André Conrad

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.

Environmental burden of disease in Europe : assessing nine risk factors in six countries

Background: Environmental health effects vary considerably with regard to their severity, type of disease, and duration. Integrated measures of population health, such as environmental burden of disease (EBD), are useful for setting priorities in environmental health policies and research. This review is a summary of the full Environmental Burden of Disease in European countries (EBoDE) project report. Objectives: The EBoDE project was set up to provide assessments for nine environmental risk factors relevant in selected European countries (Belgium, Finland, France, Germany, Italy, and the Netherlands). Methods: Disability-adjusted life years (DALYs) were estimated for benzene, dioxins, secondhand smoke, formaldehyde, lead, traffic noise, ozone, particulate matter (PM2.5), and radon, using primarily World Health Organization data on burden of disease, (inter)national exposure data, and epidemiological or toxicological risk estimates. Results are presented here without discounting or age-weighting. Results: About 3–7% of the annual burden of disease in the participating countries is associated with the included environmental risk factors. Airborne particulate matter (diameter ≤ 2.5 μm; PM2.5) is the leading risk factor associated with 6,000–10,000 DALYs/year and 1 million people. Secondhand smoke, traffic noise (including road, rail, and air traffic noise), and radon had overlapping estimate ranges (600–1,200 DALYs/million people). Some of the EBD estimates, especially for dioxins and formaldehyde, contain substantial uncertainties that could be only partly quantified. However, overall ranking of the estimates seems relatively robust. Conclusions: With current methods and data, environmental burden of disease estimates support meaningful policy evaluation and resource allocation, including identification of susceptible groups and targets for efficient exposure reduction. International exposure monitoring standards would enhance data quality and improve comparability. Citation: Hänninen O, Knol AB, Jantunen M, Lim TA, Conrad A, Rappolder M, Carrer P, Fanetti AC, Kim R, Buekers J, Torfs R, Iavarone I, Classen T, Hornberg C, Mekel OC, EBoDE Working Group. 2014. Environmental burden of disease in Europe: assessing nine risk factors in six countries. Environ Health Perspect 122:439–446; http://dx.doi.org/10.1289/ehp.1206154

Retrospective monitoring of perfluorocarboxylates and perfluorosulfonates in human plasma archived by the German Environmental Specimen Bank.

Due to the increased awareness of the ubiquitous contamination of all environmental compartments and of human beings with perfluoroalkyl substances (PFAS), voluntary withdrawals and shifts in products and manufacturing technologies, as well as in regulatory measures, have been made. To investigate whether these activities are reflected in the human exposure to PFASS, we examined human blood archived by the German Environmental Specimen Bank. Plasma samples (n=258, age range 20-29 years) covering the observation period 1982-2010 were analyzed for eleven perfluoroalkylcarboxylates (C4-C14) and five perfluoroalkylsulfonates (C4-C10) by HPLC-MS-MS. We detected perfluorooctanesulfonate (PFOS), perfluorooctanoate (PFOA), and perfluorohexanesulfonate (PFHxS) most often of all PFASs. Following a sharp increase from 1982 to 1986, median PFOS concentrations remained in the range of 20-24ng/mL until the end of the 1990s. Between 2001 and 2010, PFOS concentrations decreased steadily to 4ng/mL in plasma. Except for a similar strong increase from 1982 to 1986, we observed PFOA concentrations fluctuating between 4.8 and 6.3ng/mL in the following years. Since 2008, ESB data suggest a decreasing trend of PFOA. PFHxS concentrations increased continuously between 1982 and 2001 from about 1-2ng/mL. After nearly unchanged concentrations until 2005, a downward trend of PFHxS in plasma became apparent and in 2010 resulted in levels which were about 20% lower than those observed in the early 1980s. In the case of shorter and longer chained PFASs, quantification frequencies were between 0 and 60% and we found no indication of any temporal trends in human plasma concentrations.

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.

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.

Diisononyl 1,2-cyclohexanedicarboxylic acid (DINCH) and Di(2-ethylhexyl) terephthalate (DEHT) in indoor dust samples: Concentration and analytical problems

Possible human health effects of phthalate plasticizers have been intensely discussed during the last decade. Di(2-ethylhexyl) phthalate (DEHP), the phthalate acid ester with the largest production volume worldwide, has been substituted by new compounds like Diisononyl 1,2-cyclohexanedicarboxylic acid (DINCH) or Di(2-ethylhexyl) terephthalate (DEHT) in many applications. There are numerous reports about concentration levels of phthalates in indoor environments, but data on concentrations of these alternative plasticizers are not available yet. Also, the methods for the determination of phthalate substitutes are not yet established. This study presents the results achieved by quantification using different analytical methods. Data on the concentration of DEHT and DINCH in 953 dust samples from German households are presented. These samples were obtained in four different studies conducted from 1997 to 2009. Maximum concentrations of 110 mg DINCH/kg dust and 440 mg DEHT/kg dust were found. Especially the amount of DINCH has increased significantly after the market introduction of this plasticizer in 2002. Up to the beginning of 2006, DINCH was found in 44% of the dust samples. Dust samples collected in 2009 indicate an increased concentration for both softeners.

Estimation of dietary intake of bis(2-ethylhexyl)phthalate (DEHP) by consumption of food in the German population ☆

In the study presented here, we evaluated the exposure of the German population aged 14-80 years to bis(2-ethylhexyl)phthalate (DEHP) from consumption of food by means of deterministic and probabilistic estimations. The study was performed on the basis of an extensive review of literature from around the world reporting measured data on DEHP in food, as well as official German food control data. Only data from individual measurements were considered and used for fitting of distributions. A wide range of concentrations in non-representative samples are reported in the literature. On the basis of the available DEHP concentration data, 37 food categories were characterized which covered all major food classes. Food consumption data were taken from the diet history interviews of the German National Nutrition Survey II (Nationale Verzehrsstudie II) which was performed in 2005/2006 in a representative study population of 15,371 and is the most recent data source of this kind in Germany. Average DEHP intake was estimated deterministically using data on measured concentrations in food (medians and means) and food consumption (means). A total dietary exposure to DEHP of 3.6 (median based) and 9.3μg/kg of BW per day (based on mean values) was estimated deterministically. In addition, distributions of both concentrations and consumption figures were fitted using the @RISK best fit tool for further probabilistic estimations. This approach resulted in estimates within the same range: the estimated median DEHP intake in the whole population (both non-consumers and consumers of the foods considered) was 10.2, the arithmetic mean 14.0 and the 95th percentile 28.6μg/kg of BW per day. The respective estimates for consumers only were 12.4, 18.7 and 36.5μg/kg of BW per day. These results demonstrate that the probabilistic approach is able to estimate broader ranges of exposure even when using data representing an average intake. Moreover, it reflects the uncertainties of the estimation due to insufficient analytical data on concentrations of DEHP in food.

Glyphosate in German adults - Time trend (2001 to 2015) of human exposure to a widely used herbicide.

The broadband herbicide glyphosate (N-[phosphonomethyl]-glycine) and its main metabolite aminomethylphosphonic acid (AMPA) were analyzed by GC-MS-MS in 24h-urine samples cryo-archived by the German Environmental Specimen Bank (ESB). Samples collected in 2001, 2003, 2005, 2007, 2009, 2011, 2012, 2013, 2014, and 2015 were chosen for this retrospective analysis. All urine samples had been provided by 20 to 29 years old individuals living in Greifswald, a city in north-eastern Germany. Out of the 399 analyzed urine samples, 127 (=31.8%) contained glyphosate concentrations at or above the limit of quantification (LOQ) of 0.1μg/L. For AMPA this was the case for 160 (=40.1%) samples. The fraction of glyphosate levels at or above LOQ peaked in 2012 (57.5%) and 2013 (56.4%) after having discontinuously increased from 10.0% in 2001. Quantification rates were lower again in 2014 and 2015 with 32.5% and 40.0%, respectively. The overall trend for quantifiable AMPA levels was similar. Glyphosate and AMPA concentrations in urine were statistically significantly correlated (spearman rank correlation coefficient=0.506, p≤0.001). Urinary glyphosate and AMPA levels tended to be higher in males. The possible reduction in exposure since 2013 indicated by ESB data may be due to changes in glyphosate application in agricultural practice. The ESB will continue monitoring internal exposures to glyphosate and AMPA for following up the time trend, elucidating inter-individual differences, and contributing to the ongoing debate on the further regulation of glyphosate-based pesticides.

German Environmental Survey IV: Children's exposure to environmental tobacco smoke

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 Germanys 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 childrens ETS exposure has been achieved in Germany.

Phthalate metabolites in 24-h urine samples of the German Environmental Specimen Bank (ESB) from 1988 to 2015 and a comparison with US NHANES data from 1999 to 2012

The German Environmental Specimen Bank (ESB) continuously collects 24-h urine samples since the early 1980s in Germany. In this study we analyzed 300 urine samples from the years 2007 to 2015 for 21 phthalate metabolites (representing exposure to 11 parent phthalates) and combined the data with two previous retrospective measurement campaigns (1988 to 2003 and 2002 to 2008). The combined dataset comprised 1162 24-h urine samples spanning the years 1988 to 2015. With this detailed set of human biomonitoring data we describe the time course of phthalate exposure in Germany over a time frame of 27 years. For the metabolites of the endocrine disrupting phthalates di(2-ethylhexyl) phthalate (DEHP), di-n-butyl phthalate (DnBP) and butylbenzyl phthalate (BBzP) we observed a roughly ten-fold decline in median metabolite levels from their peak levels in the late 1980s/early 1990s compared to most recent levels from 2015. Probably, bans (first enacted in 1999) and classifications/labelings (enacted in 2001 and 2004) in the European Union lead to this drop. A decline in di-isobutyl phthalate (DiBP) metabolite levels set in only quite recently, possibly due to its later classification as a reproductive toxicant in the EU in 2009. In a considerable number of samples collected before 2002 health based guidance values (BE, HBM I) have been exceeded for DnBP (27.2%) and DEHP (2.3%) but also in recent samples some individual exceedances can still be observed (DEHP 1.0%). A decrease in concentration for all low molecular weight phthalates, labelled or not, was seen in the most recent years of sampling. For the high molecular weight phthalates, DEHP seems to have been substituted in part by di-isononyl phthalate (DiNP), but DiNP metabolite levels have also been declining in the last years. Probably, non-phthalate alternatives increasingly take over for the phthalates in Germany. A comparison with NHANES (National Health and Nutrition Examination Survey) data from the United States covering the years 1999 to 2012 revealed both similarities and differences in phthalate exposure between Germany and the US. Exposure to critical phthalates has decreased in both countries with metabolite levels more and more aligning with each other, but high molecular weight phthalates substituting DEHP (such as DiNP) seem to become more important in the US than in Germany.