Phthalates and the substitute plasticizer DINCH belong to the first group of priority substances investigated by the European Human Biomonitoring Initiative (HBM4EU) to answer policy-relevant questions and safeguard an efficient science-to-policy transfer of results. Human internal exposure levels were assessed using two data sets from all European regions and Israel. The first collated existing human biomonitoring (HBM) data (2005-2019). The second consisted of new data generated in the harmonized "HBM4EU Aligned Studies" (2014-2021) on children and teenagers for the ten most relevant phthalates and DINCH, accompanied by a quality assurance/quality control (QA/QC) program for 17 urinary exposure biomarkers. Exposures differed between countries, European regions, age groups and educational levels. Toxicologically derived Human biomonitoring guidance values (HBM-GVs) were exceeded in up to 5% of the participants of the HBM4EU Aligned Studies. A mixture risk assessment (MRA) including five reprotoxic phthalates (DEHP, DnBP, DiBP, BBzP, DiNP) revealed that for about 17% of the children and teenagers, health risks cannot be excluded. Concern about male reproductive health emphasized the need to include other anti-androgenic substances for MRA. Contaminated food and the use of personal care products were identified as relevant exposure determinants paving the way for new regulatory measures. Time trend analyses verified the efficacy of regulations: especially for the highly regulated phthalates exposure dropped significantly, while levels of the substitutes DINCH and DEHTP increased. The HBM4EU e-waste study, however, suggests that workers involved in e-waste management may be exposed to higher levels of restricted phthalates. Exposure-effect association studies indicated the relevance of a range of endpoints. A set of HBM indicators was derived to facilitate and accelerate science-to-policy transfer. Result indicators allow different groups and regions to be easily compared. Impact indicators allow health risks to be directly interpreted. The presented results enable successful science-to-policy transfer and support timely and targeted policy measures.
- MeSH
- biologický monitoring * MeSH
- dítě MeSH
- dospělí MeSH
- hodnocení rizik MeSH
- kyseliny ftalové * moč MeSH
- látky znečišťující životní prostředí * moč MeSH
- lidé MeSH
- mladiství MeSH
- monitorování životního prostředí metody MeSH
- vystavení vlivu životního prostředí analýza MeSH
- zvláčňovadla * analýza MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Geografické názvy
- Evropa MeSH
Humans are widely exposed to phthalates and their novel substitutes, and considering the negative health effects associated with some phthalates, it is crucial to understand population levels and exposure determinants. This study is focused on 300 urine samples from teenagers (aged 12-17) and 300 from young adults (aged 18-37) living in Czechia collected in 2019 and 2020 to assess 17 plasticizer metabolites as biomarkers of exposure. We identified widespread phthalate exposure in the study population. The diethyl phthalate metabolite monoethyl phthalate (MEP) and three di (2-ethylhexyl) phthalate metabolites were detected in the urine of >99% of study participants. The highest median concentrations were found for metabolites of low-molecular-weight (LMW) phthalates: mono-n-butyl phthalate (MnBP), monoisobutyl phthalate (MiBP) and MEP (60.7; 52.6 and 17.6 μg/L in young adults). 1,2-cyclohexanedicarboxylic acid diisononyl ester (DINCH) metabolites were present in 68.2% of the samples with a median of 1.24 μg/L for both cohorts. Concentrations of MnBP and MiBP were similar to other European populations, but 5-6 times higher than in populations in North America. We also observed large variability in phthalate exposures within the study population, with 2-3 orders of magnitude differences in urinary metabolites between high and low exposed individuals. The concentrations varied with season, gender, age, and lifestyle factors. A relationship was found between high levels of MEP and high overall use of personal care products (PCPs). Cluster analysis suggested that phthalate exposures depend on season and multiple lifestyle factors, like time spent indoors and use of PCPs, which combine to lead to the observed widespread presence of phthalate metabolites in both study populations. Participants who spent more time indoors, particularly noticeably during colder months, had higher levels of high-molecular weight phthalate metabolites, whereas participants with higher PCP use, particularly women, tended to have higher concentration of LMW phthalate metabolites.
- MeSH
- diethylhexylftalát * moč MeSH
- kosmetické přípravky * analýza MeSH
- kyseliny ftalové * moč MeSH
- látky znečišťující životní prostředí * moč MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- vystavení vlivu životního prostředí analýza MeSH
- životní styl MeSH
- Check Tag
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
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.
- MeSH
- dávka bez pozorovaného nepříznivého účinku MeSH
- diethylhexylftalát aplikace a dávkování analogy a deriváty moč MeSH
- dítě MeSH
- hodnocení rizik MeSH
- kreatinin moč MeSH
- kyseliny ftalové aplikace a dávkování moč MeSH
- látky znečišťující životní prostředí aplikace a dávkování moč MeSH
- lidé MeSH
- předškolní dítě MeSH
- školy MeSH
- vystavení vlivu životního prostředí analýza MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
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.
- MeSH
- dítě MeSH
- dospělí MeSH
- látky znečišťující životní prostředí analýza krev moč MeSH
- lidé MeSH
- mateřské mléko chemie MeSH
- monitorování životního prostředí statistika a číselné údaje MeSH
- vlasy, chlupy chemie MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Česká republika MeSH
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.
- MeSH
- dítě MeSH
- dospělí MeSH
- kadmium analýza moč MeSH
- kotinin analýza moč MeSH
- látky znečišťující životní prostředí analýza moč MeSH
- lidé MeSH
- matka - expozice noxám statistika a číselné údaje MeSH
- matky MeSH
- vlasy, chlupy chemie MeSH
- vystavení vlivu životního prostředí statistika a číselné údaje MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
The in vivo fate of globin adducts with styrene 7,8-oxide (SO), an electrophilic metabolic intermediate of styrene, was studied in male Wistar rats dosed intraperitoneally with racemic SO, 100mg/kg b.w. Regioisomeric hydroxy(phenyl)ethyl (HPE) adducts at Cys, N-terminal Val, Lys and His in globin were determined and their elimination from blood was followed during 60days, corresponding to life span of rat erythrocytes. In the rat urine, Nα-acetylated products of hydrolytic cleavage of the HPE adducts with Cys, Lys and His were determined. On the first day post-exposure, abundant Nα-acetyl-HPE-Cys adducts (mercapturic acids) formed via direct conjugation of SO with hepatic glutathione were excreted rapidly, but then a much slower phase of elimination reflecting formation of Nα-acetyl-HPE-Cys via cleavage of the adducted globin was observed. A two-phase elimination occurred also in urinary Nα-acetyl-HPE adducts with His and Lys. While a decline by 75-85% during the first 7days post-exposure most likely reflected elimination of adducted albumin, the subsequent slow decline until day 60 corresponded to elimination kinetics of the adducted globin. Thus, the study not only provided original data on the fate of SO-globin adducts but also allowed to reveal general toxicokinetics properties of the urinary cleavage products as a novel type of chemical exposure biomarkers.
- MeSH
- biologické markery metabolismus moč MeSH
- epoxidové sloučeniny chemie metabolismus MeSH
- globiny metabolismus moč MeSH
- hydrolýza MeSH
- krysa rodu rattus MeSH
- látky znečišťující životní prostředí chemie metabolismus moč MeSH
- monitorování životního prostředí MeSH
- potkani Wistar MeSH
- xenobiotika MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
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.
- MeSH
- dítě MeSH
- dospělí MeSH
- hmotnostní spektrometrie s elektrosprejovou ionizací MeSH
- interpretace statistických dat MeSH
- kouření epidemiologie MeSH
- kyseliny ftalové metabolismus moč MeSH
- látky znečišťující životní prostředí metabolismus moč MeSH
- lidé středního věku MeSH
- lidé MeSH
- monitorování životního prostředí metody statistika a číselné údaje MeSH
- pilotní projekty MeSH
- průzkumy a dotazníky MeSH
- tandemová hmotnostní spektrometrie MeSH
- vysokoúčinná kapalinová chromatografie MeSH
- vystavení vlivu životního prostředí analýza statistika a číselné údaje MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Česká republika MeSH
- Maďarsko MeSH
- Slovenská republika MeSH
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.
- MeSH
- dítě MeSH
- dospělí MeSH
- kadmium moč MeSH
- kouření metabolismus MeSH
- látky znečišťující životní prostředí moč MeSH
- lidé středního věku MeSH
- lidé MeSH
- limita detekce MeSH
- matky MeSH
- mladý dospělý MeSH
- monitorování životního prostředí metody MeSH
- předškolní dítě MeSH
- průřezové studie MeSH
- regresní analýza MeSH
- socioekonomické faktory MeSH
- vystavení vlivu životního prostředí analýza MeSH
- životní styl MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- předškolní dítě MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Evropa MeSH
In 2011 and 2012, the COPHES/DEMOCOPHES twin projects performed the first ever harmonized human biomonitoring survey in 17 European countries. In more than 1800 mother-child pairs, individual lifestyle data were collected and cadmium, cotinine and certain phthalate metabolites were measured in urine. Total mercury was determined in hair samples. While the main goal of the COPHES/DEMOCOPHES twin projects was to develop and test harmonized protocols and procedures, the goal of the current paper is to investigate whether the observed differences in biomarker values among the countries implementing DEMOCOPHES can be interpreted using information from external databases on environmental quality and lifestyle. In general, 13 countries having implemented DEMOCOPHES provided high-quality data from external sources that were relevant for interpretation purposes. However, some data were not available for reporting or were not in line with predefined specifications. Therefore, only part of the external information could be included in the statistical analyses. Nonetheless, there was a highly significant correlation between national levels of fish consumption and mercury in hair, the strength of antismoking legislation was significantly related to urinary cotinine levels, and we were able to show indications that also urinary cadmium levels were associated with environmental quality and food quality. These results again show the potential of biomonitoring data to provide added value for (the evaluation of) evidence-informed policy making.
- MeSH
- biologické markery analýza moč MeSH
- dítě MeSH
- dospělí MeSH
- interpretace statistických dat MeSH
- kadmium analýza moč MeSH
- kotinin moč MeSH
- kouření zákonodárství a právo moč MeSH
- látky znečišťující životní prostředí analýza moč MeSH
- lidé MeSH
- městské obyvatelstvo statistika a číselné údaje MeSH
- monitorování životního prostředí metody statistika a číselné údaje MeSH
- potrava z moře (živočišná) statistika a číselné údaje MeSH
- průzkumy a dotazníky normy MeSH
- rtuť analýza moč MeSH
- venkovské obyvatelstvo statistika a číselné údaje MeSH
- vládní regulace MeSH
- vlasy, chlupy chemie MeSH
- vystavení vlivu životního prostředí analýza statistika a číselné údaje MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Evropa MeSH
Sledování expozice látkám, široce užívaným v průmyslu, a vyhodnocení jejich koncentrací v těle člověka, je jedním z hlavních cílů biologického monitorování obyvatel. V pilotní studii byla sledována hladina metabolitů ftalátu dietylhexylftalátu (DEHP), vybraných metabolitů polyaromatických uhlovodíků a bisfenolu A v moči ve vztahu k možným expozičním zdrojům sledovaných dotazníkovým šetřením. Do studie bylo zařazeno 95 studentů nekuřáků ve věkovém rozmezí 20 až 29 let (44 mužů a 51 žen) z Prahy a Ostravy. Analyty byly stanovovány v moči pomocí metody kapalinové chromatografie s tandemovou hmotnostně-spektrometrickou detekcí typu trojitý kvadrupól (LC-MS/MS). Hodnoty metabolitů DEHP u žádného jedince nepřekročily zdravotně významné limitní hodnoty. Za pomoci dotazníku, který byl součástí studie, nebyly zjištěny žádné skutečnosti, které by významně ovlivňovaly hladiny vybraných látek v moči. Byl zjištěn pouze signifikantní vliv pohlaví u 5-OH-MEHP a sumy 5-OH-MEHP a 5-oxo-MEHP, kdy ostravské ženy mají významně vyšší hladiny metabolitů než muži.
The main target of human biomonitoring is monitoring of exposure and effects of substances used in industry and determination of their concentrations in the human body. In this pilot study the metabolite levels of phthalates, polycyclic aromatic hydrocarbons and bisphenol A were determined in urine. Their association with possible exposure sources was analyzed. The study comprised 95 adults (44 males and 51 females) aged 20 and 29 years from Prague and Ostrava. The analytes in urine samples were determined by liquid chromatography with triple quadrupole tandem mass spectrometry detection (LC-MS/MS). Metabolite levels did not exceed limit values for these biomarkers for any participant. The questionnaire survey, as part of the study, revealed no factors that might affect levels of the selected substances in urine. However, a significant gender-related difference was detected for the level of 5-OH-MEHP and sums of 5-OH-MEHP and 5-oxo-MEHP, where women from Ostrava had significantly higher metabolite values than men.
- Klíčová slova
- bisfenol A,
- MeSH
- benzhydrylové sloučeniny moč MeSH
- biologické markery moč MeSH
- biologický monitoring MeSH
- chromatografie kapalinová MeSH
- diethylhexylftalát * metabolismus moč MeSH
- dospělí MeSH
- epidemiologické monitorování MeSH
- fenoly * moč MeSH
- kyseliny ftalové moč MeSH
- látky znečišťující životní prostředí metabolismus moč MeSH
- lidé MeSH
- lineární modely MeSH
- mladý dospělý MeSH
- monitorování životního prostředí metody statistika a číselné údaje MeSH
- pilotní projekty MeSH
- polycyklické aromatické uhlovodíky * metabolismus moč MeSH
- rozložení podle pohlaví MeSH
- tandemová hmotnostní spektrometrie statistika a číselné údaje MeSH
- vystavení vlivu životního prostředí * analýza statistika a číselné údaje MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- práce podpořená grantem MeSH
