The number of anthropogenic chemicals, manufactured, by-products, metabolites and abiotically formed transformation products, counts to hundreds of thousands, at present. Thus, humans and wildlife are exposed to complex mixtures, never one chemical at a time and rarely with only one dominating effect. Hence there is an urgent need to develop strategies on how exposure to multiple hazardous chemicals and the combination of their effects can be assessed. A workshop, "Advancing the Assessment of Chemical Mixtures and their Risks for Human Health and the Environment" was organized in May 2018 together with Joint Research Center in Ispra, EU-funded research projects and Commission Services and relevant EU agencies. This forum for researchers and policy-makers was created to discuss and identify gaps in risk assessment and governance of chemical mixtures as well as to discuss state of the art science and future research needs. Based on the presentations and discussions at this workshop we want to bring forward the following Key Messages: - We are at a turning point: multiple exposures and their combined effects require better management to protect public health and the environment from hazardous chemical mixtures.<BR> - Regulatory initiatives should be launched to investigate the opportunities for all relevant regulatory frameworks to include prospective mixture risk assessment and consider combined exposures to (real-life) chemical mixtures to humans and wildlife, across sectors.<BR> - Precautionary approaches and intermediate measures (e.g. Mixture Assessment Factor) can already be applied, although, definitive mixture risk assessments cannot be routinely conducted due to significant knowledge and data gaps. <BR> - A European strategy needs to be set, through stakeholder engagement, for the governance of combined exposure to multiple chemicals and mixtures. The strategy would include research aimed at scientific advancement in mechanistic understanding and modelling techniques, as well as research to address regulatory and policy needs. Without such a clear strategy, specific objectives and common priorities, research, and policies to address mixtures will likely remain scattered and insufficient. © 2019 The Authors. Published by Elsevier Ltd.
A 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.
Das Projekt "Teilprojekt 4: Atemwegsepithel und dendritische Zellen" wird vom Umweltbundesamt gefördert und von Forschungszentrum Borstel-Leibniz-Zentrum für Medizin und Biowissenschaften durchgeführt. Ziel des Gesamtvorhabens ist es, valide Kriterien zur Abschätzung der humantoxischen Wirkung unterschiedlicher synthetischer CBNP-Modifikationen auf verschiedene funktionelle Bereiche gesunder und vorgeschädigter Lungen zu etablieren. Teilprojekt 4 untersucht dazu das Atemwegsepithel von Bronchiolen sowie dendritische Zellen und liefert einerseits einen Beitrag, die Langzeiteffekte der verschiedenen modifizierten CBNP zu untersuchen und andererseits abzuschätzen, ob vorgeschädigte Lungen bereits bei geringerer Exposition mit CBNP nanopartikelspezifische Veränderungen zeigen. In einem weiteren Projektteil soll festgestellt werden, ob eine Adsorption von Allergenen an CBNP zu einer Potenzierung der Allergenwirkung führt. Die Einzelheiten hierzu sind in der beigefügten Vorhabenbeschreibung erläutert. Die in Arbeitspaket 1 hergestellten CBNP werden in verschiedenen in vivo-Modellen eingesetzt, um die Wirkung der CBNP auf die distalen Atemwege (Bronchiolen) der Lunge zu untersuchen. Hierbei wird zwischen einmaliger Exposition vorgeschädigter Lungen und multipler Exposition bei sowohl gesunden als auch vorgeschädigten Lungen unterschieden. Die Analyse der Bronchiolen umfasst die Regulation von Enzymen xenobiotischer Stoffwechselwege, die Bildung reaktiver Sauerstoffspezies, das Auftreten von Nekrose und Apoptose sowie die Induktion pro-inflammatorischer und pro-fibrotischer Zytokine. Im zweiten Projektteil wird mit Hilfe humaner dendritischer Zellen (DC) untersucht, inwieweit die Beladung und Kopplung von CBNP mit verschiedenen Allergenen die toxikologischen und immunologischen Eigenschaften der CBNP und der Allergene beeinflusst. Mit zell- und molekularbiologischen Methoden werden dabei insbesondere das Auftreten von Nekrose und Apoptose, die Induktion proinflammatorischer Zytokine sowie die DC-/T-Zellwechselwirkung bestimmt. Die Einzelheiten des Arbeitsplanes sind in der beigefügten Vorhabenbeschreibung erläutert.
Das Forschungsvorhaben soll Grundlagen und Empfehlungen erarbeiten, um das neue Querschnittsthema Umweltgerechtigkeit im kommunalen Handeln zu implementieren. Folgende Fragen stehen dabei im Mittelpunkt: Wie lässt sich die integrierte Betrachtung von Umwelt, Gesundheit, Sozialem als Planungs- und Entscheidungsgrundlage in der kommunalen Praxis verankern? Welche Instrumente sind geeignet, der ungleichen sozialräumlichen Verteilung von gesundheitsrelevanten Umweltbelastungen und von Umweltressourcen entgegenzuwirken?, Welche Ergebnisse werden bei der modellhaften Erprobung und Validierung von Instrumenten, Verfahren und Maßnahmen zur Schaffung von mehr Umweltgerechtigkeit in ausgesuchten Kommunen erzielt?, Welche Handlungsempfehlungen lassen sich für die Implementierung des Themas Umweltgerechtigkeit in den Kommunen ableiten?<BR>Quelle: www.umweltbundesamt.de<BR>
Das Projekt "The Human Early-Life Exposome novel tools for integrating early-life environmental exposures and child health across Europe (HELIX)" wird vom Umweltbundesamt gefördert und von Fundacio Centre de Recerca en Epidemiologia Ambiental - Creal durchgeführt. The aim of HELIX is to exploit novel tools and methods (remote sensing/GIS-based spatial methods, omics-based approaches, biomarkers of exposure, exposure devices and models, statistical tools for combined exposures, novel study designs, and burden of disease methodologies), to characterise early-life exposure to a wide range of environmental hazards, and integrate and link these with data on major child health outcomes (growth and obesity, neurodevelopment, immune system), thus developing an Early-Life Exposome approach. HELIX uses six existing, prospective birth cohort studies as the only realistic and feasible way to obtain the comprehensive, longitudinal, human data needed to build this early-life exposome. These cohorts have already collected large amounts of data as part of national and EU-funded projects. Results will be integrated with data from European cohorts (greater than 300,000 subjects) and registers, to estimate health impacts at the large European scale. HELIX will make a major contribution to the integrated exposure concept by developing an exposome toolkit and database that will: 1) measure a wide range of major chemical and physical environmental hazards in food, consumer products, water, air, noise, and the built environment, in pre and postnatal periods; 2) integrate data on individual, temporal, and toxicokinetic variability, and on multiple exposures, which will greatly reduce uncertainty in exposure estimates; 3) determine molecular profiles and biological pathways associated with multiple exposures using omics tools; 4) provide exposure-response estimates and thresholds for multiple exposures and child health; and 5) estimate the burden of childhood disease in Europe due to multiple environmental exposures. This integration of the chemical, physical and molecular environment during critical early-life periods will lead to major improvements in health risk and impact assessments and thus to improved prevention strategies for vulnerable populations.
Das Projekt "Developmental effects of environment on reproductive health (DEER)" wird vom Umweltbundesamt gefördert und von Turun Yliopisto durchgeführt. Objective: The multidisciplinary research teams in this consortium have played lead roles in establishing that fetal and childhood periods are vulnerable to environmental disruption leading to common reproductive disorders. This proposal will investigate: (1) connections between normal/abnormal perinatal reproductive development and maturation of reproductive function at puberty and in adulthood; (2) systemic gene-environment interactions underlying reproductive disorders taking account of genetic susceptibility, multiple exposures (e.g. mixtures of environmental chemicals) and their timing (perinatal, peripubertal, adult); (3) connection between perinatal reproductive development and later obesity/metabolic disorders. To achieve this we will utilize large cohorts generated in previous EU projects and collect new data from these on reproductive maturation and adult function. Existing genomic and proteomics data, exposure data for greater than 100 potentially toxic environmental chemicals, lifestyle, dietary and medical history information will be analysed using integrative systems biology approaches to pinpoint critical (interacting) factors influencing development.
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