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Veröffentlichung 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 Die Deutsche Umweltstudie zur Gesundheit von Kindern und Jugendlichen, GerES V 2014-2017(2019) Bandow, Nicole; Conrad, André; Kolossa-Gehring, Marike; Murawski, Aline; Rucic, Enrico; Sawal, George; Schmied-Tobies, Maria Irene Hilde; Schwedler, GerdaDie junge Bevölkerung stand im Mittelpunkt der Deutschen Umweltstudie zur Gesundheit von Kindern und Jugendlichen, GerES V, die vom Umweltbundesamt in den Jahren 2014 bis 2017 durchgeführt wurde. Dabei wurden mittels Human-Biomonitoring Schadstoffe im Urin und Blut von 3- bis 17-jährigen Kindern und Jugendlichen untersucht, um Aussagen über die aktuelle Belastungssituation in Deutschland treffen zu können. Beispiele weiterführender Auswertungen aus GerES V werden vorgestellt: die Analyse neuer Chemikalien, die Identifizierung besonders belasteter Gruppen, der Vergleich mit vorherigen Untersuchungen, die Ermittlung von Belastungsquellen und -pfaden sowie die gesundheitliche Bewertung der Belastung. Diese Ergebnisse eignen sich als Entscheidungsgrundlage für Maßnahmen und Regelungen zum Schutz von Umwelt und Gesundheit und dienen dem Ziel, eine gesunde Zukunft der Bevölkerung zu gestalten. In: UMID : Umwelt und Mensch - Informationsdienst ; Umwelt & Gesundheit, Umweltmedizin, Verbraucherschutz / Boden- und Lufthygiene (Berlin) Institut für Wasser-. - (2019), Heft 2, Seite 7Veröffentlichung Polychlorinated biphenyls (PCB) and organochlorine pesticides (OCP) in blood plasma - results of the German environmental survey for children and adolescents 2014-2017 (GerES V)(2020) Bandow, Nicole; Conrad, André; Kolossa-Gehring, Marike; Murawski, Aline; Sawal, GeorgeThe German Environmental Survey for Children and Adolescents 2014-2017 (GerES V) investigated the current internal exposure to polychlorinated biphenyls (PCB) and organochlorine pesticides (OCP). These analyses were carried out for a population-representative sub-sample of 1135 children and adolescents (aged 3-17 years) of all 2394 GerES V participants. Blood plasma samples were analyzed for seven indicator PCB (PCB 28, PCB 52, PCB 101, PCB 118, PCB 138, PCB 153 and PCB 180) and selected OCP (hexachlorobenzene, three hexachlorocyclohexane isomers, 4,4'-DDT, 4,4'-DDD and 4,4'-DDE). Despite risk mitigation measures and bans put into force some decades ago children and adolescents living in Germany are still exposed to PCB and OCP: Highest geometric mean plasma concentrations were measured for 4,4'-DDE (0.158 g/L), followed by PCB 138 (0.049 g/L), PCB 153 (0.066 g/L) and PCB 180 (0.032 g/L). Different application patterns of compounds between former East and former West Germany are still reflected by differences in plasma concentrations. Significant differences between age groups and by sexes were found. Moreover, the influence of breastfeeding and fish consumption, which was also found in other studies, was confirmed. Comparison with the results of GerES 2003-2006 confirms a decreasing trend in blood samples observed world-wide. Currently, health-based guidance values for PCB are still exceeded, though to a very limited extent. Also, the widespread occurrence of these compounds underlines the need for further monitoring of these compounds in humans although they are no longer marketed. Quelle: https://www.sciencedirect.comVeröffentlichung Polycyclic aromatic hydrocarbons (PAH) in urine of children and adolescents in Germany - human biomonitoring results of the German Environmental Survey 2014-2017 (GerES V)(2020) Conrad, André; Kolossa-Gehring, Marike; Murawski, Aline; Roth, Alexandra; Rucic, Enrico; Schmied-Tobies, Maria Irene Hilde; Schwedler, GerdaPolycyclic aromatic hydrocarbons (PAH) mainly originate from incomplete combustion of organic materials and are, among other sources, found in traffic emissions, smoked or barbecued food, leafy vegetables, and tobacco smoke. Some PAH or their metabolites are hazardous for health and classified as carcinogenic, mutagenic, or toxic to reproduction. Urine samples from 3- to 17-year-old children and adolescents living in Germany were analysed for concentrations of metabolites of the PAH fluorene, naphthalene, phenanthrene, and pyrene in the population-representative German Environmental Survey for Children and Adolescents GerES V (2014-2017). PAH metabolites were analysed in urine samples of 516 participants and could be quantified in 88ââą Ì100% of the samples. Geometric mean concentrations were: 0.785 my g/L (0.688 my g/gcreatinine) for 1-OH-naphthalene, 4.233 my g/L (3.706 my g/gcrea) for 2-OH-naphthalene, 0.139 my g/L (0.122 my g/gcrea) for 1-OH-phenanthrene, 0.085 my g/L (0.075 my g/gcrea) for 2-OH-phenanthrene, 0.131 my g/L (0.115 my g/gcrea) for 3-OH-phenanthrene, 0.045 my g/L (0.040 my g/gcrea) for 4-OH-phenanthrene, 0.058 my g/L (0.050 my g/gcrea) for 9-OH-phenanthrene, 0.511 my g/L (0.448 my g/gcrea) for Σ-OH-phenanthrene, and 0.099 my/L (0.087 my g/gcrea) for 1-OH-pyrene. Analyses of subgroups revealed higher PAH metabolite concentrations in young children compared to adolescents, and also in residents of former East Germany compared to those living in former West Germany. Increased urinary PAH metabolite concentrations were found in participants using domestic fuel for heating or gas for cooking. Plastic objects were identified as another potential source of exposure. Urinary concentrations of naphthalene and fluorene metabolites were elevated in active smokers and to the same extent in non-smokers exposed to passive smoking. Comparison with previous cycles of GerES revealed a decrease over time and a further decline in the still significant differences in urinary PAH metabolite concentrations of participants living in former East versus West Germany. © 2020 Published by Elsevier GmbH.Veröffentlichung The methylisothiazolinone and methylchloroisothiazolinone metabolite N-methylmalonamic acid (NMMA) in urine of children and adolescents in Germany - Human biomonitoring results of the German Environmental Survey 2014-2017 (GerES V)(2020) Conrad, André; Kolossa-Gehring, Marike; Murawski, Aline; Rucic, Enrico; Schmied-Tobies, Maria Irene HildeMixtures of methylisothiazolinone and methylchloroisothiazolinone are used as biocides in cosmetics, cleaning agents, and water-based paint. A biomonitoring method to evaluate exposure to these compounds was developed using N-methylmalonamic acid (NMMA), the main metabolite of both, methylisothiazolinone and methylchloroisothiazolinone, as the exposure biomarker. First-morning void urine samples (N = 2078) of 3- to 17-year-old children and adolescents living in Germany were analysed for concentrations of NMMA in the population representative German Environmental Survey for Children and Adolescents GerES V (2014-2017). NMMA was quantified in almost all samples, with a geometric mean concentration of 6.245 My g/L (5.303 my g/gcrea) and a 95th percentile of 15.0 my g/L (12.6 ÎÌg/gcrea). Urinary concentrations could not be related to self-reported application of specific cleaning agents or personal care products, leaving potential, specific sources of exposure unrevealed as most products relevant for isothiazolinone exposure are used ubiquitously. For the first time, reference values can be derived for urinary NMMA for children and adolescents in Germany, facilitating a more substantiated exposure assessment. © 2020 Published by Elsevier GmbH.Veröffentlichung 2-Mercaptobenzothiazole in urine of children and adolescents in Germany - Human biomonitoring results of the German Environmental Survey 2014-2017 (GerES V)(2020) Conrad, André; Kolossa-Gehring, Marike; Murawski, Aline; Rucic, Enrico; Schmied-Tobies, Maria Irene Hilde; Schwedler, Gerda2-Mercaptobenzothiazole (2-MBT) is widely used as a vulcanisation accelerator and is contained in many products made from natural rubber, e.g. car tires. Additionally, it is used as a fungicide in paint or fibre. Systemically human exposure to 2-MBT can occur via dermal and oral uptake or inhalation. Locally, 2-MBT can cause skin sensitisation. The International Agency for Research on Cancer (IARC) classified 2-MBT as probably carcinogenic to humans. 516 urine samples of 3- to 17-year-old children and adolescents living in Germany were analysed for the concentration of 2-MBT in the population representative German Environmental Survey for Children and Adolescents 2014-2017 (GerES V). 2-MBT was quantified above the limit of quantification (LOQ) of 1.0 my g/L in 50% of the 516 samples analysed. The geometric mean of urinary 2-MBT concentration was 1.018 my g/L and 0.892 my g/gcreatinine, the arithmetic mean was 1.576 my g/L (1.351 myg/gcrea). The median concentration was below the LOQ. Analyses of subgroups revealed higher 2-MBT concentrations in children aged 3-5 years compared to 14- to 17-year-old adolescents. All urinary 2-MBT concentrations were well below the health-based guidance value HBM-I for children of 4.5 my g/L. Therefore, current exposure levels are - according to current knowledge - not of concern. For the first time, reference values can be derived for 2-MBT for children and adolescents in Germany. This will facilitate to recognise changing exposure levels in this population group in Germany and identification of unusually high exposures. © 2020 The Authors.Veröffentlichung Metabolites of the fragrance 2-(4-tert-butylbenzyl)propionaldehyde (lysmeral) in urine of children and adolescents in Germany - Human biomonitoring results of the German Environmental Survey 2014-2017 (GerES V)(2020) Fiedler, Nina; Kolossa-Gehring, Marike; Murawski, Aline; Rucic, Enrico; Schmied-Tobies, Maria Irene Hilde; Schwedler, GerdaThe synthetic fragrance 2-(4-tert-butylbenzyl)propionaldehyde, also known as lysmeral, butylphenyl methylpropional, lilial, or lily aldehyde, is widely used in cosmetics, personal care products, laundry detergents, and air fresheners. It is classified as suspected to be harmful to fertility and possibly endocrine disrupting. Its maximum concentration in cosmetics is limited. First-morning void urine samples (N = 2133) were analysed for several metabolites of lysmeral (Chemical Abstract Service (CAS) No.: 80-54-6). Samples were collected in the population-representative German Environmental Survey for Children and Adolescents 2014-2017 (GerES V) from German residents aged 3-17 years. Four main metabolites tert-butylbenzoic acid, lysmerol, lysmerylic acid, and hydroxy-lysmerylic acid were found in quantifiable amounts in 100%, 99%, 40%, and 23% of the samples, respectively, with geometric mean concentrations of 10.21 my g/L (8.658 my g/gcrea) for tert-butylbenzoic acid, 1.528 my g/L (1.296 my g/gcrea) for lysmerol, and below the limit of quantification of 0.2 my g/L and 0.4 my g/L for lysmerylic acid and hydroxy-lysmerylic acid, respectively. Girls had higher urinary concentrations of lysmeral metabolites than boys. Usage of fragrances, fabric softener, and personal care products, especially perfume, was positively associated with urinary concentrations of lysmeral metabolites. Source identification builds a basis to derive proposals for reduction of exposure. These results can also provide the foundation for developing reference values for urinary metabolite concentrations of lysmeral in children and adolescents in Germany that will facilitate recognising future exposure trends. © 2020 The Author(s).Veröffentlichung Benzene metabolite SPMA and acrylamide metabolites AAMA and GAMA in urine of children and adolescents in Germany - human biomonitoring results of the German Environmental Survey 2014-2017 (GerES V)(2020) Bethke, Robert; Kolossa-Gehring, Marike; Murawski, Aline; Rucic, Enrico; Schmied-Tobies, Maria Irene Hilde; Schwedler, GerdaBenzene and acrylamide are carcinogenic substances contained inter alia in tobacco smoke. The mercapturic acid metabolites of benzene, N-acetyl-S-phenyl-L-cysteine (SPMA), and of acrylamide, N-acetyl-S-(3-amino-3-oxopropyl)-cysteine (AAMA) and N-acetyl-S-(3-amino-2-hydroxy-3-oxopropyl)-cysteine (GAMA), were analysed in 2260 first-morning void urine samples from children and adolescents aged 3-17 years, participating in the population-representative German Environmental Survey on Children and Adolescents, GerES V 2014-2017. SPMA was detected in 98% of the participants with a geometric mean (GM) of 0.097 (my)g/L urine. Smokers had about 10-fold higher levels of the benzene metabolite SPMA than non-smokers. The sample comprises of 48 self-reported smokers, mainly in the oldest age group (14-17-year-olds). Second-hand smoke exposure, living near busy or very busy roads, and using domestic fuels for heating were additionally associated with higher benzene metabolite levels. SPMA levels in GerES V were lower compared to levels found in other countries, which in part however may reflect different proportions of smokers. The acrylamide metabolites AAMA and GAMA were detected in 100% of the participants with a GM of 72.6 (my)g/L urine for AAMA and 15.0 (my)g/L urine for GAMA. Smoking children and adolescents had about 2.5-fold higher AAMA levels than non-smoking ones. The frequency of consumption of french-fried potatoes and potato crisps consumption was also positively associated with urinary AAMA and GAMA levels. Compared to the urinary AAMA and GAMA levels in Germany and other countries, levels in GerES V tended to be higher than in the few studies reported. The urinary levels of the benzene biomarker SPMA, and the acrylamide biomarkers AAMA and GAMA build the basis to derive reference values for the exposure of children and adolescents in Germany. The results reveal options for exposure reduction mainly in personal choices regarding smoking and diet, but also requiring policy to maintain efforts in non-smoking regulations and improving ambient air quality. Providing these results also to the European HBM Initiative HBM4EU will contribute to gain knowledge on the exposure of the European population, the health impact of carcinogens and thus providing support for substantiated exposure assessment. © 2020 The Author(s)Veröffentlichung Alkyl pyrrolidone solvents N-methyl-2-pyrrolidone (NMP) and N-ethyl-2-pyrrolidone (NEP) in urine of children and adolescents in Germany - human biomonitoring results of the German Environmental Survey 2014-2017 (GerES V)(2021) Kolossa-Gehring, Marike; Murawski, Aline; Rucic, Enrico; Schmied-Tobies, Maria Irene Hilde; Schwedler, GerdaN-methyl-2-pyrrolidone (NMP) and its substitute N-ethyl-2-pyrrolidone (NEP) are aprotic solvents used in many technical applications, but also in carpets, and consumer products such as cleaning agents, and cosmetics. NMP and NEP are classified as reproductive toxicants. As a substance of very high concern (SVHC), NMP is included in the European REACH (Registration, Evaluation, Authorisation of Chemicals) candidate list for authorisation. NMP and NEP metabolites were measured in more than 2100 urine samples of 3- to 17-year-old children and adolescents, participating in the population-representative German Environmental Survey for Children and Adolescents 2014-2017 (GerES V). The two NMP metabolites 5-hydroxy-N-methyl-2-pyrrolidone (5-HNMP) and 2-hydroxy-N-methylsuccinimide (2-HMSI) could be detected and quantified in all urine samples, and the two NEP metabolites 5-hydroxy-N-ethylpyrrolidone (5-HNEP) and 2-hydroxy-N-ethylsuccinimide (2-HESI) in 32% and 87% of the urine samples. Geometric mean concentrations were 103.1 (my)g/L (88.21 (my)g/gcreatinine) for the sum of NMP metabolites and 11.86 Ìg/L (10.15 (my)g/gcreatinine) for the sum of NEP metabolites, thus remaining below the current health-based human biomonitoring values. For NMP, highest exposure was found in young children, but exposure pathways could not be revealed. Exposure to NEP was highest in adolescents and participants with low socio-economic status or migration background. Associations to usage of personal care products suggested the choice of products to have a distinct impact on NEP exposure. The presented data can be used by the German Human Biomonitoring Commission to derive new reference values (RV95) for NMP and NEP for children and adolescents in Germany. This will facilitate to recognise changing exposure levels in this population group in Germany. © 2020 The Author(s).Veröffentlichung Metabolites of 4-methylbenzylidene camphor (4-MBC), butylated hydroxytoluene (BHT), and tris(2-ethylhexyl) trimellitate (TOTM) in urine of children and adolescents in Germany - human biomonitoring results of the German Environmental Survey GerES V (2014-2017)(2021) Daniels, Anja; Kolossa-Gehring, Marike; Murawski, Aline; Rucic, Enrico; Schmied-Tobies, Maria Irene Hilde; Schwedler, GerdaThe UV filter 4-methylbenzylidene camphor (4-MBC), used in cosmetics, the antioxidant butylated hydroxytoluene (BHT), used inter alia as a food additive and in cosmetics, and the plasticizer tris(2-ethylhexyl) trimellitate (TOTM), used mainly in medical devices as substitute for di-(2-ethylhexyl) phthalate (DEHP), are suspected to have endocrine disrupting effects. Human biomonitoring methods that allow for assessing the internal exposure of the general population to these substances were recently developed in a German cooperation to enhance the use of human biomonitoring. First-morning void urine samples from 3- to 17-year-old children and adolescents living in Germany were analysed for metabolites of 4-MBC (N = 447), BHT (N = 2091), and TOTM (N = 431) in the population-representative German Environmental Survey on Children and Adolescents 2014-2017 (GerES V). 4-MBC metabolites were found in quantifiable amounts only in single cases and exposure levels remained well below health-based guidance values. In contrast, ubiquitous exposure to BHT became evident with a geometric mean (GM) urinary concentration of the metabolite BHT acid of 2.346 (my)g/L (1.989 (my)g/gcreatinine) and a maximum concentration of 248 (my)g/L (269 (my)g/gcrea). The highest GM concentration was found in young children aged 3-5 years, yet no specific sources of exposure could be identified. Also, TOTM metabolites were found in quantifiable amounts only in very few samples. None of these findings could be related to previous hospital treatment or exposure via house dust. The presented results will be the basis to derive reference values for exposure of children and adolescents in Germany to BHT and will facilitate to identify changing exposure levels in the general population. © 2020 The Author(s).
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