HAL du Programme national de recherche environnement-santé-travail (PNR EST)
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Traffic-related air pollution and childhood acute leukemia in France: GEOCAP nationwide case-control study
No full textInternational audienceOutdoor air pollution and particulate matter (PM) have been classified as carcinogenic to humans, and benzene exposure is known to increase the risk of leukemia in adults. Yet the evidence regarding childhood leukemia remains inconclusive. In this study, we sought to investigate whether traffic-related air pollution increases the risk of acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML).We used data from GEOCAP, an ongoing population-based case-control study conducted in France. It includes 4611 ALL and 830 AML cases, diagnosed between 2002 and 2013 and identified through the French national registry of childhood cancer, and 60,189 contemporaneous controls representative of the French pediatric population. Annual average exposures to nitrogen dioxide (NO2), fine PM (PM2.5) and Black Carbon (BC) at the geocoded address of residence at diagnosis for cases and inclusion for controls were estimated using land-use regression models. We also evaluated major roads length within 150 m of the geocoded addresses. Polytomous logistic regression was used to derive odds ratios (ORs) and 95 % confidence intervals (CI).Increased risks of AML were found with NO2 (OR per 10 μg/m3 = 1.09, 95 %CI = 1.03–1.15), PM2.5 (OR per 5 μg/m3 = 1.09, 95 %CI = 1.01–1.18) and BC exposures (OR per 0.5 10-5/m = 1.09, 95 %CI = 1.03–1.16). The length of major roads within 150 m of the residence was also associated with AML risk (OR per 300 m = 1.13, 95 %CI = 1.03–1.25). These increases in risk were more pronounced in the most urbanized areas. For ALL, inverse associations were suggested.This study provides further evidence supporting a role of traffic-related air pollution in AML risk in children
Acute exposure to environmental doses of di-n-butyl phthalate but not di-2-ethylhexyl phthalate induces mortality in isolated and cold-stressed workers of Bombus terrestris L. (Hymenoptera: Apidae)
No full textInternational audienceHighlights: • Exposure to field-realistic doses of DnBP is lethal to ∼25 % of bumblebee workers. • First evidence of NMDRC in bees after exposure to phthalates. • DnBP toxicity is lowered by DEHP in bumblebees at environmental doses. • Low-dose DnBP exposure in B. terrestris workers increase resistance to cold stress. • DnBP toxicity is nullified in a social rearing context.Abstract: Since the past decades, declining trends in bee populations have been reported worldwide. Among multiple anthropogenic factors, endocrine disruptors, such as phthalates, could negatively affect bees and contribute to this decline at environmental level of exposure. Yet, no data are available on phthalate toxicity in bees. Di-2-ethylhexyl phthalate (DEHP) and di-n-butyl phthalate (DnBP), widely used as plasticisers and adjuvants, are some of the most commonly recorded phthalates in the environment, including on social bee worker cuticles. In this study, we investigated DnBP and DEHP lethal effects on B. terrestris workers after contact exposure to environmentally relevant single-molecule and mixture treatments. Interactions with cold stress and social context were additionally investigated. Firstly, we evidenced for the first time an NMDRC for DnBP toxicity in bees, with an increased mortality of 25 %, 72 h after exposure. By contrast, DEHP did not affect worker survival and even lowered DnBP toxicity when administered as a mixture. Secondly, DnBP at low environmental doses enhanced worker resistance to cold stress, while exposure to cold stress modulated DnBP toxicity, shifting the onset of adverse effects to higher concentrations. Finally, we evidenced that social contacts mitigate DnBP toxicity. Overall, this study provided the first evidence of the detrimental effects caused by these overlooked pollutants on bees, and discusses potential metabolic disruption by phthalate exposure that may affect crucial life traits in bumblebees. Finally, this study highlighted that accounting for complex realistic mixtures and the social context of the studied species seems essential for accurately assessing the toxicity of endocrine disrupting molecules
Polymers and immersion time shape bacterial pathogen and antibiotic resistance profiles in aquaculture facilities
No full textInternational audienceMost equipment used in aquaculture farms is made of plastic. Plastics-associated biofilms may contain potential human pathogenic bacteria (PHPB) and antibiotic-resistant bacteria (ARB). Understanding the influence of farming practices on the biofouling development and composition is thus essential to control associated microbiological risks. We combined results from metabarcoding analyses, bacterial cultures, and antibiotic susceptibility testing to compare the bacterial pathobiome and resistome associated with plastic aquaculture equipment, including two polyamide nets and a polyester liner, with those associated to a hemp net and a glass control. Over the 3 months of incubation in an aquaculture farm, plastics exhibited neither higher levels of PHPB nor more multiple antibiotic resistance compared to other solid substrates, but they did present specific PHPB and ARB profiles. Bacterial members of the Vibrionaceae and Staphylococcaceae families were more abundant in plastic PHPB communities (respectively 47% and 22% of PHPB reads) than in other substrate ones (4% and 0.22% of PHPB reads). The plastic-associated antibiotic resistance profiles showed higher resistance against quinolones. These results suggest that aquaculture equipment could act as a reservoir for some PHPB and ARB, and that equipment composition and immersion time could be levers to control associated sanitary risks
Early-life exposure to mixtures of Endocrine-Disrupting Chemicals and a Multi-domain Health Score in preschool children
No full textInternational audienceBackground: Early-life exposure to endocrine-disrupting chemicals, such as phenols and phthalates, is suspected to impact various dimensions of child health. Using a multi-outcome approach, this study aimed to estimate their cumulative effect on the child cardiometabolic, respiratory and neurodevelopmental health.Methods: In 373 children of 3 years old from the SEPAGES cohort, a multi-domain health score was built from twenty-three health parameters. Fourteen metabolites of parabens, phenols, and phthalate/DINCH were measured several times during pregnancy (trimester 2 and 3) and infancy (2 and 12 months of age). Two mixture models, quantile g computation (qgcomp) and Bayesian Kernel Machine Regression (BKMR), estimated associations between increased concentration of parabens, phenols, and phthalates/DINCH and the child health score.Results: Q-gcomp showed that the paraben mixture and the phthalate mixture were associated with a poorer health score (β = -0.11, 95% Confidence Interval (CI): -0.22, 0.00 ; β = -0.14, 95% CI: -0.27, -0.01, respectively), while no significant association was found for the mixture of phenols (β = -0.06, 95% CI: -0.18, 0.06). A trend for an association was observed between the whole mixture (parabens, phenols and phthalates combined) with a poorer health score (β = -0.14, 95% CI: -0.32, 0.04). Similar patterns of association, while subject to large uncertainty, have been observed with BKMR.Discussion: This study provides further evidence for the adverse health effects of early-life exposure to parabens and phthalates. Based on their potential impact on multiple areas of child health, public health policies targeting these chemical compounds are recommended
Using Eye Tracking to Evaluate Cognitive and Visual Outcomes of Early Life Phenol Exposure
No full textInternational audienceIntroduction: Studies on behavioral effects of synthetic phenols have often relied on parent-reported questionnaires and primarily focused on prenatal exposure.Aims: We examined associations between prenatal and infancy phenol exposures and objective measures of child visual behavior and cognitive function at 2 years of age.Methods: At age 2, 151 children from the SEPAGES mother-child cohort completed eye-tracking tasks assessing four indicators: fixation duration (attentional control), novelty preference (visual recognition memory), time spent looking at eyes (social attention), and reaction time (processing speed).Phenol concentrations (two bisphenols, three parabens, benzophenone-3, triclosan) were measured in multiple urine samples collected from mothers (second and third trimesters; median: 42 samples per woman) and infants (2 and 12 months; median: 7 samples).Results: No associations were found with ∑parabens. However, individual parabens showed significant associations: ethylparaben at third trimester (T3) and 12 months (M12) was linked to shorter reaction time; at 2 months (M2), it was associated with reduced time spent looking at eyes. Propylparaben at T2 and T3 correlated with increased time spent looking at a novel face, especially in boys. Bisphenol S at T2 was associated with reduced reaction time; at M12, infants with detectable bisphenol S was linked to more time spent looking at eyes.Conclusion: Several associations observed indicate that increased phenol exposure sometimes correlated with improved eye-tracking scores. These findings align with prior literature on phenol exposure and ASD symptoms, which highlight variability by exposure window and phenol type.Given limited research and typically small sample sizes, further studies using objective markers and clinical assessments are necessary
Prenatal Exposure to Synthetic Phenols Assessed in Multiple Urine Samples and Dysregulation of Steroid Hormone Homeostasis in Two European Cohorts
No full textInternational audienceBACKGROUND: Some synthetic phenols alter hormonal pathways involved in successful pregnancy and fetal development. Despite high within-subject temporal variability of phenols, previous studies mostly utilized spot urine samples to assess pregnancy exposure. Herein, we investigated associations between pregnancy exposure to eight phenols assessed in multiple pooled urine samples and steroid hormones assessed in maternal hair reflecting cumulative hormone levels over the previous weeks to months.METHODS: We assessed phenol-hormone associations in 928 pregnant women from two pooled cohorts recruited in Spain [Barcelona Life Study Cohort (BiSC), 2018-2021] and France [Assessment of Air Pollution exposure during Pregnancy and Effect on Health (SEPAGES), 2014-2017] using pools of up to 21 samples each, collected in early pregnancy (median gestational age: 18.0 wk), as well as hair collected in late pregnancy (BiSC) or at birth (SEPAGES). We measured two bisphenols, four parabens, benzophenone-3, and triclosan along with metabolites of three adrenal ( P cortisol, P cortisone, and 11-dehydrocorticosterone) and two reproductive (progesterone and testosterone) hormones. We ran adjusted linear regressions for each exposure biomarker-outcome pair and Bayesian kernel machine regression for phenols mixture.RESULTS: Bisphenol S was associated with higher cortisol and 11-dehydrocorticosterone concentrations. Propylparaben was associated with lower levels of cortisol, cortisone, and 11-dehydrocorticosterone, while methylparaben was linked to a reduction in cortisol levels. Interestingly, associations identified for parabens were stronger for women carrying female fetuses. No associations for phenol mixture were detected.CONCLUSIONS: Our study suggests that pregnancy exposure to bisphenol S and some parabens (propyl-and methylparaben) may affect production of maternal corticosteroid hormones that are important for a successful pregnancy and fetal development
Job-exposure matrix (JEM) validity on crystalline silica among systemic sclerosis patients
No full textInternational audienceBackground: Systemic sclerosis (SSc) is the connective tissue disease with the highest individual mortality. Crystalline silica is known to be an occupational risk factor for SSc. To assess past crystalline silica exposure, we aimed to study the validity of a job exposure matrix (JEM) to assess occupational exposure to crystalline silica compared to specific occupational interviews in two populations of SSc patients.Aims: To demonstrate the reliability of JEM for the assessment of occupational exposure to hazards such as silica, in severe rare disorders like SSc.Methods: Patients from two university hospital centres underwent standardized assessment of occupational silica exposure and collected job histories through face-to-face interviews. A JEM from the French program Matgéné was used to assess silica exposure and compared to the standardized interview results. Standard metrics were computed for evaluate the accuracy of JEM.Results: 67 participants from Rennes, and 119 from Tours were included, with respectively 10.5% and 18.0% of patients with silica exposure based on the results of the interview. The JEM with 50% probability cut-off had a good performance when compared with the classic assessment method. A cumulative exposure index from JEM over 250 had an area under the curve between 0.76 and 0.79 and also a very high positive likelihood ratio (17.14 and 10.29).Conclusions: Despite limitations inherent to JEMs and associated validation methods, the JEM used in this setting provided accurate results to assess occupational exposure to crystalline silica for clinical purposes such as in SSc patients, especially to detect positive cases
Triggering tumorigenic signaling: Succinate dehydrogenase inhibitor (SDHi) fungicides induce oncometabolite accumulation and metabolic shift in human colon cells
No full textInternational audienceSuccinate dehydrogenase inhibitors (SDHi) are fungicides used worldwide to control the proliferation of fungi in crops. They act by blocking the activity of succinate dehydrogenase (SDH), a universal enzyme involved in mitochondrial functions and metabolism. While SDH-encoding genes are tumour suppressors, which loss-of-function mutations predispose to different types of rare tumors in humans, the consequences of chemical inactivation of SDH by SDHi remain largely unknown, particularly regarding their carcinogenic potential. Here, we investigated the metabolic and cellular impact of SDHi on human non-cancer and transformed colon cells. We show that SDHi inhibit SDH activity and increase the level of succinate, known to act as an oncometabolite in SDH-deficient cancers. SDHi exposure also induces a Warburg-like metabolic reprogramming typical of cancer cells, associated with transcriptomic and morphological changes promoting cell migration and invasion. These effects are enhanced in transformed colon cells carrying mutations in colorectal cancer (CRC) driver genes. These findings provide the first evidence that SDHi-mediated chemical inactivation of SDH mimics some metabolic and phenotypic features previously described in human tumors with SDH genetic deficiencies. Given that loss of SDH expression in CRC patients correlates with a poor prognosis, these patients could represent a population sensitive to SDHi exposure. Therefore, it would be wise to include them in biomonitoring programs. Finally, our work highlights the need to improve regulatory assessment procedures to take better account of SDHi mode of action, by developing relevant tests to cover the multiple key events linked to SDH inactivation and assess the resulting mitochondrial toxicity
PFAS exposures and child growth: a longitudinal study from fetal life to early childhood
No full textInternational audiencePrenatal exposure to poly- and perfluoroalkyl substances (PFAS) has been associated with lower birth weight or increased adiposity in adolescence. No study has investigated associations with longitudinal growth from conception to early childhood. We explored the association between maternal serum PFAS concentrations during pregnancy and child growth assessed repeatedly from the second trimester of pregnancy to 3 years of age.In the SEPAGES cohort, for 450 pregnant women recruited before 19 gestational weeks in Grenoble (France), we measured 26 PFAS from non-fasting maternal serum samples (median gestational age at sampling: 19.4 weeks). Cluster-based analysis identified three PFAS exposure groups (low, moderate, high). Child growth parameters (weight, height, and head parameters) were measured at second and third trimesters (ultrasound examinations), at birth and until 3 years. Using a nonlinear mixed model, we predicted growth parameters and velocities at exactly 3 months and 3 years.Compared to children belonging to the low PFAS exposure group, those belonging to the high exposure group had higher head circumference during the second trimester (ß [95% CI] = 3.60 [1.49 to 5.72] mm) and at 3 years (39.85 [1.62 to 78.08] mm) as well as higher estimated fetal weight during the second trimester (15.85 [1.48 to 30.21] g) and BMI growth velocity at 3 years (9.66 [1.73 to 17.59] g/m2/month). PFAS concentrations were not associated with growth parameters at third trimester, birth and 3 months.In this prospective study, maternal serum PFAS concentrations were associated with some child growth parameters, potentially associated with increased risk of obesity in later-life
L'exposition répétée de la tête à un signal 5G-3,5 GHz ne modifie pas le comportement mais modifie l'expression génétique intracorticale chez les souris mâles adultes
No full textInternational audienceThe fifth generation (5G) of mobile communications promotes human exposure to electromagnetic fields exploiting the 3.5 GHz frequency band. We analyzed behaviors, cognitive functions, and gene expression in mice submitted to asymmetrical head exposure to a 5G-modulated 3.5 GHz signal. The exposures were applied for 1 h daily, 5 days per week over a six-week period, at a specific absorption rate (SAR) averaging 0.19 W/kg over the brain. Locomotor activities in an open field, object location, and object recognition memories were assessed repeatedly after four weeks of exposure and did not reveal any significant effect on the locomotion/exploration, anxiety level, or memory processes. mRNA profiling was performed at the end of the exposure period in two symmetrical areas of the right and left cerebral cortex, in which the SAR values were 0.43 and 0.14 W/kg, respectively. We found significant changes in the expression of less than 1% of the expressed genes, with over-representations of genes related to glutamatergic synapses. The right cortical area differed from the left one by an over-representation of responsive genes encoded by the mitochondrial genome. Our data show that repeated head exposures to a 5G-3.5 GHz signal can trigger mild transcriptome alterations without changes in memory capacities or emotional state