HAL du Programme national de recherche environnement-santé-travail (PNR EST)
Not a member yet
917 research outputs found
Sort by
Effects of Simultaneous In‐Vitro Exposure to 5G‐Modulated 3.5 GHz and GSM‐Modulated 1.8 GHz Radio‐Frequency Electromagnetic Fields on Neuronal Network Electrical Activity and Cellular Stress in Skin Fibroblast Cells
No full textInternational audienceThe widespread deployment of 5G wireless networks alongside existing GSM technologies has increased the need to assess potential biological effects of co‐exposure to multiple radiofrequency electromagnetic fields (RF‐EMF). This study evaluates the in‐vitro impact of simultaneous exposure to 5G‐modulated 3.5 GHz and GSM‐modulated 1.8 GHz signals on neuronal electrical activity, mitochondrial reactive oxygen species (ROS) production, and cellular stress protein responses in neurons and skin fibroblasts. Primary cortical neurons and human immortalized skin fibroblasts were exposed to RF‐EMF at specific absorption rates (SAR) of 1 or 4 W/kg for 15 min or 24 h, respectively. Neuronal activity was analyzed using multi‐electrode arrays (MEAs), mitochondrial ROS production was measured using MitoSOX Red, and stress protein activity was assessed using bioluminescence resonance energy transfer (BRET) assays targeting RAS, PML, and HSF1 proteins. The results indicate no significant effects on the mean bursting rate (MBR) or mean firing rate (MFR) of cortical neurons, consistent with previous findings at similar SAR levels. Mitochondrial ROS production in fibroblasts also remained unaffected by RF‐EMF co‐exposure. BRET assays detected minor variations in the basal activity of RAS and PML and in the maximal efficacy of PMA and As₂O₃ to activate these pathways. However, these effects were small, near the detection threshold, and showed no consistent pattern across different tests or chemical treatments. No change was observed in HSF1 basal activity or responsiveness to MG132. These findings suggest that co‐exposure to 5G‐ and GSM‐modulated RF‐EMF at SAR levels up to 4 W/kg does not produce conclusive evidence of marked biological effects under the tested conditions. Observed variations, when present, are of low amplitude and likely to fall within the range of experimental variability
Evolution of depressive symptoms in the 15 years preceding dementia
No full textInternational audienceBACKGROUND: Depression has been consistently linked to the onset of dementia, but the temporality and nature of this association-whether causal, prodromal or due to shared pathophysiology-remain unresolved. Longitudinal studies with extended follow-up are necessary to clarify these relationships. This study aimed to characterise the trajectory of depressive symptoms during the 15 years preceding a dementia diagnosis, with particular attention to variations by dementia aetiology. METHODS: This nested case-control study was conducted within the Three-City Study cohort, a prospective population-based study initiated in 1999. The cohort included 9294 community-dwelling individuals aged 65 and older, followed for 15 years in three French cities (Bordeaux, Dijon, Montpellier). Depressive symptoms were assessed using the Centre for Epidemiological Studies Depression scale in 1028 dementia cases and 1028 matched controls. Trajectories of depressive symptoms were analysed over the 15 years preceding the index date (dementia diagnosis). RESULTS: No significant differences in depressive symptomatology (p=0.69) or the frequency of depressive states (OR 1.21, 95% CI 0.51 to 2.87) were observed between cases and controls 12-15 years before the index date. Gradual differences emerged over time, becoming significant 6-8 years prior to dementia onset (p<0.001) and peaking 2 years before the index date (OR 2.93, 95% CI 2.27 to 3.80). These differences were more pronounced in non-Alzheimer's dementia cases. CONCLUSIONS: Depressive symptoms progressively increased in the years leading up to dementia diagnosis, with the most pronounced elevations occurring in non-Alzheimer's dementia
Mouldy area size and asthma symptom score and control in adults: the CONSTANCES cohort
No full textInternational audienceBackground: Studies on indoor mould contamination and asthma in adults are scarce, although there is evidence of deleterious effects on childhood asthma. Associations between different mould contamination indicators and asthma were investigated in adults from the largest French prospective population-based cohort.Methods: Participants completed standardized questionnaires: on visible mould and mouldy area size (0m2, spots, <0.2m2, [0.2m2-1 m2], ]1m2-3m2] or >3m2) in bathroom, kitchen, or main living quarters (living room, bedroom) in 2019, and on respiratory health (2019-2022). Associations between indoor mould with current asthma, asthma symptom score (sum of five respiratory symptoms in the last 12 months), and uncontrolled asthma (Asthma Control Test<20) were evaluated by zero-inflated negative binomial and logistic models adjusted for age, sex, smoking, education, dwelling type and French deprivation index. Sensitivity analyses: in subgroups, stratified by dwelling type or sex, and further adjustments for region, occupant-surface ratio, body mass index, occupant (owner/tenant) and rural/urban areas were performed.Findings: Analyses included 28,596 adults (mean age: 55 years old, 55% women, 70% living in houses, 24% reported at least one asthma symptom, 7.4% current asthma of whom 15.1% had uncontrolled asthma). Visible mould and mouldy area size>3m2 were reported by 21.2% and 0.3% of participants, respectively. Visible mould in dwelling was significantly associated with current asthma, asthma symptom score and uncontrolled asthma (OR and mean score ratio (MSR) around 1.40), stronger effect in the main living quarters. Mouldy area size was significantly associated with higher risk of current asthma (all ORs≥1.29, p-trend<0.001) and increased asthma symptom score (all MSRs≥1.32, p-trend<0.001). No heterogeneity was found by dwelling type or sex. Results were consistent across sensitivity analyses.Interpretation: Mouldy area size was associated with current asthma and asthma symptom score, even for small sizes, adding new insight of the associations between mould contamination and asthma in adults
Per- and Polyfluoroalkyl Substances as Potentiators of Hepatotoxicity in an Exposome Framework: Current Challenges of Environmental Toxicology
No full textInternational audienceChronic liver diseases, including metabolic dysfunction-associated steatosic liver disease (MASLD) and hepatocellular carcinoma (HCC), are on the rise, potentially due to daily exposure to complex mixtures of chemical compounds forming part of the exposome. Understanding the mechanisms involved in hepatotoxicity of these mixtures is essential to identify common molecular targets that may highlight potential interactions at the molecular level. We illustrated this issue with two families of environmental contaminants, per- and polyfluoroalkyl substances (PFAS) and heterocyclic aromatic amines (HAAs), both of which could be involved in the progression of chronic liver diseases, and whose toxicity may be potentiated by interactions at the level of xenobiotic metabolism. In the study of exposome effects on chronic liver disease, New Approach Methodologies (NAMs) including omics analyses and data from various in vitro, in vivo and in silico approaches, are crucial for improving predictivity of toxicological studies in humans while reducing animal experimentation. Additionally, the development of complex in vitro human liver cell models, such as organoids, is essential to avoid interspecies differences that minimize the risk for humans. All together, these approaches will contribute to construct Adverse Outcome Pathways (AOPs) and could be applied not only to PFAS mixtures but also to other chemical families, providing valuable insights into mixture hepatotoxicity prediction in the study of the exposome. A better understanding of toxicological mechanisms will clarify the role of environmental contaminant mixtures in the development of MASLD and HCC, supporting risk assessment for better treatment, monitoring and prevention strategies
Occupational Exposure Patterns to Disinfectants and Cleaning Products and Its Association With Asthma Among French Healthcare Workers
No full textInternational audienceBackground: Disinfectants and cleaning products (DCPs) are important asthma risk factors among healthcare workers. However, healthcare work involves heterogenous cleaning tasks and co-exposure to many chemicals. These multidimensional aspects have rarely been considered. We aimed to identify patterns of occupational exposure to DCPs and study their associations with asthma. Methods: CONSTANCES is a French population-based cohort of ≈220,000 adults. Current asthma and asthma symptom score were defined by questionnaire at inclusion (2012-2021). Healthcare workers completed a supplementary questionnaire on their current/last held occupation, workplace, and cleaning activities that were used in unsupervised learning algorithms to identify occupational exposure patterns. Logistic and negative binomial regression models, adjusted for potential confounders, were used to assess associations with asthma outcomes. Results: In 5512 healthcare workers, four occupational exposure clusters were identified: Cluster1 (C1, 42%, reference), mainly characterized by low exposed nurses and physicians; C2 (7%), medical laboratory staff moderately exposed to common DCPs (chlorine/bleach, alcohol); C3 (41%), nursing assistants and nurses highly exposed to a few DCPs (mainly quaternary ammonium compounds); and C4 (10%), nurses and nursing assistants highly exposed to multiple DCPs (e.g., glutaraldehyde, hydrogen peroxide, and acids). Among women (n = 3734), C2 (mean score ratio [95% CI]: 1.31 [1.02; 1.68]) and C3 (1.18 [1.03; 1.36]) were associated with higher asthma symptom score, and an association was suggested between C3 and current asthma (odds ratio 1.22 [0.99; 1.51]). Conclusion:In a large population of healthcare workers, four DCP exposure patterns were identified, reflecting the heterogeneity of healthcare jobs. Two patterns, including one characterized by laboratory workers, were associated with greater asthma symptoms in women.This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.</div
Bisphenol A exposure during gestation and lactation in mice: Sex-specific consequences on oligodendrocytes and myelination
No full textInternational audienceBisphenol A (BPA), a ubiquitous environmental endocrine disruptor, is suspected of disturbing brain development through largely unknown cellular and molecular mechanisms. In the central nervous system, oligodendrocytes are responsible for forming myelin sheaths, which enhance the propagation of action potentials along axons. Disruption of axon myelination can have lifelong consequences, making oligodendrocyte differentiation and myelination critical stages of brain development. In the present study, mice were exposed to BPA during gestation and lactation through drinking water at concentrations of 25 and 250 μg.L -1 . These doses, corresponding to estimated exposures of 4 μg.kg -1 .d -1 and 40 μg.kg -1 .d -1 , respectively, led to disturbances in lipid remodeling associated with myelination in the offspring. Importantly, changes in myelin lipid composition were selectively observed in female mice and were transient, being visible only at post-natal day P15 but not at later stages (P30 and P60). In females exposed to BPA, myelin exhibited a lower proportion of phosphatidylcholines and higher proportions of other glycerophospholipid subclasses, thus resembling more mature myelin. Conversely, male myelin was not affected, likely due to its already more mature lipid composition. Additionally, transcriptomic analysis of female oligodendrocytes at P15 did not reveal any transcriptional changes in genes related to lipid metabolism, further suggesting post-transcriptional effects of BPA via chaperone-mediated protein folding and RNA splicing. In males, the altered genes were mainly associated with synaptic transmission. Finally, alterations in chromatin accessibility were also largely sex dependent and did not correlate with transcription, with the exception of the Cwc22. At this locus, BPA exposure increased chromatin accessibility in half of mice of both sexes, leading to an "unchanged/open" bimodal profile correlated with "unchanged/upregulated" gene expression. Together, these results open new insights into the sex-dependent mechanisms of BPA's effects on brain development
Exposure of the human placental primary cells to nanoplastics induces cytotoxic effects, an inflammatory response and endocrine disruption
No full textInternational audienceHumans are inevitably exposed to micro- and nanoplastics (MP/NP). These particles are able to cross the biological barriers and enter the bloodstream with levels close to 1.6 µg mL−1; MP/NP have been detected in placentas and meconium of newborns. However, the consequences of this exposure on the integrity, development and functions of the human placenta are not documented. In this study, trophoblasts purified from human placentas at term were exposed for 48 h, to two different sizes of polystyrene nanoparticles (PS-NP) of 20 nm (PS-NP20) and 100 nm (PS-NP100), at environmental and supra-environmental concentrations (0.01–100 µg mL−1). Cell viability, oxidative stress, mitochondrial dynamics, lysosomal degradation processes, autophagy, inflammation/oxidative responses and consequences for placental endocrine and angiogenic functions were assessed. PS-NP size determines their internalization rate and their behavior in trophoblasts. Indeed, PS-NP20 are more rapidly translocated, and accumulated in lysosomes as shown by confocal and TEM imaging. They induce higher cytotoxicity than PS-NP100, as early as 1 µg mL−1 (p < 0.05). In addition, they induce a pro-inflammatory cytokines response: IL-1ß is induced from 0.01 µg mL−1 for the both nanoparticle sizes; IL-6, and TNF-α are overexpressed at 100 µg mL−1 only for PS-NP20 (p < 0.05). For the first time, we report that PS-NP disrupt endocrine function, as observed by a decreased hCG release at concentrations found in human blood. This work, provides an in-depth in vitro assessment of the effects of PS-NP on the human placenta
Ambient air pollution exposure and incidence of cataract surgery: The prospective 3City-Alienor study
No full textInternational audienceCataract, the leading cause of blindness worldwide, is a multifactorial disease involving oxidative stress mechanisms. The aim of our study was to investigate the relationship between air pollution exposure and the incidence of cataract surgery. The 3C-Alienor study is a population-based cohort of residents of Bordeaux, France, aged 65 years or more, recruited in 1999-2000 and followed every 2-3 years until 2017. Cataract surgery was self-reported and checked at slit-lamp by trained professionals. Average air pollution exposure (particulate matter ≤2.5 μm (PM), black carbon (BC), nitrogen dioxide (NO)) in the 10 years preceding baseline was estimated at the participants' geocoded residential address, using temporally adjusted land use regression. Associations of 10-year average air pollution exposure with incidence of cataract were estimated using Cox proportional hazard models adjusted for confounders. The study included 829 subjects without cataract surgery prior to inclusion; the mean age at inclusion was 72.6 years (standard deviation (SD): 4.2) and 61% were women. The median (Interquartile-range (IQR)) follow-up duration was 14.1 (6.4) years during which 507 participants underwent cataract surgery. Exposure to a concentration ≥40 μg/m of NO (the current regulatory limit value in Europe) was associated with incident cataract surgery (HR = 1.46, CI (1.16, 1.84), p = 0.001). No statistically significant association was found with PM and BC. Long-term exposure to a NO concentration ≥ 40 μg/m was associated with an increased incidence of cataract surgery. Complying with current European air pollution standards could reduce cataract surgery costs and improve population quality of life
Occupational exposure to radiofrequency electromagnetic fields and brain tumor risk: Application of the INTEROCC job-exposure matrix
No full textInternational audienceRadiofrequency electromagnetic fields (RF-EMF, 100 kHz to 300 GHz) are classified by IARC as possibly carcinogenic to humans (Group 2B). This study evaluates the potential association between occupational RF-EMF exposure and brain tumor risk, utilizing for the first time, a RF-EMF job-exposure matrix (RF-JEM) developed in the multi-country INTEROCC case-control study. Cumulative and time-weighted average (TWA) occupational RF-EMF exposures were estimated for study participants based on lifetime job histories linked to the RF-JEM using three different methods: (1) by considering RF-EMF intensity among all exposed jobs, (2) by considering RF-EMF intensity among jobs with an exposure prevalence ≥ the median exposure prevalence of all exposed jobs, and (3) by considering RF-EMF intensity of jobs of participants who reported RF-EMF source use. Stratified conditional logistic regression models were used, considering various lag periods and exposure time windows defined a priori. Generally, no clear associations were found for glioma or meningioma risk. However, some statistically significant positive associations were observed including in the highest exposure categories for glioma for cumulative and TWA exposure in the 1- to 4-year time window for electric fields (E) in the first JEM application method (odds ratios [ORs] = 1.36, 95% confidence interval [95% CI] 1.08, 1.72 and 1.27, 95% CI 1.01, 1.59, respectively), as well as for meningioma for cumulative exposure in the 5- to 9-year time window for electric fields (E) in the third JEM application method (OR = 2.30, 95% CI 1.11, 4.78). We did not identify convincing associations between occupational RF-EMF exposure and risk of glioma or meningioma
Coexposure to asbestos, mineral wool, crystalline silica and refractory ceramic fibres and risk of lung cancer and mesothelioma
No full textEdition: 20251120International audienceBACKGROUND: Asbestos, mineral wool (MW), refractory ceramic fibres (RCF) and silica are among the most common exposures to mineral particles in the workplace. OBJECTIVE: To study the effect of coexposure to asbestos and MW, crystalline silica or RCFs and the risk of lung cancer and mesothelioma. METHODS: The Asbestos-Related Diseases Cohort is a surveillance programme in retired workers exposed to asbestos during their working life. Complete job histories were collected and occupational exposure to asbestos was assessed by an expert, while occupational exposure to MW, RCFs and silica was assessed using French job-exposure matrices. Cox proportional hazards models were used to estimate HR and 95% CI for lung cancer mortality and lung cancer incidence and for mesothelioma mortality or mesothelioma incidence. RESULTS: In this population of workers exposed to asbestos, in the mortality study, exposures to MW, crystalline silica and RCFs were not found to be associated with lung cancer after adjustment for smoking and asbestos, nor with mesothelioma after adjustment for asbestos. In the incidence study, there was an association between exposure to crystalline silica (ever exposed) and mesothelioma (HR(a)=1.75, 95% CI 1.17 to 2.62). CONCLUSION: Crystalline silica is not known to induce mesothelioma but coexposure to asbestos could increase the effect of asbestos on the mesothelial cells