HAL du Programme national de recherche environnement-santé-travail (PNR EST)
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Les expositions chroniques au fluorure de sodium et un mélange de perturbateurs endocriniens causent des anomalies de l'émail dentaire et de la rétine associées à des changements du métabolisme hépatique
No full textInternational audienceExposure to environmental pollutants may contribute to various health disorders, often manifesting after a prolonged period of latency. The identification of early markers is, therefore, of paramount importance.To achieve this objective, realistic models of environmental exposure were set up. Whereas most studies consider one substance or mixture with one target organ, here, in addition to the liver, two easily accessible sensitive organs, the eyes and teeth, were analyzed as good potential candidates to be original markers of environmental exposures. C57BL/6J mice were exposed to either sodium fluoride or a mixture of 15 endocrine-disrupting substances, or both, in their drinking water from the time of conception until 1 or 10 months after birth. The doses of these substances were chosen to be close to the tolerable daily intake.All mice in test groups presented lower weight gain than controls with the most significant differences observed in females 30 days after birth. Alterations in the eye retina were detected as early as 1 month of age and considerably worsened by 10 months. Dental defects were observed in all test groups at the last time point. At that age, metabolic disruptions were identified through molecular metabolomic and RNAseq analyses, while histological analyses showed no significant defects in liver.This study shows that chronic exposure to widespread toxicants resulted in hepatic metabolic disorders. However, the most evident histological and clinical signs were observed in eyes and teeth. These easily accessible stigmata may be used as early markers of low-dose exposure to environmental toxicants.</div
In Vitro Dermal Absorption of Key Colour Developers in Thermal Paper: A Focus on Bisphenol A, Bisphenol S and Pergafast 201
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Prenatal Exposure to Ambient Particulate Matter and Autism Spectrum Disorder in Children, a Case Control Study in France
No full textInternational audienceA series of epidemiological studies conducted in the United States have consistently shown an increased risk of autism spectrum disorder (ASD) in children associated with pre- and postnatal exposure to ambient particulate matter (PM). In Europe, studies are scarce and results are inconsistent. We aimed to investigate the association between prenatal exposure to PM and the risk of ASD in France. ASD cases were participants from the ELENA cohort. Controls children from the ELFE cohort were matched by sex, year (± 2) and region of birth. Prenatal exposures to PM10 and to PM2.5 were estimated between 2008 and 2013 using innovative hybrid spatio-temporal models developed for France. Conditional logistic regression models adjusted for birth season, parentu2019s age at the child birth and parental education level were run. We included 125 ASD cases and 500 controls. Prenatal PM2.5 and PM10 median (IQR) concentration estimates were respectively 16.3 (3.9) µg/m3 and 22.9 (6.6) µg/m3 in the whole sample. The conditional logistic regression models showed Odds Ratios (ORs) (Confidence Interval 95%) for ASD risk of 0.72 (0.52u20131.01) and 0.84 (0.58u20131.22) for an IQR increase in PM2.5 and PM10 prenatal levels, respectively. When restricting population of ASD cases to children born the same year of controls, ORs were 1.79 (0.80u20134.01) and 2.23 (0.71u20139.04), respectively. Our results did not show that prenatal exposures to PM2.5 and PM10 were associated with the risk of ASD in children in France. Trial Registration Number NCT02625116
Traffic-related air pollution exposure at birth and risk of childhood leukemia: results from the GEOCAP-Birth case–control study
No full textInternational audienceBackground: Air pollution, in particular due to traffic, is suspected of increasing the risk of childhood acute leukemia (AL), most of the evidence coming from epidemiological studies and literature reviews that focused on the time around diagnosis. Using data on the national scale, we tested the hypothesis that prenatal exposure to traffic-related air pollution increases the risk of childhood AL.Methods: This case–control study included 581 cases of acute lymphoblastic leukemia (ALL) and 136 cases of acute myeloid leukemia (AML), registered in the French national registry of childhood cancer and born and diagnosed between 2010 and 2015, and 11,908 controls. Exposure indicators were evaluated at the addresses at birth and included major road length in 500 m buffers, and modeled exposures of nitrogen dioxide (NO2), fine particulate matter (PM2.5) and black carbon (BC). Odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression models. Exposures were considered in categories using tertiles’ cut offs or continuously for increments of ½ interquartile range.Results: Both ALL and AML risks increased with PM2.5 exposure (OR ALL = 1.14, 95%CI = 1.08–1.20 and OR AML = 1.12, 95%CI = 1.00–1.25 for an increment of 2 µg/m3, respectively). The risk of ALL was associated with BC exposure in urban units of < 5,000 inhabitants and of 5,000–99,999 inhabitants (OR = 1.90, 95%CI = 1.22–2.97 and OR = 1.58, 95%CI = 1.16–2.17 for an increment of 0.5 10–5/m, respectively), and not in more urban municipalities. An elevated OR for AML was observed for NO2 exposure (OR = 1.4, 95%CI = 0.9–2.1 for the highest versus lowest category). There was no association with the length of major roads.Conclusion: The results support a role of exposure to air pollution at time of birth in the risk of childhood AL
Year 116 of the plastic age: a Pandora’s box as a time bomb for pregnancy? Review of clinical and fundamental data on prenatal exposure to plastics
No full textPré-dépôt HAL IPREM via X2HalInternational audiencePlastics constitute an area of interest within the context of the placental exposome. A growing body of evidence now indicates that various micro- and nanoplastics — including notably polystyrene, polypropylene, polyethylene, and polyvinylchloride — are present in the human placenta, from the basal plate to the fetal membranes. Results from in vitro and ex vivo studies have shown that these environmental pollutants can enter the maternal bloodstream and reach the placenta, where they concentrate in the syncytiotrophoblast. These so-called “plasticenta” have been observed even in uncomplicated pregnancies, and to date, no longitudinal study has confirmed harmful long-term consequences for the newborn. However, plastics appear to alter placental functions and may therefore be associated with adverse outcomes such as miscarriage, intrauterine growth restriction and preterm birth. Findings from ex vivo human studies, in vivo murine models, and in vitro experiments with micro- and nanoplastics indicate that factors such as particle type, size, concentration, surface functionalization, route of exposure, and environmental conditions play key roles in cellular uptake and subsequent alterations in cell function and phenotype. Consequently, various impairments in placental metabolic and immune functions may contribute to abnormal development of the placenta and the fetus. Maternal exposure to these ubiquitous environmental pollutants may induce prenatal and neonatal disease states. In this review, we examine the current clinical, in vivo and in vitro data on the occurrence, distribution and impact of micro- and nanoplastics in the placenta
QSAR Models for Predicting Oral Bioavailability and Volume of Distribution and Their Application in Mapping the TK Space of Endocrine Disruptors
No full textInternational audienceToxicokinetic (TK) properties are essential in the framework of chemical risk assessment and drug discovery. Specifically, a TK profile provides information about the fate of chemicals in the human body. In this context, Quantitative Structure–Activity Relationship (QSAR) models are convenient computational tools for predicting TK properties. Here, we developed QSAR models to predict two TK properties: oral bioavailability and volume of distribution at steady state (VDss). We collected and curated two large sets of 1712 and 1591 chemicals for oral bioavailability and VDss, respectively, and compared regression and classification (binary and multiclass) models with the application of several machine learning algorithms. The best predictive performance of the models for regression (R) prediction was characterized by a Q2F3 of 0.34 with the R-CatBoost model for oral bioavailability and a geometric mean fold error (GMFE) of 2.35 with the R-RF model for VDss. The models were then applied to a list of potential endocrine-disrupting chemicals (EDCs), highlighting chemicals with a high probability of posing a risk to human health due to their TK profiles. Based on the results obtained, insights into the structural determinants of TK properties for EDCs are further discussed
Longitudinal assessment of nitrate and trihalomethanes in drinking-water and breast cancer in the CONSTANCES cohort: a prospective population-based study in France
No full textInternational audienceNitrate and trihalomethanes (THMs) in drinking water are widespread and potential human carcinogens. We evaluated the association between time-varying exposure to nitrate and THMs in drinking water and female breast cancer (BC) among adults from CONSTANCES, a large French population-based prospective cohort. Our analysis included 26,669 women (18.5–72.5 years old) enrolled in 2012–2020, followed until 2021, with information on residential history, type of water consumed, type of filter used, and bathing and showering frequency. We used water quality data for 2004–2020 from the drinking surveillance national database (SISE-Eaux). Annual median concentrations of nitrate, chloroform, chlorodibromomethane, bromodichloromethane, and bromoform at the participants’ residential addresses were estimated. Waterborne ingested exposure was estimated considering type of water, filter used, and liters/day consumed. Estimated exposure in showers and baths combined residential concentrations with showers/baths duration and frequency. Incident BC cases were ascertained in the French national health data system (SNDS) for 2012–2021. Extended Cox models with attained age as time-scale and time-varying weighted average exposures, adjusted for individual and area-level covariables, were used to estimate hazard ratios (HR) and confidence intervals (CI) by exposure tertiles. Average age at enrolment was 49.3 years, and median exposure window was 13 years. Median follow-up was 5 years (153,742 person-years), resulting in 437 new BC diagnoses. Median residential nitrate, brominated (Br)-THMs and chloroform concentrations were, respectively, 15.8 mg/L, 14.2 μg/L, and 2.7 μg/L. HR (95 %CI) of BC associated with waterborne ingested nitrate (mg/day) for the second (>4.8–15.1) and third tertile (>15.1) compared to the first (≤4.8) were 1.35 (1.01–1.81) and 1.51 (1.10–2.07), respectively. Residential THM concentrations were not associated with BC, however HR (95 %CI) of BC for showering and bathing Br-THMs exposure (μg/L × min/day) was 1.18 (0.84–1.64) for the third (>125) vs. first tertile (≤51.5). Findings suggest that ingested nitrate could be a risk factor of B
Chronic exposure to tebuconazole impairs offspring growth and survival in farmland birds: An experiment in captive house sparrows
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Unraveling the Connection Between Ion Channels and Pancreatic Stellate Cell Activation
No full textInternational audienceQuiescent pancreatic stellate cells (PSCs) represent only a very low proportion of the pancreatic tissue, but their activation leads to stroma remodeling and fibrosis associated with pathologies such as chronic pancreatitis and pancreatic ductal adenocarcinoma (PDAC). PSC activation can be induced by various stresses, including acidosis, growth factors (PDGF, TGFβ), hypoxia, high pressure, or intercellular communication with pancreatic cancer cells. Activated PSC targeting represents a promising therapeutic strategy, but little is known regarding the molecular mechanisms underlying the activation of PSCs. Identification of new biomarkers of PSC activation associated with desmoplasia in chronic pancreatitis and PDAC could lead to new therapeutic targets for exocrine pancreatic disease treatments. Ion channels and transporters are transmembrane proteins involved in numerous physiological and pathological processes, including PDAC. They are well known to act as biosensors of the tissue microenvironment, and they can be easily accessible for drugs. However, their role in PSC activation is not fully understood. In this review, we briefly discuss the role of activated PSCs in pancreas inflammation and pathological fibrosis (associated with chronic pancreatitis and PDAC), and we describe the role of specific ion channels and transporters (Ca2+, K+, Na+ and Cl-) in these processes in the light of recent literature
Associations between prenatal exposure to PFAS and cardiometabolic health in preadolescents
No full textInternational audienceIntroduction: While a number of studies have examined the effects of prenatal exposure to per- and polyfluoroalkyl substances (PFAS) on childhood obesity, the results reported have been inconsistent and few studies have integrated biological markers. The aim of this study was to investigate the associations between prenatal exposure to PFAS and cardiometabolic health parameters at age 12, taking pubertal stage into consideration.Method: This study included 394 mother-child pairs enrolled in the PELAGIE mother-child cohort (France). Nine PFAS were measured in umbilical cord blood, and the children attended a clinical examination at age 12. Anthropometry, blood metabolic markers, and blood pressure were measured and used to build an internal cardiometabolic score. Linear regression and Quantile G-computation models were used to evaluate individual and mixture PFAS effects, adjusting for confounders and stratifying by sex and pubertal stage.Results: No statistically significant association was observed between prenatal exposure to PFAS and cardiometabolic score at age 12. In post-menarche girls, perfluorohexane sulfonate (PFHxS) and perfluorodecanoic acid (PFDA) were statistically significantly associated with a decrease in a number of adiposity parameters (e.g., Body mass index z-score: beta [95%CI] = -0.37 [-0.67; -0.07]), as well as a decrease in low-density lipoproteins (LDL) and leptin levels. Similar results were observed with PFAS mixture, with statistically significantly decreased tricipital skinfolds (beta [95%CI] = -1.30 [(-2.54;-0.06)]). Isolated associations, including higher systolic blood pressure, changes in cholesterol levels, and lower adiponectin levels were observed in specific subgroups.Conclusion: There is no clear evidence of an association between prenatal exposure to PFAS and the cardiometabolic health at earlier stage of pubertal development. However, inverse associations between PFAS and anthropometric measures have been observed in post-menarche girls. While the literature on this topic is scarce in pre-adolescents, these results suggest the importance of considering sex and pubertal stage in these associations