated that up to 20.6% of Slovak children and up to 45.7% of Czech children at two years of age exceeded the threshold value of 700 ng·g lipid -1 in blood. Mean TEDIs leading to values of 500 ng·g lipid -1 in blood for children up to two years ranged between 110 and 220 ng·kg -1 ·bw·day -1 , varying according to breastfeeding duration. Breast milk and prenatal exposure contributed to 71%-85% of PCBs exposure at two years of age. In contrast, the contributions of PCBs from dust and indoor air were negligible., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Human biomonitoring has become a pivotal tool for supporting chemicals' policies. It provides information on real-life human exposures and is increasingly used to prioritize chemicals of health concern and to evaluate the success of chemical policies. Europe has launched the ambitious REACH program in 2007 to improve the protection of human health and the environment. In October 2020 the EU commission published its new chemicals strategy for sustainability towards a toxic-free environment. The European Parliament called upon the commission to collect human biomonitoring data to support chemical's risk assessment and risk management. This manuscript describes the organization of the first HBM4EU-aligned studies that obtain comparable human biomonitoring (HBM) data of European citizens to monitor their internal exposure to environmental chemicals. The HBM4EU-aligned studies build on existing HBM capacity in Europe by aligning national or regional HBM studies. The HBM4EU-aligned studies focus on three age groups: children, teenagers, and adults. The participants are recruited between 2014 and 2021 in 11 to 12 primary sampling units that are geographically distributed across Europe. Urine samples are collected in all age groups, and blood samples are collected in children and teenagers. Auxiliary information on socio-demographics, lifestyle, health status, environment, and diet is collected using questionnaires. In total, biological samples from 3137 children aged 6-12 years are collected for the analysis of biomarkers for phthalates, HEXAMOLL ® DINCH, and flame retardants. Samples from 2950 teenagers aged 12-18 years are collected for the analysis of biomarkers for phthalates, Hexamoll ® DINCH, and per- and polyfluoroalkyl substances (PFASs), and samples from 3522 adults aged 20-39 years are collected for the analysis of cadmium, bisphenols, and metabolites of polyaromatic hydrocarbons (PAHs). The children's group consists of 50.4% boys and 49.5% girls, of which 44.1% live in cities, 29.0% live in towns/suburbs, and 26.8% live in rural areas. The teenagers' group includes 50.6% girls and 49.4% boys, with 37.7% of residents in cities, 31.2% in towns/suburbs, and 30.2% in rural areas. The adult group consists of 52.6% women and 47.4% men, 71.9% live in cities, 14.2% in towns/suburbs, and only 13.4% live in rural areas. The study population approaches the characteristics of the general European population based on age-matched EUROSTAT EU-28, 2017 data; however, individuals who obtained no to lower educational level (ISCED 0-2) are underrepresented. The data on internal human exposure to priority chemicals from this unique cohort will provide a baseline for Europe's strategy towards a non-toxic environment and challenges and recommendations to improve the sampling frame for future EU-wide HBM surveys are discussed.

Evidence of associations of pre- and postnatal exposure to polychlorinated biphenyls (PCBs) with cognitive development beyond early childhood is inconsistent. A previous report from this cohort observed adverse associations between early life PCB exposures and infant Bayley scores at age 16 months. The present study examines pre- and postnatal PCB exposures in relation to both behavior and cognitive development at age 45 months. Participants were 472 mother-child pairs residing in an area of eastern Slovakia characterized by environmental contamination with PCBs, which resulted in elevated blood serum concentrations. PCB-153 and PCB-118 concentrations were measured in maternal and in infant 6-, 16-, and 45-month serum samples. At age 45 months, children were administered five subtests of the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III), and mothers completed the Child Behavior Checklist (CBCL). Negative binomial and multiple linear regressions were used to estimate PCB-CBCL and PCB-WPPSI-III subtest score associations, respectively. Pre- and postnatal levels of PCB-153 and PCB-118 were not associated with cognitive performance on the WPPSI-III in this cohort. There was some suggestion that higher postnatal PCB concentrations were associated with more sleep problems and feelings of depression and anxiousness., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Indoor dust is an important exposure route to anthropogenic chemicals used in consumer products. Plasticizers are common product additives and can easily leach out of the product and partition to dust. Investigations of plasticizers typically focus on a subset of phthalate esters (PEs), but there are many more PEs in use, and alternative plasticizers (APs) are seeing greater use after recognition of adverse health effects of PEs. In this study we use full scan high resolution mass spectrometry for targeted and suspect screening of PEs and APs in house dust and to assess the potential risk of human exposure. House dust samples from Eastern Slovakia were investigated and concentrations of ∑ 12 PEs and ∑ 5 APs ranged 12-2765 μg/g and 45-13,260 μg/g, respectively. APs were at similar levels to PEs, indicating common usage of these compounds in products in homes. Evaluation of individual compound toxicity combined with human intake via dust ingestion suggested PEs are of lower priority compared to semivolatile organic compounds such as polychlorinated biphenyls due to their lower toxicity. However, cumulative risk assessment (CRA) is a more appropriate evaluation of risk, considering the presences of many PEs in dust and their similar toxic mode of action. CRA based on median toxicity reference values (TRVs) suggested acceptable risks for dust ingestion, however, the wide range of literature-derived TRVs is a large uncertainty, especially for the APs. Use of newer TRVs suggest risk from dust ingestion alone, i.e. not even considering diet, inhalation, and dermal contact. Additionally, screening of full-scan instrumental spectra identified a further 40 suspect PE compounds, suggesting the CRA based on the 12 target PEs underestimates the risk., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Serum PCB congener concentrations were measured in 602 adults living near a PCB pollution source in eastern Slovakia. We created isoconcentration maps for 21 PCB congeners by geocoding each participant's place of residence and kriging. Concentrations of PCB congeners were inversely associated with the distance of the participants' residence from the source of pollution. Congener-specific risk factors were derived, particularly for PCBs 52 and 153. We observed that the spatial distribution of serum concentrations was influenced by micro-climatic parameters and physicochemical properties of the congeners. PCB congener profiles strongly correlated with that of the PCB commercial product Delor 106, which was manufactured in the region. The isoconcentration maps indicate that the zones with the highest predicted congener concentration have a mean area of approximately 235.75±188.56km 2 and the mean enrichment of concentration of congeners in serum in these zones is about 5.12±1.36. We estimate that depending on congener approximately 23,457±18,762 individuals with PCB concentrations exceeding health-based guidance values live in these zones., (Copyright © 2018. Published by Elsevier B.V.)

In this study, 10 polybrominated diphenyl ethers (PBDEs) and 19 alternative halogenated flame retardants (AFRs) were determined in >450 human milk samples across three European countries, representing northern, western and eastern Europe. This study provides first insights into the occurrence of selected AFRs in mother milk samples and compares them among three European countries. Sums of median concentrations of the most frequently detected PBDEs were 2.16, 0.88 and 0.45ngg -1 lipid weight (lw) in Norway, the Netherlands and Slovakia, respectively. The sum of the concentrations of AFRs ranged from 0.14 to 0.25ngg -1 lw in all countries, which was 2 to 15 times less compared to Σ 7 PBDEs. The Penta-BDE replacement, bis(2-ethylhexyl) tetrabromophthalate, BEH-TEBP, was present at the greatest concentrations of any of the AFRs and in some samples exceeded concentrations of BDE 47 and BDE 153. Four AFRs including bromobenzenes (hexabromobenzene, pentabromobenzene, pentabromotoluene) and another Penta-BDE replacement (2-ethylhexyl-2,3,4,5-tetrabromobenzoate, EH-TBB) were detected in >42% of all human milk samples. Because of the potential developmental neurotoxicity of the halogenated flame retardants, infant dietary intakes via breastfeeding were estimated; in four cases the intakes of BDE 47 exceeded the reference dose indicating that the present concentrations may pose a risk for children., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Simple reaction time (SRT) has been studied in children exposed to polychlorinated biphenyls (PCBs), with variable results. In the current work we examined SRT in 146 boys and 161 girls, aged 8.53 ± 0.65 years (mean ± SD), exposed to PCBs in the environment of eastern Slovakia. We divided the children into tertiles with regard to increasing PCB serum concentration. The mean ± SEM serum concentration of the sum of 15 PCB congeners was 191.15 ± 5.39, 419.23 ± 8.47, and 1315.12 ± 92.57 ng/g lipids in children of the first, second, and third tertiles, respectively. We created probability distribution plots for each child from their multiple trials of the SRT testing. We fitted response time distributions from all valid trials with the ex-Gaussian function, a convolution of a normal and an additional exponential function, providing estimates of three independent parameters μ, σ, and τ. μ is the mean of the normal component, σ is the standard deviation of the normal component, and τ is the mean of the exponential component. Group response time distributions were calculated using the Vincent averaging technique. A Q-Q plot comparing probability distribution of the first vs. third tertile indicated that deviation of the quantiles of the latter tertile from those of the former begins at the 40th percentile and does not show a positive acceleration. This was confirmed in comparison of the ex-Gaussian parameters of these two tertiles adjusted for sex, age, Raven IQ of the child, mother's and father's education, behavior at home and school, and BMI: the results showed that the parameters μ and τ significantly (p ≤ 0.05) increased with PCB exposure. Similar increases of the ex-Gaussian parameter τ in children suffering from ADHD have been previously reported and interpreted as intermittent attentional lapses, but were not seen in our cohort. Our study has confirmed that environmental exposure of children to PCBs is associated with prolongation of simple reaction time reflecting impairment of cognitive functions., (Copyright © 2015 Elsevier Inc. All rights reserved.)