Interpreting biomarker data from the COPHES/DEMOCOPHES twin projects: Using external exposure data to understand biomarker differences among countries.

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.

Gender differences in cadmium and cotinine levels in prepubertal children.

Susceptibility to environmental stressors has been described for fetal and early childhood development. However, the possible susceptibility of the prepubertal period, characterized by the orchestration of the organism towards sexual maturation and adulthood has been poorly investigated and exposure data are scarce. In the current study levels of cadmium (Cd), cotinine and creatinine in urine were analyzed in a subsample 216 children from 12 European countries within the DEMOCOPHES project. The children were divided into six age-sex groups: boys (6-8 years, 9-10 years and 11 years old), and girls (6-7 years, 8-9 years, 10-11 years). The number of subjects per group was between 23 and 53. The cut off values were set at 0.1 µg/L for Cd, and 0.8 µg/L for cotinine defined according to the highest limit of quantification. The levels of Cd and cotinine were adjusted for creatinine level. In the total subsample group, the median level of Cd was 0.180 µg/L (range 0.10-0.69 µg/L), and for cotinine the median wet weight value was 1.50 µg/L (range 0.80-39.91 µg/L). There was no significant difference in creatinine and cotinine levels between genders and age groups. There was a significant correlation between levels of cadmium and creatinine in all children of both genders. This shows that even at such low levels the possible effect of cadmium on kidney function was present and measurable. An increase in Cd levels was evident with age. Cadmium levels were significantly different between 6-7 year old girls, 11 year old boys and 10-11 year old girls. As there was a balanced distribution in the number of subjects from countries included in the study, bias due to data clustering was not probable. The impact of low Cd levels on kidney function and gender differences in Cd levels needs further investigation.

German health-related environmental monitoring: assessing time trends of the general population's exposure to heavy metals.

The German system of a health-related environmental monitoring is based upon two instruments: The German Environmental Survey (GerES) and the Environmental Specimen Bank (ESB). The ESB is a tool to describe time trends of human exposure. Each year approx. 500 students from 4 sampling locations are analysed for their heavy metal contents in blood, blood plasma, and urine. GerES is a nationwide representative cross-sectional study that has been conducted four times up to now. Both instruments have been used to measure heavy metals over the last decades and thus provide complementary information. Both instruments are useful to describe time trends. However, combining the two has an added value, which is demonstrated for heavy metals for the first time in this paper. Major results and the changing importance of sources of exposure to heavy metals (Pb, Cd, Hg, Au, Pt, U and Ni) are shown. This leads to the following conclusion about the today's relevance of exposure in Germany. For the study participants of the city of Muenster, lead in whole blood decreased from about 70 µg/l in 1981 to levels below 15 µg/l in 2009. GerES data of young adults confirmed this time trend and GerES IV on children revealed the decreasing relevance of lead in outdoor air and in drinking water. The concentrations of mercury in urine decreased because in Germany it is no longer recommended to use amalgam fillings for children. However, GerES IV and ESB data also demonstrate that despite the decline of these heavy metals exposures to nickel and uranium originating from drinking water are still of importance.

[Concept for a German national birth cohort for environmental health research]. / Konzept für eine umweltepidemiologische Geburtskohorte des Bundes.

The German Federal Environment Agency has commissioned the conceptual work for a birth cohort study to investigate environmental health problems in children. The recruitment is intended to start as early as possible in pregnancy and to take place in several regions of Germany. To detect health risks for exposures and outcomes with low prevalence as well as gene-environment interactions, a cohort size of 100,000-200,000 parent-child pairs is needed. The concept focuses on five health issues: neurodevelopment; reproductive development; pregnancy and birth outcomes; asthma, allergies and respiratory disease; obesity, insulin resistance and diabetes. The examination of additional health conditions will be possible. The exposure assessment will cover chemical, biological and physical exposures; psychosocial factors and genetics will be assessed as well. Biological and environmental samples will be stored in a repository for future analyses. The birth cohort study will contribute to the detection of associations between environmental exposures and health conditions over the course of life, which in turn will have an impact on environmental and health policies.

[German Environmental Survey for Children (GerES IV) in the German Health Interview and Examination Survey for Children and Adolescents (KiGGS). First results]. / Kinder-Umwelt-Survey (KUS) im Rahmen des Kinder- und Jugendgesundheitssurveys (KiGGS). Erste Ergebnisse.

The German Environmental Survey for Children (GerES IV) is the environment-related module of the German Health Interview and Examination Survey for Children and Adolescents (KiGGS) of the Robert Koch Institute and the fourth GerES of the Federal Environment Agency. The main objective of GerESs is to analyse and document the extent, distribution and determinants of exposure to environmental pollutants of the German general population. GerES IV was performed from 2003 to 2006. A total of 1.790 children aged 3-14 years from 150 sampling locations participated in GerES IV. Samples of blood, urine, tap water, house dust and indoor air were analysed. Hearing tests, measurements of traffic noise and interviews to get exposure-related information were conducted. First results indicate a clear decrease of the exposure to arsenic, lead and mercury. Cotinine concentrations in urine can be used to classify the exposure of children to environmental tobacco smoke. The examination of the tap water used in the subjects' households indicates that in some households the guideline values of the German Drinking Water Ordinance were not always met. This is the case for nickel, copper and lead which are used as pipe material for domestic plumbing.

Twenty years of the German Environmental Survey (GerES): human biomonitoring--temporal and spatial (West Germany/East Germany) differences in population exposure.

The German Environmental Surveys (GerESs) are nationwide population studies, which have repeatedly been carried out in Germany since the mid-1980s. The subjects were representatively selected from the regional registration offices with regard to age, gender and community size. The first survey for adults (GerES I) was carried out in 1985/1986 (West Germany) followed by GerES IIa in 1990/1991 (West Germany) and GerES IIb in 1991/1992 (East Germany). In GerES II children were also included to some extent. In 1998, the third GerES for adults was conducted in both parts of Germany (GerES III). The current survey 2003/2006 (GerES IV) is focussing exclusively on children. A 1-year pilot study was conducted in 2001-2002 to collect information on parameters influencing the response rate and to test the suitability of the different instruments intended to be used for the main study. The main goal of the surveys is to analyse and document the extent, distribution and determinants of exposure to environmental pollutants of the German general population. Three main instruments of investigation were comprised in GerES: human biomonitoring (HBM), monitoring of the domestic environment, and collecting information on exposure pathways and living conditions via questionnaires. This paper is focussed on the general design of the GerESs, the trend over time and spatial differences (West Germany and East Germany) for HBM data on arsenic, cadmium, lead, mercury, pentachlorophenol (PCP), and polycyclic aromatic hydrocarbons (PAH). These substances have been determined in blood and/or morning urine of adults and children. All GerESs have been conducted in close connection with the National Health Interview and Examination Surveys performed by the Robert Koch-Institute, Berlin.

German Environmental Survey (GerES): human biomonitoring as a tool to identify exposure pathways.

The German Environmental Survey (GerES) is a representative population study and has been repeatedly carried out since the mid-1980s. The currently run survey (GerES IV) is the first one solely targeted on children. The GerES IV Pilot Study resulted in first insights into major exposure pathways relevant to children. These insights were made possible by the determination of pollutant concentrations in blood and urine and the additional consideration of their occurrence in the indoor environment and by using questionnaire data. The results of the GerES IV Pilot Study are presented according to major exposure pathways such as house dust, food and environmental tobacco smoke (ETS). An overview on relevant pilot study results is given. The results of GerES IV will permit the verification and substantiation of the pilot study results.

[Environmental Survey for Children-- the environmental module of KiGGS. I. Design and research program]. / Kinder-Umwelt-Survey--das Umweltmodul im KiGGS. Teil 1: Konzeption und Untersuchungsprogramm.

The German Environmental Survey for Children (GerES IV) is the environment-oriented module of the National Health Interview and Examination Survey for Children and Adolescents (KiGGS) which is being performed nationwide in Germany. From 2003 to 2006, a random subsample of 1800 children aged 3-14 years is being studied with regard to their body burden and health impairments linked to housing conditions and the personal environment- and health-relevant behaviour. The basic study programme includes the analysis of blood, urine, tap water and house dust as well as the application of an extensive questionnaire. The data gained from this population sample, which is representative for Germany's children, are the basis for deriving reference values to characterise the background exposure of children aged 3-14 years. Trends over time can be detected and the success of environmental policies verified by comparing the data with those of the German Environmental Survey 1990/92 (GerES II), also conducted in close cooperation with the National Health Survey, which included children aged 6-14 years. By linking the data from the Environmental and the Health Surveys, health-relevant environmental exposures can be detected and different scientific hypotheses can be tested. The main subjects that are being dealt with using subcollectives of GerES IV are 'VOC and eye and nasopharynx irritation', 'indoor allergens and allergic diseases of the respiratory system', 'chromium, nickel, fragrances and contact allergens', and 'noise, hearing capacity and stress hormones'.

[The Child Environment Survey]. / Kinder-Umwelt-Survey.

The German Environmental Survey (GerES) is a representative population study conducted in Germany since the mid-1980s. GerES IV is the first survey for children only; it will be conducted in close connection with the Health Survey for Children and Adolescents on a random sample of 1,800 children (3 to 14 years of age) taken from the study population of the Health Survey for Children and Adolescents. Various parameters will be analysed in blood, urine, house dust, indoor air and tap water. They include neurotoxins (PCBs, Pb, Hg), carcinogenic/cocarcinogenic substances (PAHs, benzene, halocarbons, Cd, As), substances that may cause irritation of the respiratory tract, allergies and asthma (VOC, formaldehyde, house dust mite, mould fungi, pet allergens) and substances that may have an effect on metabolism with potentially long-term consequences (such as DEHP). An additional part was devoted to the link between hearing ability, noise and stress. A one-year pilot study on 550 children and adolescents was conducted in 2001 to 2002 to collect information on parameters influencing the response rate and to test the suitability of the different instruments intended to be used for the main study.

Risk factors for perioperative adverse respiratory events in children with upper respiratory tract infections.

BACKGROUND: Anesthesia for the child who presents for surgery with an upper respiratory infection (URI) presents a challenge for the anesthesiologist. The Current prospective study was designed to determine the incidence of and risk factors for adverse respiratory events in children with URTs undergoing elective surgical procedures. METHODS: The study population included 1,078 children aged 1 month to 18 yr who presented for an elective surgical procedure. Parents were given a short questionnaire detailing their child's demographics, medical history, and presence of any symptoms of a URT. Data regarding the incidence and severity of perioperative respiratory events were collected prospectively. Adverse respiratory events (any episode of laryngospasm, bronchospasm, breath holding > 15 s, oxygen saturation < 90%, or severe cough) were recorded. In addition, parents were contacted 1 and 7 days after surgery to determine the child's postoperative course. RESULTS: There were no differences between children with active URIs, recent URIs (within 4 weeks), and asymptomatic children with respect to the incidences of laryngospasm and bronchospasm. However, children with active and recent URIs had significantly more episodes of breath holding, major desaturation (oxygen saturation < 90%) events, and a greater incidence of overall adverse respiratory events than children with no URIs. Independent risk factors for adverse respiratory events in children with active URIs included use of an endotracheal tube (< 5 yr of age), history of prematurity, history of reactive airway disease, paternal smoking, surgery involving the airway, the presence of copious secretions, and nasal congestion. Although children with URIs had a greater incidence of adverse respiratory events, none were associated with any long-term adverse sequelae. CONCLUSIONS: The current study identified several risk factors for perioperative adverse respiratory events in children with lulls. Although children with acute and recent URIs are at greater risk for respiratory complications, these results suggest that most of these children can undergo elective procedures without significant increase in adverse anesthetic outcomes.

The German Environmental Survey 1990/1992 (GerES II): reference concentrations of selected environmental pollutants in blood, urine, hair, house dust, drinking water and indoor air.

The German Environmental Survey (GerES) is a large-scale, representative population study that has been carried out three times up to now with a time interval of about 7 years. GerES I was performed in 1985/1986, GerES IIa in 1990/1991 in West Germany, and GerES IIb in 1991/1992 in East Germany, the former German Democratic Republic (GDR). In GerES II, blood, urine, and scalp hair samples of 4021 adults aged 25-69 years and of 736 children aged 6-14 years were analysed as well as environmental samples (house dust, drinking water, indoor and personal air, diet). Characteristics of the frequency distributions of the substances analysed in the different media were calculated. The geometric mean (GM) for lead, cadmium, and mercury in the blood of adults amounted to 45.3, 0.36, and 0.51 microg/l, respectively. The corresponding values of arsenic, cadmium, and mercury in urine were 6.3, 0.29, and 0.54 microg/l, respectively. The concentrations of lead in blood, cadmium in blood and urine, and mercury in blood are lower in children than in adults. The GM ofpentachlorophenol (PCP) in urine of adults was 2.67 microg/l and in urine of children, 4.15 microg/l. These results of GerES II were compared with the so-called HBM values which represent health-based exposure guidelines and have been defined by the Human Biomonitoring Commission (HBC) of the Federal Environmental Agency, interalia for lead in blood, cadmium in urine, mercury in blood and urine, and PCP in urine. They also provided asound basis for the setting of reference values to describe the status of the German population. A total of 1.8% and 0.6% of the German females in child-bearing age had a level of lead in blood higher than HBM-I (100 microg/l) and HBM-II ( 150 microg/l), respectively. One percent of the children had a blood lead level above HBM-I. House dust and drinking water were analysed to characterise exposure in the domestic environment. Arsenic, cadmium, and lead deposition in homes amounted to 5.4 ng/(m2 day), 11.7 ng/(m2 day), and 0.29 microg/(m2 day), respectively. In the content of vacuum cleaner bags, concentrations were 2.1,0.9, and 5.9 microg/g. PCP, lindane and permethrin could be detected in the house dust of most German households. The pollutant load of the drinking water is significantly influenced by the corrosion of pipe materials and fittings. The new EC limit value of 10 microg/l for lead was exceeded in 7.7% of the first draw samples. The relatively high percentage (14%) of samples from East Germany that exceeded the current German guideline value for formaldehyde of 0.1 ppm in indoor air may be explained by the widespread use of contaminated particleboard in the former GDR.

[Pyrethroids in house dust of the German housing population--results of 2 nationwide cross-sectional studies]. / Pyrethroide im Hausstaub der deutschen Wohnbevölkerung--Ergebnisse zweier bundesweiter Querschnittstudien.

As a part of the German Environmental Surveys performed in 1985/86 (West Germany), 1990/91 (West Germany) and 1991/92 (East Germany), dust samples were collected in the households of about 1600 randomly selected adults (25 to 69 years) and an analysis of these samples was performed in respect of their content of 8 different pyrethroids and of the synergist piperonyl butoxide (PBO). In the 1990-92 survey about 90% of the samples contained permethrin in concentrations above the limit of quantification. This showed permethrin to be the most widespread of the 8 compounds investigated. The geometric mean of the permethrin content in domestic dust was 0.22 mg/kg. Only about 8% of the samples contained one or more of the other investigated substances (cyfluthrin, lambda-cyhalothrin, cypermethrin, alpha-cypermethrin, deltamethrin, empenthrin, d-phenothrin) in quantifiable amounts. About 76% of the samples contained quantifiable amounts of PBO. In East Germany the geometric mean of the PBO content (0.21 mg/kg) was significantly higher than in West Germany (0.07 mg/kg), but no difference for permethrin was found. Significant associations could be shown for the permethrin content and the application of biocides as well as for the PBO content and regional factors (size of community, type of dwelling area). Samples collected in 1985/86 (West Germany) showed a geometric mean for permethrin of 0.06 mg/kg and for PBO of 0.07 mg/kg. Comparing the values of 1985/86 and 1990/91, a significant increase can be observed for permethrin, whereas the PBO concentration remained constant.