Association among serum per- and polyfluoroalkyl substances, lipid profile and metabolic syndrome in Czech adults, HBM-EHES survey 2019.

OBJECTIVES: Per- and polyfluoroalkyl substances (PFASs) are a large group of persistent synthetic chemicals widely used commercially. They accumulate increasingly in all environmental components and enter the organisms, including humans. Some of them are associated with the risk of harm to health, among others with metabolic disorders. To test the associations between blood serum levels of PFASs and blood lipid profile as well as metabolic syndrome, we linked human biomonitoring with the Czech Health Examination Survey (CZ-EHES) conducted in 2019. METHODS: A total of 168 participants of the CZ-EHES survey aged 25-64 years were examined including anthropometrical data and analyses for serum PFAS and blood lipid levels. Extended model approach in multiple linear regression models was used for identification of the associations between serum levels of 11 PFASs and lipid profile components. The relation between PFAS serum levels and metabolic syndrome prevalence was tested using a logistic regression model. RESULTS: Six PFASs were detected over the limit of quantification in at least 40% cases and were examined in subsequent analyses: perfluorodecanoic acid (PFDA), perfluorohexane sulfonic acid (PFHxS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorooctane sulfonic acid (PFOS), perfluoroundecanoic acid (PFUdA). The most dominant was PFOS with the mean value amounting to 4.81 ng/ml. After adjusting for potential confounders, we found a significant positive association between serum PFHxS and blood total cholesterol (p = 0.005) as well as LDL-cholesterol (p = 0.008). Significant positive association was also found between PFDA and HDL-cholesterol levels (p = 0.010). No significant associations were detected between PFASs and triglycerides, and between PFASs and metabolic syndrome. CONCLUSIONS: We found some evidence of a significant association between blood serum PFAS levels and blood cholesterol levels. Our results did not confirm an association between serum PFASs and the metabolic syndrome prevalence.

Biomonitoring of PFOA, PFOS and PFNA in human milk from Czech Republic, time trends and estimation of infant's daily intake.

BACKGROUND: Perfluoralkylated substances (PFASs) are persistent and bioaccumulative environmental contaminants. They are included on the list of emergent compounds monitored in the frame of HBM4EU project. OBJECTIVES: To analyze PFASs levels in human milk samples collected in the period 2006 through 2017, to follow their time trends, to assess the PFASs exposure in breastfed infants, to calculate the daily intake of PFASs and to compare it with the tolerable daily/weekly) intakes and to quantify risk from exposure using the hazard quotient and hazard index approach. MATERIAL AND METHODS: A broad spectrum of PFASs were analyzed by means of UHPLC-MS/MS in primipara human milk samples collected in four consecutive time periods 2006, 2010/11, 2014, and 2017; N = 46, 183, 164 and 232, respectively. Mothers living in urban and suburban residences were recruited after their delivery at maternity hospitals, and milk samples were taken within 2 and 8 weeks after delivery. The questionnaire was focused on possible sources of exposure, dietary habits and lifestyle. RESULTS: Only perfluorooctane sulfonate (PFOS) and perfluorooctanoid acid PFOA (in 2017, also perfluorononanoic acid (PFNA)) were quantified in more than 90% of analyzed human milk samples. In all sampling periods, the levels of PFOA were higher than those of PFOS (p < 0.05). A significant downward temporal trend (p < 0.001) was observed for both PFOA and PFOS levels. The median concentrations in sampling years 2006, 2010/11, 2014, and 2017 were 0.075, 0.059, 0.035, and 0.023 ng/mL for PFOA and 0.045, 0.031, 0.029, and 0.020 ng/mL for PFOS, respectively. In 2017, PFNA was also quantified in 99% of samples with the median concentration of 0.007 ng/mL. The levels of PFASs correlated with maternal sea fish consumption. No maternal age-related relationship was observed. Using the tolerably daily intake (TDI) values for PFOS and PFOA set by the European Food Safety Authority (EFSA) in 2008, the calculated daily intakes from breastfeeding were clearly below these limits. Using the new, more conservative EFSA Provisional Tolerably Weekly Intake (PTWI) values set in 2018, we demonstrated a considerable exceedance of PTWI, with a hazard index above 1. CONCLUSION: Significant time-related decreasing trends in the PFOS and PFOA levels in human milk were observed. Nevertheless, the body burden of infants from breastfeeding might pose an enhanced health risk to infants when the current PTWI values are applied. These findings strongly support the present EU efforts to phase out PFOA, its salts and PFOA related compounds. Since PFOS exposure there has still been widely detected despite PFOS usage reduction measures, the major exposure routes should be further monitored and, if possible, eliminated.

Exposure to Mixed Phthalates in Czech Preschool and School Children.

Knowledge of population exposure to phthalates based on the urinary metabolite levels is of the highest importance for health risk assessment. Such data are scarce in the Czech population. In the study conducted in 2016, six urinary phthalate metabolites were analysed in a total of 370 first morning urine samples of healthy children aged 5 and 9 years, namely mono(2-ethylhexyl) phthalate (MEHP), mono(2-ethyl-5-hydroxyhexyl) phthalate (5OH-MEHP), mono(2-ethyl-5-oxohexyl) phthalate (5oxo-MEHP), mono-benzyl phthalate (MBzP), mono-iso-butyl phthalate (MiBP), and mono-n-butyl phthalate (MnBP). The two latter mono-butyl phthalate isoforms dominated among all samples with geometric means of 63.0 µg/L (MnBP) and 44.1 µg/L (MiBP), followed by 5OH-MEHP (20.6 µg/L), 5oxo-MEHP (12.9 µg/L), MBzP (3.65 µg/L), and MEHP (2.31 µg/L). Daily intake (DI) of the parent phthalates was estimated using the creatinine-based model. The highest DI values were found for di-n-butyl phthalate (DnBP) (median 2.5 µg/kg bw/day; 95th percentile 7.8 µg/kg bw/day) and di-2-ethylhexyl phthalate (DEHP) (median 2.3 µg/kg bw/day; 95th percentile 8.9 µg/kg bw/day) in 5-year-old children. The tolerable daily intake (TDI) set by the European Food Safety Authority (EFSA) was exceeded in case of DnBP (in 1% of 9-year-olds and in 3% of 5-year-olds). Exposure risk was assessed based on hazard quotients calculation and cumulative approach for similar health effect. The combined exposure to four phthalates expressed by hazard index (HI) for reprotoxicity revealed exceeding of HI threshold in 14% of 5-year-olds and in 9% of 9-year-olds. These findings strongly support the need to reduce the burden of children by phthalates.

Assessment of vitamin D status in Czech children.

OBJECTIVE: Vitamin D deficiency is a global health problem. The aim of this study was to determine the proportion of Czech children with vitamin D deficiency and examine related factors. METHODS: The study subjects were 419 healthy children aged 5 and 9 years. Severe vitamin D deficiency was defined as a serum 25(OH)D level of < 25 nmol/L (3% of children), deficiency as that of 25-50 nmol/L (24% of children), insufficiency as that of 50-75 nmol/L (40% of children) and sufficiency as that of > 75 nmol/L (34% of children). RESULTS: Serum 25(OH)D levels varied mainly with season. The highest levels of 25(OH)D were reached in autumn (median: 79.0 nmol/L), followed by summer (median: 67.8 nmol/L) and winter (median: 56.0 nmol/L). The lowest median value (49.8 nmol/L) was detected in spring. CONCLUSION: Children with sufficiency 25(OH)D levels were more frequently exposed to the sun and exposed a larger part of their body to the sun while spending time outdoors. Levels of 25(OH)D were also associated with using vitamin D supplements within six weeks before sampling.

Urinary Cadmium and Cotinine Levels and Hair Mercury Levels in Czech Children and Their Mothers Within the Framework of the COPHES/DEMOCOPHES Projects.

The COPHES/DEMOCOPHES twin project was performed in 2011-2012 in 17 European countries to harmonize all steps of the human biomonitoring survey. Urinary cadmium, cotinine, phthalate metabolites, and hair mercury were measured in children (N = 120, 6-11 years) and their mothers of reproductive age, living in urban or rural areas. Cadmium in mothers' and children's urine was detected at a geometric mean (GM) concentration 0.227 and 0.109 µg/L, respectively; 95th percentile (P95) was 0.655 and 0.280 µg/L in mothers and children, respectively. No age-related, education-related, or urban versus rural differences were observed within the frame of each population group. Cadmium urinary level in mothers was about twofold compared with children. Higher levels were obtained in all smoking mothers but not in occasionally smoking or mothers and children exposed to environmental tobacco smoke (ETS). Mercury values in mothers were significantly higher in urban than in rural populations but not in children. GM and P95 for mercury in children's hair were 0.098 and 0.439 µg/g and in mothers' hair were 0.155 and 0.570 µg/g. Concentrations for mercury in the Czech samples were lower than European average. Hair mercury increased significantly with consumption of fish or seafood and with number of amalgam tooth fillings (in children). A positive association was found with family educational level. No influence of age was observed. Urinary cadmium and hair mercury levels were lower than health-based guidelines with one exception. High levels of urinary cotinine were found in the 12 smoking mothers (GM approximately 500 µg/L); lower levels in occasionally smoking mothers, N = 11 (34.5 µg/L). The mean cotinine levels in nonsmoking mothers who reported daily exposure to ETS was 10.7 µg/L. A similar mean value (10.8 µg/L) was obtained in six children who had daily exposure to ETS. In children without exposure to ETS, the mean cotinine level was 1.39 µg/L urine. Cotinine in the urine of children demonstrates limited protection of the Czech children against exposure to ETS.

Case study: Possible differences in phthalates exposure among the Czech, Hungarian, and Slovak populations identified based on the DEMOCOPHES pilot study results.

OBJECTIVE: Phthalates and their metabolites are classified as endocrine modulators. They affect the hormonal balance in both children and adults. The aim of this publication was to compare the urinary levels of phthalate metabolites in selected populations of the Czech Republic (CZ), Slovakia (SK), and Hungary (HU) in relation to the sources of phthalate exposure identified by means of questionnaire (personal care products, floor and wall coverings, plastic toys, and some kinds of foods). METHODS: Data were obtained through the twin projects COPHES (COnsortium to Perform Human biomonitoring on a European Scale) and DEMOCOPHES (DEMOnstration of a study to COordinate and Perform Human biomonitoring on a European Scale) from 2009 to 2012. The target groups were children aged 6-11 years old and their mothers up to 45 years of age. The metabolites of phthalates (monomethyl phthalate (MMP), monoethyl phthalate (MEP), monobenzyl phthalate (MBzP), mono-cyclohexyl phthalate (MCHP), mono-(2-ethylhexyl) phthalate (MEHP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (5OH-MEHP), and mono-(2-ethyl-5-oxohexyl) phthalate (5OXO-MEHP)) were analysed in first morning urine samples. After enzymatic glucuronide cleavage, the urine sample analyses were performed using ultra-high-performance liquid chromatography-electrospray ionization tandem mass spectrometry (UHPLC-ESI-MS/MS) in one laboratory that qualified in the External Quality Assessment exercises organised by COPHES. RESULTS: Significant differences in phthalate exposure between countries were revealed for children only but not for mothers. The concentrations of 5-OH-MEHP (P<0.001), 5OXO-MEHP (P<0.001), and their sum (P<0.001) were the highest in SK compared to CZ and HU. The health based guidance values for the sum of DEHP metabolites 5-OH MEHP and 5OXO-MEHP established by the German Commission for biomonitoring of 300 µg/L and 500 µg/L for women adults and children, respectively, were only exceeded in one mother and three boys. A significant difference was also found for MEP (P=0.0149), with the highest concentrations detected in HU. In all countries, the increasing frequency of using personal care products significantly elevated the concentrations of MEP. CONCLUSION: Some differences were observed between countries in the concentrations of individual urinary phthalate metabolites in children. However, the questionnaire results give no direct explanation for the differences between the countries except the variation in using personal care products.

Exposure determinants of cadmium in European mothers and their children.

The metal cadmium (Cd) is a widespread environmental pollutant with documented adverse effects on the kidneys and bones from long-term environmental exposure, but with insufficiently elucidated public health consequences such as risk of cardiovascular disease, hormone-related cancer in adults and developmental effects in children. This study is the first pan-European human biomonitoring project that succeeded in performing harmonized measurements of Cd in urine in a comparable way in mother-child couples from 16 European countries. The aim of the study was to evaluate the overall Cd exposure and significant determinants of Cd exposure. A study population of 1632 women (24-52 years of age), and 1689 children (5-12 years of age), from 32 rural and urban areas, was examined within a core period of 6 months in 2011-2012. Women were stratified as smokers and non-smokers. As expected, smoking mothers had higher geometric mean (gm) urinary cadmium (UCd; 0.24 µg/g crea; n=360) than non-smoking mothers (gm 0.18 µg/g crea; n=1272; p<0.0001), and children had lower UCd (gm 0.065 µg/g crea; n=1689) than their mothers at the country level. Non-smoking women exposed to environmental tobacco smoke (ETS) at home had 14% (95% CI 1-28%) higher UCd than those who were not exposed to ETS at home (p=0.04). No influence of ETS at home or other places on UCd levels was detected in children. Smoking women with primary education as the highest educational level of the household had 48% (95% CI 18-86%) higher UCd than those with tertiary education (p=0.0008). The same observation was seen in non-smoking women and in children; however they were not statistically significant. In children, living in a rural area was associated with 7% (95% CI 1-13%) higher UCd (p=0.03) compared to living in an urban area. Children, 9-12 years had 7% (95% CI 1-13%) higher UCd (p=0.04) than children 5-8 years. About 1% of the mothers, and 0.06% of the children, exceeded the tolerable weekly intake (TWI) appointed by EFSA, corresponding to 1.0 µg Cd/g crea in urine. Poland had the highest UCd in comparison between the 16 countries, while Denmark had the lowest. Whether the differences between countries are related to differences in the degree of environmental Cd contamination or to differences in lifestyle, socioeconomic status or dietary patterns is not clear.

Lessons learnt on recruitment and fieldwork from a pilot European human biomonitoring survey.

Within the European Environment and Health Action Plan an initiative to establish a coherent human biomonitoring approach in Europe was started. The project COPHES (COnsortium to Perform Human biomonitoring on a European Scale ) developed recommendations for a harmonized conduct of a human biomonitoring (HBM) survey which came into action as the pilot study DEMOCOPHES (DEMOnstration of a study to COordinate and Perform Human biomonitoring on a European Scale). Seventeen European countries conducted a survey with harmonized instruments for, inter alia, recruitment, fieldwork and sampling, in autumn/winter 2011/2012. Based on the countries' experiences of conducting the pilot study, following lessons learnt were compiled: the harmonized fieldwork instruments (basic questionnaire, urine and hair sampling) turned out to be very valuable for future HBM surveys on the European scale. A school approach was favoured by most of the countries to recruit school-aged children according to the established guidelines and country specific experiences. To avoid a low participation rate, intensive communication with the involved institutions and possible participants proved to be necessary. The communication material should also include information on exclusion criteria and offered incentives. Telephone contact to the participants the day before fieldwork during the survey can prevent the forgetting of appointments and first morning urine samples. To achieve comparable results on the European scale, training of interviewers in all issues of recruitment, fieldwork and sampling through information material and training sessions is crucial. A survey involving many European countries needs time for preparation and conduct. Materials for quality control prepared for all steps of recruitment, fieldwork and sampling proved to be important to warrant reliable results.

Policy recommendations and cost implications for a more sustainable framework for European human biomonitoring surveys.

The potential of Human Biomonitoring (HBM) in exposure characterisation and risk assessment is well established in the scientific HBM community and regulatory arena by many publications. The European Environment and Health Strategy as well as the Environment and Health Action Plan 2004-2010 of the European Commission recognised the value of HBM and the relevance and importance of coordination of HBM programmes in Europe. Based on existing and planned HBM projects and programmes of work and capabilities in Europe the Seventh Framework Programme (FP 7) funded COPHES (COnsortium to Perform Human Biomonitoring on a European Scale) to advance and improve comparability of HBM data across Europe. The pilot study protocol was tested in 17 European countries in the DEMOCOPHES feasibility study (DEMOnstration of a study to COordinate and Perform Human biomonitoring on a European Scale) cofunded (50%) under the LIFE+ programme of the European Commission. The potential of HBM in supporting and evaluating policy making (including e.g. REACH) and in awareness raising on environmental health, should significantly advance the process towards a fully operational, continuous, sustainable and scientifically based EU HBM programme. From a number of stakeholder activities during the past 10 years and the national engagement, a framework for sustainable HBM structure in Europe is recommended involving national institutions within environment, health and food as well as European institutions such as ECHA, EEA, and EFSA. An economic frame with shared cost implications for national and European institutions is suggested benefitting from the capacity building set up by COPHES/DEMOCOPHES.

Communication in a Human biomonitoring study: Focus group work, public engagement and lessons learnt in 17 European countries.

A communication strategy was developed by The Consortium to Perform Human Biomonitoring on a European Scale (COPHES), as part of its objectives to develop a framework and protocols to enable the collection of comparable human biomonitoring data throughout Europe. The framework and protocols were tested in the pilot study DEMOCOPHES (Demonstration of a study to Coordinate and Perform Human biomonitoring on a European Scale). The aims of the communication strategy were to raise awareness of human biomonitoring, encourage participation in the study and to communicate the study results and their public health significance. It identified the audiences and key messages, documented the procedure for dissemination of results and was updated as the project progressed. A communication plan listed the tools and materials such as press releases, flyers, recruitment letters and information leaflets required for each audience with a time frame for releasing them. Public insight research was used to evaluate the recruitment material, and the feedback was used to improve the documents. Dissemination of results was coordinated in a step by step approach by the participating countries within DEMOCOPHES, taking into account specific national messages according to the needs of each country. Participants received individual results, unless they refused to be informed, along with guidance on what the results meant. The aggregate results and policy recommendations were then communicated to the general public and stakeholders, followed by dissemination at European level. Several lessons were learnt that may assist other future human biomonitoring studies. Recruitment took longer than anticipated and so social scientists, to help with community engagement, should be part of the research team from the start. As a European study, involving multiple countries, additional considerations were needed for the numerous organisations, different languages, cultures, policies and priorities. Therefore, communication documents should be seen as templates with essential information clearly indicated and the option for each country to tailor the material to reflect these differences. Future studies should consider setting up multidisciplinary networks of medical professionals and communication experts, and holding training workshops to discuss the interpretation of results and risk communication. Publicity and wide dissemination of the results helped to raise awareness of human biomonitoring to the general public, policy makers and other key stakeholders. Effective and timely communication, at all stages of a study, is essential if the potential of human biomonitoring research to improve public health is to be realised.

Fish consumption patterns and hair mercury levels in children and their mothers in 17 EU countries.

The toxicity of methylmercury (MeHg) in humans is well established and the main source of exposure is via the consumption of large marine fish and mammals. Of particular concern are the potential neurodevelopmental effects of early life exposure to low-levels of MeHg. Therefore, it is important that pregnant women, children and women of childbearing age are, as far as possible, protected from MeHg exposure. Within the European project DEMOCOPHES, we have analyzed mercury (Hg) in hair in 1799 mother-child pairs from 17 European countries using a strictly harmonized protocol for mercury analysis. Parallel, harmonized questionnaires on dietary habits provided information on consumption patterns of fish and marine products. After hierarchical cluster analysis of consumption habits of the mother-child pairs, the DEMOCOPHES cohort can be classified into two branches of approximately similar size: one with high fish consumption (H) and another with low consumption (L). All countries have representatives in both branches, but Belgium, Denmark, Spain, Portugal and Sweden have twice as many or more mother-child pairs in H than in L. For Switzerland, Czech Republic, Hungary, Poland, Romania, Slovenia and Slovakia the situation is the opposite, with more representatives in L than H. There is a strong correlation (r=0.72) in hair mercury concentration between the mother and child in the same family, which indicates that they have a similar exposure situation. The clustering of mother-child pairs on basis of their fish consumption revealed some interesting patterns. One is that for the same sea fish consumption, other food items of marine origin, like seafood products or shellfish, contribute significantly to the mercury levels in hair. We conclude that additional studies are needed to assess and quantify exposure to mercury from seafood products, in particular. The cluster analysis also showed that 95% of mothers who consume once per week fish only, and no other marine products, have mercury levels 0.55 µg/g. Thus, the 95th percentile of the distribution in this group is only around half the US-EPA recommended threshold of 1 µg/g mercury in hair. Consumption of freshwater fish played a minor role in contributing to mercury exposure in the studied cohort. The DEMOCOPHES data shows that there are significant differences in MeHg exposure across the EU and that exposure is highly correlated with consumption of fish and marine products. Fish and marine products are key components of a healthy human diet and are important both traditionally and culturally in many parts of Europe. Therefore, the communication of the potential risks of mercury exposure needs to be carefully balanced to take into account traditional and cultural values as well as the potential health benefits from fish consumption. European harmonized human biomonitoring programs provide an additional dimension to national HMB programs and can assist national authorities to tailor mitigation and adaptation strategies (dietary advice, risk communication, etc.) to their country's specific requirements.

A regional comparison of children's blood cadmium, lead, and mercury in rural, urban and industrial areas of six European countries, and China, Ecuador, and Morocco.

OBJECTIVES: The authors aimed to evaluate whether blood cadmium (B-Cd), lead (B-Pb) and mercury (B-Hg) in children differ regionally in 9 countries, and to identify factors correlating with exposure. MATERIAL AND METHODS: The authors performed a cross-sectional study of children aged 7-14 years, living in 2007-2008 in urban, rural, or potentially polluted ("hot spot") areas (ca. 50 children from each area, in total 1363 children) in 6 European and 3 non-European countries. The authors analyzed Cd, Pb, and total Hg in blood and collected information on potential determinants of exposure through questionnaires. Regional differences in exposure levels were assessed within each country. RESULTS: Children living near industrial "hot-spots" had B-Cd 1.6 (95% CI: 1.4-1.9) times higher in the Czech Republic and 2.1 (95% CI:1.6-2.8) times higher in Poland, as compared to urban children in the same countries (geometric means [GM]: 0.13 µg/l and 0.15 µg/l, respectively). Correspondingly, B-Pb in the "hot spot" areas was 1.8 (95% CI: 1.6-2.1) times higher than in urban areas in Slovakia and 2.3 (95% CI: 1.9-2.7) times higher in Poland (urban GM: 19.4 µg/l and 16.3 µg/l, respectively). In China and Morocco, rural children had significantly lower B-Pb than urban ones (urban GM: 64 µg/l and 71 µg/l, respectively), suggesting urban exposure from leaded petrol, water pipes and/or coal-burning. Hg "hot spot" areas in China had B-Hg 3.1 (95% CI: 2.7-3.5) times higher, and Ecuador 1.5 (95% CI: 1.2-1.9) times higher, as compared to urban areas (urban GM: 2.45 µg/l and 3.23 µg/l, respectively). Besides industrial exposure, traffic correlated with B-Cd; male sex, environmental tobacco smoke, and offal consumption with B-Pb; and fish consumption and amalgam fillings with B-Hg. However, these correlations could only marginally explain regional differences. CONCLUSIONS: These mainly European results indicate that some children experience about doubled exposures to toxic elements just because of where they live. These exposures are unsafe, identifiable, and preventable and therefore call for preventive actions. Int J Occup Med Environ Health. 2023;36(3):349-64.

From science to policy: How European HBM indicators help to answer policy questions related to phthalates and DINCH exposure.

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.

Exposure to Phthalates in European Children, Adolescents and Adults since 2005: A Harmonized Approach Based on Existing HBM Data in the HBM4EU Initiative.

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.

Human bio-monitoring study--toxic elements in blood of women.

The article describes bio-monitoring study concerning recent and long-term exposure of Czech women to toxic metals. Blood cadmium, mercury and lead levels were measured in groups of women with various life styles, etc., to have comparable results in the course of a long study period; a strong emphasis was laid on the quality control of the whole process during the study. Higher cadmium level was found in smokers compared to non-smokers, lower mercury level was found in the group of women who never eat fish. A slight increase of blood lead level with age was observed. No significant differences were found between localities in a given period. Our results do not differ from those gained in other European countries.

Application of a pharmacokinetic model in characterizing sources of polychlorinated biphenyl exposure and determining threshold daily intakes for adverse health effects in infants and toddlers.

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·glipid-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·glipid-1 in blood. Mean TEDIs leading to values of 500 ng·glipid-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.

Urinary mutagenicity and genotoxic risk in children with psoriasis after therapeutic exposure to polycyclic aromatic hydrocarbons and ultraviolet radiation.

The Goeckerman regimen (GR) for the treatment of psoriasis comprises dermal application of crude coal tar (polycyclic aromatic hydrocarbons, PAHs) and exposure to ultraviolet radiation (UVR). PAHs and UVR are mutagenic and carcinogenic agents. We evaluated dermal absorption of PAHs as well as the mutagenic and genotoxic effects of GR in 16 children with psoriasis, by determining levels of 1-hydroxypyrene (1-OHP), 1-,2-,3-,4-hydroxyphenanthrene, (1-OHPhe, 2-OHPhe, 3-OHPhe, and 4-OHPhe), urinary mutagenicity (Salmonella mutagenicity assay, Ames test) and numbers of chromosomal aberrations in peripheral lymphocytes (CA), in urine and/or blood, before and after GR. The Psoriasis Area and Severity Index (PASI) score was used to evaluate clinical efficacy of GR. Compared with pre-treatment levels, there were significant increases in urinary concentrations of 1-OHP (p<0.001), 1-OHPhe (p<0.001), 2-OHPhe (p<0.001), 3-OHPhe (p<0.001), and 4-OHPhe (p<0.01), indicating a high degree of dermal absorption of PAHs. There were also significantly increased numbers of revertants in the Ames test in two different strains (YG1041-S9, p<0.01; YG1041+S9, p<0.001; TA98+S9, p<0.01), which demonstrates urinary mutagenicity. We also found a significant increase in the number of CA (p<0.001) and significantly decreased number of CA (p<0.01) at 81 days post-treatment, suggesting that GR has a temporary genotoxic effect. The PASI scores were significantly decreased after GR (p<0.001), confirming the clinical benefit of GR. In conclusion, our results demonstrate mutagenic and temporary genotoxic effects of GR in the group of 16 treated child patients.

Dynamics of PCB exposure in the past 50 years and recent high concentrations in human breast milk: Analysis of influencing factors using a physiologically based pharmacokinetic model.

In this study we reconstruct the long-term exposure of Czech mothers to polychlorinated biphenyls (PCBs) and determine the causes of high contamination of breast milk by indicator PCBs (iPCBs). A data set containing information from more than 1000 primiparous women from the Czech Republic was used, including iPCB concentrations in breast milk, individual physiology and living characteristics. The time series of PCB intakes for the whole period from the beginning of PCB production in 1958 until 2011 were reconstructed. We estimated the individual lifetime exposure of mothers for all iPCBs, i.e. congeners 28, 52, 101, 118, 138, 153 and 180, using a physiologically based pharmacokinetic (PBPK) model. Various model scenarios were investigated to determine the influence of physiology, age at delivery, past dietary exposure, and food composition on concentrations in breast milk for all iPCBs. The highest contributions to the presence of iPCBs in breast milk were observed for food composition. The main factor determining the concentration of higher-chlorinated PCBs (138, 153 and 180) was past exposure. The most important parameter for identification of children's postnatal exposure through breast milk was the time-span from the maximum of the exposure peak to the birth of the child. The current concentrations of iPCBs in breast milk in the Czech population are still high because the maximum of the exposure peak occurred more than 10 years later than in other European countries and was very broad, e.g. covered more than 10 years.

Exposure of Prague's homeless population to lead and cadmium, compared to Prague's general population.

Homelessness is a growing problem in the Czech Republic where homeless people represent a specific minority group beset by many problems linked to their divergent lifestyle. It was therefore expected that the homeless population would be at greater risk of exposure to environmental pollutants than the general population. The aim of our study was to compare blood lead (B-Pb) and blood cadmium (B-Cd) levels in the homeless population (HP) with those obtained from the Human Biomonitoring Project (CZ-HBM), which used blood donors considered representative of the general population (GP). We present data obtained between 2004 and 2006 for B-Pb and B-Cd in 257 Prague homeless adults and compare them to B-Pb and B-Cd levels in 104 Prague adult blood donors from the CZ-HBM project in 2005. The mean (geometric) B-Pb levels in men were 36.5 (HP) and 35.4microg/l (GP), which is not significantly different. However, statistically significant differences were observed between men and women in the GP (P<0.001), but not in HP; B-Pb levels in women (34.8microg/l) did not differ from those of HP men (36.5microg/l), but were significantly (P<0.001) higher than those of GP women (25.8microg/l). B-Pb levels were not influenced by smoking. B-Cd levels in the homeless nonsmokers (geometric means 1.06 and 1.18microg/l in men and women, respectively) were more than 2.5 times higher than in the nonsmoking GP (0.36 and 0.38microg/l for men and women, respectively). B-Cd levels were significantly (P<0.001) influenced by smoking in both groups, but, surprisingly, the values in GP smokers (men=0.96microg/l, women=0.93microg/l) were lower than those in HP nonsmokers (men=1.06microg/l, women=1.18microg/l). A positive correlation was found between cadmium and lead in both men (P<0.05) and women (P<0.01). Our results indicate that the homeless population under study might be exposed to lead and cadmium more extensively than the general population of Prague and that homeless women represent a particularly vulnerable population group.

Serum concentrations of indicator PCB congeners in the Czech adult population.

In 2006, levels of seven indicator polychlorinated biphenyl congeners (PCB28, 52, 101, 118, 138, 153, and 180) in blood serum of 202 blood donors residing for more than 2 years in five urban areas included in the Czech Human Biomonitoring project were measured by GC/MS/MS method. PCB congeners 138, 153 and 180 accounted for about 97% of the sum of the indicator congeners analyzed. Overall, the median and 95th percentile of the most abundant congener PCB 153 were 438 ng/g lipid and 1079 ng/g lipid, respectively. The highest median levels were found in Uherské Hradiste (669 ng/g lipid) and Ostrava (672 ng/g lipid in males compared to 341 ng/g lipid in females). Serum PCB concentrations were significantly associated with age, gender, place of residence and smoking habit, but not with body mass index and education. The results suggest the importance of PCB body burden in the Czech general population and the existence of hot spots.