HAL du Programme national de recherche environnement-santé-travail (PNR EST)
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Development of a standardized in vitro approach to evaluate microphysical, chemical, and toxicological properties of combustion-derived fine and ultrafine particles
No full textInternational audienceUltrafine particles represent a growing concern in the public health community but their precise role in many illnesses is still unknown. This lack of knowledge is related to the experimental difficulty in linking their biological effects to their multiple properties, which are important determinants of toxicity. Our aim is to propose an interdisciplinary approach to study fine (FP) and ultrafine (UFP) particles, generated in a controlled manner using a miniCAST (Combustion Aerosol Standard) soot generator used with two different operating conditions (CAST1 and CAST3). The chemical characterization was performed by an untargeted analysis using ultra-high resolution mass spectrometry. In conjunction with this approach, subsequent analysis by gas chromatography–mass spectrometry (GC–MS) was performed to identify polycyclic aromatic hydrocarbons (PAH). CAST1 enabled the generation of FP with a predominance of small PAH molecules, and CAST3 enabled the generation of UFP, which presented higher numbers of carbon atoms corresponding to larger PAH molecules. Healthy normal human bronchial epithelial (NHBE) cells differentiated at the air-liquid interface (ALI) were directly exposed to these freshly emitted FP and UFP. Expression of MUC5AC, FOXJ1, OCLN and ZOI as well as microscopic observation confirmed the ciliated pseudostratified epithelial phenotype. Study of the mass deposition efficiency revealed a difference between the two operating conditions, probably due to the morphological differences between the two categories of particles. We demonstrated that only NHBE cells exposed to CAST3 particles induced upregulation in the gene expression of IL-8 and NQO1. This approach offers new perspectives to study FP and UFP with stable and controlled properties
Cardiac Cell Exposure to Electromagnetic Fields: Focus on Oxdative Stress and Apoptosis
No full textInternational audienceExposure to electromagnetic fields (EMFs) is a sensitive research topic. Despite extensive research, to date there is no evidence to conclude that exposure to EMFs influences the cardiovascular system. In the present study, we examined whether 915 MHz EMF exposure affects myocardial antioxidative and apoptotic status in vitro and in vivo. No statistically significant difference in the apoptotic cell profile and antioxidant capacity was observed between controls and short-term EMF-exposed mouse cardiomyocytes and H9C2 cardiomyoblasts. Compared with sham-exposed controls, mice subjected to a 915 MHz EMF for 48 h and 72 h had no significant effect on structural tissue integrity and myocardial expression of apoptosis and antioxidant genes. Therefore, these results indicate that short-term exposure to EMF in cardiac cells and tissues did not translate into a significant effect on the myocardial antioxidant defense system and apoptotic cell death
Diabetes, metabolic syndrome and prostate cancer risk: Results from the EPICAP case-control study
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Hepatic metabolism of chlorinated derivatives of bisphenol A (ClxBPA) and interspecies differences between rats and humans
No full textInternational audienceDuring chlorination treatments of drinking water, aqueous bisphenol A (BPA) can react with chlorine to form chlorinated derivatives of BPA (mono, di, tri and tetra-chlorinated derivatives) or Cl(x)BPA. These emerging substances are endocrine disruptors associated with obesity, type II diabetes (TD2M) and myocardial infarction. Cl(x)BPA are present in different human biological matrices but their toxicokinetics remain unknown. The aim of this study was to measure and compare the metabolic kinetics in the liver of four Cl(x)BPA (ClBPA, Cl(2)BPA, Cl(3)BPA and Cl(4)BPA) between compounds and between species (Sprague-Dawley rats vs humans). To estimate their metabolic constants (V-max, K-m, Intrinsic clearance), metabolic assays were performed in hepatocyte suspensions. Assays revealed that metabolic constants of Cl(x)BPA can greatly vary depending on substances and species. While ClBPA and Cl(2)BPA show similar unbound intrinsic clearances (ClintU) in rat incubation media, values for Cl(3)BPA and Cl(4)BPA are very different (3.109 and 0.684 mL/min/106 hepatocytes, respectively). Unlike in rats, human results are quite different as Cl(3)BPA and Cl(4)BPA have similar unbound intrinsic clearances, while ClBPA and Cl(2)BPA diverge (0.350 and 1.363 mL/min/106 hepatocytes, respectively). In both species, Cl(2)BPA and Cl3BPA have relatively similar clearances, and ClBPA is very different from Cl(4)BPA. Although we quantified the proportion of sulfo- and glucurono-metabolites, other metabolites may have been formed (e.g., glutathione, disulfate, or oxidative metabolites). This study showed that chlorination had an impact on hepatic intrinsic clearance of Cl(x)BPA in rats and humans and measured values will be valuable for the development of PBPK models for use in exposure assessment
Repeated exposure of macrophages to synthetic amorphous silica induces adaptive proteome changes and a moderate cell activation
No full textInternational audienceSynthetic amorphous silica (SAS) is a nanomaterial used in a wide variety of applications, including the use as a food additive. Two types of SAS are commonly employed as a powder additive, precipitated silica and fumed silica. Numerous studies have investigated the effects of synthetic amorphous silica on mammalian cells. However, most of them have used an exposure scheme based on a single dose of SAS. In this study, we have used instead a repeated 10-day exposure scheme in an effort to better simulate the occupational exposure encountered in daily life by consumers and workers. As a biological model, we have used the murine macrophage cell line J774A.1, as macrophages are very important innate immune cells in the response to particulate materials. In order to obtain a better appraisal of the macrophage responses to this repeated exposure to SAS, we have used proteomics as a wide-scale approach. Furthermore, some of the biological pathways detected as modulated by the exposure to SAS by the proteomic experiments have been validated through targeted experiments. Overall, proteomics showed that precipitated SAS induced a more important macrophage response than fumed SAS at equal dose. Nevertheless, validation experiments showed that most of the responses detected by proteomics are indeed adaptive, as the cellular homeostasis appeared to be maintained at the end of the exposure. For example, the intracellular glutathione levels or the mitochondrial transmembrane potential at the end of the 10 days exposure were similar for SAS-exposed cells and for unexposed cells. Similarly, no gross lysosomal damage was observed after repeated exposure to SAS. Nevertheless, important functions of macrophages such as phagocytosis, TNF alpha, and interleukin-6 secretion were up-modulated after exposure, as was the expression of important membrane proteins such as the scavenger receptors, MHC-II, or the MAC-1 receptor. These results suggest that repeated exposure to low doses of SAS slightly modulates the immune functions of macrophages, which may alter the homeostasis of the immune system
Évaluation des effets d'une contamination chimique complexe d'origine industrielle d'un petit cours d'eau forestier (Vosges, France) : une approche interdisciplinaire
No full textInternational audienceLa contamination observée depuis plusieurs années dans la rivière Cleurie (Vosges, France) constitue un cadre de travail idéal pour étudier la contamination des écosystèmes aquatiques par des pesticides. En raison d’activités industrielles (textiles), ce petit cours d’eau vosgien de tête de bassin versant forestier présente des concentrations élevées de pesticides (dont le glyphosate et son principal produit de dégradation, l’acide aminométhylphosphonique – AMPA) mais inférieures aux normes environnementales. De fortes concentrations d’azurants optiques et de colorants sont également fréquemment observées, induisant un changement de coloration de l’eau spectaculaire. Les données disponibles, basées sur les indicateurs classiques (diatomées, invertébrés), indiquent pourtant une relativement bonne qualité de l’eau le long du linéaire. Du fait que les rejets soient localisés au niveau d’une zone naturelle d'intérêt écologique (site Natura 2000), que la Cleurie est une rivière très pêchée et que ces entreprises constituent une source essentielle d’emplois dans la vallée, ce site représente un cas d’étude sensible du point de vue socio-économique. Dans ce contexte, un projet interdisciplinaire est mené afin d’identifier des indicateurs/marqueurs globaux permettant de caractériser (1) la pression toxique in situ ainsi que (2) ses effets sur un compartiment clé du milieu aquatique (biofilms) mais également (3) la circulation des savoirs scientifiques produits entre les différents acteurs (scientifiques, pouvoirs publics, citoyens…) impliqués dans une controverse locale mais qui s’inscrit dans celle plus générale et ancienne sur la toxicité des pesticides
Urban environment and cognitive and motor function in children from four European birth cohorts
No full textInternational audienceBackground: The urban environment may influence neurodevelopment from conception onwards, but there is no evaluation of the impact of multiple groups of exposures simultaneously. We investigated the association between early-life urban environment and cognitive and motor function in children.Methods: We used data from 5403 mother-child pairs from four population-based birth-cohorts (UK, France, Spain, and Greece). We estimated thirteen urban home exposures during pregnancy and childhood, including: built environment, natural spaces, and air pollution. Verbal, non-verbal, gross motor, and fine motor functions were assessed using validated tests at five years old. We ran adjusted multi-exposure models using the Deletion-Substitution-Addition algorithm.Results: Higher greenness exposure within 300 m during pregnancy was associated with higher verbal abilities (1.5 points (95% confidence interval 0.4, 2.7) per 0.20 unit increase in greenness). Higher connectivity density within 100 m and land use diversity during pregnancy were related to lower verbal abilities. Childhood exposure to PM2.5 mediated 74% of the association between greenness during childhood and verbal abilities. Higher exposure to PM2.5 during pregnancy was related to lower fine motor function (-1.2 points (-2.1, -0.4) per 3.2 μg/m3 increase in PM2.5). No associations were found with non-verbal abilities and gross motor function.Discussion: This study suggests that built environment, greenness, and air pollution may impact child cognitive and motor function at five years old. This study adds evidence that well-designed urban planning may benefit children's cognitive and motor development
Quantitative Health Risk Assessment of the Chronic Inhalation of Chemical Compounds in Healthcare and Elderly Care Facilities
No full textInternational audiencePrevious studies have described the chemical pollution in indoor air of healthcare and care facilities. From these studies, the main objective of this work was to conduct a quantitative health risk assessment of the chronic inhalation of chemical compounds by workers in healthcare and elderly care facilities (hospitals, dental and general practitioner offices, pharmacies and nursing homes). The molecules of interest were 36 volatile and 13 semi-volatile organic compounds. Several professional exposure scenarios were developed in these facilities. The likelihood and severity of side effects that could occur were assessed by calculating the hazard quotient for deterministic effects, and the excess lifetime cancer risk for stochastic effects. No hazard quotient was greater than 1. Three compounds had a hazard quotient above 0.1: 2-ethyl-1-hexanol in dental and general practitioner offices, ethylbenzene and acetone in dental offices. Only formaldehyde presented an excess lifetime cancer risk greater than 1 × 10−5 in dental and general practitioner offices (maximum value of 3.8 × 10−5 for general practitioners). The health risk for chronic inhalation of most compounds investigated did not appear to be of concern. Some values tend to approach the acceptability thresholds justifying a reflection on the implementation of corrective actions such as the installation of ventilation systems
Exposure to ambient air pollution and cognitive decline: Results of the prospective Three-City cohort study
No full textInternational audienceBACKGROUND: Growing epidemiological evidence suggests an adverse relationship between exposure to air pollutants and cognitive decline. However, there is still some heterogeneity in the findings, with inconsistent results depending on the pollutant and the cognitive domain considered. We wanted to determine whether air pollution was associated with global and domain-specific cognitive decline. METHODS: This analysis used data from the French Three-City prospective cohort (participants aged 65 and older at recruitment and followed for up to 12 years). A battery of cognitive tests was administered at baseline and every 2 years, to assess global cognition (Mini Mental State Examination, MMSE), visual memory (Benton Visual Retention Test), semantic fluency (Isaacs Set Test) and executive functions (Trail Making Tests A and B). Exposure to fine particulate matter (PM(2.5)), nitrogen dioxide (NO(2)) and black carbon (BC) at the participants' residential address during the 5 years before the baseline visit was estimated with land use regression models. Linear mixed models and latent process mixed models were used to assess the association of each pollutant with global and domain-specific cognitive decline. RESULTS: The participants' (n = 6380) median age was 73.4 years (IQR: 8.0), and 61.5% were women. At baseline, the median MMSE score was 28 (IQR: 3). Global cognition decline, assessed with the MMSE, was slightly accelerated among participants with higher PM(2.5) exposure: one IQR increment in PM(2.5) (1.5 µg/m(3)) was associated with accelerated decline (β: -0.0060 [-0.0112; -0.0007] standard unit per year). Other associations were inconsistent in direction, and of small magnitude. CONCLUSION: In this large population-based cohort, higher PM(2.5) exposure was associated with accelerated global cognition decline. We did not detect any significant association for the specific cognitive domains or the other pollutants. Evidence concerning PM(2.5) effects on cognition is growing, but more research is needed on other ambient air pollutants
Sequential removal of human antibiotics as a function of the dynamic of organic matter fractions and 3D fluorescence during sludge composting
No full textInternational audienceThis study investigated the fate of antibiotics during composting and its relationship with organic matter fractionation. Sludge was spiked with roxithmmycin (ROX), chlortetracycline (CTC), oxytetracycline (OTC), and cipmfloxacin (CIP), at 3 different levels. Accelerated solvent extraction (ASE) and liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) were used for the extraction and the quantification of antibiotics. Sludge composting effectively removed parent compounds (p 0.05). The thermophilic stage was responsible for ROX removal, and the maturation stage was more implicated in removing CTC and OTC. Chemical accessibility and 3D fluorescence showed that high level of antibiotics affected the behavior of organic fractions. ROX removal was more associated with decreasing the most accessible fractions. The removals of CTC and OTC was more associated with the depletion of the complex organic matter. The observed results were confirmed by PCA and dendrograms analysis that confirmed the relationship between antibiotics removal and the evolution of organic pools. On the other hand, germination test indicated that cress and turnip were more sensitive to high antibiotic concentration. These results have been explored for the first time and they are recommended for controlling antibiotic removal based on organic matter fractionation