Margarete Seiwert

DEHP metabolites in urine of children and DEHP in house dust

Urine samples from the 2001/2002 pilot study for the German Environmental Survey on children (GerES IV) were analysed for concentrations of the primary DEHP metabolite MEHP (mono(2-ethylhexyl)phthalate) and two secondary DEHP metabolites SOH-MEHP (2-ethyl-5-hydroxy-hexylphthalate) and 5oxo-MEHP (2-ethyl-5-oxo-hexylphthalate). Urine samples had been taken from 254 children aged 3 to 14. In addition, DEHP was analysed in house dust samples. These samples had been collected with vacuum cleaners in the homes of the children. The geometric mean (GM) was 7.9 microg/l for MEHP in urine, and the GMs for the secondary metabolites 5OH-MEHP and 5oxo-MEHP were 52.1 microg/l and 39.9 microg/l. 5OH-MEHP and 5oxo-MEHP concentrations were highly correlated (r = 0.98). The correlations of 5OH-MEHP and 5oxo-MEHP with MEHP were also high (r = 0.72 and r = 0.70). The concentrations of 5OH-MEHP and 5oxo-MEHP were 8.0-fold and 6.2-fold higher than the concentrations of MEHP. The ratios 5OH-MEHP/Soxo-MEHP and 5oxo-MEHP/MEHP decreased with increasing age. Boys showed higher concentrations than girls for all three metabolites of DEHP in urine. Children aged 13-14 had the lowest mean concentrations of the secondary metabolites in urine. The house dust analyses revealed DEHP contamination of all samples. The GM was 508 mg/kg dust. No correlation could be observed between the levels of any of the urinary DEHP metabolites and those of DEHP in house dust.

GerES IV: phthalate metabolites and bisphenol A in urine of German children.

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.

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 µg/l, respectively. The corresponding values of arsenic, cadmium, and mercury in urine were 6.3, 0.29, and 0.54 µg/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 of pentachlorophenol (PCP) in urine of adults was 2.67 µg/l and in urine of children, 4.15 µg/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, inter alia for lead in blood, cadmium in urine, mercury in blood and urine, and PCP in urine. They also provided a sound 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 µg/l) and HBM-II (150 µg/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 µg/(m2 day), respectively. In the content of vacuum cleaner bags, concentrations were 2.1, 0.9, and 5.9 µg/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 µg/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.

Di- n -butylphthalate and butylbenzylphthalate — urinary metabolite levels and estimated daily intakes: pilot study for the German Environmental Survey on children

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 μg/l (136 μg/g creatinine) for MnBP and 19.7 μg/l (15.3 μg/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) μg/kg body weight (bw)/day for DnBP and 0.42 (range: 0.06–13.9; 95th percentile: 2.57) μg/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) μg/kg bw/day for DnBP and a median of 0.77 (range: 0.05–31.3; 95th percentile: 4.48) μg/kg bw/day for BBzP. Using the creatinine model, 28 (11.7%) of the 239 children exceeded the TDI for DnBP of 10 μg/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.

First steps toward harmonized human biomonitoring in Europe: demonstration project to perform human biomonitoring on a European scale.

Background For Europe as a whole, data on internal exposure to environmental chemicals do not yet exist. Characterization of the internal individual chemical environment is expected to enhance understanding of the environmental threats to health. Objectives We developed and applied a harmonized protocol to collect comparable human biomonitoring data all over Europe. Methods In 17 European countries, we measured mercury in hair and cotinine, phthalate metabolites, and cadmium in urine of 1,844 children (5–11 years of age) and their mothers. Specimens were collected over a 5-month period in 2011–2012. We obtained information on personal characteristics, environment, and lifestyle. We used the resulting database to compare concentrations of exposure biomarkers within Europe, to identify determinants of exposure, and to compare exposure biomarkers with health-based guidelines. Results Biomarker concentrations showed a wide variability in the European population. However, levels in children and mothers were highly correlated. Most biomarker concentrations were below the health-based guidance values. Conclusions We have taken the first steps to assess personal chemical exposures in Europe as a whole. Key success factors were the harmonized protocol development, intensive training and capacity building for field work, chemical analysis and communication, as well as stringent quality control programs for chemical and data analysis. Our project demonstrates the feasibility of a Europe-wide human biomonitoring framework to support the decision-making process of environmental measures to protect public health. Citation Den Hond E, Govarts E, Willems H, Smolders R, Casteleyn L, Kolossa-Gehring M, Schwedler G, Seiwert M, Fiddicke U, Castaño A, Esteban M, Angerer J, Koch HM, Schindler BK, Sepai O, Exley K, Bloemen L, Horvat M, Knudsen LE, Joas A, Joas R, Biot P, Aerts D, Koppen G, Katsonouri A, Hadjipanayis A, Krskova A, Maly M, Mørck TA, Rudnai P, Kozepesy S, Mulcahy M, Mannion R, Gutleb AC, Fischer ME, Ligocka D, Jakubowski M, Reis MF, Namorado S, Gurzau AE, Lupsa IR, Halzlova K, Jajcaj M, Mazej D, Snoj Tratnik J, López A, Lopez E, Berglund M, Larsson K, Lehmann A, Crettaz P, Schoeters G. 2015. First steps toward harmonized human biomonitoring in Europe: demonstration project to perform human biomonitoring on a European scale. Environ Health Perspect 123:255–263; http://dx.doi.org/10.1289/ehp.1408616

Environmental surveys, specimen bank and health related environmental monitoring in Germany.

Production of chemicals, use of products and consumer goods, contamination of food as well as todays 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.

Nicotine and cotinine in adults’ urine: The German Environmental Survey 1998

In 1998, the German Environmental Survey (GerES III) recruited approximately 5000 adults between the ages of 18 and 69 years. The study population for these analyses consisted of 1580 smokers (34% of the total population) and 3126 nonsmokers. Nicotine and cotinine concentrations in urine were determined by HPLC methods with UV-detection and corrected for creatinine. Nicotine and cotinine concentrations differed between smokers and nonsmokers by factors of 10–100. The multiple linear regression models used for the analyses of nicotine detection in the urine of smokers explained 43.2% and 42.3% of the total volume-specific and creatinine-specific variances, respectively. Cigarette smoking was the major factor responsible for 41% of the total variance. The explained variances of the cotinine results were larger, 51.0% and 49.3% of the total variance were volume-specific and creatinine-specific, respectively. More than 20% of nonsmokers in GerES III were exposed to environmental tobacco smoke at home, at work or in other places. The logistic regression analysis approach used for the group of nonsmokers showed the greatest effects for those exposed to tobacco smoke at home (adjusted OR varied between 4 and 6). These results were seen for nicotine as well as for cotinine excretion. Exposure to tobacco smoke in the workplace doubled the risk for the detection of nicotine and cotinine in urine. When other risk factors such as age, sex, social status, community size, season of urine collection, and the consumption of food containing nicotine such as potatoes, cabbage, tea were included, the effect estimates for tobacco smoke exposure remained unchanged. A new federal bill to diminish environmental tobacco smoke (ETS) exposure in the workplace was recently passed in Germany, but protection of nonsmokers from smoking family members at home needs more attention.

A systematic approach for designing a HBM Pilot Study for Europe

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.

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 todays 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.

Reference values for lead, cadmium and mercury in the blood of adults from the metropolitan area of Sao Paulo, Brazil

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 60 μgPb/L and 4 μgHg/L for men and 47 μgPb/L and 4 μgHg/L for women. RVs in the older group were 80 μgPb/L and 5 μgHg/L for men and 63 μgPb/L and 6 μgHg/L for women. The RV for Cd was 0.6 μg/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.