[Show abstract][Hide abstract] ABSTRACT: Abstract 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 reanalyses. 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.
International Journal of Hygiene and Environmental Health 06/2014; 217(6):653–666. · 3.05 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Abstract The objective of COPHES (Consortium to Perform Human biomonitoring on a European Scale) was to develop a harmonised approach to conduct human biomonitoring on a European scale. COPHES developed a systematic approach for designing and conducting a pilot study for an EU-wide cross-sectional human biomonitoring (HBM) study and for the implementation of the fieldwork procedures. The approach gave the basis for discussion of the main aspects of study design and conduct, and provided a decision making tool which can be applied to many other studies. Each decision that had to be taken was listed in a table of options with their advantages and disadvantages. Based on this the rationale of the decisions could be explained and be transparent. This was important because an EU-wide HBM study demands openness of all decisions taken to encourage as many countries as possible to participate and accept the initiative undertaken. Based on this approach the following study design was suggested: a cross-sectional study including 120 children aged 6–11 years and their mothers aged up to 45 years from each participating country. For the pilot study the children should be sampled in equal shares in an urban and a rural location. Only healthy children and mothers (no metabolic disturbances) should be included, who have a sufficient knowledge of the local language and have been living at least for 5 years at the sampling location. Occupational exposure should not be an exclusion criterion. Recruitment should be performed via inhabitant registries or schools as an alternative option. Measures suitable to increase the response rate should be applied. Preferably, the families should be visited at home and interviewed face-to-face. Various quality control measures to guarantee a good fieldwork performance were recommended. This comprehensive overview aims to provide scientists, EU officials, partners and stakeholders involved in the EU implementation process full transparency of the work carried out in COPHES. Thus this report presents the discussion and consensus in COPHES on the main aspects of designing and conducting fieldwork of a human biomonitoring study. Furthermore, it provides an example for a systematic approach that may be useful to other research groups or pan-European research initiatives. In the study protocol that will be published elsewhere these aspects are elaborated and additional aspects are covered (Casteleyn et al., 2012). Meanwhile the respective pilot study DEMOCOPHES had been conducted and assessed. The results and lessons learned will be published elsewhere.
International Journal of Hygiene and Environmental Health 01/2014; 217(2-3):312-322. · 3.05 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Human biomonitoring is an important tool for the evaluation of environmental exposure to contaminants. The data that are obtained from these studies might be compared to appropriate reference values (RVs) in a specific population. The RVs were derived from the rounded values of the upper limit of the 95th confidence interval of the 95th percentile for lead (Pb), cadmium (Cd) and mercury (Hg) in blood from adults in the metropolitan area of Sao Paulo (MASP), Brazil to investigate the association between blood metals and sociodemographic and lifestyle factors. Blood samples from 653 nonsmoking blood donors without occupational exposure to the studied metals were collected in 2006. Our evaluations distinguished a younger group (18-39 years) and an older group (40-65 years). RVs in the younger group were 60μgPb/L and 4μgHg/L for men and 47μgPb/L and 4μgHg/L for women. RVs in the older group were 80μgPb/L and 5μgHg/L for men and 63μgPb/L and 6μgHg/L for women. The RV for Cd was 0.6μg/L for adults aged 18-65 years. Pb and Cd levels demonstrated a significant association with sex and age. Male blood contained 50% more Pb, and the older group exhibited 23% more Pb. Fish consumption and amalgam fillings were primarily related to Hg levels. RVs for lead were similar to the Czech Republic and Germany but higher than the US population. The RV for Cd in Brazil was well below the RVs of these countries. The RVs for Hg in Brazil were similar to the US but higher than Germany and the Czech Republic.
International journal of hygiene and environmental health 06/2012; · 2.64 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Human biomonitoring of nickel has gained interest in environmental medicine due to its wide distribution in the environment and its allergenic potential. There are indications that the prevalence of nickel sensitization in children is increased by nickel exposure and that oral uptake of nickel can exacerbate nickel dermatitis in nickel-sensitive individuals. Urinary nickel measurement is a good indicator of exposure. However, data on nickel levels in urine of children are rare. For the first time, the German Environmental Survey on children (GerES IV) 2003-2006 provided representative data to describe the internal nickel exposure of children aged 3-14years in Germany. Nickel was measured after enrichment in the organic phase of urine by graphite furnace atomic absorption spectrometry with Zeeman background correction. Nickel levels (n=1576) ranged from <0.5 to 15μg/l. Geometric mean was 1.26μg/l. Multivariate regression analysis showed that gender, age, socio-economic status, being overweighted, consumption of hazelnut spread, nuts, cereals, chocolate and urinary creatinine were significant predictors for urinary nickel excretion of children who do not smoke. 20.2% of the variance could be explained by these variables. With a contribution of 13.8% the urinary creatinine concentration was the most important predictor. No influence of nickel intake via drinking water and second hand smoke exposure was observed.
International journal of hygiene and environmental health 04/2012; · 2.64 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The German Federal Environment Agency carried out its fourth German Environmental Survey (GerES IV), which is the first survey on children only and the environment-related module of the German Health Interview and Examination Survey for Children and Adolescents (German acronym: KiGGS), conducted by the Robert Koch Institute (RKI). The German Environmental Surveys are nationwide population studies conducted to determine the exposure to environmental pollutants, to explore exposure pathways and to identify sub-groups with higher exposure. GerES IV was conducted on randomly selected 1790 children aged 3-14 years from the cross-sectional sample of KiGGS. The participants of GerES IV lived in 150 sampling locations all over Germany. Field work was carried out from May 2003 to May 2006. The response rate in GerES IV was 77.3%. Due to the fact that participation in GerES IV was limited to children that had previously participated in the KiGGS study, the total response rate in GerES IV resulted in 52.6%. Response rates did neither differ significantly between West and East Germany, nor between different community sizes, age groups and gender. The basic study programme included blood samples, morning urine, tap water and house dust as well as comprehensive questionnaire-based interviews. In addition, subgroups were studied with regard to "noise, hearing capacity and stress hormones", "chemical contamination of indoor air" and "biogenic indoor contamination". A key element of the field work in GerES IV was a home visit to carry out interviews, conduct measurements and collect samples. An exception was blood sampling which was carried out within KiGGS. The quality of field work, data collection, evaluation, and chemical, biological and physical analyses was successfully evaluated by internal and external quality assurance. This comprehensive overview aims at giving other research groups the opportunity to compare different study designs or to adapt their own design to get comparable results.
International journal of hygiene and environmental health 03/2012; 215(4):435-48. · 2.64 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The COPHES network started to test the feasibility of a coherent human biomonitoring (HBM) approach by conducting a Pilot Study (DEMOCOPHES). A prerequisite for a successful implementation of an EU-wide approach is, inter alia, that fieldwork can be conducted in a harmonised way in all participating countries.
To develop a common protocol for fieldwork was a challenging task because country-specific restrictions and
definitions had to be integrated. The developed and harmonized protocols, strategies and scientific tools finally supplied the basis to recruit and examine internal exposure of 120 mother and child pairs to mercury, cadmium, cotinine and phthalates in 17 and BPA in 8 countries.
During the implementation of the protocols in the countries it was revealed that a selection of children via schools was preferred to a selection via inhabitant registries in most countries, and that the definition of the degree of urbanization of the sampling locations had to be country specific. Participation rate in most countries was lower than expected although in several countries a choice between a home or an examination centre visit was offered. Countries only demanded minor changes of the questionnaires provided. Elements for quality control were successfully applied: fieldwork manuals, interviewer training and check-lists for internal and external quality control.
An EU-wide HBM approach is feasible on the basis of a well reasoned recruitment concept and SOPs for all steps of fieldwork. The lessons learned from DEMOCOPHES fieldwork and the respective recruitment help to optimize this approach.
COPHES and DEMOCOPHES are funded by the EU (FP7 244237 and LIFE09ENV/BE/000410).
Keywords: HBM,fieldwork, COPHES, DEMOCOPHES, recruitment, EU-wide, lessons learned
[Show abstract][Hide abstract] ABSTRACT: Production of chemicals, use of products and consumer goods, contamination of food as well as today's living conditions are related to a substantial exposure of humans to chemicals. Safety of human beings and the environment has to be safeguarded by producers and government. Human biomonitoring (HBM) has proven to be a useful and powerful tool to control human exposure and facilitate risk assessment. Therefore, the German Federal Environment Agency (Umweltbundesamt, UBA) employs two major HBM tools, the German Environmental Survey (GerES) and the German Environmental Specimen Bank (ESB). GerES is a nationwide population representative study on HBM and external human exposure, which has, inter alia, been used to identify lead in tap water, lead dustfall, time spent in traffic, and age of dwelling as exposure sources for lead and, thus, to derive risk reduction measures. The ESB is a permanent monitoring instrument and an archive for human specimens. Retrospective monitoring of phthalates and bisphenol A provides a continuous historical record of human exposure in Germany, over the last decades. Additionally it revealed that estimations of human exposure based on production and consumption data may supply misleading information on human exposure. HBM data demonstrated that (a) the use if the restricted isomer di-n-butylphthalat decreased while di-i-butylphthalate levels remained constant and (b) human bisphenol A exposure might be overestimated without monitoring data. The decrease of polycyclic aromatic hydrocarbon-exposure proves the success of German environmental policy after German re-unification. In addition to GerES and ESB UBA is involved in different co-operation networks, the two most prominent of which are (1) the harmonization of HBM in Europe (ESBIO; Expert Team to Support Biomonitoring in Europe, COPHES/DEMOCOPHES; Consortium to Perform Human Biomonitoring on a European Scale/Demonstration of a study to Coordinate and Perform Human Biomonitoring on a European Scale) and (2) the co-operation between BMU and the German Chemical Industry Association (VCI). In the latter project emphasis will be placed on substances with a potential relevance for health and on substances to which the general population might potentially be exposed to a considerable extent and for which HBM methods are not available up to now.
International journal of hygiene and environmental health 12/2011; 215(2):120-6. · 2.64 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Different aspects of the environmental tobacco smoke (ETS) exposure of children in Germany have been investigated in the German Environmental Survey for Children (GerES IV). The field work of GerES IV was conducted from 2003 to 2006 using questionnaires, indoor air monitoring and human biomonitoring. About half of Germany's 3- to 14-year-old children lived in households with at least one smoker. The number of smokers in the household had a significant influence on the concentrations of several indoor air contaminants (VOC and aldehydes). Human biomonitoring data on cotinine were used to identify the levels of exposure to ETS. Urinary cotinine is correlated with several predictors of ETS and is also associated with other toxicants in non-smoking children, e.g. cadmium. Temporal comparison indicated that in the last 15 years no decrease of children's ETS exposure has been achieved in Germany.
[Show abstract][Hide abstract] ABSTRACT: Urine samples from GerES IV were analysed for concentrations of the metabolites of DEHP (MEHP, 5OH-MEHP, 5oxo-MEHP, 5cx-MEPP, and 2cx-MMHP), DnBP and DiBP (MnBP and MiBP), BBzP (MBzP), DiNP (7OH-MMeOP, 7oxo-MMeOP and 7cx-MMeHP), and bisphenol A (BPA) to assess the exposure of German children on a representative basis. 600 morning urine samples had been randomly chosen from stored 1800 GerES IV samples originating from 3 to 14 year old children living in Germany. All metabolites could be detected in nearly all urine samples (N=599). Descriptive data analysis leads to mean concentrations of 5-OH-MEHP and 5-oxo-MEHP of 48microg/l and 37microg/l, respectively. The mean concentration of 7OH-MMeOP was 11microg/l. MnBP, MiNP, MBzP showed mean levels of 96microg/l, 94microg/l, and 18microg/l, respectively. The concentrations of the phthalate metabolites decreased with increasing age. Compared to German adults all children showed three to five fold higher urine concentrations than adults analysed in the same decade. For some children the levels of the sum of 5OH-MEHP and 5oxo-MEHP in urine were higher than the German human biomonitoring value (HBM I) of 500mcirog/l, which indicates that adverse health effects cannot be excluded for these subjects with sufficient certainty. The mean concentration of BPA in urine was 2.7microg/l. A rough calculation of the daily intakes on the basis of the measured concentrations in urine resulted in daily intakes two orders of magnitude lower than the current EFSA reference dose of 50microg/kgbw/d.
International journal of hygiene and environmental health 10/2009; 212(6):685-92. · 2.64 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: As the current extent of Environmental Tobacco Smoke (ETS) exposure of children in Germany is unknown, it was investigated in the German Environmental Survey (GerES IV) for Children from 2003 to 2006 using questionnaires and analyses of cotinine in urine and benzene and formaldehyde in indoor air. About half of the 3- to 14-year-old children in Germany live in households with at least one smoker. Smoking at home is one of the most important predictors for benzene concentrations in indoor air. Cotinine concentrations in urine can be used to identify the levels of exposure to ETS. Multivariate analysis yields several relevant predictors for ETS exposure of children in Germany.
International Journal of Environment and Health. 01/2008; 2(3-4):397-409.
[Show abstract][Hide abstract] ABSTRACT: German Environmental Surveys (GerESs) are large scale population studies which have been carried out on adults in 1985/86, 1990/92 and 1998 and on children aged 6-14 years in 1990/92. GerES IV is the first survey focussing exclusively on children [Becker, K., Schulz, C., Babisch, W., Dürkop, J., Roskamp, E., Seiwert, M., Szewzyk, R., Ullrich, D., Seifert, B., 2005. German Environmental Survey for Children (GerES IV) 2003-2006. Pullut. Atmos. 188, 475-479]. GerES IV included a representative sample of 1790 children aged 3-14 of the participants of the National Health Interview and Examination Survey on Children and Adolescents. The primary goal of GerES IV is not only to analyse and document the extent, distribution and determinants of German children's exposure to environmental pollutants but to discover links between environmental exposure and health. Results will help develop preventive measures and advance further research. They might provide the basis for environmental and public health policy decisions. Precondition to achieve this task is a description of the data on exposures and the data on health outcomes. This work is currently performed at the Federal Environment Agency. First results show a remarkable decrease of the blood lead level of German children aged 6-14 years from 32.3 microg/l in 1990/92 (GerES II) to 16.3 microg/l in GerES IV which is the lowest mean lead concentration determined in German studies so far. None of the children had a value exceeding 100 microg/l. In GerES IV, the following health-related issues will be primarily examined: the relationship between sensitisation against mould spores and the occurrence of mould in households, irritation of eyes and respiratory system caused by formaldehyde, other aldehydes, or total volatile organic compounds (TVOC); the impact of non-occupational noise on hearing loss, stress and sleep disturbances, and the connection between contact allergies, nickel and scents. 9.5% of the children showed a sensitisation to at least one of the moulds examined (Penicillium (notatum) chrysogenum, Aspergillus versicolor, Wallemia sebi, Eurotium spp., Alternaria alternata). The most frequent sensitisation was against Penicillium chrysogenum. GerES IV might broaden the knowledge in terms of environmental causes of health outcomes. Children of smoking mothers showed higher mean cotinine concentrations than children living with a smoking father, regardless whether they smoked daily or occasionally. Results from the GerES IV pilot study showed a relation between environmental tobacco smoke (ETS) exposure and an increased susceptibility to infections and inflammations of the middle ear.
International Journal of Hygiene and Environmental Health 11/2007; 210(5):535-40. · 3.05 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We analysed urine samples from the 2001/2002 pilot study of the German Environmental Survey on Children (GerES IV) for the concentrations of the di-n-butylphthalate (DnBP) metabolite mono-n-butylphthalate (MnBP) and the butlybenzylphthalate (BBzP) metabolite mono-benzyl-phthalate (MBzP). The study population consisted of 239 children (106 boys, 133 girls) aged between 2 and 14 years (median 8.5 years). We applied two calculation models to estimate the daily intake for the two parent phthalates from metabolite excretion. One was based on the creatinine-related metabolite concentrations; the other was based on the volume-related metabolite concentrations. Median urinary metabolite concentrations were 174 microg/l (136 microg/g creatinine) for MnBP and 19.7 microg/l (15.3 microg/g creatinine) for MBzP. Such levels have been determined in German children before. Compared to the USA, German median MnBP levels were about 3-10 times higher, whereas MBzP levels were in the same range. Median daily intakes calculated with the creatinine-based model were 4.07 (range: 0.66-76.4; 95th percentile: 14.9) microg/kg body weight (bw)/day for DnBP and 0.42 (range: 0.06-13.9; 95th percentile: 2.57) microg/kg bw/day for BBzP. Daily intakes calculated with the volume-based model were approximately two times higher with a median of 7.61 (range: 0.91-110; 95th percentile: 30.5) microg/kg bw/day for DnBP and a median of 0.77 (range: 0.05-31.3; 95th percentile: 4.48) microg/kg bw/day for BBzP. Using the creatinine model, 28 (11.7%) of the 239 children exceeded the TDI for DnBP of 10 microg/kg bw/day defined by the European Union. Employing the volume model, 89 (37.2%) children exceeded the TDI. For BBzP, no preventive limit values (TDI or RfD) were exceeded. For both phthalates and independent of the model, we found increasing daily intakes with decreasing age. Between 25% (creatinine model) and 50% (volume model) of the 2-4-year old children had daily intakes for DnBP above the TDI.
Journal of Exposure Science and Environmental Epidemiology 08/2007; 17(4):378-87. · 3.19 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Di(2-ethylhexyl)phthalate (DEHP) is a general-purpose plasticizer for polyvinyl chloride (PVC) and has become a ubiquitous environmental contaminant. It is suspected to be an endocrine disrupting/modulating substance in humans. Children are of special concern due to their developmental state. In our study we estimated the daily DEHP intake of 239 children aged 2-14 years by extrapolating from their urinary levels of the DEHP metabolites mono-(2-ethyl-5-hydroxyhexyl)phthalate (5OH-MEHP), mono-(2-ethyl-5-oxohexyl)phthalate (5oxo-MEHP) and mono-(2-ethylhexyl)phthalate (MEHP). We applied two calculation models based upon the volume and the creatinine-related urinary metabolite concentrations. Applying the volume- or the creatinine-based calculation model we determined a median daily DEHP intake of 7.8 or 4.3 microg/kgbody weight (bw)/day and a 95th percentile of 25.2 or 15.2 microg/kgbw/day. Three children (1%) exceeded the value of the tolerable daily intake (TDI) of the European Food Safety Authority of 50 microg/kgbw/day, while 7.5% or 3% (depending on the calculation model) exceeded the reference dose (RfD) of 20 microg/kgbw/day of the US Environmental Protection Agency. In general, DEHP exposure was decreasing with increasing age and boys had higher exposures than girls. Our findings suggest that the majority of the children in the general population is exposed to quantities of DEHP below the TDI and the RfD. However, many children scoop out the preventive limit values to a considerable degree and in individual cases we observed substantial transgressions. Younger children seem to be more severely burdened, which may be due to a higher food consumption related to their bw, mouthing behaviour and/or playing near the ground.
International Journal of Hygiene and Environmental Health 02/2007; 210(1):35-42. · 3.05 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Organophosphorus pesticides and pyrethroids are widely used in German agriculture and residential settings. Their occurrence in human biological samples can be used as an indicator for the exposure of children to these compounds. Using multivariate evaluation the routes of exposure can be identified. In the pilot study of GerES IV, metabolites of pyrethroids and organophosporus pesticides were analysed in urine of children aged 2-17 years (n = 396 and 363). The 95th percentiles for the metabolites of the pyrethroids in urine were: cis-DCCA 0.74 microg/l, trans-DCCA 1.7 microg/l, DBCA 0.52 microg/l, F-PBA < 0.1 microg/l, and 3-PBA 2.4 microg/l. 3-PBA was detected in 90% of the samples. The 95th percentiles for the organophosphorus metabolites in urine were: DMP 118 microg/l, DEP 20 microg/l, DMTP 124 microg/l, DETP 11 microg/l, DMDTP 11 microg/l, DEDTP < 1.0microg/l. DMTP was the metabolite most frequently detected in the samples (90%). Based on the metabolites analysed in urine the exposure to organophosphorus pesticides is mainly influenced by age, consumption of fresh fruits and fruit juice, living in an urban area, and season. A rough estimation revealed that the ADI values for organophosphorus pesticides might be exceeded. However, these results require further exploration. The exposure to pyrethroids is influenced by age, sampling location, consumption of boiled vegetables, and the use of biocides indoors at home. In addition, a significant correlation between permethrin in house dust and the metabolite concentrations in urine could be observed. Thus it seems likely that ingestion of house dust contributes to children's exposure.
International Journal of Hygiene and Environmental Health 05/2006; 209(3):221-33. · 3.05 Impact Factor