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Veröffentlichung Walkability aus Sicht der Umweltwissenschaft(2014) Bunge, Christiane; Conrad, AndréVeröffentlichung 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(2017) Koch, Holger M.; Apel, Petra; Schütze, Andre; Conrad, André; Pälmke, Claudia; Kolossa-Gehring, Marike; Brüning, Thomas; Rüther, MariaThe German Environmental Specimen Bank (ESB) continuously collects 24-h urine samples since theearly 1980s in Germany. In this study we analyzed 300 urine samples from the years 2007 to 2015 for 21phthalate metabolites (representing exposure to 11 parent phthalates) and combined the data with twoprevious retrospective measurement campaigns (1988 to 2003 and 2002 to 2008). The combined datasetcomprised 1162 24-h urine samples spanning the years 1988 to 2015. With this detailed set of humanbiomonitoring data we describe the time course of phthalate exposure in Germany over a time frame of27 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 inmedian metabolite levels from their peak levels in the late 1980s/early 1990s compared to most recentlevels from 2015. Probably, bans (first enacted in 1999) and classifications/labelings (enacted in 2001 and2004) in the European Union lead to this drop. A decline in di-isobutyl phthalate (DiBP) metabolite levelsset 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) havebeen exceeded for DnBP (27.2%) and DEHP (2.3%) but also in recent samples some individual exceedancescan 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 levelshave also been declining in the last years. Probably, non-phthalate alternatives increasingly take overfor the phthalates in Germany. A comparison with NHANES (National Health and Nutrition ExaminationSurvey) data from the United States covering the years 1999 to 2012 revealed both similarities anddifferences in phthalate exposure between Germany and the US. Exposure to critical phthalates hasdecreased in both countries with metabolite levels more and more aligning with each other, but highmolecular weight phthalates substituting DEHP (such as DiNP) seem to become more important in theUS than in Germany.
© 2016 Elsevier GmbH. All rights reservedVeröffentlichung Glyphosate in German adults - Time trend (2001 to 2015) of human exposure to a widely used herbicide(2017) Conrad, André; Schröter-Kermani, Christa; Hoppe, Hans-Wolfgang; Kolossa-Gehring, Marike; Pieper, Silvia; Rüther, MariaVeröffentlichung Gesundheitliche Auswirkungen von Maßnahmen und Technologien der Energiewende(2016) Conrad, André; Plaß, DietrichVeröffentlichung Human biomonitoring reference values: Differences and similarities between approaches for identifying unusually high exposure of pollutants in humans(2019) Apel, Petra; Conrad, André; Kolossa-Gehring, Marike; Rucic, Enrico; Vogel, NinaIn exposure and risk assessment, the indication of unusually high exposure levels in humans to chemicals has been considered as an important objective for decades. To realize this objective, reference values (RV) need to be derived. However, while there is a tendency towards using the 95th percentile as a basis for deriving these reference values there is still no consensus. Moreover, side approaches have evolved including deriving RVs based on other percentiles, reporting multiple RVs or only reporting percentiles. The purpose of this article is to give an overview of the current literature, to point out differences and similarities between existing approaches, and to highlight important criteria for the derivation of RVs. We observe the majority of studies to base RVs on the 95th percentile and its 95% confidence interval which can been justified by statistical paradigms, present arguments for a single defined reference value, and discuss characteristics which call for more consistency. To conclude, our overview provides a first step towards a more homogenous and standardized derivation procedure to identify unusually high exposures in exposure science. © 2018 The Authors. Published by Elsevier GmbH.Veröffentlichung Toxic gender? The role of sex and gender in chemicals management(2019) Arning, Jürgen; Conrad, André; Debiak, Malgorzata; Kolossa-Gehring, Marike; Sauer, Arn Thorben; Steinkühler, NadjaVeröffentlichung Benefits of cooperation among large-scale cohort studies and human biomonitoring projects in environmental health research: An exercise in blood lead analysis of the Environment and Child Health International Birth Cohort Group(2019) Nakayama, Shoji F.; Conrad, André; Espina, Carolina; Kamijima, Michihiro; Kolossa-Gehring, Marike; Murawski, AlineA number of prospective cohort studies are ongoing worldwide to investigate the impact of foetal and neonatal exposures to chemical substances on child health. To assess multiple exposure (mixture) effects and low prevalence health outcomes it is useful to pool data from several studies and conduct mega-data-analysis. To discuss a path towards data harmonization, representatives from several large-scale birth cohort studies and a biomonitoring programme formed a collaborative group, the Environment and Child Health International Birth Cohort Group (ECHIBCG). In this study, an intra-laboratory trial was performed to harmonize existing blood lead measurements within the groups' studies. Then, decentralized analyses were conducted in individual countries' laboratories to evaluate blood lead levels (BLL) in each study. The measurements of pooled BLL samples in French, German and three Japanese laboratories resulted in an overall mean blood lead concentration of 8.66 ng¯1 (95% confidence interval: 8.59-8.72 ng¯1) with 3.0% relative standard deviation. Except for China's samples, BLL from each study were comparable with mean concentrations below or close to 10ng¯1. The decentralized multivariate analyses revealed that all models had coefficients of determination below 0.1. Determinants of BLL were current smoking, age >35 years and overweight or obese status. The three variables were associated with an increase in BLL in each of the five studies, most strongly in France by almost 80% and the weakest effect being in Norway with only 15%; for Japan, with the far largest sample (~18,000), the difference was 36%. This study successfully demonstrated that the laboratory analytical methods were sufficiently similar to allow direct comparison of data and showed that it is possible to harmonize the epidemiological data for joint analysis. This exercise showed the challenges in decentralized data analyses and reinforces the need for data harmonization among studies. © 2019 The Authors. Published by Elsevier GmbH.Veröffentlichung Trends in characteristics of 24-h urine samples and their relevance for human biomonitoring studies - 20 years of experience in the German Environmental Specimen Bank(2019) Lermen, Dominik; Bartel-Steinbach, Martina; Conrad, André; Gwinner, Frederik; Kolossa-Gehring, Marike; Weber, TillTo document trends in human exposure to environmental pollutants, the German Environmental Specimen Bank (ESB) has been routinely collecting and archiving 24-h urine samples from young adults at four sampling sites in Germany on an annual basis. For the purpose of normalizing measured analyte concentrations, urinary creatinine (UC), specific gravity (SG), conductivity (CON), and total urine volume (UVtot) of 24-h urine samples have also been recorded. These parameters are however susceptible to variation over time, as well as within/among participants and normalization against them can thus affect the interpretation of data regarding exposure to environmental pollutants. To evaluate the influence of normalization against these parameters, we first sought to determine variations of these parameters with regard to differences between sexes and trends over time. We analysed data from 8619 urine samples collected from 1997 to 2016. We observed an inverse relation between UVtot and UC, SG, and CON. We also found differences between sexes for UC, SG and CON, but not UVtot. UC, SG, and CON showed significant decreasing trends over time in both sexes. In contrast, a significant increase of over 30% in UVtot, independent of participant age and BMI, was revealed. This increase in UVtot and the concomitant sample dilution is likely to have an impact on measured analyte concentrations in 24-h urine samples. Hence, normalization of urinary concentrations is warranted when interpreting time trends of human exposure. Next, urinary calcium (Ca2+) concentrations of ESB participants were used to demonstrate the effects of normalization against each of the four urine parameters. From 1997 to 2016, measured Ca2+ concentrations showed a statistically significant but scientifically implausible decrease. Normalization of Ca2+ concentrations against UVtot (by calculating the total daily excretion), UC, or CON, but not SG, eliminated this decrease. Consistent with previous work, Ca2+ concentrations in urine and total daily Ca2+ excretion were higher for males than females. Normalization against UC, SG, or CON, however, attenuated this difference. Thus, to avoid misinterpretation in trend analysis and sex-specific excretion in 24-h urine samples, the calculation of the total daily excretion is recommended.Veröffentlichung Toxic gender? The role of sex and gender in chemicals management(2019) Arning, Jürgen; Conrad, André; Debiak, Malgorzata; Kolossa-Gehring, Marike; Sauer, Arn Thorben; Steinkühler, NadjaVeröffentlichung Hexamoll® DINCH and DPHP metabolites in urine of children and adolescents in Germany. Human biomonitoring results of the German Environmental Survey GerES V, 2014-2017(2019) Conrad, André; Kolossa-Gehring, Marike; Rucic, Enrico; Schmied-Tobies, Maria Irene Hilde; Schulz, Christine; Schwedler, GerdaThe production and use of the plasticisers Hexamoll® DINCH (di-(iso-nonyl)-cyclohexane-1,2-dicarboxylate) and DPHP (di-(2-propylheptyl) phthalate) have increased after both chemicals were introduced into the market in the early 2000s as substitutes for restricted high molecular weight phthalates. During the population representative German Environmental Survey (GerES) of Children and Adolescents (GerES V, 2014-2017), we collected urine samples and measured the concentrations of DINCH and DPHP metabolites in 2228 and in a subsample of 516 participants, respectively. We detected DINCH and DPHP metabolites in 100% and 62% of the 3-17 years old children and adolescents, respectively. Geometric means of DINCH metabolites were 2.27 myg/L for OH-MINCH, 0.93 myg/L for oxo-MINCH, 1.14 myg/L for cx-MINCH and 3.47 myg/L for DINCH (Sigma of OH-MINCH + cx-MINCH). Geometric means of DPHP metabolites were 0.30 myg/L for OH-MPHP, 0.32 myg/L for oxo-MPHP and 0.64 myg/L for DPHP (Sigma of OH-MPHP + oxo-MPHP). The 3-5 years old children had almost 3-fold higher DINCH biomarkers levels than adolescents (14-17 years). Higher concentrations of DPHP biomarkers among young children only became apparent after creatinine adjustment. Urinary levels of DINCH but not of DPHP biomarkers were associated with the levels of the respective plasticisers in house dust. When compared to HBM health-based guidance values, we observed no exceedance of the HBM-I value of 1 mg/L for DPHP (Sigma of OH-MPHP + oxo-MPHP). However, 0.04% of the children exceeded the health based guidance value HBM-I of 3 mg/L for DINCH (Sigma of OH-MINCH + cx-MINCH). This finding shows that even a less toxic replacement of restricted chemicals can reach exposures in some individuals, at which, according to current knowledge, health impacts cannot be excluded with sufficient certainty. In conclusion, we provide representative data on DINCH and DPHP exposure of children and adolescents in Germany. Further surveillance is warranted to assess the substitution process of plasticisers, and to advise exposure reduction measures, especially for highly exposed children and adolescents. Providing the results to the European HBM Initiative HBM4EU will support risk assessment and risk management not only in Germany but also in Europe. © 2019 The Authors. Published by Elsevier GmbH