Person: Conrad, André
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Conrad
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André
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Veröffentlichung Long-term monitoring of mercury in young German adults: Time trend analyses from the German Environmental Specimen Bank, 1995-2018(2022) Bartel-Steinbach, Martina; Lermen, Dominik; Conrad, André; Gwinner, Frederik; Kolossa-Gehring, Marike; Weber, TillAs highlighted in the Minamata Convention, Mercury (Hg) in its various forms poses a substantial risk to human health and the environment. The health relevance of Hg is also recognized by the European Human Biomonitoring Initiative (HBM4EU), which classifies Hg as a priority substance, since considerable knowledge and data gaps on Hg exposure levels and their changes over time still exist in Europe. The German Environmental Specimen Bank (German ESB) provides valuable policy relevant data and long-term trends of substance exposure on a national level for international comparison and evaluation. In this study we analysed data of the German ESB on Hg exposure of young adults aged 20 to 29 including data on urinary Hg levels from 1995 to 2018 and whole blood Hg levels from 2001 to 2010. Results show a clear decrease in both, about 86% in urine total daily Hg excretion from 1995 (0.76 (micro)g/L) to 2018 (0.11 (micro)g/L) (n = 10,069) and about 57% in blood concentrations of Hg from 2001 (1.76 (micro)g/L) to 2010 (0.77 (micro)g/L) (n = 4085). Over the investigated timeframe only a few values exceeded the toxicologically derived health based guidance value HBM I for blood and urine, with these exceedances decreasing over time in line with the general trend. The factors mostly influencing Hg excretion identified in this study are dental amalgam as well as fish and seafood consumption. Besides other factors (e.g. age and sex), also airborne Hg exposure appears to be a low but evident influencing factor in Germany. Although a considerable decrease in internal Hg exposure is recognized in the last decades, the current low-level exposure may cause adverse health effects especially to vulnerable groups such as pregnant women and children. To further elucidate and evaluate current exposure sources and to reduce human exposure to Hg, continuous environmental and human biomonitoring is needed. © 2022 The Authors.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 Per- and polyfluoroalkyl substances in blood plasma - Results of the German Environmental Survey for children and adolescents 2014-2017 (GerES V)(2020) Conrad, André; Duffek, Anja; Kolossa-Gehring, Marike; Lange, Rosa; Rucic, Enrico; Schulte, Christoph; Wellmitz, JörgThe 5th cycle of the German Environmental Survey (GerES V) investigated the internal human exposure of children and adolescents aged 3-17 years in Germany to per- and polyfluoroalkyl substances (PFAS). The fieldwork of the population-representative GerES V was performed from 2014 to 2017. In total, 1109 blood plasma samples were analysed for 12 PFAS including perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), and perfluorohexane sulfonic acid (PFHxS). PFOS was quantified in all and PFOA in almost all samples, demonstrating ubiquitous exposure. The highest geometric mean concentrations measured were 2.49 ng/mL for PFOS, followed by PFOA (1.12 ng/mL) and PFHxS (0.36 ng/mL), while concentrations of other PFAS were found in much lower concentrations. The 95th percentile levels of PFOS and PFOA were 6.00 and 3.24 ng/mL, respectively. The results document a still considerable exposure of the young generation to the phased out chemicals PFOS and PFOA. The observed exposure levels vary substantially between individuals and might be due to different multiple sources. The relative contribution of various exposure parameters such as diet or the specific use of consumer products need to be further explored. Although additional investigations on the time trend of human exposure are warranted, GerES V underlines the need for an effective and sustainable regulation of PFAS as a whole. Source: © 2020 Elsevier GmbHVeröffentlichung Developing human biomonitoring as a 21st century toolbox within the European exposure science strategy 2020-2030(2022) Jeddi, Maryam Zare; Conrad, André; Hopf, Nancy B.; Louro, Henriqueta; Kolossa-Gehring, MarikeHuman biomonitoring (HBM) is a crucial approach for exposure assessment, as emphasised in the European Commissionâ€Ìs Chemicals Strategy for Sustainability (CSS). HBM can help to improve chemical policies in five major key areas: (1) assessing internal and aggregate exposure in different target populations; 2) assessing exposure to chemicals across life stages; (3) assessing combined exposure to multiple chemicals (mixtures); (4) bridging regulatory silos on aggregate exposure; and (5) enhancing the effectiveness of risk management measures. In this strategy paper we propose a vision and a strategy for the use of HBM in chemical regulations and public health policy in Europe and beyond. We outline six strategic objectives and a roadmap to further strengthen HBM approaches and increase their implementation in the regulatory risk assessment of chemicals to enhance our understanding of exposure and health impacts, enabling timely and targeted policy interventions and risk management. These strategic objectives are: 1) further development of sampling strategies and sample preparation; 2) further development of chemical-analytical HBM methods; 3) improving harmonisation throughout the HBM research life cycle; 4) further development of quality control / quality assurance throughout the HBM research life cycle; 5) obtain sustained funding and reinforcement by legislation; and 6) extend target-specific communication with scientists, policymakers, citizens and other stakeholders. HBM approaches are essential in risk assessment to address scientific, regulatory and societal challenges. HBM requires full and strong support from the scientific and regulatory domain to reach its full potential in public and occupational health assessment and in regulatory decision-making. © 2022 The AuthorsVeröffentlichung Glyphosate and aminomethylphosphonic acid (AMPA) in urine of children and adolescents in Germany - Human biomonitoring results of the German Environmental Survey 2014-2017 (GerES V)(2021) Conrad, André; Kolossa-Gehring, Marike; Lemke, Nora; Murawski, Aline; Schmied-Tobies, Maria Irene HildeSince the 1970s, glyphosate has become the most used herbicide of the world. The general population is ubiquitously exposed to glyphosate. Its long-term toxicity, carcinogenic potential and other health effects are controversially discussed. Even though the possible health impacts of glyphosate are of global concern, no population-wide monitoring of glyphosate was done yet. This study presents the worldwide first population-representative data on glyphosate and its metabolite aminomethylphosphonic acid (AMPA) for children and adolescents. 2144 first-morning void urine samples of 3-17-year-old children and adolescents living in Germany were analysed for concentrations of glyphosate and AMPA in the German Environmental Survey for Children and Adolescents 2014-2017 (GerES V). In 52 % of the samples (46 % for AMPA) the urinary glyphosate concentrations were above the limit of quantification of 0.1 (microgramm)/L. The geometric mean concentrations were 0.107 (microgramm)/L (0.090 (microgramm)/gcreatinine) for glyphosate and 0.100 (microgramm)/L (0.085 (microgramm)/gcreatinine) for AMPA. No clear association between exposure to glyphosate or AMPA and vegetarian diet or consumption of cereals, pulses, or vegetables could be identified. The low quantification rate and the 95th percentiles for glyphosate and AMPA of around 0.5 (microgramm)/L demonstrate an overall low exposure of the young population in Germany. Quelle: © Elsevier 2021Veröffentlichung Metabolites of the substitute plasticiser Di-(2-ethylhexyl) terephthalate (DEHTP) in urine of children and adolescents investigated in the German Environmental Survey GerES V, 2014-2017(2020) Conrad, André; Koch, Holger Martin; Kolossa-Gehring, Marike; Rucic, Enrico; Schmied-Tobies, Maria Irene Hilde; Schwedler, GerdaMetabolites of di-(2-ethylhexyl) terephthalate (DEHTP), a substitute for ortho-based phthalate plasticisers like di-(2-ethylhexyl) phthalate (DEHP), were analysed in 2112 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. The major metabolite 5cx-MEPTP was detected in all urine samples with a geometric mean (GM) of 7.39 (my)g/L, with highest levels in the mg/L range. The GM for the other metabolites were 0.55 (my)g/L for 5OH-MEHTP, 0.54 (my)g/L for 5oxo-MEHTP and below the limit of quantification (LOQ) for 2cx-MMHTP. As already observed for other plasticisers and their substitutes, the youngest children (3-5 years) had 2-2.5-fold higher urinary DEHTP metabolite levels compared to 14-17 years old adolescents. High urinary levels of DEHTP metabolites were associated with high DEHTP concentrations in house dust. None of the samples analysed exceeded the toxicologically derived German human biomonitoring guidance value (HBM-I-Value) of 1.8 mg/L for 5cx-MEPTP. Comparison with DEHTP levels reported in other HBM studies worldwide confirmed a widespread exposure of children, adolescents and adults, with considerably higher exposures (2.6-7 fold) reported in the United States. In GerES V, exposure data for 12 different phthalates and the phthalate substitute DINCH were generated as well. Together with the data for DEHTP presented in this manuscript, GerES V allows a current and comprehensive overview on the concurrent exposure of German children and adolescents to common plasticisers. Further evaluation of aggregate exposure characteristics shall support efforts to reduce chemical hazard burden from plasticisers in Germany and beyond. © 2020 The Author(s).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 Time course of phthalate cumulative risks to male developmental health over a 27-year period: Biomonitoring samples of the German Environmental Specimen Bank(2020) Apel, Petra; Kortenkamp, Andreas; Conrad, André; Koch, Holger Martin; Kolossa-Gehring, Marike; Rüther, MariaIn several human biomonitoring surveys, changes in the usage patterns of phthalates have come to light, but their influence on the risks associated with combined exposures is insufficiently understood. Based on the largest study to date, the 27-year survey of urinary phthalate metabolite levels in 24-hour urine samples from the German Environmental Specimen Bank, we present a deep analysis of changing phthalate exposures on mixture risks. This analysis adopts the Hazard Index (HI) approach based on the five phthalates DBP, DIBP, BBP, DEHP and DINP. Calculations of the hazard index for each study participant included updated phthalate reference doses for anti-androgenicity (RfDAAs) that take account of new evidence of phthalates' developmental toxicity. The Maximum Cumulative Ratio (MCR) approach was used to establish whether a subjectâ€Ìs combined exposure was dominated by one phthalate or was influenced by several phthalates simultaneously. Generally, over the years there was a shift towards lower HIs and higher MCRs, reflecting an increased complexity of the combined exposures. The decade from 1988 to about 1999 was characterised by rather high HIs of between 3 and 7 (95th percentile) which were driven by exposure to DBP and DEHP, often exceeding their single acceptable exposures. Traditional single phthalate risk assessments would have underestimated these risks by up to 50%. From 2006 onwards, no study participant experienced exposures above acceptable levels for a single phthalate, but combined exposures were still in excess of HI = 1. From 2011 onwards most individuals stayed below HI = 1. In interpreting these results, we caution against the use of HI = 1 as an acceptable limit and develop proposals for improved and more realistic mixture risk assessments that take account of co-exposures to other anti-androgenic substances also capable of disrupting the male reproductive system. From this perspective, we regard HIs between 0.1 and 0.2 as more appropriate for evaluating combined phthalate exposures. Assessed against lowered HIs of 0.1 - 0.2, the combined phthalate exposures of most study participants exceeded acceptable levels in all study years, including 2015. Continued monitoring efforts for phthalate combinations are required to provide the basis for appropriate risk management measures. © 2020 The Authors.Veröffentlichung Sensitive and selective quantification of glyphosate and aminomethylphosphonic acid (AMPA) in urine of the general population by gas chromatography-tandem mass spectrometry(2020) Connolly, Alison; Koslitz, Stephan; Bury, Daniel; Conrad, André; Kolossa-Gehring, MarikeGlyphosate is the highest volume herbicide used worldwide, and its main biodegradation product is aminomethylphosphonic acid (AMPA), both are listed as priority substances in the Human Biomonitoring for Europe (HBM4EU) initiative which aims at improving policy by filling knowledge gaps by targeted research. The objective of the current study was to advance the sensitivity of an existing gas chromatography-tandem mass spectrometry analytical method to measure environmental population exposures. A 50% lower limit of quantification of 0.05 (my)g/L was achieved for both analytes by slight modifications in sample work-up, and use of another isotope labelled internal standard. In a pilot study, 41 urine samples from the general German population were analysed, of which glyphosate and AMPA could be quantified in 66% and 90% of the samples respectively, which is sufficient to reliably describe distributions of urinary concentrations in the non-occupationally exposed population. © 2020 The AuthorsVeröffentlichung 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.com