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New insights into the regulation of cyp3a65 expression in transgenic tg(cyp3a65:GFP) zebrafish embryos
No full textInternational audienceFacing the need for alternative models allowing assessment of metabolic-endocrine disrupting chemicals (MDCs), especially in poorly investigated tissues such as the intestine, we recently developed a transgenic zebrafish embryo in vivo model, tg(cyp3a65:GFP), expressing the Green Fluorescent Protein (GFP) under the control of the zebrafish cyp3a65 promoter, ortholog of human cyp3a4, a gene coding for a key enzyme of intestinal xenobiotic and endobiotic metabolism. In this study, we aimed to better understand the regulation of cyp3a65 expression by zfPXR, zfAhR2, and zfGR zebrafish orthologs of well-known human xenosensors PXR and AhR, and steroid nuclear receptor GR. For this purpose, we performed zebrafish embryo tg(cyp3a65:GFP) (co)exposures to a variety of agonists (clotrimazole, TCDD, fluticasone propionate) and antagonists (econazole nitrate, CH223181, RU486), which were characterized using in vitro zebrafish reporter gene assays. We show that zfPXR and zfAhR2 cooperate to positively regulate cyp3a65 expression, involving different transcription factors and their interaction. Moreover, for the first time, we show that zfGR agonist strongly inhibits the constitutive expression of cyp3a65, and we hypothesized the possible involvement of the transcriptional factor zfHNF4α. These results provide a better understanding of the regulation of zebrafish cyp3a65 expression, highlighting the complex interaction between different transcription factors, which is consistent with the multiple regulatory pathways of cyp3a4 in humans. Our data support the idea that this gene is a target of multiple contaminants capable of interacting with zfPXR, zfAhR2 and zfGR and highlights the relevance of the tg(cyp3a65:GFP) model to screen chemicals potentially acting as MDCs based on their modes of action at the intestinal level, which could be relevant for hazard assessment of chemicals for human and environmental health
Spatial Decision Support System for Multi-Risk Assessment of Post-Mining Hazards
No full textInternational audienceThe closure of coal and lignite mines has the potential to result in long-term environmental risks and socio-economic issues. To solve these, this research aims to improve the hazard assessment and risk management of former mining regions in a European project funded by the Research Fund for Coal and Steel. A multidisciplinary approach integrated historic, geological, topographical, environmental, and socio-economic data to create a methodology to support stakeholders at different decision-making levels in risk assessment and possible mitigation. For this purpose, a spatial decision support system was developed using a multi-hazard, multi-risk methodology. The individual hazards (post-mining, natural, and technical) are weighted using expert knowledge, their interaction analyzed, and then combined into a spatial multi-hazard index. Together with the other risk factors of social vulnerability and exposure, a comprehensive spatial risk map can be created automatically for individual regions using open-source components. In addition, GIS and statistical tools enable further analysis and visualization for decision-making by the relevant stakeholders. The methodology was validated through the examination of a first case study conducted in the post-mining region of the southern Ruhr area in Germany. The methodology and tool created significant results in two test scenarios, and will be tested and improved using other European mining sites during the next stages of the project
Human health risk assessment of lead exposure from soil ingestion in a French pilot study: insights from the application of a new bioaccessibility approach
No full textInternational audienceDespite the consensus on the importance of considering the bioavailability of metal(loid)s by measuring their bioaccessibility when assessing exposure, integrating these parameters into risk calculations often involves proprietary approaches that lack adequate justification. This is the case with the in vitro unified bioaccessibility method (UBM), which is widely used in Europe to assess the bioaccessibility of metal(loid)s in the event of soil ingestion. This study proposes a comprehensive operational approach that incorporates bioaccessibility to refine human exposure and risk assessments. A pilot study of 45 Pb-contaminated soil samples collected in and around Paris highlighted the importance of carefully following soil preparation protocols. Specifically, sieving the soil to 250 μm without mechanical milling is recommended for determining both bioaccessible and total concentrations. A simplified test using dilute hydrochloric acid can predict the bioaccessibility of metal(loid)s in first-tier screening. This affordable, single-extraction method is easy to use in analytical laboratories and is both fast and reproducible. For second-tier validation studies, the UBM protocol should be applied to a limited number of samples. With the new approach, the relative bioavailability can be directly calculated using an in vivo/in vitro equation in the stomach compartment, thus, enabling UBM validation. The results of the pilot study demonstrated that to refine exposure assessments, adjusting chronic daily intake using relative bioavailability data was more effective than were classical approaches based on total concentrations. This method offers a promising perspective for stakeholders in managing polluted sites and soils
Main conclusions and perspectives from the collective scientific assessment of the effects of plant protection products on biodiversity and ecosystem services along the land–sea continuum in France and French overseas territories
No full textInternational audiencePreservation of biodiversity and ecosystem services is critical for sustainable development and human well-being. However, an unprecedented erosion of biodiversity is observed and the use of plant protection products (PPP) has been identified as one of its main causes. In this context, at the request of the French Ministries responsible for the Environment, for Agriculture and for Research, a panel of 46 scientific experts ran a nearly 2-year-long (2020-2022) collective scientific assessment (CSA) of international scientific knowledge relating to the impacts of PPP on biodiversity and ecosystem services. The scope of this CSA covered the terrestrial, atmospheric, freshwater, and marine environments (with the exception of groundwater) in their continuity from the site of PPP application to the ocean, in France and French overseas territories, based on international knowledge produced on or transposable to this type of context (climate, PPP used, biodiversity present, etc.). Here, we provide a brief summary of the CSA's main conclusions, which were drawn from about 4500 international publications. Our analysis finds that PPP contaminate all environmental matrices, including biota, and cause direct and indirect ecotoxicological effects that unequivocally contribute to the decline of certain biological groups and alter certain ecosystem functions and services. Levers for action to limit PPP-driven pollution and effects on environmental compartments include local measures from plot to landscape scales and regulatory improvements. However, there are still significant gaps in knowledge regarding environmental contamination by PPPs and its effect on biodiversity and ecosystem functions and services. Perspectives and research needs are proposed to address these gaps
Human and zebrafish mineralocorticoid receptors reporter cell assays to assess the activity of chemicals
No full textInternational audienceThe action of environmental chemicals (ECs) on the mineralocorticoid receptor (MR) has beensuggested to impair physiological processes regulated by this nuclear receptor. However, it remainsunderstudied both as target of ECs and with respect to potential species-specific differences. In thisregard, we have developed reporter cell lines to identify the response to different steroids, ECs andurban wastewater (WW) sample extracts of human MR (hMR) and zebrafish MR (zfMR). Most of thesteroids had a higher efficacy on zfMR than hMR while the ECs were antagonists to both hMR andzfMR, with a lower potency on the latter. Interestingly, WW sample extracts revealed the presence ofMR activity with a greater activity on zfMR compared to hMR, suggesting the presence of steroids inWW. These screening tools have proven to be powerful tools for characterizing the interaction ofchemicals with MRs and revealing their presence in environmental samples
Thermo-hydro-mechanical responses of a high-level radioactive waste repository: Effects of short- and long-term nonlinear behavior of the host rock
No full textInternational audienceThis paper aims to model the thermo-hydro-mechanical (THM) responses of a high-level waste (HLW) repositoryto the heat released from the waste package by considering short- and long-term nonlinear behavior (damage,plasticity, creep) of the host rock. This results from a benchmark exercise involving three modelling teams on theFrench HLW concept disposal. This work focuses only on the thermo-mechanical pressurization of the host rock.Two representative constitutive models are considered to describe the behavior of the host rock. The first oneconsists in an anisotropic elasto-plastic-creep model, including stiffness and strength anisotropy. The secondmodel is a double phase field model with both tensile and compressible damage mechanism, associated withplasticity and creep. Parameters of these two models are calibrated based on the data acquired from both laboratory tests on samples and field observation.Comparisons between poro-elastic and non-linear simulations show that the short-term nonlinear behavioronly affects the THM responses in the near field of the host rock, while creep leads to a decrease in fluid pressurebuild-up and stress in both the near and far fields. An unsaturated condition prescribed on the HLW cell wallbefore heating reduces the fluid pressure and stress within the host rock
Maternal exposure to pesticides and gestational diabetes mellitus in the Elfe Cohort
No full textInternational audienceBackground: Gestational diabetes mellitus (GDM) increases risks of adverse perinatal outcomes and metabolic disorders in offspring. Some endocrine-disrupting chemicals are presumed to interfere with glucose metabolism. We aimed to assess the association between non-occupational exposures to pesticides and the risk of GDM.Methods: The study was conducted on 11 512 women (791 with GDM) from the French nationwide Elfe cohort. Among 114 suspected pesticides identified using a toxicogenomic approach, 62 with detection frequency ≥10 % were analyzed across three sources of exposure: residential use (self-reported, n = 18), agricultural (geographic information system, n = 14) and dietary (estimated by a food-frequency questionnaire and monitoring data of pesticide residues in foods, n = 30). The association between exposure to pesticides (no or low vs. high) and the occurrence of GDM was tested with single and multi-source adjusted logistic regression models.Results: In the multi-source model, dietary exposure to glyphosate (aOR = 0.6, 95 %CI: 0.5,0.9) or agricultural exposure (aOR = 0.8, 95 %CI:0.6,1.0) were associated with lower odds of GDM. The same effect was identified for two dietary pesticides: epoxiconazole (aOR = 0.6, 95 %CI: 0.5,0.8) and penconazole (aOR = 0.8, 95 %CI: 0.6,1.0). Dietary exposure to cypermethrin (aOR = 1.2, 95 %CI:1.0,1.5) and agricultural exposure to myclobutanil (aOR = 1.4, 95 %CI:1.1,1.9) were associated with higher odds of GDM. No significant association was identified for the residential use of pesticides.Conclusion: This toxico-genomic-based study identifies five pesticides associated with GDM through agricultural or dietary exposure. These findings provide new insights into environmental contributors to GDM. Further research is needed to elucidate the underlying toxicological mechanisms and confirm these associations
Comparative study of three cellular materials under blast and sustained shock wave
No full textInternational audienceThis study investigates the mechanical response of three cellular materials—polyisocyanurate (PIR), autoclaved aerated concrete (AAC), and Aluminum Lightweight Foam (ALF, Nufoam® 140)—under blast and shock loading conditions. The research aims to provide experimental data for optimizing building protection against explosion hazards. Laboratory-scale tests were conducted using a shock tube to generate blast and sustained shock waves. The materials’ responses were analyzed using high-speed imaging and digital image correlation. Results indicate that PIR exhibits significant deformation under sustained shocks but shows recovery under blast loading. AAC demonstrates erosion-based energy dissipation, with material loss concentrated at the extremities. ALF, serving as a reference, shows excellent mechanical energy dissipation. The study highlights the potential of these materials for applications requiring both thermal insulation and blast resistance, contributing to the development of predictive tools and larger-scale experiment designs
Investigating turbulence and turbulent flame propagation in dust clouds
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Bioaccessibilité des métaux/métalloïdes dans les sols : un indicateur pertinent en santé-environnement
No full textInternational audienceLa bioaccessibilité orale simulant la digestion humaine est un outil de plus en plus utilisé et reconnu pour affiner l’exposition de l’Homme aux éléments métalliques en lien avec l’ingestion de particules de sol [1]. Le test in vitro normé UBM (ISO 17924:2019 [2]) est recommandé dans la méthodologie nationale de gestion des sites et sols pollués, actuellement validé in vivo/in vitro pour As, Cd et Pb. Pour As, la Haute Autorité de Santé (HAS ; [3]) recommande de dépister les populations dès lors que la concentration en As bioaccessible est supérieure à 25 mg/kg. Deux études illustrent la pertinence de la bioaccessibilité comme indicateur santé-environnement. La première visait à réaliser une étude statistique de la distribution en As bioaccessible à l’échelle nationale en considérant les sols du RMQS. Ainsi, sur les 353 échantillons considérés, à une exception près, les concentrations bioaccessibles sont inférieures à la valeur seuil de 25 mg/kg, avec une bioaccessibilité moyenne inférieure à 10 %. La seconde étude visait à élargir la portée du test UBM à d’autres éléments métalliques, notamment Cr et Ni. Leur bioaccessibilité montre des valeurs moyennes relativement faibles (< 10 % pour Cr et < 20 % pour Ni), indiquant qu’une part importante de la concentration totale de ces éléments est retenue dans le sol et peu disponible lors de la digestion. Ces résultats, très prometteurs, montrent l’intérêt de prendre en compte ce paramètre dans l’évaluation des risques sanitaires, mais sa validation est nécessaire au préalable par l’essai de biodisponibilité, réalisé sur un modèle porcelet