L'exposition maternelle aux pesticides

National audienceLes voies d’exposition aux pesticides sont multiples : par ingestion, inhalation ou contact cutané. On estime à un million, le nombre de femmes susceptibles d’être exposées (5% des femmes actives), directement ou indirectement, à ces substances dans leur environnement professionnel. Un nombre croissant d’études épidémiologiques suggère un impact de l’exposition aux pesticides pendant la grossesse sur la santé des enfants à la naissance ainsi que sur leur développement. Or, la connaissance des déterminants des niveaux d’imprégnation de pesticides de la population générale est aujourd’hui encore inégale en France

Characterization of environmental multi-exposure to pesticides in pregnant women

extended abstractInternational audienceThe objective was to develop a multi-residue approach to quantify different pesticides in urine from pregnant women and to assess their determinants of exposure. 244 urine samples from a mother-child cohort were analyzed by UHPLC/QTOFMS after a sample preparation step to look for 42 different molecules. Bayesian statistical analyses were used to study the determinants of exposure to >10% detected pesticides. Methylated organophosphorous (OP) were the most concentrated (600 µg/L). Determinants of exposure were: location in rural zone and proximity / presence of crops, diet, and smoking status. Surprisingly, an inverse association between the presence of potatoes or peas crops in the town of residence and urinary metabolites of pyrethroids was found

Deciphering the prenatal chemical exposome using placenta and metabolomics

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Organophosphate flame retardants: a review of indoor contamination and human exposure in Europe, and human health effects.

International audienc

Potential input from metabolomics for exploring and understanding the links between environment and health.

International audienceHumans may be exposed via their environment to multiple chemicals as a consequence of human activities and use of synthetic products. Little knowledge is routinely generated on the hazards of these chemical mixtures. The metabolomic approach is widely used to identify metabolic pathways modified by diseases, drugs, or exposures to toxicants. This review, based on the state of the art of the current applications of metabolomics in environmental health, attempts to determine whether metabolomics might constitute an original approach to the study of associations between multiple, low-dose environmental exposures in humans. Studying the biochemical consequences of complex environmental exposures is a challenge demanding the development of careful experimental and epidemiological designs, in order to take into account possible confounders associated with the high level of interindividual variability induced by different lifestyles. The choices of populations studied, sampling and storage procedures, statistical tools used, and system biology need to be considered. Suggestions for improved experimental and epidemiological designs are described. Evidence indicates that metabolomics may be a powerful tool in environmental health in the identification of both complex exposure biomarkers directly in human populations and modified metabolic pathways, in an attempt to improve understanding the underlying environmental causes of diseases. Nevertheless, the validity of biomarkers and relevancy of animal-to-human extrapolation remain key challenges that need to be properly explored

Évaluation des effets sur le neurodéveloppement de l’exposition prénatale et postnatale aux produits phytopharmaceutiques. Présentation du projet NEUROPHYTO

International audiencePrenatal and neonatal periods are windows of vulnerability to environmental chemical contaminants. A growing number of epidemiological and toxicological studies suggest that exposure to pesticides during these periods may impact the health of children at birth as well as their development, with potential delayed adverse effects.The NEUROPHYTO project is a new research project that aims to evaluate the exposure to pesticides of French children from prenatal period to early childhood and to study the possible effects of these exposures on their motor and neuropsychological development. New exposure data will be generated: levels of 140 pesticides and metabolites will be measured in biological samples (urine and hair) of 200 children from the national cohort Elfe (French longitudinal study of children). The levels of active substance(s) in the brain will be estimated using a mathematical model and then related to early neurodevelopmental effects. Two approaches will be used to better identify and characterize these links. The first strategy will rely on epidemiological methods and the second will be based on the understanding of the neurotoxicity mechanisms of the substances. Finally, a child-specific risk analysis will provide support to public policies by targeted evidence during pre- and post-natal windows of vulnerability.Les périodes prénatale et néonatale constituent des fenêtres de sensibilité vis-à-vis des contaminants chimiques de l’environnement. Un nombre croissant d’études épidémiologiques et toxicologiques suggère que l’exposition aux pesticides pendant ces périodes pourrait impacter la santé des enfants à la naissance ainsi que leur développement, avec des retentissements possibles tout au long de la vie.Le projet NEUROPHYTO est un nouveau projet de recherche qui vise à évaluer les expositions aux produits phytosanitaires d’enfants français lors de la période prénatale à la petite enfance et à étudier les effets possibles de ces expositions sur leur développement moteur et neuropsychologique. De nouvelles données d’exposition seront produites : les concentrations de 140 pesticides et métabolites seront mesurés dans les échantillons biologiques (urine et cheveux) de 200 enfants de la cohorte nationale Elfe (Etude longitudinale française depuis l’enfance). Les concentrations de substance(s) active(s) dans le cerveau seront estimées par modélisation puis mis en relation avec des effets neurodéveloppementaux précoces. Deux approches seront mises en œuvre afin de mieux identifier et caractériser ces liens : l’une épidémiologique et l’autre basée sur la compréhension des mécanismes de neurotoxicité des substances. Enfin, une analyse spécifique des risques pour les enfants permettra d’appuyer les politiques publiques en apportant des éléments ciblés sur les fenêtres de sensibilité pré et postnatales

Preclinical development of a docetaxel nanocarrier to enhance prostate cancer radiosensitivity.

International audienceBackground: From 30% to 50% of high risk prostate cancer patients who undergo radiation therapy (RT) will have a biochemical failure. Combining chemotherapy, such as Docetaxel (DXL), with RT can enhance its efficiency. Multidrug resistance mechanisms often limit drug efficacy by decreasing tumor cell intracellular concentration of drugs. There is interest to develop nanocarrier of DXL to maintain drug inside cancer cells by improving its efficacy. The purpose of this study was to develop a titanate-nanotube (TiONt)-DXL nanocarrier (nanohybrid) and to evaluate its in vivobiodistribution as well as its radiosensitizing efficacy in association with RT on a hormone-independent prostate cancer model. Methods: DXL molecules were grafted on TiONts using PEG-3000 molecules to generate the nanohybrid. In vitrocytotoxic activity of the nanohybrid was evaluated on PC-3 cell line using MTS assay. After intratumoral injection, biodistribution analysis was performed by SPEC-CT imaging of mice bearing subcutaneous PC-3 human prostate tumors. To evaluate the benefit of nanohybrid and RT association, tumors were irradiated using 3 fractions of 4Gy administrated after the injection of nanohybrids. Nine groups of 7 mice were used to evaluate nanohybrid and RT association efficacy : untreated, control with buffer IT injection, +/- RT, free DXL, +/- RT, TiONt +/- RT and TiONt-DXL +/- RT. Mice behavior, health status and tumor volume were monitored twice a week until tumor growth recovery. Results: Biodistribution kinetics showed that more than 70% of nanohybrids were localized into the tumor 96 hours after injection. Mice receiving nanohybrid-RT exhibited a significant tumor growth delay to reach a volume of 1,000mm 3 compared to mice receiving free DXL-RT: 73.7 days (median, [58.9-89]) vs 56 days (median, [31.5-74]) (p=0.0127). Conclusions: TiONt-DXL improves RT efficacy compared to free DXL. These results suggest that local control might be enhanced by TiONt-DXL. TiONt-DXL can be injected as a radiosensitizer in men harboring high risk localized prostate cancer with needles during prostate brachytherapy procedure

Interactions between disinfection by products in drinking water and genetic susceptibility variants in relation to adverse reproductive outcomes (the Hiwate study)

Aplinkotyros katedraVytauto Didžiojo universiteta