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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 Environmental health surveillance in a future European health information system(2018) Joas, Anke; David, Madlen; Schöpel, Miriam; Kolossa-Gehring, Marike; Schwedler, GerdaBackground To date Health information (HI) in the European Union does not comprise indicators or other information related to impacts of hazardous chemicals in consumer products, food, drinking water or air on the health status of the population. Therefore, we inventorised and evaluated the potential of environmental health surveillance and research data sources in the European population to provide HBM-based indicators of internal human exposure and health impact of relevant chemicals. Methods We established an up-dated inventory of European cross-sectional Human Biomonitoring (HBM) surveys and of birth cohorts, and compared chemicals and chemical groups addressed by HBM with indicators and health end points collected via European Core Health Indicators (ECHI), in birth registries, as well as in environmental and food data bases and health registries to see on how data collection could be aligned. Finally, we investigated study designs of HBM survey and health examination surveys for potential synergies. Results The inventory covers a total of 11 European cross-sectional national programmes and a large number of birth cohorts and includes information on study population, age groups, covered substances, sampled matrices, and frequency. The comparison of data collections shows that there are many overlaps between environmental chemicals with environmental and health reporting. HBM data could be linked with ECHI indicators for work-related risks, body mass index (BMI), and low birth weight, with perinatal disease, neurologic disorders, and some chronic diseases, or with data bases for e.g. indoor air, food, or consumer products. Existing initiatives to link data collections at European Environment Agency (EEA) and Joint Research Center (JRC) or at World Health Organization (WHO) are good options to further develop linkage of HBM with exposures sources and health end points. Conclusions There is potential to use HBM based information in a number of public health policies, and this would help to align reporting to international commitments. Environmental health surveillance based on HBM and HBM-based indicators, is an excellent tool to inform public health policies about risks from environmental chemicals, and the EU health information system would benefit from additional HBM-based indicators for monitoring exposure burden from environmental chemicals. Considerable efforts are needed to align and establish routine data collections and to develop a surveillance system and indicators which may inform public health policies. © The Author(s). 2018Veröffentlichung Mothers and children are related, even in exposure to chemicals present in common consumer products(2019) Koppen, Gudrun; Govarts, Eva; Kolossa-Gehring, Marike; Vanermen, Guido; Schwedler, GerdaBackground Phthalates, bisphenol A (BPA) and triclosan (TCS) are detectable in the vast majority of people. Most humans are continuously exposed to these chemicals due to their presence in food or in everyday consumer products. The measurement of these compounds in family members may help to explore the impact of major lifestyle factors on exposure. Mothers and (young) children are especially interesting to study, as they mostly share considerable parts of daily life together. Materials and methods Phthalate metabolites, bisphenol A (BPA) and triclosan (TCS) were measured in first morning void urine, collected in mother-child pairs (n=129) on the same day. The mothers (27-45y) and their children (6-11y) were recruited in the Brussels agglomeration and rural areas of Belgium in the context of the European COPHES-DEMOCOPHES human biomonitoring project. Face-to-face questionnaires gathered information on major exposure sources and lifestyle factors. Exposure determinants were assessed by multiple linear regression analysis. Results The investigated compounds were detectable in nearly all mothers (92.8-100%) and all children (95.2-100%). The range (P90 vs. P10) of differences in urinary concentrations within each age group was for most compounds around 10-20 fold, and was very high for TCS up to 35 and 350-fold in children and mothers respectively. Some participants exceeded the tolerable daily intake guidelines as far as they were available from the European Food Safety Authority (EFSA). Overall, for BPA, the urinary concentrations were similar among both age groups. Most urinary phthalate metabolites were higher in children compared to the mothers, except for monoethyl phthalate (MEP). TCS levels were generally higher in the mothers. Despite the difference in mothers' and children's urinary concentrations, the creatinine-corrected levels were correlated for all biomarkers (Spearman rank r=0.32 to 0.66, p<0.001). Furthermore, for phthalates, similar home and lifestyle factors were associated with the urinary concentrations in both age groups: home renovation during last two years or redecoration during the last year for di-ethyl phthalate (DEP); PVC in home for di-n-butyl phthalate (DnBP), di-iso-butyl phthalate (DiBP) and butyl benzyl phthalate (BBzP), and personal care products use for DiBP and DnBP. Based on questionnaire information on general food type consumption patterns, the exposure variability could not be explained. However, comparing the phthalate intake from the current study with earlier assessed Belgian food intake calculations for both ages, food in general was estimated to be the major intake source for di-ethyl hexyl phthalate (DEHP), with diminishing importance for BBzP, DiBP and DnBP. Conclusion Our results confirm, that children and their mothers, sharing diets and home environments, also share exposure in common consumer products related chemicals. By collecting morning urine levels on the same day, and using basic questionnaires, suspected exposure routes could be unraveled.Veröffentlichung A pilot study on the feasibility of European harmonized Human Biomonitoring: Strategies towards a common approach, challenges and opportunities(2015) Casteleyn, Ludwine; Dumez, Birgit; Becker, Kerstin; Den Hond, Elly; Schoeters, Greet; Castaño, Argelia; Koch, Holger Martin; Angerer, Jürgen; Esteban, Marta; Exley, Karen; Sepai, Ovnair; Bloemen, Louis; Fiddicke, Ulrike; Horvath, Milena; Knudsen, Lisbeth E.; Joas, Anke; Joas, Reinhard; Biot, Pierre; Koppen, C.; Dewolf, M.-C.; Katsonouri, Andromachi; Hadjipanayis, Adamos; Cerna, Milena; Krskova, A.; Kolossa-Gehring, Marike; Nielsen, Jeanette K.S.; Jensen, J.F.; Rudnai, Peter; Közepesy, S.; Mulcahy, M.F.R.; Mannion, R.; Gutleb, Arno C.; Fischer, M.E.; Ligocka, Danuta; Jakubowski, M.; Reis, M.Fátima; Namorado, S.; Lupsa, Ioana-Rodica; Schwedler, Gerda; Gurzau, Anca ElenaIn 2004theEuropeanCommissionandMemberStatesinitiatedactivitiestowardsaharmonizedap-
proach forHumanBiomonitoringsurveysthroughoutEurope.Themainobjectivewastosustainen-
vironmental healthpolicybybuildingacoherentandsustainableframeworkandbyincreasingthe
comparability ofdataacrosscountries.Apilotstudy totestcommonguidelinesforsettingupsurveys
wasconsideredakeystepinthisprocess.Throughabottom-upapproachthatincludedallstakeholders,
a jointstudyprotocolwaselaborated.
FromSeptember2011tillFebruary2012,17Europeancountriescollecteddatafrom1844mother-
child pairsintheframeofDEMOnstrationofastudytoCoordinateandPerformHumanBiomonitoring
on aEuropeanScale(DEMOCOPHES). Mercury inhairandurinarycadmiumandcotininewereselected
as biomarkersofexposurecoveredbysufficient analyticalexperience.PhthalatemetabolitesandBi-
sphenol Ainurinewereaddedtotakeintoaccountincreasingpublicandpoliticalawarenessfor
emerging typesofcontaminantsandtotestlessadvancedmarkers/markerscoveredbylessanalytical
experience.Extensiveeffortstowardschemo-analyticalcomparabilitywereincluded.
The pilotstudyshowed thatcommonapproachescanbefoundinacontextofconsiderablediffer-
ences withrespecttoexperienceandexpertize,socio-culturalbackground,economicsituationandna-
tional priorities.ItalsoevidencedthatcomparableHumanBiomonitoringresultscanbeobtainedinsuch
context.AEuropeannetworkwasbuilt,exchanging information,expertise andexperiences,andpro-
viding trainingonallaspectsofasurvey.Akeychallengewas finding therightbalancebetweenarigid
structure allowingmaximalcomparabilityanda flexibleapproachincreasingfeasibilityandcapacity
building. NextstepsinEuropeanharmonizationinHumanBiomonitoringsurveysincludetheestab-
lishment ofajointprocessforprioritizationofsubstancestocoverandbiomarkerstodevelop,linking
biomonitoring surveyswithhealthexaminationsurveysandwithresearch,andcopingwiththediverse
implementations ofEUregulationsandinternationalguidelineswithrespecttoethicsandprivacy.
©2014ElsevierInc.Allrightsreserved.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 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 Phthalate metabolites in urine of children and adolescents in Germany. Human biomonitoring results of the German Environmental Survey GerES V, 2014-2017(2020) Conrad, André; Daniels, Anja; Kolossa-Gehring, Marike; Lange, Rosa; Rucic, Enrico; Schmied-Tobies, Maria Irene Hilde; Schulz, Christine; Schwedler, GerdaDuring the population representative German Environmental Survey of Children and Adolescents (GerES V, 2014-2017) 2256 first-morning void urine samples from 3 to 17 years old children and adolescents were analysed for 21 metabolites of 11 different phthalates (di-methyl phthalate (DMP), di-ethyl phthalate (DEP), butylbenzyl phthalate (BBzP), di-iso-butyl phthalate (DiBP), di-n-butyl phthalate (DnBP), di-cyclohexyl phthalate (DCHP), di-n-pentyl phthalate (DnPeP), di-(2-ethylhexyl) phthalate (DEHP), di-iso-nonyl phthalate (DiNP), di-iso-decyl phthalate (DiDP) and di-n-octyl phthalate (DnOP)). Metabolites of DMP, DEP, BBzP, DiBP, DnBP, DEHP, DiNP and DiDP were found in 97-100% of the participants, DCHP and DnPeP in 6%, and DnOP in none of the urine samples. Geometric means (GM) were highest for metabolites of DiBP (MiBP: 26.1 my g/L), DEP (MEP: 25.8 my g/L), DnBP (MnBP: 20.9 my g/L), and DEHP (cx-MEPP: 11.9 my g/L). For all phthalates but DEP, GMs were consistently higher in the 3-5 years old children than in the 14-17 years old adolescents. For DEHP, the age differences were most pronounced. All detectable phthalate biomarker concentrations were positively associated with the levels of the respective phthalate in house dust. In GerES V we found considerably lower phthalate biomarker levels than in the preceding GerES IV (2003-2006). GMs of biomarker levels in GerES V were only 18% (BBzP), 23% (MnBP), 23% (DEHP), 29% (MiBP) and 57% (DiNP) of those measured a decade earlier in GerES IV. However, some children and adolescents still exceeded health-based guidance values in the current GerES V. 0.38% of the participants had levels of DnBP, 0.08% levels of DEHP and 0.007% levels of DiNP which were higher than the respective health-based guidance values. Accordingly, for these persons an impact on health cannot be excluded with sufficient certainty. The ongoing and substantial exposure of vulnerable children and adolescents to many phthalates confirms the need of a continued monitoring of established phthalates, whether regulated or not, as well as of potential substitutes. With this biomonitoring approach we provide a picture of current individual and cumulative exposure developments and body burdens to phthalates, thus providing support for timely and effective chemicals policies and legislation. © 2020 The Authors. Published by Elsevier GmbH.Veröffentlichung 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 Interpreting biomarker data from the COPHES-DEMOCOPHES twin projects: Using lifestyle and environmental data to understand biomarker differences among countries(2013) Den Hond, Elly; Govarts, Eva; Koppen, Gudrun; Willems, Hanny; Joas, Reinhard; Casteleyn, Ludwine; Joas, Anke; Biot, Pierre; Aerts, Dominique; Angerer, Jürgen; Berglund, Marika; Bloemen, Louis; Castaño, Argelia; Fiddicke, Ulrike; Crettaz, Pierre; Esteban, Marta; Exley, Karen; Fabianova, Eleonora; Fischer, Marc; Gutleb, Arno Christian; Hadjipanayis, Adamos; Halzlova, Katarina; Horvat, Milena; Jakubowski, Marek; Katsonouri, Andromachi; Kolossa-Gehring, Marike; Koch, Holger; Krskova, Andrea; Lehmann, Andreas; Ligocka, Danuta; Lupsa, Ioana-Rodica; Mazej, Darja; Mulcahy, Maurice; Namorado, Sónia; Nielsen, Jeanette; Schwedler, GerdaIn 2011 and 2012, the COPHES/DEMOCOPHES twin projects performed a first ever harmonized human biomonitoring survey in 17 European countries. In more than 1800 mother-child pairs, cadmium, cotinine and certain phthalate metabolites were measured in urine, and total mercury in hair samples. The presentation provides an overview of the analyses that studied whether it was feasible to interpret the observed differences in biomarker values among different countries, using external databases on environmental quality and lifestyle.
Despite the fact that harmonised biomonitoring data was available from 17 different European countries, the assessment was hampered by a lack of consistent data on lifestyle and environmental quality. This implied that most analyses could only be performed for about half to two thirds of the participating countries. Nonetheless, it was feasible to relate aggregated fish consumption data to mercury in hair, to relate the strength of anti-smoking legislation to urinary cotinine levels, and to find a borderline significant relationship between cadmium levels in air or food and urinary cadmium levels across DEMOCOPHES countries. However, the challenge to integrate environmental exposure and lifestyle data with biomarker data is to have data available on a similar geographical resolution and therefore remains a pitfall for human biomonitoring to achieve its true potential for evidence-based policy making.
With many thanks to the COPHES consortium funded by DG RTD under FP7 and DEMOCOPHES co-funded under Life+, as well as the Ministries of the DEMOCOPHES countries, for the support. www.eu-hbm.infoRoel Smolders, et al.: Interpreting biomarker data from the COPHES-DEMOCOPHES twin projects: Using lifestyle and environmental data to understand biomarker differences among countries. In: Abstracts / The 9thInternational Symposium on Biological Monitoring in Occupational and Environmental Health. 2013, Manchester, S. 33