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Predicting the in vivo pulmonary toxicity induced by acute exposure to poorly soluble nanomaterials by using advanced in vitro methods
International audienceBackground: Animal models remain at that time a reference tool to predict potential pulmonary adverse effects of nanomaterials in humans. However, in a context of reduction of the number of animals used in experimentation, there is a need for reliable alternatives. In vitro models using lung cells represent relevant alternatives to assess potential nanomaterial acute toxicity by inhalation, particularly since advanced in vitro methods and models have been developed. Nevertheless, the ability of in vitro experiments to replace animal experimentation for predicting potential acute pulmonary toxicity in human still needs to be carefully assessed. The aim of the study was to evaluate the differences existing between the in vivo and the in vitro approaches for the prediction of nanomaterial toxicity and to find advanced methods to enhance in vitro predictivity. For this purpose, rats or pneumocytes in co-culture with macrophages were exposed to the same poorly soluble and poorly toxic TiO2 and CeO2 nanomaterials, by the respiratory route in vivo or using more or less advanced methodologies in vitro. After 24 h of exposure, biological responses were assessed focusing on pro-inflammatory effects and quantitative comparisons were performed between the in vivo and in vitro methods, using compatible dose metrics. Results: For each dose metric used (mass/alveolar surface or mass/macrophage), we observed that the most realistic in vitro exposure method, the air-liquid interface method, was the most predictive of in vivo effects regarding biological activation levels. We also noted less differences between in vivo and in vitro results when doses were normalized by the number of macrophages rather than by the alveolar surface. Lastly, although we observed similarities in the nanomaterial ranking using in vivo and in vitro approaches, the quality of the data-set was insufficient to provide clear ranking comparisons. Conclusions: We showed that advanced methods could be used to enhance in vitro experiments ability to predict potential acute pulmonary toxicity in vivo. Moreover, we showed that the timing of the dose delivery could be controlled to enhance the predictivity. Further studies should be necessary to assess if air-liquid interface provide more reliable ranking of nanomaterials than submerged methods
A bioenergetics model of the entire life cycle of the three-spined stickleback, gasterosteus aculeatus
A whole life-cycle bioenergetic model based on the dynamic energy budget (DEB) theory was proposed for the three-spined stickleback (Gasterosteus aculeatus). To develop this model, experiments on growth and reproduction were performed: adult and juvenile growth, size at first reproduction and amount of eggs spawned by females were monitored under different feeding levels and temperatures. The DEB parameters were estimated, using Bayesian statistics, based on the data produced during these experiments and on other data found in the literature. The model fitted accurately the different data used for the calibration process and, in addition, predicted accurately the data sets used to assess its predictability. Our bioenergetic model of the whole life cycle of the three-spined stickleback accounting for environmental variations could contribute in many ways to improved ecological assessment: supporting change of scale from individual to populations; developing new biomarkers of exposure and effect; analysing ecotoxicity tests with biology-based models
Refining uptake and depuration constants for fluoroalkyl chemicals in Chironomus riparius larvae on the basis of experimental results and modelling
[Departement_IRSTEA]Eaux [TR1_IRSTEA]BELCA [ADD1_IRSTEA]Systèmes aquatiques soumis à des pressions multiplesThe aims of this study were to determine depuration rates for a range of per- and polyfluoroalkyl substances (PFASs) using Chironomus riparius, and to test a concentration-dependency hypothesis for the long-chain perfluorotridecanoic acid (PFTrDA) for this species. Midge larvae were exposed to field sediments collected downstream of a fluorotelomer plant, and to the same sediment spiked with PFTrDA. Elimination kinetics results indicated complete elimination of all PFASs by chironomids after 42 h. These data were used to develop two PFTrDA bioaccumulation models accounting for chironomid growth and for compound concentration dependency or not. There was much better agreement between observed and simulated data under the concentration-dependency hypothesis than under the alternative one (passive diffusion). The PFTrDA uptake rate derived from the concentration-dependency model equaled 0.013 ± 0.008 goc gww h−1, and the depuration rate 0.032 ± 0.009 h−1
Evaluation et développement de méthodologies analytiques pour la mesure de composés organiques dans le domaine de l’environnement et de la santé
Contribution à la caractérisation des émissions de nanoparticules au poste de travail
International audienc
Alpha band analysis in resting EEG after exposure to radiofrequency signal (900 MHz) : EEG/MEG study combined with an anatomic MRI
International audienceWith the extensive use of mobile phones (MP) several studies have been realized to understand the effects of radiofrequency exposure on brain activity. The results show changes in the alpha band spectral power. To better understand the cortical structures involved in these changes after MP exposure (900 MHz), we carried out electroencephalography and magnetoencephalography recording followed by the anatomical magnetic resonance imaging on healthy volunteers. Participants were selected according to inclusion criteria. They were healthy males or females, aged between 18 and 35, non-smokers and with regular sleep habits. Data analyses of 10 subjects are still under process and ready results will be presented at the conference
Approche intégrative pour étudier les effets biologiques des progestatifs sur le poisson zèbre et leur occurrence environnementale
National audienc
Actions du réseau Norman : partager les connaissances et harmoniser les pratiques pour une meilleure exploitation de l’analyse non-ciblée dans le domaine environnemental
International audienc
Assessment of Ozone or Not-Treated Wastewater Ecotoxicity Using Mechanism-Based and Zebrafish Embryo Bioassays
International audienceToxicity of wastewater treatment plant (WWTP) effluents is usually assessed with standardized bioassays, as e.g. the Fish Embryo Toxicity test (FET), but assessment of sub-lethal toxic effects requires to develop more adapted tests. The present work aimed to add the recording of several sub-lethal endpoints in exposed zebrafish embryo-larval stages in order to increase the sensitivity of residual toxicity evaluation of WWTP effluents using a semi-quantitative method (iFET score). This approach was complemented with the genotoxicity assessment on the exposed embryos, a sub-acute hazard particularly relevant to evaluate a potential chronic toxicity risk of low and multi-contaminated environmental matrices. Additionally, endocrine activities of effluents were quantified using human reporter cell lines. This test battery was applied to the assessment of the residual toxicity of five biological treatment effluents, further treated or not using various ozonation treatments intended to improve pharmaceutical compounds removal. Acute toxicity towards zebrafish embryos was very low. However, iFET score approach proposed was able to reveal residual toxicity through the presence of developmental abnormalities in all samples tested. Additionally, a low residual genotoxicity was measured in embryos exposed to two of the WWTP effluents when all excepted one exhibited a residual endocrine activity potential in the ng/L range providing complementary information on the occurrence of endocrine active chemicals and their reduction by different processes. To sum up, such a simplified and ecologically relevant test battery was found sensitive enough to characterize and differentiate various residual effluent’s ecotoxicity at contaminant levels of environmental concern
Best Available Techniques: An integrated method for multicriteria assessment of reference installations
International audienceThe Industrial Emission Directive (IED) has strengthened the requirement to apply Best Available Techniques (BATs) first introduced by the IPPC Directive. The so-called “Sevilla Process”, which is the formal European process to define and revise BATs, is based upon an exchange of information among different stakeholders and relies on data analysis and expert judgements. If the process to collect and to share information between stakeholders at sectoral and installation levels is well defined, the determination of BATs and BAT-Associated Environmental Levels has evolved along with the revision of the BAT REFerence documents (BREFs). Nevertheless, no formal tool to support the analysis exists. The objective of this article is to present a 5-steps methodology aimed to classify installations according to two multicriteria approaches, either a representative angle or a performant approach, and then to identify reference installations, which would help to propose reference values and possible BATs. The methodology is supported by statistical tools (Principal Component analysis, hierarchical clustering) and algorithmic approach (MissForest). The application to French dairy sectors has validated the methodology and mathematical tools used. Two reference classes has been identified for the representative approach and 19 installations selected. For the performant installations, seven (7) installations has been selected. BATAELs for COD flow are proposed considering these classifications and an effort rate comprised between 23 and 96% has been revealed