The Human Biomonitoring for Europe initiative (HBM4EU) aims to study the exposure of citizens to chemicals and potentially associated health effects. One objective of this project has been to build a network of laboratories able to answer to the requirements of European human biomonitoring studies. Within the HBM4EU quality assurance and quality control scheme (QA/QC), a number of interlaboratory comparison investigations (ICIs) and external quality assurance schemes (EQUASs) were organized to ensure data consistency, comparability and reliability. Bisphenols are among the prioritized substance groups in HBM4EU, including bisphenol A (BPA), bisphenol S (BPS) and bisphenol F (BPF) in human urine. In four rounds of ICI/EQUAS, two target concentration levels were considered, related to around P25 and P95 of the typical exposure distribution observed in the European general population. Special attention was paid to the conjugated phase II metabolites known to be most dominant in samples of environmentally exposed individuals, through the analysis of both native samples and samples fortified with glucuronide forms. For the low level, the average percentage of satisfactory results across the four rounds was 83% for BPA, 71% for BPS and 62% for BPF. For the high level, the percentages of satisfactory results increased to 93% for BPA, 89% for BPS and 86% for BPF. 24 out of 32 participating laboratories (75%) were approved for the analyses of BPA in the HBM4EU project according to the defined criterion of Z-scores for both low and high concentration levels in at least two ICI/EQUAS rounds. For BPS and BPF, the number of qualified laboratories was 18 out of 27 (67%) and 13 out of 28 (46%), respectively. These results demonstrate a strong analytical capability for BPA and BPS in Europe, while improvements may be needed for BPF.

• MeSH
• Benzhydryl Compounds * urine   MeSH
• Biological Monitoring * MeSH
• Phenols MeSH
• Laboratories MeSH
• Humans MeSH
• Reproducibility of Results MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Europe MeSH

AIM: Human exposure to organic pollutants (some of them also called endocrine disruptors) can be associated with adverse metabolic health outcomes including type 2 diabetes. The goal of this study was to compare the urine levels of bisphenol A and phthalate metabolites in subgroups of patients with metabolic syndrome composed of patients with and without three important components of metabolic syndrome (hypertension, dyslipidemia and diabetes). METHODS: We have investigated 24 hr urine samples of 168 patients with metabolic syndrome from the Metabolic Outpatient Department of General University Hospital in Prague. Using standard metabolic syndrome criteria, we classified patients as dyslipidemic (n=87), hypertensive (n=96), and type 2 diabetic (n=58). Bisphenol A and 15 metabolites of phthalates were evaluated in relation to creatinine excretion. Samples were analysed with enzymatic cleavage of glucuronide using ultra-high-performance liquid chromatography-electrospray ionization tandem mass spectrometry in one laboratory with external quality control. RESULTS: Four metabolites, mono-n-butyl phthalate, mono-(2-ethyl-5-hydroxyhexyl) phthalate, mono-(2-ethyl-5-oxohexyl) phthalate, and mono-(2-ethyl-5-carboxypentyl) phthalate showed significantly higher levels in diabetic compared to non-diabetic patients (p<0.001, p=0.002, p=0.002, and p=0.005, respectively). The differences remained significant after adjustment to hypertension, dyslipidemia, age, and BMI. No difference was found between either the hypertensive and non-hypertensive or dyslipidemic and non-dyslipidemic patients. There was no significant relation of bisphenol A level to diabetes, hypertension, dyslipidemia, age, and BMI. CONCLUSIONS: Urine levels of four phthalate metabolites were significantly higher in type 2 diabetics independently on specified predictors. Phthalate levels can be in relation to beta cell dysfunction in type 2 diabetic patients but this study is not able to show if the relation is causal.

• MeSH
• Benzhydryl Compounds urine   MeSH
• Biomarkers urine   MeSH
• Diabetes Mellitus, Type 2 urine   MeSH
• Dyslipidemias urine   MeSH
• Phenols urine   MeSH
• Hypertension urine   MeSH
• Phthalic Acids urine   MeSH
• Middle Aged MeSH
• Humans MeSH
• Metabolic Syndrome urine   MeSH
• Pilot Projects MeSH
• Chromatography, High Pressure Liquid MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Czech Republic 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.

• Keywords
• bisfenol A,
• MeSH
• Benzhydryl Compounds urine   MeSH
• Biomarkers urine   MeSH
• Biological Monitoring MeSH
• Chromatography, Liquid MeSH
• Diethylhexyl Phthalate * metabolism   urine   MeSH
• Adult MeSH
• Epidemiological Monitoring MeSH
• Phenols * urine   MeSH
• Phthalic Acids urine   MeSH
• Environmental Pollutants metabolism   urine   MeSH
• Humans MeSH
• Linear Models MeSH
• Young Adult MeSH
• Environmental Monitoring methods   statistics & numerical data   MeSH
• Pilot Projects MeSH
• Polycyclic Aromatic Hydrocarbons * metabolism   urine   MeSH
• Sex Distribution MeSH
• Tandem Mass Spectrometry statistics & numerical data   MeSH
• Environmental Exposure * analysis   statistics & numerical data   MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Young Adult MeSH
• Male MeSH
• Female MeSH
• Publication type
• Research Support, Non-U.S. Gov't MeSH

COPHES/DEMOCOPHES has its origins in the European Environment and Health Action Plan of 2004 to "develop a coherent approach on human biomonitoring (HBM) in Europe". Within this twin-project it was targeted to collect specimens from 120 mother-child-pairs in each of the 17 participating European countries. These specimens were investigated for six biomarkers (mercury in hair; creatinine, cotinine, cadmium, phthalate metabolites and bisphenol A in urine). The results for mercury in hair are described in a separate paper. Each participating member state was requested to contract laboratories, for capacity building reasons ideally within its borders, carrying out the chemical analyses. To ensure comparability of analytical data a Quality Assurance Unit (QAU) was established which provided the participating laboratories with standard operating procedures (SOP) and with control material. This material was specially prepared from native, non-spiked, pooled urine samples and was tested for homogeneity and stability. Four external quality assessment exercises were carried out. Highly esteemed laboratories from all over the world served as reference laboratories. Web conferences after each external quality assessment exercise functioned as a new and effective tool to improve analytical performance, to build capacity and to educate less experienced laboratories. Of the 38 laboratories participating in the quality assurance exercises 14 laboratories qualified for cadmium, 14 for creatinine, 9 for cotinine, 7 for phthalate metabolites and 5 for bisphenol A in urine. In the last of the four external quality assessment exercises the laboratories that qualified for DEMOCOPHES performed the determinations in urine with relative standard deviations (low/high concentration) of 18.0/2.1% for cotinine, 14.8/5.1% for cadmium, 4.7/3.4% for creatinine. Relative standard deviations for the newly emerging biomarkers were higher, with values between 13.5 and 20.5% for bisphenol A and between 18.9 and 45.3% for the phthalate metabolites. Plausibility control of the HBM results of all participating countries disclosed analytical shortcomings in the determination of Cd when using certain ICP/MS methods. Results were corrected by reanalyzes. The COPHES/DEMOCOPHES project for the first time succeeded in performing a harmonized pan-European HBM project. All data raised have to be regarded as utmost reliable according to the highest international state of the art, since highly renowned laboratories functioned as reference laboratories. The procedure described here, that has shown its success, can be used as a blueprint for future transnational, multicentre HBM projects.

• MeSH
• Benzhydryl Compounds urine   MeSH
• Biomarkers urine   MeSH
• Child MeSH
• Adult MeSH
• Phenols urine   MeSH
• Internationality MeSH
• Cadmium urine   MeSH
• Cotinine urine   MeSH
• Creatinine urine   MeSH
• Phthalic Acids urine   MeSH
• Laboratories MeSH
• Environmental Pollutants urine   MeSH
• Humans MeSH
• Mothers MeSH
• Environmental Monitoring * standards   MeSH
• Reproducibility of Results MeSH
• Environmental Exposure analysis   MeSH
• Check Tag
• Child MeSH
• Adult MeSH
• Humans MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Geographicals
• Europe MeSH

• MeSH
• Benzhydryl Compounds * pharmacokinetics   urine   adverse effects   therapeutic use   MeSH
• Diabetes Mellitus, Type 2 * drug therapy   metabolism   urine   MeSH
• Glycosuria * chemically induced   complications   MeSH
• Glycated Hemoglobin metabolism   secretion   MeSH
• Drug Evaluation MeSH
• Clinical Trials, Phase II as Topic MeSH
• Humans MeSH
• Randomized Controlled Trials as Topic MeSH
• Body Weight Changes MeSH
• Check Tag
• Humans MeSH
• Publication type
• Comment MeSH
• Overall MeSH