Hair-Derived Exposome Exploration of Cardiometabolic Health: Piloting a Bayesian Multitrait Variable Selection Approach.

peer reviewedCardiometabolic health is complex and characterized by an ensemble of correlated and/or co-occurring conditions including obesity, dyslipidemia, hypertension, and diabetes mellitus. It is affected by social, lifestyle, and environmental factors, which in-turn exhibit complex correlation patterns. To account for the complexity of (i) exposure profiles and (ii) health outcomes, we propose to use a multitrait Bayesian variable selection approach and identify a sparse set of exposures jointly explanatory of the complex cardiometabolic health status. Using data from a subset (N = 941 participants) of the nutrition, environment, and cardiovascular health (NESCAV) study, we evaluated the link between measurements of the cumulative exposure to (N = 33) pollutants derived from hair and cardiometabolic health as proxied by up to nine measured traits. Our multitrait analysis showed increased statistical power, compared to single-trait analyses, to detect subtle contributions of exposures to a set of clinical phenotypes, while providing parsimonious results with improved interpretability. We identified six exposures that were jointly explanatory of cardiometabolic health as modeled by six complementary traits, of which, we identified strong associations between hexachlorobenzene and trifluralin exposure and adverse cardiometabolic health, including traits of obesity, dyslipidemia, and hypertension. This supports the use of this type of approach for the joint modeling, in an exposome context, of correlated exposures in relation to complex and multifaceted outcomes

Multiple pesticides in mothers' hair samples and children's measurements at birth: Results from the French national birth cohort (ELFE)

International audienceBackground - A growing body of studies now suggests that the general population is continuously and ubiquitously exposed to numerous pesticides. However, studies investigating the possible role of environmental exposure to pesticides on fetal growth have focused on a limited set of substances, despite the hundreds of modern pesticides currently available. Aim - To explore the relation between maternal hair concentrations of 64 pesticides and metabolites and their newborns' measurements at birth, with data from the ELFE French nationwide birth cohort. Methods - We measured 64 compounds (10-100% detection) in bundles of hair 9 cm long collected at birth from 311 women who gave birth in France in 2011. We assessed their associations with birth weight, length, and head circumference, adjusted for potential confounders, and used elastic net regularization to simultaneously select the strongest predictors of measurements at birth. Selected variables were multiply imputed for missing values, and unpenalized estimators were assessed by standard linear regression. Results - We observed statistically significant associations between maternal hair concentrations of seven pesticides or pesticide metabolites and birth measurements (weight: fipronil sulfone; length: TCPy, bitertanol, DEP, and isoproturon; head circumference: tebuconazole and prochloraz). Analyses restricted to boys identified 12 additional compounds: 8 independently associated with birth weight (3Me4NP, DCPMU, DMST, fipronil, mecoprop, propoxur, fenhexamid, and thiabendazole), 2 with birth length (dieldrin and β-endosulfan), and 6 with head circumference (β-endosulfan, β-HCH, fenuron, DCPMU, propoxur, and thiabendazole). Conclusion - Our results suggest that prenatal exposure to 19 pesticides or metabolites from various chemical families may influence measurements at birth. As with any exploratory research findings, results should be interpreted cautiously, until they are replicated or verified by further epidemiological or mechanistic studies

Projet NEUROPHYTO : Evaluation des effets sur le neurodéveloppement de l’exposition prénatale et postnatale aux produits phytopharmaceutiques

National audienceLes périodes prénatale et néonatale constituent des fenêtres de sensibilité particulières 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 a comme premier objectif de décrire l’exposition de 200 enfants de la cohorte nationale Elfe à une large gamme de produits phytosanitaires, allant de la période in utero aux 3 ans et demi grâce aux dosages de biomarqueurs d’exposition dans les urines et dans les cheveux.Une évaluation de l’exposition interne notamment au niveau de tissus cibles tels que le cerveau sera réalisée grâce à des modèles toxicocinétiques à fondement physiologique pour la petite enfance. Une fois ces profils de doses internes établis pour les enfants, deux grands volets seront mis en œuvre afin de développer les connaissances sur les liens entre expositions et effets sur le neurodéveloppement. Un premier volet sera consacré à la mise en œuvre d’une approche épidémiologique basée sur l’étude des données sur le développement neuropsychologique et moteur des enfants de la cohorte Elfe. Le second volet sera dédié à l’amélioration des connaissances mécanistiques sur les liens entre l’exposition aux produits phytosanitaires et l’apparition de troubles neurodéveloppementaux, via des méthodologies innovantes. Des modèles computationnels seront développés et de nouveaux ‘adverse outcome pathways’ (AOPs) seront proposés.Ce projet permettra d’appuyer les politiques publiques en apportant des éléments ciblés sur les fenêtres de sensibilité pré- et post-natales ainsi qu’une analyse des valeurs toxicologiques de référence existantes incluant la proposition de valeurs dédiées à l’évaluation des risques d’effets neurodéveloppementaux chez les enfants

Impact of Protein-Enriched Plant Food Items on the Bioaccessibility and Cellular Uptake of Carotenoids

Carotenoids are lipophilic pigments which have been associated with a number of health benefits, partly related to antioxidant effects. However, due to their poor solubility during digestion, carotenoid bioavailability is low and variable. In this study, we investigated the effect of frequently consumed proteins on carotenoid bioaccessibility and cellular uptake. Whey protein isolate (WPI), soy protein isolate (SPI), sodium caseinate (SC), gelatin (GEL), turkey and cod, equivalent to 0/10/25/50% of the recommended dietary allowance (RDA, approx. 60g/d), were co-digested gastro-intestinally with carotenoid-rich food matrices (tomato and carrot juice, spinach), and digesta further studied in Caco-2 cell models. Lipid digestion, surface tension and microscopic visualization were also carried out. Co-digested proteins positively influenced the micellization of carotenes (up to 3-fold, depending on type and concentration), especially in the presence of SPI (p < 0.001). An increased cellular uptake was observed for xanthophylls/carotenes (up to 12/33%, p < 0.001), which was stronger for matrices with an initially poor carotenoid micellization (i.e., tomato juice, p < 0.001), similar to what was encountered for bioaccessibility. Turkey and cod had a weaker impact. Significant interactions between carotenoids, lipids and proteins were observed during digestion. Co-digested proteins generally improved lipid digestion in all matrices (p < 0.001), especially for carrot juice, though slight decreases were observed for GEL. Protein impact on the surface tension was limited. In conclusion, proteins generally improved both carotenoid bioaccessibility and cellular uptake, depending on the matrices and carotenoid-type (i.e., carotene vs. xanthophylls), which may be relevant under specific circumstances, such as intake of carotenoid-rich food items low in lipids

Multiple pesticide analysis in hair samples of pregnant French women Results from the ELFE national birth cohort

International audienceBackground - A growing body of evidence suggests that prenatal exposure to pesticides might impair fetal development. Nonetheless, knowledge about pesticide exposure of pregnant women, especially in Europe, is largely restricted to a limited panel of molecules. Aim - To characterize the concentration of 140 pesticides and metabolites in hair strands from women in the ELFE French nationwide birth cohort. Methods - Among cohort members who gave birth in northeastern and southwestern France in 2011, we selected those with a sufficient available mass of hair (n = 311). Bundles of hair 9 cm long were collected at delivery. We screened 111 pesticides and 29 metabolites, including 112 selected a priori based on their reported usage or detection in the French environment. The bundles of hair from 47 women were split into three segments to explore the intraindividual variability of the exposure. Intraclass correlation coefficients (ICCs) were computed for the chemicals with a detection frequency >70%. Results - We detected a median of 43 chemicals per woman (IQR 38-47). Overall, 122 chemicals (>20 chemical families) were detected at least once, including 28 chemicals detected in 70-100% of hair samples. The highest median concentrations were observed for permethrin (median: 37.9 pg/mg of hair), p-nitrophenol (13.2 pg/mg), and pentachlorophenol (10.0 pg/mg). The ICCs for the 28 chemicals studied ranged from 0.59 to 0.94. Conclusion - Pregnant women are exposed to multiple pesticides simultaneously from various chemical families, including chemicals suspected to be reproductive toxicants or endocrine disruptors. The ICCs suggest that the intraindividual variability of pesticide concentrations in hair is lower than its interindividual variability

Neurobehavioral toxicity of a repeated exposure (14 days) to the airborne polycyclic aromatic hydrocarbon fluorene in adult Wistar male rats.

Fluorene is one of the most abundant polycyclic aromatic hydrocarbons in air and may contribute to the neurobehavioral alterations induced by the environmental exposure of humans to PAHs. Since no data are available on fluorene neurotoxicity, this study was conducted in adult rats to assess the behavioral toxicity of repeated fluorene inhalation exposure. Male rats (n = 18/group) were exposed nose-only to 1.5 or 150 ppb of fluorene 6 hours/day for 14 consecutive days, whereas the control animals were exposed to non-contaminated air. At the end of the exposure, animals were tested for activity and anxiety in an open-field and in an elevated-plus maze, for short-term memory in a Y-maze, and for spatial learning in an eight-arm maze. The results showed that the locomotor activity and the learning performances of the animals were unaffected by fluorene. In parallel, the fluorene-exposed rats showed a lower level of anxiety than controls in the open-field, but not in the elevated-plus maze, which is probably due to a possible difference in the aversive feature of the two mazes. In the same animals, increasing blood and brain levels of fluorene monohydroxylated metabolites (especially the 2-OH fluorene) were detected at both concentrations (1.5 and 150 ppb), demonstrating the exposure of the animals to the pollutant and showing the ability of this compound to be metabolized and to reach the cerebral compartment. The present study highlights the possibility for a 14-day fluorene exposure to induce some specific anxiety-related behavioral disturbances, and argues in favor of the susceptibility of the adult brain when exposed to volatile fluorene

Association of hair polychlorinated biphenyls and multiclass pesticides with obesity, diabetes, hypertension and dyslipidemia in NESCAV study.

peer reviewedObesity, diabetes, hypertension and dyslipidemia are well-established risk factors for cardiovascular diseases (CVDs), and have been associated with exposure to persistent organic pollutants. However, studies have been lacking as regards effects of non-persistent pesticides on CVD risk factors. Here, we investigated whether background chronic exposure to polychlorinated biphenyls (PCBs) and multiclass pesticides were associated with the prevalence of these CVD risk factors in 502 Belgian and 487 Luxembourgish adults aged 18-69 years from the Nutrition, environment and cardiovascular health (NESCAV) study 2007-2013. We used hair analysis to evaluate the chronic internal exposure to three PCBs, seven organochlorine pesticides (OCs) and 18 non-persistent pesticides. We found positive associations of obesity with hexachlorobenzene (HCB), β-hexachlorocyclohexane (β-HCH) and chlorpyrifos, diabetes with pentachlorophenol (PCP), fipronil and fipronil sulfone, hypertension with PCB180 and chlorpyrifos, and dyslipidemia with diflufenican and oxadiazon, among others. However, we also found some inverse associations, such as obesity with PCP, diabetes with γ-HCH, hypertension with diflufenican, and dyslipidemia with chlorpyrifos. These results add to the existing evidence that OC exposure may contribute to the development of CVDs. Additionally, the present study revealed associations between CVD risk factors and chronic environmental exposure to currently used pesticides such as organophosphorus and pyrethroid pesticides