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Nanoparticles biodistribution studies: Optimization of lung digestion protocols for TiO2 NPs analyses by single particle-ICP-MS
No full textInternational audienceInductively coupled plasma mass spectrometry (ICP-MS) is at that time the most used tool to quantify (oxide) metallic NPs in organs or tissues. It implies a sample mineralization and therefore a dosage of the metal in ionic form. In the nanotoxicology field, it is important to distinguish the substance form (particulate / ionic) as it could modulate the toxicity. Inductively Coupled Plasma Mass Spectrometry used in a single particle mode (spICP-MS) appears to be the technique of choice to measure in a single analysis the nanoparticle number concentration, the size distribution and the ionic concentration of a sample. Many studies exist on quantifying gold or silver NPs using sp-ICP-MS in aqueous suspension but few on titanium oxide NPs in biological matrices. To perform an ICP-MS analysis in single particle mode, a digestion of the organ is required. It must involve a protocol strong enough to remove all the organic matter, but gentle enough to avoid nanoparticle grain-sized modification. In this study, we first compared the efficiency of two digestion methods, an enzymatic digestion and an alkaline digestion. Thus, a rat lung was spiked (miming an intratracheal instillation) with a known quantity of TiO2 NPs (NM100 from JRC) in suspension. This spiked level was around 1g/L. It is not related to a real exposition but was chosen only to evaluate the performance of the two protocols. Then, the spiked organ was homogenized using a freezer mill and afterwards digested with TMAH (Tetramethylammonium hydroxide) for the alkaline digestion, and proteinase K for the enzymatic digestion. Finally, analyses were done by two approaches: - a total quantification (acid mineralization and ICP-OES analysis) of Ti to evaluate the yield of recovery. - a sp-ICP-MS analysis to assess if the concentrations measured after an enzymatic or alkaline digestion are similar to the classic ICP-MS concentration measurement. Enzymatic digestions show the best yields with a good reproducibility. Single particle-ICP-MS analyses are still processing and seem to agree with total concentration values
Lung toxicity of industrial particles
No full textInternational audienceThe frame of the Nanoreg2 European project, which aimed at helping industrials partners to safely design nanomaterials, we studied in vivo toxicity of different nanomaterials produced by industry. Three industrial partners provided five nanomaterials. Two silicium nanomaterials were studied, one without and one with a carbon coating (named Si and Si-WC). Two carbon nanofibers with different degrees of purity and graphitization). And finally, one graphene. To study the lung toxicity of these products, we exposed rats to 0.1, 1 and 2 mg/kg of nanomaterials with one endo-tracheal instillation. Animals were then killed 24h, 3 and 28 days after exposure. Broncho-Alveolar Lavages (BAL) were performed in order to count and identify BAL cells but also to dose inflammatory cytokines secreted in BAL supernatant. Lungs were also fixed and analyzed by an histo-pathologist. The coated Si (Si-WC) induced a greater lung inflammatory response which was also more persistent in time compared to the response observed with Si without coating. Si-WC treated group developed within the lung parenchyma, interstitial thickening which were slightly more intense than Si particle treated group. Bronchial alterations were presents only in the highest exposed groups, but slightly more frequently observed in Si-WC40 exposed groups, but a minimal dose related effects tend to be observed for both particles. A dose related effect was observed for the presence of particle rich macrophages density suggesting a high clearance activity, only for Si-WC40 treated groups. The less pure carbon nanofiber induced a higher lung inflammatory response just after exposure which did not last in time. A very similar histologic lung profile was observed for both carbon nanofibers exposed groups with higher lesionnal score at early stages than late stages, suggesting an efficient clearance of the particles. No dose related effect has been observed. Bronchial alterations were observed only at the highest dose for both particles. However, a slightly more important number of bronchiolitis obliterans was observed after less pure carbon nanofiber exposure but tend to decrease in time. A dose related effect was observed for the presence of particle rich macrophages density suggesting a high clearance activity. The graphene induced the most important inflammatory response, but it did not last in time. Alveolar and bronchi alterations were quite high after graphene powder exposure. The lesions were slightly less intense with time suggesting an ongoing recovery. No dose-related effect could be observed. Within the bronchi, hyperplasia associated with inflammation leading to bronchial obstruction (bronchiolitis obliterans) was observed for all doses and all times after graphene powder exposure. Particles rich macrophages were not as high as expected, suggesting a less efficient clearance process, thus consistent with more alveolar and bronchi lesions
Assessment of long-term exposure to airborne pollution in France (1990-2010)
No full textInternational audienceBackground: Long-term exposure to air pollution has been consistently associated with adverse health effects and reduced life expectancy. Air pollution is a mixture of multiple pollutants originating from a large variety of sources and includes various substances classified as carcinogenic or probably carcinogenic to humans. Identifying the long-term effects of these airborne pollutants requires the computation of the spatio-temporal variability of concentration to estimate the exposure of the population. Aim : To provide an accurate assessment of long-term air pollution exposure (including airborne PM10, PM2.5, NO2, O3, BaP, PCB, PCDD/F and cadmium (cd) exposure in the whole France and in a case-control study nested in the French national prospective women’s cohort (E3N). Methods: Hourly airborne pollutant concentrations over the study period (1990-2010) were computed using a chemistry- transport model (CHIMERE) with a spatial resolution of 7x7km2. Cohort’s subjects were manually geocoded and annual concentrations were attributed to each subject’s address (n=19669). Results: Simulation scenarios of air pollutant concentrations show the variability of the pollutant sources over time with general decreasing levels of pollutant concentrations in air. At the E3N subject’s address, we observed a decline of concentration for all pollutants (PM10:-41%; PM2.5:-45%; NO2:-34%; PCB:-74%; PCDD/F:-87%, Cd:-68%; BaP:-45%) except for O3 (-0.04%). The percentage of subject exposed to an annual concentration exceeding WHO recommendation (PM10: 20 μg/m3; PM2.5: 10 μg/m3) decrease form 74% to 8% for PM10 and from 99% to 64% for PM2.5. We also observed strong territorial inequalities with differences in atmospheric concentrations that could be greater than a factor of five between regions. Conclusions: Findings from this study will be essential to increase the accuracy of the assessment of long-term airborne pollution exposure and will improve the results of epidemiological studies. The spatial resolution of concentrations will be improved by using complementary models such as land use regression
Perfluorooctane Sulfonate Toxicokinetics at Different Temperatures Using a Rainbow Trout Physiologically-Based Toxicokinetic Model
No full textInternational audienceThis study is part of a project aiming to improve our understanding of the toxicokinetics of perfluoro-alkyl substances (- PFOS, perfluorohexane sulfonate and perfluorononanoate - PFNA) in fish, using the rainbow trout (Onchorynchus mykiss) as model species. The project involves a combination of dietary exposure experiments and physiologically-based toxicokinetic (PBTK) modelling. We developed first a 10-compartment PBTK model to elucidate PFOS kinetics in adult rainbow trout. This PBTK model included various physiological characteristics: blood perfusion to each organ, plasmatic fraction, PFOS free fraction, and growth of individuals. The parameters were optimized using Bayesian inference. This development was based on an experimental dataset, where fish were first fed daily with spiked food, and allowed to depurate for an equivalent duration [1]. We evaluated the relative importance of different absorption as well as elimination routes, and the role of the entero-hepatic cycle. This model was then used to explore the effects of temperature on PFOS toxicokinetics. The modulation of physiological processes induced by temperature was introduced into the model structure thanks to Arrhenius law. These processes included food absorption, ventilation rate, growth, cardiac output, urinary, biliary and fecal clearances, and relative blood flow distribution to organs. We hypothesized that temperature could also affect PFOS tissue:plasma or tissue:blood partition coefficients. Simulations were performed for water temperatures of 7°C, 11 °C, 15 °C and 19°C and compared to experimental data [1, 2]. The simulation having the lowest Root Mean Squared Error was obtained when all physiological processes were modulated according to temperature. Overall, the model outcomes suggest that PFOS toxicokinetics was more affected by temperature induced changes in partition coefficients than in fish physiology. A sensitivity analysis is ongoing in order to confirm and refine this result
Hydro-mechanical modeling of internal erosion in dike
No full textInternational audienceInstability in geotechnical structures such as dikes or earth dams may be induced by internal erosion. In this phenomenon, finer soil particles are plucked off from the solid matrix by seepage flow and transported through the pore domain over time. Due to the loss of a part of the solid phase, the mechanical properties of the soil are progressively degraded, and, with time, earthen structures are under considerable risk of failure. Research on this topic is still fairly new and much more needs to be understood. In this study, a hydro-mechanical model based on porous continuous medium theory has been proposed to assess how internal erosion impacts the safety of earthen structures. An elasto-plastic constitutive model for sand-silt mixtures has been developed to describe the effect of the evolution of both porosity and fines content induced by internal erosion upon the behavior of the soil skeleton. The model is developed within finite element method framework. It is applied to a dike subjected to internal erosion induced by the presence of a karstic cavity beneath the alluvium layer
Evaluation of ACSM response to different mixtures of organic and inorganic solutions, and assessing the impact on organic source apportionment results
No full textInternational audienceReal time and long-term monitoring of aerosol chemical species is the subject of great scientific concerns and numerous technological developments. The Aerodyne Aerosol Chemical Speciation monitor (ACSM) has been developed for this purpose. It is currently operational at over 60 monitoring stations worldwide, with almost half of them being located in Europe (notably within the Aerosols, Clouds, and Trace gases Research InfraStructure). Understanding the reponse of these instruments to different chemical species and quantifying any possible artefacts is essential if we are to use these measurements for comparative studies and for model evaluation and development. A few recent studies have illustrated such possible measurement artefacts, notably at the mz44 peak (Crenn et al, 2015, Frohlich et al, 2015). The related variability in instrument response has been linked to an artefact response to inorganic aerosol (Pieber et al.,2016), however more recent work has illustrated that this response is dependent on aerosol mixing state (Freney et al., 2019). Here, we present results of laboratory experiments where the mz44 artefact was evaluated for various inorganic and organic mixtures, and a co-located measurement campaign in ambient air..
Investigation of ammonium nitrate contaminants based on computational chemistry approach
No full textInternational audienceAmmonium nitrate (AN) was involved in a number of major accidents in the last century. Safety issues related to the use of ammonium nitrate is far from being achieved: insufficient knowledge are still available about the interaction mechanisms of ammonium nitrate with contaminants despite significant efforts. This paper proposes to investigate AN’s contaminants, which can be grouped into three categories depending on their action when they are in contact with ammonium nitrate: promoters, inhibitors, and inerts. The aim of this study is to identify possible common reaction pathways inside of each category to finally build a predictive tool able to determine if a contaminant may involve a chemical incompatibility with AN or not, with the help of computational chemistry approach
French Market Surveillance of the CE-marked explosives and pyrotechnic articles
No full textInternational audienceThe Directive 2013/29/EU for conformity assessment procedures of all pyrotechnic articles [1] and the Directive 2014/28/EU for explosives for civil uses [2], require each Member State to carry out Union Market Surveillance and control of pyrotechnic articles and civilian explosives entering the Union market (Article 39 of Directive 2013/29/EU and Article 41 of Directive 2014/28/EU). Accidental Risks Division of INERIS has a testing laboratory accredited by COFRAC (French Accreditation Body) according to the ISO/IEC 17025 standard for the testing of explosives, pyrotechnic articles and fireworks for both these Directives. In the context of French market surveillance of CE-marked explosives and pyrotechnic articles and in relation to its long-term experience in testing these products, INERIS, has been charged by the French Ministry of Ecological and Solidarity Transition (MTES) of the evaluation of these products since 2006. In this paper, we will give some information about the procedures used by INERIS in the framework of French market surveillance (identification of articles from internet sites, validation of selected articles by French administration, purchase and collection directly in public shops, reception, identification/registration and storage in magazines dedicated for fireworks and explosives located on INERIS site at Verneuil-en-Halatte). Sometimes, inspectors of French Ministry can also collect pyrotechnic articles in warehouses and manufacturing sites during their regular inspections and send them to INERIS for control. Financed by French administration, approximately, 100 pyrotechnic articles per year are subject to conformity assessment in this context. After description of INERIS testing facilities, some general features from recent years (2013-2018) will be discussed in this paper in terms of tested pyrotechnic articles and explosives and relating identified minor, major and critical nonconformities associated to labeling, conception and functioning requirements. An annual report is provided by INERIS to French Ministry that alerts on product non-conformities with French importers and notified bodies responsible for the putting on the market of these articles
Determining the nanoparticle-algae interaction in the bioaccumulation process
No full textInternational audienceThe use of engineered nanomaterials (NMs) raises concern regarding their fate in environmental compartments and their potential effects on aquatic organisms. One of the singularities of these substances is their duality of action, both physical and chemical. In the chain of events leading to the occurrence of a deleterious effect, the interaction between a NM and a biological organism is one essential event. Therefore, understanding the links between the properties of NMs and the physical interaction phenomenon (adhesion, internalization) with aquatic organisms, is essential in a context of a priori hazard assessment and for the categorization of these substances within a regulatory purpose. This work aims at determining the interaction of various NMs with freshwater microalgae, to gain a better understanding of its implication in bioaccumulation and biological effect. Green algae with different cell wall composition were separately exposed to different NMs suspensions. Flow cytometry and microscopic observation showed evidence of NMs-algae interaction. A dose-dependent response is observed for every type of NMs and a cell wall specificity is showed. So far, two parameters were identified as having a major role in the NMalgae interaction: i) the cell wall composition, as each algae had a different response to the set of tested NMs; and ii) the NMs physicchemical properties; because for a given algae cell wall type, a different degree of increased algal complexity was observed according to each NM
