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Standardization of nanoecotoxicology to facilitate grouping strategies for engineered nanomaterials
International audienceNanoecotoxicology hypothesizes that alterations to a nanoform's physical structure can influence ecotoxicology. Grouping and read-across approaches have been proposed to streamline hazard assessments and reduce the burden of regulatory approval. The NanoReg2 project investigated the capacity of historical ecotoxicity data to support read-across approaches and found that the data were insufficient and the information reported was inconsistent. To explore the potential for grouping in ecotoxicology, the NanoReg2 project created a harmonized ecotoxicological database using nanomaterials representative of those available on the European Single Market. Relationships between pristine physicochemical properties, system-dependent changes to physical structure, and ecotoxicological responses were explored using mixed modelling. The study also explored the application of the NanoGENOTOX SOP to ecotoxicology to investigate the application of bovine serum albumin to create stable stock suspensions.Results demonstrated that nanomaterials can be grouped based on their core element (carbon, silicon, titanium, and zinc) and that inherent properties (initial size, density, surface area, purity) could be correlated to biological responses. Results also demonstrated that the use of bovine serum albumin influences the ecotoxicological potential of the tested nanomaterials, which may be attributed to their stability in suspension. While results were promising, initial physicochemical properties are autocorrelated, which challenges discrimination between nanoforms. The NanoReg2 project identified two barriers to implementing grouping approaches: inconsistent test preparations and limited access to historical data. To address these issues, developing FAIR (Findable, Accessible, Interoperable, and Reusable) data is necessary to integrate ecotoxicology into regulatory paradigms
A novel multiphysics-multiscale approach for seepage-induced erosion in granular slopes
International audienceGroundwater-induced internal erosion of finer soil fractions is critical for initiating granularslope collapse, but developing accurate computational models to capture coupled unsaturatedseepage, particle migration, and hydro-mechanical property evolution of soils remainschallenging. This study proposes a novel three-phase five-component mathematical modelbased on mixture theory to describe multiphysics phenomena in seepage-induced erosion ingap-graded granular soils. To enhance model accuracy, an improved micromechanics-basedmultiscale model is integrated to account for the specific moisture content and gradingdependentmechanical behavior of the porous medium experiencing seepage erosion. Thecomputational framework innovatively employs an enhanced stabilized finite element methodto eliminate numerical oscillations, validated via comparison with analytical solutions. Thespatio-temporal evolution of the eroded zone and hydro-mechanical response of a reconstitutedflume slope were successfully identified. Numerical results show volumetric settlements andshear sliding are major consequences of internal erosion, with soil property degradation near the slope toe accelerating failure. Neglecting internal erosion delays predicted failure onset andunderestimates collapse severity. The proposed framework proves efficient and reliable forpredicting seepage-induced slope failure initiation
QSAR Models for Predicting Oral Bioavailability and Volume of Distribution and Their Application in Mapping the TK Space of Endocrine Disruptors
International audienceToxicokinetic (TK) properties are essential in the framework of chemical risk assessment and drug discovery. Specifically, a TK profile provides information about the fate of chemicals in the human body. In this context, Quantitative Structure–Activity Relationship (QSAR) models are convenient computational tools for predicting TK properties. Here, we developed QSAR models to predict two TK properties: oral bioavailability and volume of distribution at steady state (VDss). We collected and curated two large sets of 1712 and 1591 chemicals for oral bioavailability and VDss, respectively, and compared regression and classification (binary and multiclass) models with the application of several machine learning algorithms. The best predictive performance of the models for regression (R) prediction was characterized by a Q2F3 of 0.34 with the R-CatBoost model for oral bioavailability and a geometric mean fold error (GMFE) of 2.35 with the R-RF model for VDss. The models were then applied to a list of potential endocrine-disrupting chemicals (EDCs), highlighting chemicals with a high probability of posing a risk to human health due to their TK profiles. Based on the results obtained, insights into the structural determinants of TK properties for EDCs are further discussed
A new alternative method using cyp3a65 expression in transgenic zebrafish embryos to assess metabolic endocrine-disrupting chemicals in the intestine
International audienceMetabolic endocrine-disrupting chemicals (MDCs) contribute to the development andincreasing incidence of metabolic disorders, highlighting the need for relevant assays to identifythem. Several alternative models to mammals, notably the zebrafish, have been developed, butnone of these assays account for the mode of action and effects of MDCs on intestine. Thisstudy aimed to 1) establish and characterize a transgenic embryo model expressing GFP underthe control of the zebrafish cyp3a65 gene, ortholog of the human cyp3a4, 2) set-up an originalzebrafish embryo-based bioassay to study the Effects of Metabolic Endocrine disRuptors in Gutof zebrafish Embryos (EMERGE). Spatiotemporal expression of cyp3a65-GFP and temporalendogenous cyp3a65 was characterized using fluorescence imaging of GFP,immunohistochemistry and RT-qPCR, under both normal and exposed conditions toclotrimazole and TCDD (respectively zfPXR and zfAhR2 agonists). Then, twenty-twochemicals were screened for their potential activity using the EMERGE assay. We report anearly and dynamic expression of cyp3a65 in the developing intestine which is disrupted in atime and concentration dependent manner by zfPXR and zfAhR2 agonists. Using EMERGE,we report that various environmental chemicals can significantly up- or down regulate cyp3a65expression, most of them being newly identified as targeting the intestine and disrupt thiscritical metabolic enzyme. In conclusion, EMERGE represents a new easy to use assay to screenmetabolic disrupting activity of chemicals in a non-mammalian model. The data collectedsuggest it could provide valuable insights into the effects of substances on cyp3a4 in humansand may emerge as a valuable assay for assessing human-relevant effects
Session : Risques Industriels Majeurs et Environnements - colloque RIODD 2025
International audienceMajor Industrial Risks (MIR) linked to industrial activities remain serious and ongoing problems, as demonstrated by the AZF disaster in 2001 and the fire at the Lubrizol chemical plant in Rouen in 2019. These issues continue to be the focus of researchers with an insider's perspective who are attentive to the prevention of MIR within these complex socio-technical systems.This work complements that which addresses the issue of MIR from an external perspective, for example through territories (Bécot, Le Naour, 2023, Flanquart, 2016) or through public action (Bonnaud, Martinais, 2008). However, the current period is marked by new challenges that raise the question of RIMs anew. Consider, for example, global warming.Les Risques Industriels Majeurs (RIM) liés aux activités industrielles restent des problèmes sérieux toujours d'actualité comme l'ont montré la catastrophe d’AZF en 2001 et l’incendie de l’usine chimique Lubrizol en 2019 à Rouen. Ces questions font toujours l'objet de l'attention de chercheurs ayant une approche de l'intérieur et attentifs à la fabrique de la prévention des RIM au sein de ces systèmes socio-techniques complexes.Ces travaux sont complémentaires de ceux qui abordent la question des RIM par l’externe, par les territoires par exemple (Bécot, Le Naour, 2023, Flanquart, 2016) ou par l’action publique (Bonnaud, Martinais, 2008). Or, la période actuelle est marquée par de nouveaux enjeux qui posent à nouveaux frais la question des RIM. Songeons par exemple au réchauffement climatique
CARTHAGE, Contribution de l’Air dans les Risques et Transferts Associés aux HAP en Agricultures Urbaines : gestion et évaluation
Les formes de végétalisation à visée entre autres alimentaire augmentent en France et se diversifient dans les villes. Au regard de cet essor, et du peu de données disponibles dans la littérature, il importe de connaître les enjeux sanitaires associés à la culture de végétaux en milieu urbain et péri-urbain. Notamment, les Hydrocarbures Aromatiques Polycycliques (HAP) sont des polluants reconnus comme des traceurs d’intérêt de la qualité de l’air en milieu urbain. Le projet CARTHAGE, via la mise en place de différentes modalités d’expérimentations en conditions réelles au droit de micro-fermes urbaines de Paris et d’Ile-de-France, vise à évaluer : - la contribution de la pollution atmosphérique à la contamination des végétaux en HAP ; - l’influence de la qualité de l’air sur les rendements agricoles et la perception des consommateurs, achetant les végétaux cultivés en milieu urbain ; - l’exposition et les risques sanitaires liés aux HAP pour les travailleurs et usagers des micro-fermes urbaines. Des recommandations sont formulées à l’issue de ces travaux pour réduire les expositions et les risques sanitaires pour les exploitants et les consommateurs de fruits et légumes
Temporal change of outdoor RF-EMF levels in four European countries: a microenvironmental measurement study
International audienceIntroductionOver the past two decades, the amount of transmitted mobile data has increased rapidly. It is unknown whether the implementation of the new technologies enabling this has resulted in changes of outdoor radio-frequency electromagnetic fields (RF-EMF) exposure. Therefore, microenvironmental measurements were used to investigate temporal trends in RF-EMF exposure between 2016 and 2023, in the Netherlands, Switzerland, Belgium and Spain, following a similar protocol across campaigns. Microenvironmental measurements refer to exposure measurements performed at predefined small areas that have been differentiated with a specific function in that particular area. This allowed us to compare exposure trends between countries and years.MethodsThe data was collected as part of the ACCEDERA (2016–2018), ETAIN (2023), and GOLIAT (2023) projects, walking repeatedly the same routes with RF-EMF exposimeters. Identical microenvironments were identified in each country and measurements of the exposure from mobile base stations, mobile phones and the total exposure were compared across years.ResultsComparing measurements between 6 and 14 unique microenvironments in each country, our data did not suggest significant changes in the exposure from the mobile base station origin (total downlink exposure) between baseline measurements in 2016 to follow up and 2023 for the four countries. Across all countries and years the median values of the mobile base station exposure ranged from 0.11 mW/m2 (Switzerland, 2023) to 0.62 mW/m2 (Netherlands, 2018). There was no consistent trend in the individual microenvironments across the countries.ConclusionsOur measurements of RF-EMF outdoor exposure levels across included microenvironment groups do not indicate change in exposure levels between 2016 and 2023 despite an increase in mobile data traffic by a factor of 8 in Western Europe1
A Quantitative Method for Characterizing of Structures’ Debris Release
International audienceThe characterization of airborne submicrometric composite structures’ debris is a challenge in the field of environmental monitoring and control. The work presented here aims to develop a new quantitative method to measure elemental mass concentrations via particle sampling and Transmission Electron Microscopy—Energy-Dispersive X-ray Spectroscopy (TEM-EDS). The principle is to collect airborne particles on a porous TEM grid, then add a certain mass of reference particles, and compare the relative mass percentages of elements from reference and sample particles via EDS. Diverse pairs of airborne particles (RbCl, CsCl, NaCl, SrCl2, Ga(NO3)3, braking particles) were deposited on one TEM grid, and the experimental elemental mass ratios were measured by EDS and compared with the theoretical values. Results show that the quantitative and homogeneous collection of reference particles, such as RbCl, on the TEM grid could be suitable. For all the tested conditions, the absolute deviations between the theoretical elemental mass ratios and the experimental ratios remain lower than 8%. Thus, the mass concentration of Fe from the braking aerosol is calculated as 107 µg/m3. Compared to the cumbersome real-time instrument, this new method for mass characterization appears to be convenient, and requires a short time of aerosol sampling at the workplace. This approach ensures safety and practicability when assessing, e.g., the exposure risk of hazardous materials
In vitro assessment of aryl hydrocarbon, estrogen, and androgen receptor-mediated activities of secondary organic aerosols formed from the oxidation of polycyclic aromatic hydrocarbons and furans
International audienceBiomass burning constitutes a significant source of fine particulate matter (PM2.5) in the atmosphere, particularly during winter due to residential wood heating. This source also emits substantial quantities of volatile and semi-volatile organic compounds, leading through (photo-)chemical and physical processes, to the formation of secondary organic aerosols (SOAs), accounting for a significant fraction of PM2.5. The current understanding of the biological effects of SOA resulting from the oxidation of major gaseous precursors emitted by biomass burning (e.g., polycyclic aromatic hydrocarbons (PAHs), phenols, furans) is still limited. Mechanism-based in vitro cellular bioassays targeting toxicologically relevant modes of action have proven valuable in assessing and quantifying the overall biological activity of complex mixtures like SOA, thereby revealing the presence of toxicologically relevant compounds. The main objective of this study was to investigate, using a battery of in vitro mechanism-based cellular bioassays, the aryl hydrocarbon (AhR), estrogen (ER), and androgen receptor (AR)-mediated activities of laboratory-generated SOA resulting from the oxidation of four PAHs and three furans. SOA was produced using an oxidation flow reactor (OFR) under either daytime (OH radicals) or nighttime (NO3 radicals) conditions. Furan-derived SOA did not exhibit any biological activity with the targeted endpoints. PAH-derived SOA, formed from AhR weakly or inactive PAHs, showed significant AhR-mediated activities. Notably, SOA resulting from naphthalene and acenaphthylene + acenaphthene demonstrated the highest AhR activation potency, with greater activities observed for SOA formed through NO3 radical oxidation. No endocrine-disrupting activity was observed for the PAH-derived SOA, similar to the individual parent PAHs (with the exception of fluorene and phenanthrene PAHs which were weekly anti-androgenic). These findings underscore the substantial contribution of PAH-derived SOA to the AhR-mediated activities of PM