HAL du Programme national de recherche environnement-santé-travail (PNR EST)
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Rapid Detection of Aflatoxins in Ground Maize Using Near Infrared Spectroscopy
No full textInternational audienceAflatoxins are carcinogenic mycotoxins that may contaminate many crops and more especially maize. To protect consumers from these contaminants, many countries set up low regulatory thresholds of few µg/kg. The control of food requires time-consuming analysis for which sampling is a key step. It would therefore of key sanitary and economic relevance to develop rapid, sensitive and accurate methods that could even be applied on line at harvest, to identify batches to be excluded as soon as possible. In this study, we analyzed more than 500 maize samples taken at harvest during 3 years for their aflatoxin contamination using HPLC-MS. Among them, only 7% were contaminated but sometimes at levels largely exceeding European regulations. We demonstrate that Near InfraRed Spectroscopy (NIRS) could be of great help to classify cereal samples according to their level of aflatoxin contamination (below or higher than E.U. regulation). To build the model, all AF contaminated samples as well as an equivalent number of AF free samples were used. NIRS performance was not sufficient to quantify the toxins with adequate precision. However, its ability to discriminate naturally contaminated maize samples according to their level of contamination with aflatoxins in relation to European regulations using a quadratic PCA-DA model was excellent. Accuracy of the model was 97.4% for aflatoxin B1 and 100% for total aflatoxins
Adenomyotic Lesions Are Induced in the Mouse Uterus after Exposure to NSAID and EE2 Mixtures at Environmental Doses
No full textInternational audienceThe aim of this study was to assess the long-term effect of exposure to environmentally relevant doses of non-steroidal anti-inflammatory drugs (NSAIDs; ibuprofen, and diclofenac) and 17β-ethinylestradiol (EE2) on the mouse uterus. NSAID-EE2 mixtures were administered in the drinking water from gestational day 8 until 8 weeks post-birth (i.e., during embryo development, lactation, puberty, and sexual maturity). The incidence of adenomyosis lesions (presence of endometrial glands in the inner myometrium) increased up to 60% in the uterus of 8-week-old exposed females (F1) and to 85% in F2 females (exposed father). Histological analysis revealed aberrant proliferation and apoptosis, vacuolization of epithelial cells, and increased incidence of abnormal glands in the luminal and glandular epithelium in F1 and F2 uteri. Moreover, myofibroblast proportion (alpha-smooth muscle actin (α-SMA) expression analysis) and collagen expression (Picrosirius red stain; a fibrosis hallmark) were increased in F1 and F2 endometrium. Connexin-43 was aberrantly distributed in the endometrial stroma and glands of F1 and F2 uteri. Conversely, uterine 17β-estradiol and progesterone levels were not affected in F1 and F2 females. These findings demonstrated that in mice, chronic exposure to NSAID and EE2 mixtures at environmental doses intergenerationally affects uterine physiology, particularly the endometrium. It may serve as a model to study the pathophysiology of human adenomyosis
Nonlinear compartmental modeling to monitor ovarian follicle population dynamics on the whole lifespan
No full textInternational audienceIn this work, we introduce a compartmental model of ovarian follicle development all along lifespan, based on ordinary differential equations. The model predicts the changes in the follicle numbers in different maturation stages with aging. Ovarian follicles may either move forward to the next compartment (unidirectional migration) or degenerate and disappear (death). The migration from the first follicle compartment corresponds to the activation of quiescent follicles, which is responsible for the progressive exhaustion of the follicle reserve (ovarian aging) until cessation of reproductive activity. The model consists of a datadriven layer embedded into a more comprehensive, knowledge-driven layer encompassing the earliest events in follicle development. The data-driven layer is designed according to the most densely sampled experimental dataset available on follicle numbers in the mouse. Its salient feature is the nonlinear formulation of the activation rate, whose formulation includes a feedback term from growing follicles. The knowledge-based, coating layer accounts for cutting-edge studies on the initiation of follicle development around birth. Its salient feature is the coexistence of two follicle subpopulations of different embryonic origins. We then setup a complete estimation strategy, including the study of theoretical identifiability, the elaboration of a relevant optimization criterion combining different sources of data (the initial dataset on follicle numbers, together with data in conditions of perturbed activation, and data discriminating the subpopulations) with appropriate error models, and a model selection step. We finally illustrate the model potential for experimental design (suggestion of targeted new data acquisition) and in silico experiments
Chronic occupational exposures to irritants and asthma in the CONSTANCES cohort
No full textInternational audienceObjectives The impact of chronic occupational exposures to irritants on asthma remains discussed. We studied the associations between occupational exposures and asthma, with specific interest for chronic exposure to irritants, including disinfectants and cleaning products (DCPs) and solvents. Methods Cross-sectional analyses included 115 540 adults (55% women, mean age 43 years, 10% current asthma) working at inclusion in the French population-based CONSTANCES cohort (2012–2020). Current asthma was defined by ever asthma with symptoms, medication or asthma attacks (past 12 months), and the asthma symptom score by the sum of 5 respiratory symptoms (past 12 months). Both lifetime and current occupational exposures were assessed by the Occupational Asthma-specific Job-Exposure Matrix. Associations were evaluated by gender using logistic and binomial negative regressions adjusted for age, smoking status and body mass index. Results In women, associations were observed between current asthma and lifetime exposure to irritants (OR 1.05, 95% CI 1.00 to 1.11), DCPs (1.06, 95% CI 1.00 to 1.12) and solvents (1.06, 95% CI 0.98 to 1.14). In men, only lifetime exposure to DCPs (1.10, 95% CI 1.01 to 1.20) was associated with current asthma. Lifetime exposure to irritants was associated with higher asthma symptom score both in women (mean score ratio: 1.08, 95% CI 1.05 to 1.11) and men (1.11, 95% CI 1.07 to 1.15), especially for DCPs (women: 1.09, 95% CI 1.06 to 1.13, men: 1.21, 95% CI 1.15 to 1.27) and solvents (women 1.14, 95% CI 1.10 to 1.19, men: 1.10, 95% CI 1.05 to 1.15). For current exposures, no consistent associations were observed with current asthma and asthma symptom score. Conclusions Lifetime occupational exposures to irritants were associated with current asthma and higher asthma symptom score. These exposures should be carefully considered in asthma management
ToF-SIMS imaging shows specific lipophilic vitamin alterations in chronic reprotoxicity caused by the emerging contaminant Pravastatin in Gammarus fossarum.
No full textInternational audienceBlood lipid-lowering agents, such as Pravastatin, are among the most frequently used pharmaceuticals released into the aquatic environment. Although their effects on humans are very well understood, their consequences on freshwater organisms are not well known, especially in chronic exposure conditions. Gammarus fossarum is commonly used as sentinel species in ecotoxicology because of its sensitivity to a wide range of environmental contaminants and the availability of standardized bioassays. Moreover, there is an increased interest in linking molecular changes in sentinel species, such as gammarids, to observed toxic effects. Here, we performed a reproductive toxicity assay on females exposed to different concentrations of pravastatin (30; 300; 3,000 and 30,000 ng L−1) during two successive reproductive cycles and we applied ToF-SIMS imaging to evaluate the effect of pravastatin on lipid homeostasis in gammarids. Reproductive bioassay showed that pravastatin could affect oocyte development in Gammarus fossarum inducing embryotoxicity in the second reproductive cycle. Mass spectrometry imaging highlighted the disruption in vitamin E production in the oocytes of exposed female gammarids at the second reproductive cycle, while limited alterations were observed in other lipid classes, regarding both production and tissue distribution. The results demonstrated the interest of applying spatially resolved lipidomics by mass spectrometry imaging to assess the molecular effects induced by long-term exposure to environmental pharmaceutical residues in sentinel species
Biocide and other semi-volatile organic compound concentrations in settled indoor dust of CRESPI daycare centers and implication for public health
No full textInternational audienceThis study investigates the presence of biocides and other semi-volatile organic compounds (SVOCs) in cleaning products used in daycare centers and health impact through ingestion of settled dust by young children. In Paris metropolitan, 106 daycares area were investigated between 2019-2022. Fifteen substances were analyzed in settled indoor dust by gas chromatography-tandem mass spectrometry. Detection rates and concentrations ranged from 5 to 100%, an
L’alimentation, source d’exposition précoce aux perturbateurs endocriniens: L'alimentation, source d'exposition précoce aux perturbateurs endocriniens Exposition précoce aux Perturbateurs ENDocriniens via l'ALImentation et santé REspiratoire des enfants
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Le rôle des perturbateurs endocriniens dans l’apparition et le développement des maladies hépatiques: La larve de poisson-zèbre comme modèle d’étude in vivo pour évaluer les effets cocktail de perturbateurs endocriniens sur la progression pathologique des NAFLD
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Early-life exposures to phenols, parabens and phthalates and preschool children fat mass in the SEPAGES cohort
No full textInternational audienceObjective: Short half-life chemicals may play a role in adiposity growth. Most early-life studies relied on one or few urine samples, which inadequately represents exposure over the course of pregnancy or early infancy. In addition, childhood adiposity is often estimated from body mass index that doesn’t not accurately represent body composition. Our aim was to investigate associations between early-life exposures to phenols, parabens and phthalates and fat mass percent at three years. We further assessed potential effect modification by sex. Material and Methods: In SEPAGES cohort, we measured 8 phenols, 4 parabens, 13 phthalates and 2 non-phthalate plasticizer metabolites from weekly pooled urine sample collected from 341 mothers during pregnancy (three urine samples a day, median 18 and 34 gestational weeks), and from their infant (one urine sample a day, at 2 (phenols only) and 12 months). Children had a clinical exam around three years of age with standardized measurements of skinfold thickness and bioelectrical impedance analysis (BodyStat 1500 MDD). Fat mass percent was computed using the Goran equation. Associations between each exposure biomarker and fat mass were investigated using adjusted linear regression models.Results: Urinary levels of bisphenol S, mono-benzyl phthalate (MBzP), monoethyl phthalate (MEP) and mono-n-butyl phthalate at second trimester were positively associated with percent fat mass at three years of age. Exposure to triclosan at third trimester was negatively associated with fat mass percent. During pregnancy MBzP and MEP showed effect modification by sex, after gender stratification positive associations were stronger among girls. There were no significant results for postnatal exposures. Conclusion: This study suggests associations between prenatal exposures to short half-life chemicals and percent fat mass in preschool children, a risk factor of obesity in later-life. Furthermore, this study showed an impact of prenatal bisphenol S exposure, highlighting the need for investigation of this overlooked compound
Intra-breath changes in respiratory mechanics are sensitive to history of respiratory illness in preschool children: the SEPAGES cohort
No full textInternational audienceBackground: Intra-breath oscillometry has been proposed as a sensitive means of detecting airway obstruction in young children. We aimed to assess the impact of early life wheezing and lower respiratory tract illness on lung function, using both standard and intra-breath oscillometry in 3 year old children.Methods: History of doctor-diagnosed asthma, wheezing, bronchiolitis and bronchitis and hospitalisation for respiratory problems were assessed by questionnaires in 384 population-based children. Association of respiratory history with standard and intra-breath oscillometry parameters, including resistance at 7 Hz (R7), frequency-dependence of resistance (R7-19), reactance at 7 Hz (X7), area of the reactance curve (AX), end-inspiratory and end-expiratory R (Rel, ReE) and X (XeI, XeE), and volume-dependence of resistance (ΔR = ReE - Rel) was estimated by linear regression adjusted on confounders.Results: Among the 320 children who accepted the oscillometry test, 281 (88%) performed 3 technically acceptable and reproducible standard oscillometry measurements and 251 children also performed one intra-breath oscillometry measurement. Asthma was associated with higher Rel, ReE, ΔR and R7 and wheezing was associated with higher ΔR. Bronchiolitis was associated with higher R7 and AX and lower Xel and bronchitis with higher Rel. No statistically significant association was observed for hospitalisation.Conclusions: Our findings confirm the good success rate of oscillometry in 3-year-old children and indicate an association between a history of early-life wheezing and lower respiratory tract illness and lower lung function as assessed by both standard and intra-breath oscillometry. Our study supports the relevance of using intra-breath oscillometry parameters as sensitive outcome measures in preschool children in epidemiological cohorts