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.

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.

Childhood respiratory allergies and symptoms in highly polluted area of Central Europe.

The study investigated the associations between the prevalence of the childhood respiratory diseases and the long-term exposure to air pollution in the burdened area of Moravian-Silesian Region in the Czech Republic. The health data were collected during 2014 in 7,239 children 5, 9, 13 and 17 years of age. Exposure to PM10 and NO2 in the residence addresses was based on dispersion models and GIS based traffic-related indicators. PM10 levels were positively associated with both lifetime (OR 1.35; 95%CI 1.09-1.67) and current (OR 1.32; 95%CI 1.05-1.67) allergic rhinitis; current asthma was associated negatively. The associations between traffic indicator and respiratory health were not found. On the other hand, marked positive associations were found between the respiratory diseases and symptom severity structured into ordinal variables, and PM10 and NO2. Modelled long-term exposure to air pollution was associated with childhood allergic rhinitis and deterioration of the respiratory symptoms.

25 years of HBM in the Czech Republic.

Since 1991 a human biomonitoring network has been established in the Czech Republic as part of the Environmental Health Monitoring System, which was set out by the Government Resolution. During the last quarter-century, important data was obtained to characterize exposure to both children and adult populations to significant toxic substances from the environment, to development trends over time, to establish reference values and compare them with existing health-related values. Moreover, the saturation of population with several essential substances as selenium, zinc, copper or iodine has also been monitored. Development of analytical and statistical methods led to increase the capacity building, improvement of QA/QC in analytical laboratories and interpretation of results. The obtained results are translated to policy actions and are used in health risk assessment processes at local and national levels.

Specific and combined subjective responses to noise and their association with cardiovascular diseases.

INTRODUCTION: Noise is one of the most extensive environmental factors affecting the general population. The present study is focused on the association between discomfort caused by noise and the incidence of certain diseases (ischaemic heart disease, stroke and hypertension). MATERIALS AND METHODS: This cross-sectional questionnaire study, conducted in 10 cities in the Czech Republic, comprises two stages with 3592 obtained questionnaires in the first phase and 762 in the second phase. Twelve variables describe subjective responses to noise from different sources at different times of day. The intensity of the associations between variables was measured by correlation coefficient. Logistic regression was used for fitting models of morbidity, and confounders such as age and socio-economic status were included. The hypotheses from the first phase were independently validated using data from the second phase. RESULTS: The general rates of noise annoyance/sleep disturbance had greater correlation with traffic noise variables than with neighbourhood noise variables. Factors significantly associated with diseases are: for hypertension - annoyance by traffic noise (the elderly, odds ratio (OR) 1.4) and sleep disturbance by traffic and neighbourhood noise (the elderly, OR 1.6); for ischaemic heart disease - the general rate of noise annoyance (all respondents, OR 1.5 and the adults 30-60 years, OR 1.8) and the general rate of annoyance and sleep disturbance (all respondents, OR 1.3); for stroke - annoyance and sleep disturbance by traffic and neighbourhood noise (all respondents, OR 1.8). CONCLUSION: Factors that include multiple sources of noise or non-specific noise are associated with the studied diseases more frequently than the source-specific factors.

Asthma Exacerbations and Symptom Variability in Children Due to Short-term Ambient Air Pollution Changes in Ostrava, Czech Republic.

AIM: The Ostrava region suffers from high levels of air pollution during winter inversions. We investigated the association between short-term elevations of air pollutant concentrations and worsening of respiratory problems, use of asthma medication and restriction of daily activities in asthmatic patients in Ostrava. METHODS: One-hundred and forty-seven child and adolescent patients (aged 6-18 years) with a confirmed diagnosis of mild to moderate persistent asthma were included in the study. Participants' parents completed diaries covering the period of November 2013 to February 2014; this analysis included 18,228 person-days. Daily smoothed maps of outdoor concentrations of particulate matter (PM10), nitrogen dioxide (NO2) and sulphur dioxide (SO2) were constructed from routine monitoring data, and participants' daily exposures were estimated on the basis of time spent at home and at school. The associations between health outcomes and exposure to air pollutants were estimated using the multiple logistic regression method. RESULTS: The odds ratios (OR) of the combined outcome for wheezing and/or difficulty in breathing, per 10 µg/m³ increase in the mean 24-h exposure were 1.07 (95% confidence interval 1.04-1.11) for PM10, 1.30 (1.18-1.44) for NO2, and 1.37 (1.18-1.59) for SO2. Additional inhaler use (in addition to usual medication) was also more frequent at higher air pollutant concentrations; the odds ratios per 10 µg/m³ increase in the mean 24-h exposure were 1.05 (1.02-1.07) for PM10, 1.19 (1.10-1.30) for NO2, and 1.26 (1.11-1.43) for SO2. Associations were less consistent for other health outcomes. CONCLUSIONS: These results suggest moderately strong associations between air pollutant concentrations and respiratory difficulties among asthmatic children and adolescents. More detailed analyses are required to confirm these preliminary findings.

The mercury burden of the Czech population: An integrated approach.

In this paper an integrated approach in assessment of the population exposure from various sources of total mercury (THg) oral intake in the Czech Republic is presented. The information on total mercury levels in diet, drinking water, surface urban soil and body fluids and tissues stem from the Czech national Environmental Health Monitoring System (EHMS) operated since 1994. The THg concentration was determined by the special atomic absorption spectrophotometer AMA 254. The data on THg content in food from the sales network were collected in 12 cities. The estimated average dietary intake representing more than 95% of weight of usual diet composition ranged 1-2% of the JECFA/FAO WHO provisional tolerable weekly intake (PTWI) value for total mercury (5 microg/kg b.w./week). Data on drinking water quality stem from the nationwide monitoring database. The content of THg in drinking water is generally low; only 0.2% of the Czech population supplied with drinking water from the distribution networks (total of 92% of the population) has a mercury intake from drinking water higher than 1% PTWI and not exceeding 5% PTWI. The estimation of potential mercury intake by unintentional consumption of soil in small children was based on THg content in surface soil of a total of 324 nursery schools in 24 cities and towns. Median value was 0.16 mg/kg. Human biomonitoring was performed in 9 Czech cities. In 2007, the mercury median values in blood of adults (N=412) were 0.85 and 0.89 microg/l in males and in females, respectively; urine median value in adults was 1.10 microg/g creatinine. In 2008, the blood median value in children (N=324) amounted to 0.35 microg/l; urine median value is 0.16 microg/g creatinine. In children's hair the median THg value was 0.18 microg/g. The correlation between fish consumption and blood THg levels was observed in both adults and children. Also the biomonitoring outputs did not reveal a substantial burden of the population.