Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
CONTEXT: Chlordecone, an environmentally persistent organochlorine insecticide used intensively in banana culture in the French West Indies until 1993, has permanently polluted soils and contaminated foodstuffs. Consumption of contaminated food is the main source of exposure nowadays. We sought to identify main contributors to blood chlordecone concentration (BCC) and to validate an exposure indicator based on food intakes. MATERIAL AND METHODS: We used a food frequency questionnaire (FFQ) completed by a sample of 194 pregnant women to estimate their dietary exposure to chlordecone and compared it to blood levels. In a first approach, chlordecone daily intake was estimated as the product of daily eaten quantity of 214 foodstuffs, multiplied by their chlordecone content, and summed over all items. We then predicted individual blood chlordecone concentration with empirical weight regression models based on frequency of food consumption, and without contamination data. RESULTS: Among the 191 subjects who had BCC determination, 146 (76%) had detectable values and mean BCC was 0.86 ng/mL (range < LOD-13.2). Mean per capita dietary intake of chlordecone was estimated at 3.3 microg/day (range: 0.1-22.2). Blood chlordecone levels were significantly correlated with food exposure predicted from the empirical weight models (r=0.47, p<0.0001) and, to a lesser extent, with chlordecone intake estimated from food consumption and food contamination data (r=0.20, p=0.007). Main contributors to chlordecone exposure included seafood, root vegetables, and Cucurbitaceous. CONCLUSION: These results show that the Timoun FFQ provides valid estimates of chlordecone exposure. Estimates from empirical weight models correlated better with blood levels of chlordecone than did estimates from the dietary intake assessment.
ISSN: 0013-9351

inserm-00517109
http://www.hal.inserm.fr/inserm-00517109
http://www.hal.inserm.fr/inserm-00517109/document
http://www.hal.inserm.fr/inserm-00517109/file/Pesticide_exposureofpregnantwomeninGuadeloupe.pdf
DOI : 10.1016/j.envres.2009.10.015

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
BACKGROUND: The insecticide chlordecone was extensively used in the French West Indies to control banana root borer. Its persistence in soils has led to the widespread pollution of the environment, and human beings are still exposed to this chemical. Chlordecone has been shown to impair neurological and behavioural functions in rodents when exposed gestationally or neonatally. OBJECTIVES: The aim of the study was to evaluate the impact of prenatal and postnatal exposure to chlordecone on the cognitive, visual, and motor development of 7-month-old infants from Guadeloupe. METHODS: Infants were tested at 7 months (n=153). Visual recognition memory and processing speed were assessed with the Fagan Tests of Infant Intelligence (FTII), visual acuity with the Teller Acuity Card, and fine motor development with the Brunet-Lezine. Samples of cord blood and breast milk at 3 months (n=88) were analyzed for chlordecone concentrations. Postnatal exposure was determined through breast feeding and frequency of contaminated food consumption by the infants. RESULTS: Cord chlordecone concentrations in tertiles were associated with reduced novelty preference on the FTII in the highly exposed group (β=-0.19, p=0.02). Postnatal exposure through contaminated food consumption was marginally related to reduced novelty preference (β=-0.14, p=0.07), and longer processing speed (β=0.16, p=0.07). Detectable levels of chlordecone in cord blood were associated with higher risk of obtaining low scores on the fine motor development scale (OR=1.25, p<0.01). CONCLUSION: These results suggest that pre- and postnatal low chronic exposure to chlordecone is associated with negative effects on cognitive and motor development during infancy.
ISSN: 0013-9351

hal-00875939
https://hal.archives-ouvertes.fr/hal-00875939
DOI : 10.1016/j.envres.2012.07.006
PUBMED : 22910562

Éditeur(s) : HAL CCSD
Résumé : International audience
Studies report that foetal exposure to paracetamol by maternal consumption can interfere with male reproductive development. Moreover, recent biomonitoring data report widespread presence of paracetamol in German and Danish populations, suggesting exposure via secondary (non-pharmaceutical) sources such as metabolic conversion from the ubiquitous industrial compound aniline. In this study we investigated the extent to which paracetamol and aniline can interfere with female reproductive development. Intrauterine exposure to paracetamol by gavage of pregnant dams resulted in shortening of the anogenital distance in adult offspring, suggesting that foetal hormone signalling had been disturbed. Female offspring of paracetamol-exposed mothers had ovaries with diminished follicle reserve and reduced fertility. Foetal gonads of exposed animals had also reduced gonocyte numbers, suggesting that the reduced follicle count in adults could be due to early disruption of germ cell development. However, ex vivo cultures of ovaries from 12.5 days post coitum foetuses showed no decrease in proliferation or expression following exposure to paracetamol. This suggests that the effect of paracetamol occurs prior to this developmental stage. Accordingly, using embryonic stem cells as a proxy for primordial germ cells we show that paracetamol is an inhibitor of cellular proliferation, but without cytotoxic effects. Collectively, our data show that intrauterine exposure to paracetamol at levels commonly observed in pregnant women, as well as its precursor aniline, may block primordial germ cell proliferation, ultimately leading to reduced follicle reserves and compromised reproductive capacity later in life
Toxicological Sciences

hal-01259211
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01259211
DOI : 10.1093/toxsci/kfv332
PUBMED : 26732887

Éditeur(s) : HAL CCSD BioMed Central
Résumé : International audience
BACKGROUND: Sampling design is a key issue when establishing species inventories and characterizing habitats within highly heterogeneous landscapes. Sampling efforts in such environments may be constrained and many field studies only rely on subjective and/or qualitative approaches to design collection strategy. The region of Cacao, in French Guiana, provides an excellent study site to understand the presence and abundance of Anopheles mosquitoes, their species dynamics and the transmission risk of malaria across various environments. We propose an objective methodology to define a stratified sampling design. Following thorough environmental characterization, a factorial analysis of mixed groups allows the data to be reduced and non-collinear principal components to be identified while balancing the influences of the different environmental factors. Such components defined new variables which could then be used in a robust k-means clustering procedure. Then, we identified five clusters that corresponded to our sampling strata and selected sampling sites in each stratum. RESULTS: We validated our method by comparing the species overlap of entomological collections from selected sites and the environmental similarities of the same sites. The Morisita index was significantly correlated (Pearson linear correlation) with environmental similarity based on i) the balanced environmental variable groups considered jointly (p = 0.001) and ii) land cover/use (p-value<0.001). The Jaccard index was significantly correlated with land cover/use-based environmental similarity (p-value = 0.001). CONCLUSIONS: The results validate our sampling approach. Land cover/use maps (based on high spatial resolution satellite images) were shown to be particularly useful when studying the presence, density and diversity of Anopheles mosquitoes at local scales and in very heterogeneous landscapes.
BMC Ecology

pasteur-00914104
https://hal-riip.archives-ouvertes.fr/pasteur-00914104
https://hal-riip.archives-ouvertes.fr/pasteur-00914104/document
DOI : 10.1186/1472-6785-13-45
PUBMED : 24289184

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
Few studies have been undertaken to assess the possible effects of bisphenol A (BPA) on the reproductive hormone balance in animals or humans with often contradictory results. We investigated possible direct endocrine disruption by BPA of the fetal testes of 2 rat strains (14.5-17.5 days post-coitum) and humans (8-12 gestational weeks) and under different culture conditions. BPA concentrations of 10-8M and 10-5M for 72h reduced testosterone production by the Sprague-Dawley fetal rat testes, while only 10-5M suppressed it in the Wistar strain. The suppressive effects at 10-5M were seen as early as 24h and 48h in both strains. BPA at 10-7-10-5M for 72h suppressed the levels of fetal rat Leydig cell insulin-like factor 3 (INSL3). BPA exposure at 10-8M, 10-7M, and 10-5M for 72h inhibited testosterone production in fetal human testes. For the lowest doses, the effects observed occurred only when no gonadotrophin was added to the culture media and were associated with a poorly preserved testicular morphology. We concluded that (i) BPA can display anti-androgenic effects both in rat and human fetal testes; (ii) it is essential to ascertain that the divergent effects of endocrine disruptors between species in vitro do not result from the culture conditions used, and/or the rodent strain selected; (iii) the optimization of each in vitro assay for a given species should be a major objective rather than the search of an hypothetical trans-species consensual model-system, as the organization of the testis is intrinsically different between mammalian species; (iv) due to the uncertainty existing on the internal exposure of the human fetal testis to BPA, and the insufficient number of epidemiological studies on the endocrine disruptive effects of BPA, caution should be taken in the extrapolation of our present results to the human reproductive health after fetal exposure to BPA.
ISSN: 1932-6203

hal-01121759
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01121759
PUBMED : 25706302
DOI : 10.1371/journal.pone.0117226

Éditeur(s) : HAL CCSD
Résumé : Background. Chlorine is the most widely used disinfectant for drinking water treatment. During treatment process, the natural organic matter present in water reacts with chlorine to form disinfection by-products (DBPs), such as trihalomethanes (THMs) and haloacetic acids (HAAs), the most occurring ones. Several identified DBPs were recognized carcinogens or fetotoxic in animals. We conducted two epidemiological studies to assess the health effects of human exposure to DBPs regarding cancer and reproduction. Association between THM exposure and the risk of bladder cancer: a pooled analysis of 3 European case-control studies. The study included 2381 cases and 3086 controls from 3 case-control studies (France, Finland, Spain). Environmental exposure to SPCs was measured by THM concentrations in water distribution systems, retrospectively estimated through the 40-year exposure window. Information about water uses (tap water ingestion, showers and baths, swimming-pool attendance) was available. An increased risk of bladder cancer was observed, in men only, with increasing THM concentrations in water systems and duration of exposure to chlorinated surface water. No association was observed with exposure through tap water ingestion. Exposure through showers, baths and swimming in pools (available in Spanish study only) was associated with an increased risk of bladder cancer. Three North-American case-control studies were joined to the three European ones into a meta-regression. No specific dose-response relationship was identified for European studies. A global dose-response relationship was consequently estimated, including 4351 cases and 7055 controls. Association between DBP exposure and the risk of preterm birth and Intra-Uterine Growth Retardation (IUGR). This study was conducted within the PELAGIE cohort (3400 pregnant women included in early pregnancy, in Brittany, France, between 2002 and 2006). Exposure during pregnancy was measured by 2 indicators: THM concentrations in water distribution systems and a biomarker of HAA ingestion, the level of trichloroacetic acid in maternal urine at inclusion (in a nested case-control study). The regulatory database SISE-Eaux was used to estimate THMs concentrations in the water distribution systems. Water uses during pregnancy (ingested tap water, swimming-pool attendance, showers and bath frequencies and duration) were collected with questionnaires. Our results suggest an association between prenatal exposure to DBPs (THMs and HAAs) and the risk of IUGR. No association was found with the risk of preterm birth.
Contexte. La chloration est le traitement le plus utilisé pour désinfecter l’eau distribuée à la population. Lors du traitement, des sous-produits de chloration (SPCs) se forment par réaction de la matière organique naturelle présente dans l’eau avec le chlore. Les produits les plus présents sont les trihalométhanes (THMs), les acides haloacétiques (HAAs). Des études toxicologiques (animales et in vitro) ont montré la génotoxicité et/ou carcinogénicité et la reprotoxicité de certains SPCs. Nous avons mené deux études évaluant les effets sur la santé humaine de l’exposition aux SPCs, dans le domaine du cancer et de la reproduction. Association entre exposition aux THMs et risque de cancer de la vessie : une analyse poolée de 3 études cas-témoins européennes. Cette analyse a inclus 2381 cas et 3086 témoins issus de 3 études cas-témoins (France, Espagne, Finlande). L’exposition environnementale aux SPCs a été mesurée par la concentration en THMs estimée rétrospectivement dans les réseaux de distribution d’eau au cours des 40 années de la fenêtre d’exposition. Les usages de l’eau connus sont l’ingestion, les douches et les bains, la fréquentation de piscine (étude espagnole seulement). Une relation croissante a été observée entre le niveau environnemental de THMs, la durée d’exposition à une eau de surface chlorée et le risque de cancer de la vessie, chez les hommes uniquement. Aucune association n’a été observée avec l’exposition via l’ingestion d’eau du robinet. L’exposition via les douches, les bains et la piscine est apparue liée au risque de cancer de la vessie. Trois études cas-témoins nord-américaines ont été intégrées dans une méta-régression. Aucune spécificité européenne de la relation dose-réponse n’a été mise en évidence. Une relation dose-réponse globale incluant 4351 cas et 7055 témoins a été estimée. Association entre exposition aux SPCs et risque de prématurité et de retard de croissance intra-utérin (RCIU). Cette étude est issue de la cohorte bretonne Pélagie (3400 femmes enceintes recrutées en début de grossesse entre 2002 et 2006). L’exposition pendant la grossesse a été mesurée à l’aide de 2 indicateurs : la concentration en THMs de l’eau distribuée dans les réseaux et le dosage d’un biomarqueur urinaire (acide trichloroacétique) pour un sous-échantillon de femmes (étude cas-témoins nichée). Les niveaux dans les réseaux proviennent de la base de données réglementaire SISE-Eaux. Les usages de l’eau du robinet par les femmes pendant la grossesse ont été collectés par questionnaire (quantité d’eau du robinet bue, fréquentation de la piscine, fréquence et durée des douches et des bains). Notre étude suggère une association entre l’exposition prénatale aux SPCs et le risque de RCIU. Aucune association n’est observée avec le risque de prématurité.
https://tel.archives-ouvertes.fr/tel-00927735

Droits : info:eu-repo/semantics/OpenAccess
NNT : 2013REN1B008
tel-00927735
https://tel.archives-ouvertes.fr/tel-00927735
https://tel.archives-ouvertes.fr/tel-00927735/document
https://tel.archives-ouvertes.fr/tel-00927735/file/COSTET_DEIBER_Nathalie4.pdf

Éditeur(s) : EDP Sciences
Résumé : Martinique is a French overseas department whose economy relies heavily on agriculture. Organochlorine pesticides, mainly chlordecone, were used for banana cultivation to eradicate banana weevil over a period of 40 years. Chlordecone is chemically stable,and has a strong affinity for fatty tissues. It is therefore able to bioaccumulate in animals and thereby represent a threat to ecosystems and man. Soils from banana plantations in Martinique are heavily contaminated with chlordecone. Possible transfer of these molecules from agricultural watersheds to the aquatic environment and the organisms that live in it is feared. The hypothesis that ecosystems of Martinique might be highly contaminated with this organochlorine pesticide was investigated. Chlordecone levels were measured in various freshwater and marine species. Data show a heavy contamination of many carnivorous and detritivorous species (fish and prawns). Concentrations measured in wild or farmed tilapia are among the highest ever reported in the literature. Some coastal species (fish and lobster) were also found to be contaminated, although to a lesser extent. Given the biogeochemical behavior of chlordecone, the most likely route of contamination is food. Detected concentrations in marine organisms are below the tolerated limits established by authorities. however. the impact of other sources of exposure, namely, contaminated water and root vegetables, remains to be investigated.
Aquatic Living Resources (0990-7440) (EDP Sciences), 2006-04 , Vol. 19 , N. 2 , P. 181-187

Droits : EDP Sciences, IFREMER, IRD 2006
http://archimer.ifremer.fr/doc/2006/publication-1662.pdf
DOI:10.1051/alr:2006016
http://archimer.ifremer.fr/doc/00000/1662/

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
Digestive tubules of Strombidae are composed by three cell types: digestive cells, vacuolated cells, and crypt cells. The last one is characterized by the presence of intracellular granules identified as spherocrystals. Such structures are known to occur in basophilic cells of gastropod digestive gland, where they are supposed to be involved in the regulation of some minerals and in detoxification. In this study, energy-dispersive X-ray analysis (EDX) and energy filtered transmission electron microscopy (EFTEM) were used to determine the elemental content of spherocrystals in two Strombidae, Strombus gigas and Strombus pugilis. In freshly collected individuals of both species, the following elements were detected: Ca, Fe, Mg, P, and Zn. Aluminum and Mn were also detected in S. gigas. Their presence in spherocrystals indicates that, in Strombidae, spherocrystals are involved in the regulation of minerals and essential trace metals. In order to answer the question ''are spherocrystals involved in nonessential trace metals scavenging?,'' artificial cadmium and lead exposure by both waterborne and dietary pathways was applied to S. pugilis. No evidence of cadmium (Cd(NO3)2) or lead (Pb(NO3)2) provided by food was found in spherocrystals. Cadmium provided in water (Cd(NO3)2 and CdCl2) causes structural modifications of the digestive gland; however, this element was not trapped in spherocrystals. These results suggest that spherocrystals are not involved in detoxification of such nonessential trace metals.
ISSN: 1059-910X

hal-00743762
https://hal.univ-antilles.fr/hal-00743762
DOI : 10.1002/jemt.21073

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Perinatal exposure to endocrine-disrupting chemicals may affect thyroid hormones homeostasis and impair brain development. Chlordecone, an organochlorine insecticide widely used in the French West Indies has known estrogenic and progestin properties, but no data is available, human or animal, on its action on thyroid hormone system. Our aim was to evaluate the impact of perinatal exposure to chlordecone on the thyroid hormone system of a sample of infants from the Timoun mother-child cohort in Guadeloupe and their further neurodevelopment. Chlordecone was measured in cord blood and breast milk samples. Thyroid stimulating hormone (TSH), free tri-iodothyronine (FT3), free thyroxine (FT4) were determined in child blood at 3 months (n=111). Toddlers were further assessed at 18 months using an adapted version of the Ages and Stages Questionnaire (ASQ). Cord chlordecone was associated with an increase in TSH in boys, whereas postnatal exposure was associated with a decrease in FT3 overall, and in FT4 among girls. Higher TSH level at 3 months was positively associated with the ASQ score of fine motor development at 18 months among boys, but TSH did not modify the association between prenatal chlordecone exposure and poorer ASQ fine motor score. Perinatal exposure to chlordecone may affect TSH and thyroid hormone levels at 3 months, differently according to the sex of the infant. This disruption however did not appear to intervene in the pathway between prenatal chlordecone exposure and fine motor child development.
ISSN: 0013-9351

hal-01134317
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01134317
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01134317/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01134317/file/Perinatal%20exposure%20to%20chlordecone_accepted.pdf
PUBMED : 25747818

Éditeur(s) : HAL CCSD Elsevier Masson
Résumé : National audience
The immune system contributes to maintaining the integrity of the organism. It can be the target of many xenobiotics, and immunotoxicology attempts to analyze the immunological alterations caused by exposure to these xenobiotics. Several environmental pollutants are strongly suspected of acting on the immune system to cause a decrease in the organism protective functions. Thus, polycyclic aromatic hydrocarbons, well known for their carcinogenic effects, have also been shown to induce immunosuppressive effects, pro-inflammatory actions and some hypersensitivity reactions, involved in the development of various pathologies. These different immunotoxic effects have mainly been identified by experimental studies on animals and our knowledge of the effects on humans remains incomplete. To better understand the immunotoxic effects of exposure to environmental pollutants and their consequences for human health, it is appropriate to strengthen immunotoxicology studies on humans.
Le système immunitaire contribue à la surveillance et au maintien de l’intégrité de l’organisme. Il peut être la cible de nombreux xénobiotiques, et l’immunotoxicologie s’attache à étudier les différentes atteintes immunologiques induites par l’exposition à ces xénobiotiques. De nombreux polluants environnementaux sont fortement suspectés d’agir sur le système immunitaire pour entraîner une diminution des fonctions de protection de l’organisme. Ainsi, les hydrocarbures aromatiques polycycliques, bien connus pour leurs effets cancérogènes, se sont révélés également capables d’induire des effets immunosuppresseurs, d’entraîner des actions pro-inflammatoires et de majorer certaines réactions d’hypersensibilité, impliqués dans le développement de diverses pathologies. Ces différents effets immunotoxiques ont surtout été identifiés par des études expérimentales chez l’animal et la transposition de ces effets à l’homme reste incomplète. Pour mieux appréhender les effets immunotoxiques de l’exposition aux polluants environnementaux et leurs conséquences sur la santé humaine, il convient donc de renforcer les études en immunotoxicologie chez l’homme.
ISSN: 1775-8785

hal-01467562
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01467562
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01467562/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01467562/file/Effets%20immunotoxiques%20des%20polluants%20environnementaux_accepted.pdf
DOI : 10.1016/j.admp.2016.09.003

Éditeur(s) : HAL CCSD
Résumé : International audience
A mode stirred reverberation chamber (RC) is designed to conduct in vivo studies in the 60-GHz band. This exposure system has suitable features for experiments on animals. An interface, for temperature measurements using an infrared (IR) camera, is designed in the chamber wall in order to measure the specific absorption rate and/or the power density inside the chamber.
BIOEM 2016
Gand, Belgium

hal-01377564
https://hal.archives-ouvertes.fr/hal-01377564
https://hal.archives-ouvertes.fr/hal-01377564/document
https://hal.archives-ouvertes.fr/hal-01377564/file/bioem%202016_2_final.pdf

Éditeur(s) : HAL CCSD Taylor & Francis
Résumé : International audience
Humans 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.
ISSN: 1093-7404

hal-00976116
https://hal-univ-rennes1.archives-ouvertes.fr/hal-00976116
https://hal-univ-rennes1.archives-ouvertes.fr/hal-00976116/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-00976116/file/Potential_input_from_metabolomics_accepted.pdf
DOI : 10.1080/10937404.2013.860318

Éditeur(s) : HAL CCSD National Institute of Environmental Health Sciences
Résumé : International audience
BACKGROUND: Glycol ethers are present in a wide range of occupational and domestic products. Animal studies have suggested that some of them may affect ovarian function. OBJECTIVE: To study the relation between women's exposure to glycol ethers and time to pregnancy. METHODS: Urine from randomly selected women in the PELAGIE mother-child cohort who had samples collected before 19 weeks of gestation was tested to measure eight glycol ether metabolites by chromatography coupled to mass spectrometry. Time to pregnancy was collected at the beginning of the pregnancy by asking women how many months they took to conceive. Associations between metabolite levels and time to pregnancy were estimated in 519 women with complete data using discrete-time Cox proportional hazards models to adjust for potential confounders. RESULTS: Glycol ether metabolites were detected in 6% (for ethoxyacetic acid) to 93% (for phenoxyacetic and butoxyacetic acids) of urine samples. Phenoxyacetic acid was the only metabolite with a statistically significant association with longer time to pregnancy (fecundability OR 0.82; 95% CI: 0.63, 1.06 for the second and third quartile combined; fecundability OR 0.70; 95% CI: 0.52, 0.95 for a fourth-quartile (≥1.38 mg/L) vs. first-quartile concentration (<0.14 mg/L)). This association remained stable after multiple sensitivity analyses. CONCLUSION: Phenoxyacetic acid, which was present in most of the urine samples tested in our study, was associated with increased time to pregnancy. This metabolite and its main parent compound, 2-phenoxyethanol, are plausible causes of decreased fecundability, but may also be surrogates for potential co-exposures frequently present in cosmetics.
ISSN: 0091-6765

hal-00866023
https://hal-univ-rennes1.archives-ouvertes.fr/hal-00866023
https://hal-univ-rennes1.archives-ouvertes.fr/hal-00866023/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-00866023/file/Urinary_Glycol_Ether-accepted.pdf
DOI : 10.1289/ehp.1206103

Éditeur(s) : HAL CCSD Oxford University Press (OUP): Policy B1 - Oxford Open Option B Oxford University Press (OUP)
Résumé : International audience
BACKGROUNDA very large proportion of the literature on the endocrine disruptors categorized as anti-androgens deals with phthalates, which are produced in large amounts for use as plastic emollients and additives. In this review, we bring together and analyse work on the effects of phthalates in animals and humans at different stages of their development to assess whether or not their possible anti-androgenic properties represent a significant threat to human health.METHODSThe database PubMed was systematically searched for all English language articles until July 2013 in each subject area discussed.RESULTSWe provide an up-to-date exhaustive, comparative and critical assessment of both in vivo and in vitro studies undertaken to explore the effects of phthalates on the human testis from fetal life to adulthood. These results are compared and discussed in the light of the key data reported in the literature for mice and rats.CONCLUSIONSThe current literature highlights the fact that (i) there is a huge difference between the number of studies performed in animals and in humans, with many fewer for humans; (ii) there are differences in the way rats, mice, primates and humans respond to phthalates, for reasons that need to be further explored; (iii) more work is required to clarify the contradictions, in the few existing human epidemiological studies at all stages of development, which may be partly explained by varying methods of exposure assessment; (iv) in accordance with recent findings in rodents, it cannot be excluded that transgenerational effects of phthalates and/or epigenetic changes exist in humans; (v) a number of methodological limitations need to be solved for the in vitro and xenografting models using human fetal testis to fulfil their 'missing link' role between epidemiological studies in humans and rodent models; and (vi) epidemiological and in vitro studies generally converge sufficiently to conclude that phthalate anti-androgenicity is plausible in adult men.
ISSN: 1355-4786

inserm-00869540
http://www.hal.inserm.fr/inserm-00869540
DOI : 10.1093/humupd/dmt050
PUBMED : 24077978

Éditeur(s) : HAL CCSD Frontiers
Résumé : International audience
Glufosinate ammonium (GLA) is one of the most widely used herbicides in agriculture. As is the case for most pesticides, potential adverse effects of GLA have not been studied from the perspective of developmental neurotoxicity. Early pesticides exposure may weaken the basic structure of the developing brain and cause permanent changes leading to a wide range of lifelong effects on health and/or behavior. Here, we addressed the developmental impact of GLA by exposing female mice to low dose GLA during both pre- and postnatal periods and analyzed potential developmental and behavioral changes of the offspring during infancy and adulthood. A neurobehavioral test battery revealed significant effects of GLA maternal exposure on early reflex development, pup communication, affiliative behaviors, and preference for social olfactory cues, but emotional reactivity and emotional memory remained unaltered. These behavioral alterations showed a striking resemblance to changes seen in animal models of Autistic Spectrum Disorders. At the brain level, GLA maternal exposure caused some increase in relative brain weight of the offspring. In addition, reduced expression of Pten and Peg3 - two genes implicated in autism-like deficits - was observed in the brain of GLA-exposed pups at postnatal day 15. Our work thus provides new data on the link between pre- and postnatal exposure to the herbicide GLA and the onset of autism-like symptoms later in life. It also raises fundamental concerns about the ability of current safety testing to assess risks of pesticide exposure during critical developmental periods.
ISSN: 1662-5153

hal-01121829
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01121829
PUBMED : 25477793
DOI : 10.3389/fnbeh.2014.00390
PUBMEDCENTRAL : PMC4238406

Éditeur(s) : HAL CCSD Nature Publishing Group
Résumé : International audience
The widely-used herbicide atrazine (ATZ) is detected in ground and surface water in many countries. Several studies in animals have demonstrated that ATZ has endocrine-disrupting effects on male and female reproduction in many vertebrate species. In this study, we investigated the effects of ATZ exposure on meiosis, a key step in gametogenesis in mammals. The treatment was initiated before oocyte entry into meiosis, which occurs during the embryonic period in females. We found that embryonic exposure to ATZ increases the level of 8-oxo-guanine in the nucleus of meiotic cells, reflecting oxidative stress and affecting meiotic double-strand break repair, chromosome synapsis and crossover numbers. Finally, embryonic exposure to ATZ reduces the number of primordial follicles and increases the incidence of multi-oocyte follicles in adult mice. Our data demonstrate that embryonic exposure to ATZ disrupts prophase I of meiosis and affects normal follicle formation in female mice.
ISSN: 2045-2322

hal-01560149
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01560149
DOI : 10.1038/s41598-017-03738-1
PUBMED : 28615648

Éditeur(s) : HAL CCSD Springer Verlag
Résumé : International audience
: Human exposure to xenobiotics is usually estimated by indirect methods. Biological monitoring has emerged during the last decade to improve assessment of exposure. However, biomonitoring is still an analytical challenge, because the amounts of sample available are often very small yet analysis must be as thorough and sensitive as possible. The purpose of this work was to develop an untargeted "exposomics" approach by using ultra-high-performance liquid chromatography coupled to high-resolution mass spectrometry (UHPLC-HRMS), which was applied to the characterization of pesticide metabolites in urine from pregnant women from a French epidemiological cohort. An upgradable list of pesticides commonly used on different crops, with their metabolites (more than 400 substances) was produced. Raw MS data were then processed to extract signals from these substances. Metabolites were identified by tandem mass spectrometry; putative identifications were validated by comparison with standards and metabolites generated by experiments on animals. Finally, signals of identified compounds were statistically analyzed by use of multivariate methods. This enabled discrimination of exposure groups, defined by indirect methods, on the basis of four metabolites from two fungicides (azoxystrobin, fenpropimorph) used in cereal production. This original approach applied to pesticide exposure can be extended to a variety of contaminant families for upstream evaluation of exposure from food and the environment.
ISSN: 1618-2642

hal-00875889
https://hal.archives-ouvertes.fr/hal-00875889
DOI : 10.1007/s00216-013-7136-2
PUBMED : 23892877

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Recent research has linked early life exposure to selective serotonin reuptake inhibitor medications (SSRIs) to modifications of social behaviors in children. Serotonin is a key regulator of neurodevelopment, social behaviors and mental health, and with the growing use of SSRIs to treat maternal affective disorders during the perinatal period, questions have been raised about the benefits and risks of perinatal SSRI exposure on the developing child. This review will highlight how perinatal SSRIs affect maternal care and neurodevelopmental outcomes related to social affiliative behaviors in offspring; such as play behaviors, social interactions, reproductive behaviors, and maternal care of the next generation. We will also review how early life exposure to SSRIs can alter related neurobiology, and the epigenome. Both clinical research and findings from animal models will be discussed. Understanding the impact of perinatal SSRIs on neurobehavioral outcomes will improve the health and well-being of subsequent generations.
ISSN: 0149-7634

hal-01619303
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01619303
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01619303/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01619303/file/Perinatal%20selective%20serotonin%20reuptake%20inhibitor%20medication_revised.pdf
DOI : 10.1016/j.neubiorev.2017.04.023

Éditeur(s) : HAL CCSD MDPI
Résumé : International audience
Lead in childhood is well known to be associated with poor neurodevelopment. As part of a study on maternal anemia and offspring neurodevelopment, we analyzed blood lead level (BLL) with no prior knowledge of lead exposure in 225 mothers and 685 offspring 1 to 2 years old from Allada, a semi-rural area in Benin, sub-Saharan Africa, between May 2011 and May 2013. Blood samples were analyzed by inductively coupled plasma mass spectrometry. Environmental assessments in households and isotopic ratio measurements were performed for eight children with BLL extgreater 100 µg/L. High lead levels (BLL extgreater 50 µg/L) were found in 44% of mothers and 58% of children. The median BLL was 55.1 (interquartile range 39.2-85.0) and 46.6 (36.5-60.1) µg/L, respectively. Maternal BLL was associated with offspring's consumption of piped water and animals killed by ammunition. Children's BLL was associated with presence of paint chips in the house and consumption of animals killed by ammunition. In this population, with 98% of children still breastfed, children's BLL was highly associated with maternal BLL on multivariate analyses. Environmental measures and isotopic ratios supported these findings. Offspring may be highly exposed to lead in utero and probably via breastfeeding in addition to lead paint exposure
ISSN: 1660-4601

hal-01296778
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01296778
DOI : 10.3390/ijerph13030316
PUBMED : 26978384

Éditeur(s) : HAL CCSD Endocrine Society
Résumé : International audience
The Developmental Origins of Health and Disease (DOHaD) paradigm is one of the most rapidly expanding areas of biomedical research. Environmental stressors that can impact on DOHaD encompass a variety of environmental and occupational hazards as well as deficiency and oversupply of nutrients and energy. They can disrupt early developmental processes and lead to increased susceptibility to disease/dysfunctions later in life. Presentations at the fourth Conference on Prenatal Programming and Toxicity in Boston, in October 2014, provided important insights and led to new recommendations for research and public health action. The conference highlighted vulnerable exposure windows that can occur as early as the preconception period and epigenetics as a major mechanism than can lead to disadvantageous "reprogramming" of the genome, thereby potentially resulting in transgenerational effects. Stem cells can also be targets of environmental stressors, thus paving another way for effects that may last a lifetime. Current testing paradigms do not allow proper characterization of risk factors and their interactions. Thus, relevant exposure levels and combinations for testing must be identified from human exposure situations and outcome assessments. Testing of potential underpinning mechanisms and biomarker development require laboratory animal models and in vitro approaches. Only few large-scale birth cohorts exist, and collaboration between birth cohorts on a global scale should be facilitated. DOHaD-based research has a crucial role in establishing factors leading to detrimental outcomes and developing early preventative/remediation strategies to combat these risks
ISSN: 0013-7227

hal-01187409
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01187409
DOI : 10.1210/EN.2015-1350
PUBMED : 26241067