38 research outputs found

    Effects of co-exposure to CS2 and noise on hearing and balance in rats: continuous versus intermittent CS2 exposures

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    Background: carbon disulfide (CS2) exacerbates the effect of noise on hearing, and disrupts the vestibular system. The goal of this study was to determine whether these effects are also observed with intermittent CS2 exposure. Methods: rats were exposed for 4 weeks (5 days/week, 6 h/day) to a band noise at 106 dB SPL either alone or combined with continuous (63 ppm or 250 ppm) or intermittent (15 min/h or 2 Ă— 15 min/h at 250 ppm) CS2. Hearing function was assessed by measuring distortion product otoacoustic emissions (DPOAEs); balance was monitored based on the vestibulo-ocular reflex (VOR). Functional measurements were performed before, at the end of exposure and 4 weeks later. Histological analyses of the inner ear were also performed following exposure and after the 4-week recovery period. Results: the results obtained here confirmed that CS2 exposure exerts two differential temporary effects on hearing: (1) it attenuates the noise-induced DPOAE decrease below 6 kHz probably through action on the middle ear reflex when exposure lasts 15 min per hour, and (2) continuous exposure to 250 ppm for 6 h extends the frequency range affected by noise up to 9.6 kHz (instead of 6 kHz with noise alone). With regard to balance, the VOR was reversibly disrupted at the two highest doses of CS2 (2 Ă— 15 min/h and continuous 250 ppm). No morphological alterations to the inner ear were observed. Conclusion: these results reveal that short periods of CS2 exposure can alter the sensitivity of the cochlea to noise at a dose equivalent to only 10 times the short-term occupational limit value, and intermittent exposure to CS2 (2 Ă— 15 min/h) can alter the function of the vestibular system

    Contribution à l'étude de l'adsorption et de la désorption de composés organiques volatils chlorés sur charbons actifs

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    Ce travail de thèse est consacré à l'étude de l'adsorption et de la désorption de l'eau et de composés organiques volatils (COVs) chlorés en mode statique (isothermes d'adsorption) et en mode dynamique (courbes de percée) sur des charbons actifs (CAs) de diverses natures (CAs granulaires et fibres de carbone activées). Le but visé est la séparation des constituants d'un mélange de COVs chlorés sur lit fixe de CA en présence ou non de vapeur d'eau. Nous avons montré que la texture poreuse et la chimie de surface des matériaux ainsi que les caractéristiques physico-chimique des sondes ont un rôle prépondérant sur leurs mécanismes et leurs cinétiques d'adsorption (ou de désorption). Une attention particulière a été portée sur l'influence de la présence d'humidité : aux forts taux d'humidité relative, les propriétés d'adsorption (capacité et cinétique) des CAs vis à vis des COVs sont considérablement affectées. La séparation du couple dichlorométhane/trichloroéthylène est très satisfaisante quelles soient les conditions expérimentales. Enfin, une étude exploratoire sur les possibilités d'hydrophobisation des CAs par greffage de groupements apolaires en phase liquide a été entreprise pour limiter les effets de la présence d'eau.Adsorption and desorption of water and chlorinated volatile organic compounds (VOCs) in static (adsorption isotherms) and dynamic conditions (breakthrough curves) have been performed on different activated carbons (ACs) (granulated ACs and activated carbons fibers) with different textural characteristics and surface chemistry. The main objective of this study is to separate the different component of a chlorinated VOCs mixture in the presence or not of water vapor. It appears that both porous texture and surface chemistry of ACs as physicochemical characteristics of the probes have a strong influence on their adsorption (or desorption) process (mechanism and kinetics). A special attention has been drawn on the influence of the water presence: at high relative humidity rate, ACs adsorption properties (adsorbed amount and kinetics) for chlorinated VOCs are strongly affected. Separation of the dichloromethane/trichloroethylene mixture has been successfully realized whatever the experimental conditions. Last, an exploratory study on the AC hydrophobisation possibilities by the graphting of non-polar groups in liquid phase has been undertaken in order to limit the water presence effects.NANCY1-SCD Sciences & Techniques (545782101) / SudocSudocFranceF

    Étude de la neurotoxicité d'un Polluant Organique Persistant chez le rat (effets à court et à long terme de l'inhalation répétée de fluorène sur le développement sensori-moteur du jeune et le comportement à l'âge adulte)

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    La pollution atmosphérique est omniprésente du fait de nombreuses sources émettrices de composés chimiques. Dans ce contexte, les Hydrocarbures Aromatiques Polycycliques (HAP) sont largement diffusés dans l air et ont déjà montré des effets délétères sur la santé.Ce travail a consisté en l évaluation de la neurotoxicité du fluorène, composé choisi comme molécule représentative de la pollution liée aux HAP, chez le rat adulte exposé par voie i.p., par voie orale ou par inhalation. Le modèle d exposition par inhalation a ensuite été appliqué à l étude des effets du polluant sur le développement sensori-moteur et l activité comportementale de l animal exposé in utero ou au cours de la lactation.Ces études ont montré que le fluorène était susceptible d affecter le niveau d anxiété et l activité locomotrice du rat adulte exposé directement et indirectement au polluant, et n avait aucun effet sur les capacités d apprentissage. En revanche, aucune atteinte majeure de la maturation des fonctions sensori-motrices n a été mise en évidence. L analyse de la présence du composé et de trois de ses métabolites a par ailleurs montré que le polluant était capable de traverser la barrière hémato-encéphalique et d être métabolisé au niveau du cerveau. Les réponses physiologiques et comportementales étant variables entre les études, les effets induits par le fluorène dépendent donc de la voie d entrée, du niveau de contamination et du moment d exposition.Ces résultats ont ainsi révélé chez l animal la toxicité comportementale du fluorène à des niveaux de contamination réalistes, confirmant ainsi le risque sanitaire de l exposition aux HAP tout au long de la vie des individusActually air pollution is ubiquitous due to the emission of chemical compound from many sources. In this context, Polycyclic Aromaric Hydrocarbons (PAH)related compounds are widely distributed in the air and have shown deleterious health effects.Fluorene was chosen as a representative compound of PAHs pollution. This work consisted in the evaluation of its neurotoxic effects in adult animals, exposed i.p., orally or by exposure nose-only. The inhalation model of exposure was then applied to the study of its effects on sensorimotor development and on behavioral activity of animals exposed in utero or during lactation.The results showed that fluorene is able to induce behavioral changes in adult animals exposed directly or indirectly on the level of anxiety and the locomotor activity, whereas no effect on learning and memory abilities has been observed. However, no defect on the development of motor and sensory functions was demonstrated. Furthermore, the analysis of the presence of the compound and three of its metabolites showed that the pollutant was able to cross the blood brain barrier and can be metabolized in the brain. Moreover, variations have been observed concerning behavioral and physiological responses between studies, showing that effects induced by fluorene are dependent on the way of administration, the level of contamination and the time of exposure.In conclusion, these results demonstrate in animals the behavioral toxicity of fluorene at levels of contamination corresponding to human cases of exposure, confirming so the risk of PAH exposure throughout lifeNANCY-INPL-Bib. électronique (545479901) / SudocSudocFranceF

    An update of skin permeability data based on a systematic review of recent research

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    Abstract The cutaneous absorption parameters of xenobiotics are crucial for the development of drugs and cosmetics, as well as for assessing environmental and occupational chemical risks. Despite the great variability in the design of experimental conditions due to uncertain international guidelines, datasets like HuskinDB have been created to report skin absorption endpoints. This review updates available skin permeability data by rigorously compiling research published between 2012 and 2021. Inclusion and exclusion criteria have been selected to build the most harmonized and reusable dataset possible. The Generative Topographic Mapping method was applied to the present dataset and compared to HuskinDB to monitor the progress in skin permeability research and locate chemotypes of particular concern. The open-source dataset (SkinPiX) includes steady-state flux, maximum flux, lag time and permeability coefficient results for the substances tested, as well as relevant information on experimental parameters that can impact the data. It can be used to extract subsets of data for comparisons and to build predictive models

    Biomarkers of toluene exposure in rats: mercapturic acids versus traditional indicators (urinary hippuric acid and o -cresol and blood toluene)

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    International audience1. Toluene (TOL) is a neurotoxic, ototoxic and reprotoxic solvent which is metabolized via the glutathione pathway, producing benzylmercapturic, o-, m-and p-toluylmercapturic acids (MAs). These metabolites could be useful as biomarkers of TOL exposure. 2. The aims of this work were 1) to provide data on MAs excretion in rat urine following TOL exposure by inhalation, 2) to compare them to data from traditional TOL biomarkers i.e., TOL in blood (Tol-B), and urinary hippuric acid (HA) and o-cresol (oCre), and 3) to establish the relationships between these different indicators and the airborne TOL concentration (Tol-A). 3. Sprague-Dawley rats were exposed to a range of TOL concentrations. Blood and urine were collected and analyzed to determine biomarker levels. 4. Levels of the four MAs correlate strongly with Tol-A (comparable to the correlation with Tol-B). 5. MAs are thus clearly superior to oCre and HA as potential markers of exposure to TOL.Le toluène (TOL) est un solvant CMR qui peut être métabolisé par la voie du glutathion, ce qui conduit à la production de quatre acides mercapturiques (AMs) : les acides benzylmercapturique et o-, m-et p-toluylmercapturique. Ces métabolites peuvent être utiles en tant que d’indicateurs biologiques d'exposition au TOL. Les objectifs de ce travail étaient : de fournir des données sur l'excrétion des AMs dans l'urine de rat après une exposition par inhalation au TOL ; de les comparer aux données obtenues avec les biomarqueurs traditionnels du TOL i.e. le toluène sanguin (Tol-S), et les indicateurs urinaires que sont l'acide hippurique (AH) et l’o-crésol (oCre) et d'établir les relations entre ces différents indicateurs et la concentration atmosphérique en TOL (Tol-A). Pour cela, des rats Sprague-Dawley ont été exposés à différents niveaux de TOL. Leur sang et leurs urines ont été prélevés et analysés afin de déterminer les niveaux de chaque biomarqueur. Il a ainsi été établi que les niveaux des quatre AMs étaient fortement corrélés avec ToL-A (comparable à la celle observée avec Tol-S). En conclusion, il apparait que les AMs sont nettement supérieurs à AH et oCre en tant que marqueurs potentiels de l'exposition au TOL

    Exposure to TiO2 Nanostructured Aerosol Induces Specific Gene Expression Profile Modifications in the Lungs of Young and Elderly Rats

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    Although aging is associated with a higher risk of developing respiratory pathologies, very few studies have assessed the impact of age on the adverse effects of inhaled nanoparticles. Using conventional and transcriptomic approaches, this study aimed to compare in young (12–13-week-old) and elderly (19-month-old) fisher F344 rats the pulmonary toxicity of an inhaled nanostructured aerosol of titanium dioxide (TiO2). Animals were nose-only exposed to this aerosol at a concentration of 10 mg/m3 for 6 h per day, 5 days per week for 4 weeks. Tissues were collected immediately (D0), and 28 days after exposure (D28). A pulmonary influx of neutrophilic granulocytes was observed in exposed rats at D0, but diminished with time while remaining significant until D28. Similarly, an increased expression of several genes involved in inflammation at the two post-exposure time-points was seen. Apart from an age-specific pulmonary influx of lymphocyte, only slight differences in physio-pathological responses following TiO2 exposure between young and elderly animals were noticed. Conversely, marked age-related differences in gene expression profiles were observed making possible to establish lists of genes specific to each age group and post-exposure times. These results highlight different signaling pathways that were disrupted in rats according to their age
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