HAL du Programme national de recherche environnement-santé-travail (PNR EST)
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A Co-Culture Model of the Human Respiratory Tract to Discriminate the Toxicological Profile of Cationic Nanoparticles According to Their Surface Charge Density
No full textInternational audienceThis study aimed at discriminating with sensitivity the toxicological effects of carbon dots (CDs) with various zeta potential (ζ) and charge density (Qek) in different cellular models of the human respiratory tract. One anionic and three cationic CDs were synthetized as follows: CD-COOH (ζ = −43.3 mV); CD-PEI600 (Qek = 4.70 µmol/mg; ζ = +31.8 mV); CD-PEHA (Qek = 3.30 µmol/mg; ζ = +29.2 mV) and CD-DMEDA (Qek = 0.01 µmol/mg; ζ = +11.1 mV). Epithelial cells (A549) and macrophages (THP-1) were seeded alone or as co-cultures with different A549:THP-1 ratios. The obtained models were characterized, and multiple biological responses evoked by CDs were assessed in the mono-cultures and the best co-culture model. With 14% macrophages, the 2:1 ratio co-culture best mimicked the in vivo conditions and responded to lipopolysaccharides. The anionic CD did not induce any effect in the mono-cultures nor in the co-culture. Among the cationic CDs, the one with the highest charge density (CD-PEI600) induced the most pronounced responses whatever the culture model. The cationic CDs of low charge density (CD-PEHA and CD-DMEDA) evoked similar responses in the mono-cultures, whereas in the co-culture, the three cationic CDs ranked according to their charge density (CD-PEI600 > CD-PEHA > CD-DMEDA), when taking into account their inflammatory effect. Thus, the co-culture system developed in this study appears to be a sensitive model for finely discriminating the toxicological profile of cationic nanoparticles differing by the density of their surface charges
Dopaminergic and serotonergic changes in rabbit fetal brain upon repeated gestational exposure to diesel engine exhaust
No full textInternational audienceLimited studies in humans and in animal models have investigated the neurotoxic risks related to a gestational exposure to diesel exhaust particles (DEP) on the embryonic brain, especially those regarding monoaminergic systems linked to neurocognitive disorders. We previously showed that exposure to DEP alters monoaminergic neurotransmission in fetal olfactory bulbs and modifies tissue morphology along with behavioral consequences at birth in a rabbit model. Given the anatomical and functional connections between olfactory and central brain structures, we further characterized their impacts in brain regions associated with monoaminergic neurotransmission. At gestational day 28 (GD28), fetal rabbit brains were collected from dams exposed by nose-only to either a clean air or filtered DEP for 2 h/day, 5 days/week, from GD3 to GD27. HPLC dosage and histochemical analyses of the main monoaminergic systems, i.e., dopamine (DA), noradrenaline (NA), and serotonin (5-HT) and their metabolites were conducted in microdissected fetal brain regions. DEP exposure increased the level of DA and decreased the dopaminergic metabolites ratios in the prefrontal cortex (PFC), together with sex-specific alterations in the hippocampus (Hp). In addition, HVA level was increased in the temporal cortex (TCx). Serotonin and 5-HIAA levels were decreased in the fetal Hp. However, DEP exposure did not significantly modify NA levels, tyrosine hydroxylase, tryptophan hydroxylase or AChE enzymatic activity in fetal brain. Exposure to DEP during fetal life results in dopaminergic and serotonergic changes in critical brain regions that might lead to detrimental potential short-term neural disturbances as precursors of long-term neurocognitive consequences
Mode of Action of Neonicotinoid Insecticides Imidacloprid and Thiacloprid to the Cockroach Pameα7 Nicotinic Acetylcholine Receptor
No full textInternational audienceThe functional expression of the cockroach Pameα7 nicotinic acetylcholine receptor subunit has been previously studied, and was found to be able to form a homomeric receptor when expressed in Xenopus laevis oocytes. In this study, we found that the neonicotinoid insecticide imidacloprid is unable to activate the cockroach Pameα7 receptor, although thiacloprid induces low inward currents, suggesting that it is a partial agonist. In addition, the co-application or 5 min pretreatment with 10 µM imidacloprid increased nicotine current amplitudes, while the co-application or 5 min pretreatment with 10 µM thiacloprid decreased nicotine-evoked current amplitudes by 54% and 28%, respectively. This suggesting that these two representatives of neonicotinoid insecticides bind differently to the cockroach Pameα7 receptor. Interestingly, the docking models demonstrate that the orientation and interactions of the two insecticides in the cockroach Pameα7 nAChR binding pocket are very similar. Electrophysiological results have provided evidence to suggest that imidacloprid and thiacloprid could act as modulators of the cockroach Pameα7 receptors
Comparison of a barcode-based smartphone application to a questionnaire to assess the use of cleaning products at home and their association with asthma symptoms
No full textInternational audienceHousehold disinfectant and cleaning products (HDCPs) assessment is challenging in epidemiological research. We hypothesized that a newly-developed smartphone application was more objective than questionnaires in assessing HDCPs. Therefore, we aimed to compare both methods, in terms of exposure assessments and respiratory health effects estimates. The women of the SEPAGES birth cohort completed repeated validated questionnaires on HDCPs and respiratory health and used an application to report HDCPs and scan products barcodes, subsequently linked with an ingredients database. Agreements between the two methods were assessed by Kappa coefficients. Logistic regression models estimated associations of HDCP with asthma symptom score. The 101 participants (18 with asthma symptom score ≥1) scanned 617 different products (580 with available ingredients list). Slight to fair agreements for sprays, bleach and scented HDCP were observed (Kappa: 0.35, 0.25, 0.11, respectively). Strength of the associations between HDCP and asthma symptom score varied between both methods but all odds ratios (OR) were greater than one. The number of scanned products used weekly was significantly associated with the asthma symptom score (adjusted-OR [CI 95%]: 1.15 [1.00–1.32]). This study shows the importance of using novel tools in epidemiological research to objectively assess HDCP and therefore reduce exposure measurement errors
The role of nutritional factors in asthma: Challenges and opportunities for epidemiological research
No full textInternational audienceThe prevalence of asthma has nearly doubled over the last decades. Twentieth century changes in environmental and lifestyle factors, including changes in dietary habits, physical activity and the obesity epidemic, have been suggested to play a role in the increase of asthma prevalence and uncontrolled asthma worldwide. A large body of evidence has suggested that obesity is a likely risk factor for asthma, but mechanisms are still unclear. Regarding diet and physical activity, the literature remains inconclusive. Although the investigation of nutritional factors as a whole (i.e., the “diet, physical activity and body composition” triad) is highly relevant in terms of understanding un-derlying mechanisms, as well as designing effective public health interventions, their combined effects across the life course has not received a lot of attention. In this review, we discuss the state of the art regarding the role of nutritional factors in asthma, for each window of exposure. We focus on the methodological and conceptual challenges encountered in the investigation of the complex time-dependent interrelations between nutritional factors and asthma and its control, and their interaction with other determinants of asthma. Lastly, we provide guidance on how to address these challenges, as well as suggestions for future research
Puumala Virus Variants Circulating in Forests of Ardennes, France: Ten Years of Genetic Evolution
No full textInternational audienceIn Europe, Puumala virus (PUUV) transmitted by the bank vole (Myodes glareolus) is the causative agent of nephropathia epidemica (NE), a mild form of haemorrhagic fever with renal syndrome. In France, very little is known about the spatial and temporal variability of the virus circulating within bank vole populations. The present study involved monitoring of bank vole population dynamics and PUUV microdiversity over a ten-year period (2000–2009) in two forests of the Ardennes region: Elan and Croix-Scaille. Ardennes region is characterised by different environmental conditions associated with different NE epidemiology. Bank vole density and population parameters were estimated using the capture/marking/recapture method, and blood samples were collected to monitor the overall seroprevalence of PUUV in rodent populations. Phylogenetic analyses of fifty-five sequences were performed to illustrate the genetic diversity of PUUV variants between forests. The pattern of the two forests differed clearly. In the Elan forest, the rodent survival was higher, and this limited turn-over resulted in a lower seroprevalence and diversity of PUUV sequences than in the Croix-Scaille forest. Uncovering the links between host dynamics and virus microevolution is improving our understanding of PUUV distribution in rodents and the NE risk
Impact of Textile on Electromagnetic Power and Heating in Near-Surface Tissues at 26 GHz and 60 GHz
No full textInternational audienceWith the development of 5th generation (5G) networks the operating frequencies have been progressively expanding towards millimeter waves (MMW). In some exposure scenarii, presence of textiles impacts the interaction of the electromagnetic field radiated by wireless devices with human tissues. We investigate the impact of a textile layer in contact or in proximity of skin on the power transmission coefficient, absorbed power density and temperature rise using a near-surface tissue model at 26GHz and 60 GHz. Cotton and wool are considered as representative textiles. Our results demonstrate that the textile in contact with skin increases the absorbed power density up to 41.5% at 26 GHz and 34.4% at 60 GHz. The presence of an air gap between a textile and skin modifies the electromagnetic power deposition in the tissues depending on the thicknesses and permittivity. The temperature rise increases compared to the nude skin by up to 52% at 26 GHz and 46% at 60 GHz with the textile in direct contact with skin. With an air gap, for typical textile thicknesses, the temperature variations range from -3.5% to 20.6% and from -11.1% to 20.9% at 26 GHz and 60 GHz, respectively
Co‐Designed Exposure Protocol in the Study of Idiopathic Environmental Intolerance Attributed to Electromagnetic Fields
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Evaluation of the Effect of Chronic 94 GHz Exposure on Gene Expression in the Skin of Hairless Rats In Vivo
No full textInternational audienceMillimeter waves (MMW) are broadband frequencies that have recently been used in several applications in wireless communications, medical devices and nonlethal weapons [i.e., the nonlethal weapon, Active Denial Systems, (ADS) operating at 94-95 GHz, CW]. However, little information is available on their potential effects on humans. These radio-frequencies are absorbed and stopped by the first layer of the skin. In this study, we evaluated the effects of 94 GHz on the gene expression of skin cells. Two rat populations consisting of 17 young animals and 14 adults were subjected to chronic long-term 94 GHz MMW exposure. Each group of animals was divided into exposed and sham subgroups. The two independent exposure experiments were conducted for 5 months with rats exposed 3 h per day for 3 days per week to an incident power density of 10 mW/cm, which corresponded to twice the ICNIRP limit of occupational exposure for humans. At the end of the experiment, skin explants were collected and RNA was extracted. Then, the modifications to the whole gene expression profile were analyzed with a gene expression microarray. Without modification of the animal's temperature, long-term chronic 94 GHz-MMW exposure did not significantly modify the gene expression of the skin on either the young or adult rats
Maternal exposure to pesticides and risk of childhood lymphoma in France: A pooled analysis of the ESCALE and ESTELLE studies (SFCE)
No full textInternational audienceBackground: Few studies have assessed the relation between maternal prenatal pesticides use and childhood lymphoma risk, some reporting a positive association with non-Hodgkin lymphoma (NHL). We investigated the association between maternal exposure to pesticides during pregnancy and childhood Hodgkin (HL) and non-Hodgkin lymphoma.Methods: We pooled data from the two French national population-based case-control studies ESCALE (2003-2004) and ESTELLE (2010-2011). Data on domestic and occupational exposures to pesticides during pregnancy were obtained through standardised maternal interviews. Logistic regression models were used to compute odds ratios (OR) and 95% confidence intervals (CI) for HL and NHL, by pesticide category adjusted for potential confounders. Analyses by histological subtypes were also performed.Results: We included 328 H L, 305 non-Hodgkin NHL and 2,415 controls. Around 40% of control mothers reported having used pesticides during index pregnancy, of whom 95% reported insecticides use. Maternal use of herbicides and fungicides occurred mostly in combination with insecticides. Insecticides use was more frequently reported in cases than controls (ORNHL = 1.6 [95%CI 1.3-2.1], p = 0.0001; ORHL = 1.3 [95%CI 1.0-1.7], p = 0.03). This association appeared more marked for Burkitt lymphoma and mixed cellularity classical HL. No obvious association was observed with occupational pesticides exposure during pregnancy.Conclusion: These results suggest that maternal domestic use of insecticides during pregnancy might be related to both childhood NHL and HL. Further larger studies are urgently needed