HAL du Programme national de recherche environnement-santé-travail (PNR EST)
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Modèles expérimentaux pour l'étude des effets de l'acétomiphène et des AINS sue la fonction de reproduction
No full textInternational audienceNonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin (acetylsalicylic acid), diclofenac and ibuprofen (IBU), and analgesic drugs, such as acetaminophen (APAP, or paracetamol), are widely used to treat inflammation and pain. APAP and IBU are over-the-counter drugs and are among the most commonly taken drugs in the first trimester of pregnancy, even in combination. Furthermore, these drugs and their metabolites are released in the environment, and can be frequently detected in wastewater, surface water, and importantly in drinking water. Although their environmental concentrations are much lower than the therapeutics doses, this suggests an uncontrolled low-dose exposure of the general population, including pregnant women and young children, two particularly at risk populations. Epidemiological studies show that exposure to these molecules in the first and second trimester of gestation can favor genital malformations in new-born boys. To investigate the cellular, molecular and mechanistic effects of exposure to these molecules, ex vivo studies with human or rodent gonadal explants and in vivo experiments in rodents have been performed in the past years. This review recapitulates recent data obtained in rodent models after in utero or postnatal exposure to these drugs. The first part of this review discusses the mechanisms by which NSAIDs and analgesics may impair gonadal development and maturation, puberty development, sex hormone production, maturation and function of adult organs, and ultimately fertility in the exposed animals and their offspring. Like other endocrine disruptors, NSAIDs and APAP interfere with endocrine gland function and may have inter/transgenerational adverse effects. Particularly, they may target germ cells, resulting in reduced quality of male and female gametes, and decreased fertility of exposed individuals and their descendants. Then, this review discusses the effects of exposure to a single drug (APAP, aspirin, or IBU) or to combinations of drugs during early embryogenesis, and the consequences on postnatal gonadal development and adult reproductive health. Altogether, these data may increase medical and public awareness about these reproductive health concerns, particularly in women of childbearing age, pregnant women, and parents of young children
River Biofilms Microbiome and Resistome Responses to Wastewater Treatment Plant Effluents Containing Antibiotics
No full textInternational audienceContinuous exposure to low concentrations of antibiotics (sub-minimal inhibitory concentration: sub-MIC) is thought to lead to the development of antimicrobial resistance (AMR) in the environmental microbiota. However, the relationship between antibiotic exposure and resistance selection in environmental bacterial communities is still poorly understood and unproven. Therefore, we measured the concentration of twenty antibiotics, resistome quality, and analyzed the taxonomic composition of microorganisms in river biofilms collected upstream (UPS) and downstream (DWS) (at the point of discharge) from the wastewater treatment plant (WWTP) of Poitiers (France). The results of statistical analysis showed that the antibiotic content, resistome, and microbiome composition in biofilms collected UPS were statistically different from that collected DWS. According to Procrustes analysis, microbial community composition and antibiotics content may be determinants of antibiotic resistance genes (ARGs) composition in samples collected DWS. However, network analysis showed that the occurrence and concentration of antibiotics measured in biofilms did not correlate with the occurrence and abundance of antibiotic resistance genes and mobile genetic elements. In addition, network analysis suggested patterns of co-occurrence between several ARGs and three classes of bacteria/algae: Bacteroidetes incertae sedis , Cyanobacteria / Chloroplast , and Nitrospira , in biofilm collected UPS. The absence of a direct effect of antibiotics on the selection of resistance genes in the collected samples suggests that the emergence of antibiotic resistance is probably not only due to the presence of antibiotics but is a more complex process involving the cumulative effect of the interaction between the bacterial communities (biotic) and the abiotic matrix. Nevertheless, this study confirms that WWTP is an important reservoir of various ARGs, and additional efforts and legislation with clearly defined concentration limits for antibiotics and resistance determinants in WWTP effluents are needed to prevent their spread and persistence in the environment
In Vivo Functional Ultrasound (fUS) Real‐Time Imaging and Dosimetry of Mice Brain Under Radiofrequency Exposure
No full textInternational audienceThis study aims to analyze in real-time the potential modifications induced by low-level continuous-wave and Global System for Mobile Communications radiofrequency (RF) exposure at 1.8 GHz on brain activation in anesthetized mice. A specific in vivo experimental setup consisting of a dipole antenna for the local exposure of the brain was fully characterized. A unique neuroimaging technique based on a functional ultrasound (fUS) probe was used to observe the areas of mice brain activation simultaneously to the RF exposure with unprecedented spatial and temporal resolution (~100 μm, 1 ms) following manual whisker stimulation using a brush. Numerical and experimental dosimetry was carried out to characterize the exposure and to guarantee the validity of the biological results. Our results show that the fUS probe can be efficiently used during in vivo exposure without interference with the dipole. In addition, we conclude that exposure to brain-averaged specific absorption rate levels of 2 and 6 W/kg does not introduce significant changes in the time course of the evoked fUS response in the left barrel field cortex. The proposed technique represents a valuable instrument for providing new insights into the possible effects induced on brain activation under RF exposure. For the first time, brain activity under mobile phone exposure was evaluated in vivo with fUS imaging, paving the way for more realistic exposure configurations, i.e. awake mice and new signals such as the 5 G networks. © 2022 Bioelectromagnetics Society
Bacteriophages vehiculate a high amount of antibiotic resistance determinants of bacterial origin in the Orne River ecosystem
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Risk factors for shoulder disorders among French workers: prospective cohort study
No full textInternational audienceObjectives: Shoulder disorders are common in the working population. This longitudinal study aimed to explore the relationships between personal factors and occupational organisational, psychosocial, and biomechanical factors and the incidence of shoulder disorders.Methods: A total of 3710 workers in the Pays de la Loire region (Loire Valley area, France) were randomly included by their occupational physician in the Cosali cohort between 2002 and 2005. All workers completed a self-administered questionnaire about personal factors and work exposure, and using a standardised physical examination, occupational physicians diagnosed shoulder disorders. Between 2007 and 2010, 1611 workers were re-examined by their occupational physician. The 1,320 workers free of shoulder disorders at baseline were studied. A conceptual model was developed in which relationships between organisational, psychosocial, biomechanical, and personal factors at baseline and the incidence of shoulder disorders were assumed. Structural equation modelling was used to test the model.Results: Shoulder disorders were directly associated with biomechanical factors and age but not with psychosocial factors. However, skill discretion and psychological demand influenced shoulder disorders indirectly through biomechanical factors. Exposure to a work pace dependent on an automatic rate and to a work pace dependent on customers' demands were associated with biomechanical and psychosocial factors, but not directly to shoulder disorders.Conclusions: This study identified the complex direct and indirect relationships between occupational factors and shoulder disorders. Our data confirmed our conceptual causation model: organisational and psychosocial factors were associated with biomechanical factors, while biomechanical factors were associated with the incidence of shoulder disorders
Survey of Exposure to RF Electromagnetic Fields in the Connected Car
No full textInternational audienceFuture vehicles will be increasingly connected to enable new applications and improve safety, traffic efficiency and comfort, through the use of several wireless access technologies, ranging from vehicle-to-everything (V2X) connectivity to automotive radar sensing and Internet of Things (IoT) technologies for intra-car wireless sensor networks. These technologies span the radiofrequency (RF) range, from a few hundred MHz as in intra-car network of sensors to hundreds of GHz as in automotive radars used for in-vehicle occupant detection and advanced driver assistance systems. Vehicle occupants and road users in the vicinity of the connected vehicle are thus daily immersed in a multi-source and multi-band electromagnetic field (EMF) generated by such technologies. This paper is the first comprehensive and specific survey about EMF exposure generated by the whole ensemble of connectivity technologies in cars. For each technology we describe the main characteristics, relevant standards, the application domain, and the typical deployment in modern cars. We then extensively describe the EMF exposure scenarios resulting from such technologies by resuming and comparing the outcomes from past studies on the exposure in the car. Results from past studies suggested that in no case EMF exposure was above the safe limits for the general population. Finally, open challenges for a more realistic characterization of the EMF exposure scenario in the connected car are discussed
Experimental Exposure to Tebuconazole Affects Metabolism and Body Condition in a Passerine Bird, the House Sparrow ( Passer domesticus )
No full textInternational audienceTriazole compounds are among the most widely used fungicides in agroecosystems to protect crops from potential fungal diseases. Triazoles are suspected to have an impact on nontarget species due to their interactions with nonfungal sterol synthesis, and wild birds are likely to be contaminated by triazole fungicides because many of them live in agroecosystems. We experimentally tested whether exposure to environmental concentrations of a triazole could alter key integrative traits (metabolic rates and body condition) of an agroecosystem sentinel species, the house sparrow (Passer domesticus). Wild-caught adult sparrows were maintained in captivity and exposed (exposed group) or not (control group) for 7 continuous months to tebuconazole through drinking water. The metabolic rates of exposed and control sparrows were then measured at two different temperatures (12 °C and 25 °C), which correspond, respectively, to the thermoregulation and thermoneutrality temperatures of this species. We found that exposed sparrows had lower resting metabolic rates (i.e., measured at thermoneutrality, 25 °C) than controls. However, the thermoregulatory metabolic rates (i.e., measured at 12 °C) did not differ between exposed and control sparrows. Although the body mass and condition were not measured at the beginning of the exposure, sparrows at the time of the metabolic measurements 7 months after the onset of such exposure had a higher body condition than controls, supporting further the idea that tebuconazole affects metabolic functions. Our study demonstrates for the first time that the use of tebuconazole can alter metabolism and could potentially lead to adverse effects in bird
Tracking the immune response by MRI using biodegradable and ultrasensitive microprobes
No full textInternational audienceMolecular magnetic resonance imaging (MRI) holds great promise for diagnosis and therapeutic monitoring in a wide range of diseases. However, the low intrinsic sensitivity of MRI to detect exogenous contrast agents and the lack of biodegradable microprobes have prevented its clinical development. Here, we synthetized a contrast agent for molecular MRI based on a previously unknown mechanism of self-assembly of catechol-coated magnetite nanocrystals into microsized matrix-based particles. The resulting biodegradable microprobes (M3P for microsized matrix-based magnetic particles) carry up to 40,000 times higher amounts of superparamagnetic material than classically used nanoparticles while preserving favorable biocompatibility and excellent water dispersibility. After conjugation to monoclonal antibodies, targeted M3P display high sensitivity and specificity to detect inflammation in vivo in the brain, kidneys, and intestinal mucosa. The high payload of superparamagnetic material, excellent toxicity profile, short circulation half-life, and widespread reactivity of the M3P particles provides a promising platform for clinical translation of immuno-MRI
Tropospheric Ozone Alters the Chemical Signal Emitted by an Emblematic Plant of the Mediterranean Region: The True Lavender (Lavandula angustifolia Mill.)
No full textInternational audienceAmong air pollutants, tropospheric ozone (O3) is one of the most stressful for organisms due to its strong oxidative potential. For instance, high ozone concentration ([O3]) has the potential to affect (i) the emission of volatile organic compounds (VOCs) by plants and (ii) the lifetime of these VOCs in the atmosphere, and consequently disturb crucial signals in the interactions between plants and other organisms. However, despite the determinant role of VOCs emitted by flowers for pollinator attraction, a very limited number of studies have investigated the impact of O3 on floral VOCs. In this study, we investigated the effect of high [O3] episodes on the VOCs emitted by a flowering Mediterranean plant: the true lavender (Lavandula angustifolia Mill., Lamiaceae). To do so, in controlled conditions, we exposed (i) the entire plant to high but realistic [O3] (200 ppb for 5 h) and (ii) only the VOCs emitted by lavender to increasing [O3] (0, 40, 80, 120, and 200 ppb). We sampled VOCs of lavender in both conditions and analyzed them by Gas Chromatography-Mass Spectrometry in order to qualify and quantify the flowering lavender’s emissions and the reaction of VOCs with O3 in the atmosphere. Our results showed that exposure to high [O3] during a short period (5 h) did not affect the emission of VOCs by flowering lavender. Incidentally, we also showed that the chemical signal varied in quantities and proportions over the day. Moreover, we showed that after their emission by the plant, composition of the VOCs changed quantitatively and qualitatively in an atmosphere containing [O3] naturally observed nowadays. Quantities of several of the major terpenes emitted by lavender decreased drastically during O3 exposure, whereas concentrations of some VOCs increased, such as carbonyls and carboxylic acids, which are probably reaction products of terpenes with O3. Exposure to high [O3] thus directly affected the proportions of VOCs in the atmosphere. Because pollinators generally use a blend of VOCs in particular proportions as a signal to localize flowers, the numerous pollinators of lavender may experience difficulty in recognizing specific floral odors during frequent and moderate [O3] episodes in the Mediterranean region.</p
Predicting mosquito repellents for clothing application from molecular fingerprint-based artificial neural network SAR models
No full textInternational audienceSpraying repellents on clothing limits toxicity and allergy problems that can occur when the repellents are directly applied to skin. This also allows the use of higher doses to ensure longer lasting effects. As the number of repellents available on the market is limited, it is necessary to propose new ones, especially by using in silico methods that reduce costs and time. In this context SAR models were built from a dataset of 2027 chemicals for which repellent activity on clothing was measured against Aedes aegypti. The interest of using either the ECFP or MACCS fingerprints as input neurons of a three-layer perceptron was evaluated. Transformation of MACCS bit strings into disjunctive tables led to interesting results. Models obtained with both types of fingerprints were compared to a model including physicochemical and topological descriptors