Éditeur(s) : HAL CCSD BMJ Publishing Group
Résumé : International audience
OBJECTIVES: The time from the prenatal period through early childhood is an important window of vulnerability for the developing immune and respiratory systems, both sensitive to environmental chemicals such as solvents. This study sought to examine the effects of solvent exposure during the prenatal and postnatal periods on wheezing, eczema and food allergies in early childhood. METHODS: This study, based on the PELAGIE cohort, included 1505 mother-child pairs with measurements of prenatal and postnatal solvent exposures and data on wheezing, eczema or food allergies. The maternal occupation reported at inclusion, in early pregnancy allowed us to define prenatal occupational solvent exposure (by three specific job-exposure matrices). Data on prenatal and postnatal domestic solvent exposure, that is exposure to products that contain solvents, were obtained from self-administered questionnaires, once at inclusion and again when the child was 2 years old. Outcome data was collected at the 2-year follow-up. Associations between exposures and outcomes were estimated by logistic regression models, after adjustment for potential confounders. RESULTS: No association was observed between prenatal exposure to solvents and the outcomes studied. Postnatal exposure was associated with an increased risk of wheezing (OR=1.80 (95% CI 1.25 to 2.59)) which persisted after adjustment for prenatal exposure. No significant association was observed with eczema or food allergies. CONCLUSIONS: Postnatal exposure to solvent-containing products in the home may increase the risk of wheezing in early childhood. Follow-up studies are needed to determine if the health effects observed at age 2 persist at later ages.
ISSN: 1351-0711

hal-01063913
https://hal.archives-ouvertes.fr/hal-01063913
DOI : 10.1136/oemed-2013-102036
PUBMED : 24996679

Éditeur(s) : HAL CCSD Oxford University Press (OUP)
Résumé : International audience
STUDY QUESTION: Is prenatal exposure to persistent organic pollutants (POPs) associated with variations of sex hormone levels in cord blood? SUMMARY ANSWER: Prenatal exposure to a number of POPs is associated with a disruption of hormone levels in cord blood, with sex specificities. WHAT IS KNOWN ALREADY: Epidemiological studies have reported disorders of reproductive health, in relation with POPs exposure during early life and the endocrine disruption properties of these chemicals have been suggested as possible mechanisms. STUDY DESIGN, SIZE, DURATION: A subset of 282 mother-child pairs was selected from the prospective population-based PELAGIE birth cohort (n = 3421, 2002-2006, Brittany, France). Pregnant women were recruited before 19 weeks of gestation and followed until delivery. PARTICIPANTS/MATERIALS, SETTING, METHODS: Sex hormone levels including sex hormone-binding globulin (SHBG), estradiol (E2), total testosterone (T), free testosterone (fT = T/SHBG) and the aromatase index (AI = T/E2) were measured in 282 cord blood samples. Anti-Müllerian hormone (AMH) was measured in male newborns only. Pesticide concentrations of α-endosulfan, β-hexachlorocyclohexane (β-HCH), γ-HCH, dieldrin, pp'-dichlorodiphenyldichloroethylene (p,p'-DDE), hexachlorobenzene (HCB), heptachlor epoxide (HCE), as well as PCBs (congeners 153, 187 and the sum of anti-estrogenic PCBs 118, 138, and 170) and decabrominated diphenyl ether (BDE209) were also measured in cord blood. Associations between sex hormones and POPs exposure were explored using multiple linear regressions adjusted for potential confounders. MAIN RESULTS AND THE ROLE OF CHANCE: High PCB levels were associated with an increase of SHBG (P-trend extless 0.01) and AMH (P-trend extless 0.05) and a decrease of fT (P-trend extless 0.05) and AI (P-trend extless 0.01). High pesticide levels, particularly α-endosulfan and HCE, were associated with an increase of SHBG (P extless 0.05) and E2 (P extless 0.01) and a decrease of fT (P extless 0.05) and AI (P extless 0.01). Several of these associations were stronger, or specific, among male or female newborns. The associations were not altered in the sensitivity analyses. LIMITATIONS, REASONS FOR CAUTION: The study population was of relatively small sample size, and some compounds rarely detected in cord blood. The high level of correlation between POPs makes it difficult to identify the most contributing POPs. Hormone measurements were performed at birth (in cord blood) and may not adequately represent the infant endocrine system. Multiple statistical testing may have led to false-positive associations. WIDER IMPLICATIONS OF THE FINDINGS: Our results are in discordance with those reported in the only published study of the kind but in accordance with studies about prenatal exposure to other endocrine disruptors such as phthalates. These findings may help understanding the pathways involved in adverse reproductive outcomes associated with POPs exposure. STUDY FUNDING/COMPETING INTERESTS: The PELAGIE cohort is funded by Inserm, French Ministry of Health, French Ministry of Labor, InVS, ANR, ANSES, and French Ministry of Ecology. None of the authors has any competing interest to declare
ISSN: 0268-1161

hal-01220641
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01220641
DOI : 10.1093/humrep/dev260
PUBMED : 26493407

Éditeur(s) : HAL CCSD
Résumé : International audience
BACKGROUND: Persistent organic pollutants may affect the immune and respiratory systems, but available evidence is based on small study populations. We studied the association between prenatal exposure to dichlorodiphenyldichloroethylene (DDE) and polychlorinated biphenyl 153 (PCB 153) and children's respiratory health in European birth cohorts. METHODS: We included 4608 mothers and children enrolled in 10 birth cohort studies from 7 European countries. Outcomes were parent-reported bronchitis and wheeze in the first 4 years of life. For each cohort, we performed Poisson regression analyses, modeling occurrences of the outcomes on the estimates of cord-serum concentrations of PCB 153 and DDE as continuous variables (per doubling exposure) and as cohort-specific tertiles. Summary estimates were obtained through random-effects meta-analyses. RESULTS: The risk of bronchitis or wheeze (combined variable) assessed before 18 months of age increased with increasing DDE exposure (relative risk [RR] per doubling exposure = 1.03 [95% confidence interval = 1.00-1.07]). When these outcomes were analyzed separately, associations appeared stronger for bronchitis. We also found an association between increasing PCB 153 exposure and bronchitis in this period (RR per doubling exposure = 1.06 [1.01-1.12]) but not between PCB 153 and wheeze. No associations were found between either DDE or PCB 153 and ever-wheeze assessed after 18 months. Inclusion of both compounds in the models attenuated risk estimates for PCB 153 tertiles of exposure, whereas DDE associations were more robust. CONCLUSION: This large meta-analysis suggests that prenatal DDE exposure may be associated with respiratory health symptoms in young children (below 18 months), whereas prenatal PCB 153 levels were not associated with such symptoms.
Epidemiology (Cambridge, Mass.)

hal-01063930
https://hal.archives-ouvertes.fr/hal-01063930
DOI : 10.1097/EDE.0000000000000097
PUBMED : 24776790

Éditeur(s) : HAL CCSD Institute of Electrical and Electronics Engineers
Résumé : International audience
An effective solution for increasing the exposure uniformity and efficiency of biological samples in in vitro bioelectromagnetic experiments at 60 GHz is proposed by introducing a novel choke ring antenna (CRA). The CRA is optimized to provide a uniform exposure of samples, whose dimensions are equivalent to those of a standard 35-mm Petri dish, positioned close to the antenna aperture, i.e., 10-20 wavelengths. The antenna prototype is fabricated in metallized foam. The realized exposure efficiency of the sample exceeds 55% (if estimated for an exposure uniformity better than - 0.5 dB). To validate the numerical results, the field intensity profiles on the surface of a high-water-content phantom have been experimentally obtained using a high-resolution infrared camera. Compared to the standard open-ended waveguide and horn antennas, typically used for millimeter-wave dosimetry, a twofold advantage of the proposed CRA is demonstrated, namely, the improvement of the exposure efficiency by a factor of 1.5 to 2 with a simultaneous reduction of the exposure distance by a factor of 8-2, respectively, depending on the type of the reference antenna. These advantages make the proposed CRA an excellent candidate for 60-GHz short-range exposure systems for in vitro bioelectromagnetic studies.
ISSN: 0018-9480

hal-00874349
https://hal.archives-ouvertes.fr/hal-00874349
DOI : 10.1109/TMTT.2013.2255619

Éditeur(s) : HAL CCSD BioScientifica
Résumé : International audience
Paracetamol/acetaminophen (N-Acetyl-p-Aminophenol; APAP) is the preferred analgesic for pain relief and fever during pregnancy. It has therefore caused concern that several studies have reported that prenatal exposure to APAP results in developmental alterations in both the reproductive tract and the brain. Genitals and nervous system of male mammals are actively masculinised during foetal development and early postnatal life by the combined actions of prostaglandins and androgens, resulting in the male-typical reproductive behaviour seen in adulthood. Both androgens and prostaglandins are known to be inhibited by APAP. Through intrauterine exposure experiments in C57BL/6 mice, we found that exposure to APAP decreased neuronal number in the sexually dimorphic nucleus (SDN) of the preoptic area (POA) in the anterior hypothalamus of male adult offspring. Likewise, exposure to the environmental pollutant and precursor of APAP, aniline, resulted in a similar reduction. Decrease in neuronal number in the SDN-POA is associated with reductions in male sexual behaviour. Consistent with the changes, male mice exposed in uteri to APAP exhibited changes in urinary marking behaviour as adults and had a less aggressive territorial display towards intruders of the same gender. Additionally, exposed males had reduced intromissions and ejaculations during mating with females in oestrus. Together, these data suggest that prenatal exposure to APAP may impair male sexual behaviour in adulthood by disrupting the sexual neurobehavioral programming. These findings add to the growing body of evidence suggesting the need to limit the widespread exposure and use of APAP by pregnant women.
ISSN: 1470-1626

hal-01560285
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01560285
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01560285/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01560285/file/Prenatal%20exposures%20to%20paracetamol-accepted.pdf
DOI : 10.1530/REP-17-0165

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) : HAL CCSD MDPI
Résumé : International audience
Congenital anomalies are the main causes of preterm and neonatal mortality and morbidity. We investigated the association between congenital anomalies and mothers' exposure to air pollution during pregnancy by combining risk estimates for a variety of air pollutants (SO2, NO2, PM10, PM2.5, CO and O3) and anomaly defect outcomes. Seventeen articles were included in the systematic review and thirteen studies were taken into account in the meta-analysis. Combined estimated were calculated separately according to whether the exposure metric was continuous or categorical. Only one significant combination was; NO2 concentrations were significantly associated with coarctation of the aorta (OR = 1.20 per 10 ppb, 95% CI, (1.02, 1.41)). This finding could stem from strong heterogeneity in study designs. Improved exposure assessment methods, in particular more accurate spatial measurements or modeling, standardized definition of cases and of better control of confounders are highly recommended for future congenital anomalies research in this area.
ISSN: 1660-4601

hal-01118609
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01118609
PUBMED : 25089772
DOI : 10.3390/ijerph110807642
PUBMEDCENTRAL : PMC4143824

Résumé : Les pathologies inflammatoires démyélinisantes primitives du système nerveux central (SNC) sont dominées par deux entités : la sclérose en plaques (SEP) et la neuromyélite optique (NMO). Ces deux pathologies se différencient par : 1. leur phénotype, la NMO se caractérisant par une myélite extensive dans le plan transversal et longitudinal et peu de lésions encéphaliques initiales ; 2. leur sévérité, le pronostic de la NMO étant moins bon que celui de la SEP ; 3. leur mécanisme immunologique, puisque l’immunité humorale domine nettement dans la NMO, cette pathologie répondant peu ou pas aux traitementshabituellement prescrits dans la SEP. Un anticorps sérique (IgG-NMO) a été retrouvé chez les patients atteints de NMO avec une sensibilité de 50-70% et une spécificité de 90-100%. Cet anticorps a pour cible le principal canal hydrique du SNC, l’aquaporine-4 (AQP4), qui se situe principalement sur les pieds astrocytaires jalonnant la barrière hémato-encéphalique. La SEP est relativement familière des neurologues car décrite sur le plan épidémiologique et dans son histoire naturelle depuis plus d’un siècle à travers de larges séries réalisées parfois en population générale. Son approche thérapeutique progresse suite à des essais contrôlés qui s’accumulent depuis maintenant près de 20 ans. Toutefois, la majorité des travaux ont été effectués chez les populations Caucasiennes en raison de sa plus grande fréquence dans ces populations. A l’inverse, la NMO garde encore un relatif mystère à cause de sa relative rareté, l’établissement très récent de critères diagnostiques et une physiopathologie très récemment éclaircie par la découverte de l’IgG-NMO qui a indiscutablement suscité un regain d’intérêt de cette affection. Ainsi, son incidence est quasiment inconnue de même que sa susceptibilité génétique. La progression du handicap de la NMO qu’il soit visuel ou moteur à l’évidence sévère, ne repose toujours pas sur des chiffres précis, la description des lésions neuroradiologiques reste encore très embryonnaire. Enfin, même s’il existe un consensus pour traiter énergiquement les poussées de NMO et les espacer, il n’existe quasiment aucune étude prospective.
Introduction: Aim of the study is to describe épidemiology, phenotype and treatment of demyelinating inflammatory diseases of the central nervous system (CNS) namely multiple sclerosis (MS) and neuromyelitis optica (NMO) in French West Indies.Epidemiology: MS emerged in the French West Indian (FWI) population with an incidence of 1.27/100 000 (CI 95%: 1.16-1.38) for the period 1992-2007 while incidence of NMO remained stable at 0.19/100,000 (CI 95%: 0.15–0.23). Both migration in Metropolitean France (MF) and decrease of sun exposure were risk factors for MS acquisition in FWI. Phenotype and treatment of NMO: NMO is a very rapidly disabling disease with median times to reach DSS 3, 6 and 8 of one year, 8 years and 22 years respectively. However, treatment by plasma exchanges were shown to reduce sequellae of NMO attacks ; mitoxantrone and rituximab reduced significantly annualized relapse rate (ARR) from 1.7 to 0.29 (p<10-4) and from 1,34 to 0,56 (p=0.0005) respectively, improving dramatically natural course of NMO.Phenotype and treatment of MS: Absence of Migration in MF in MS patients was found to be the strongest independent predictive factor of disability progression to DSS 6 (hazard ratio, 2.59; p=0.0002); beside short time to DSS3 (p=0.005), later age at onset (p=0.005), and multi-symptomatic onset (p=0.03). Treatment of MS by interferon beta-1 had a moderate impact in MS while natalizimab proved to be highly effective by reducing drastically ARR and inflammatory parameters on magnetic resonance imaging. Conclusion: Spectrum of demyelinating inflammatory disorders of CNS has reversed in French West Indies with overrepresentation of MS. Agressive therapy is needed to improve prognosis of NMO. Rapidly increasing of its incidence makes MS a new public health problem in French West Indies.

http://www.theses.fr/2012AGUY0511/document

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) : Actes de Colloque: Avancées et nouvellles technologies en toxinologie, éditeurs: Julien BARBIER, Evelyne BENOIT, Pascale MARCHOT, César MATTEI, Denis SERVENT
Résumé : Over the past seven years, methods available for the detection of phycotoxins have been extensively reviewed in a number of international expert committees, such as the consultations organised by FAO/IOC/WHO and EFSA, as well as by individual scientists. These reviews have shown that the methods available have severe limitations for the use in official control, either due to their limited scope and detection capability or due to a lack of calibration standards, reference materials and validation efforts. The present review focuses on recent developments in the detection of phycotoxins in several areas of applied research. Not being able to exhaustively describe all recent developments, the review focussed on three areas of interest to the authors: (i) detection of ultra-trace amounts of toxins, (ii) metabolism of toxins and their localisation in biological tissues, and (iii) approaches to detect unknown toxins or analogues of known toxins. Miniaturisation in combination with physico-chemical techniques appears to be a very efficient approach to detect low trace amounts of individual toxin analogues. In particular, the detection of azaspiracids and okadaic acid and analogues, using micro-filtration and on-line pre-concentration techniques, has shown to be useful for the characterisation of various algal and shellfish species. In the area of interactions of toxins with shellfish and mammalian systems, it is noted that several studies on biomarkers reveal either protein biomarkers of exposure to toxins or potential pathways of metabolism of the toxins themselves. A particular focus is given to recent findings in the areas of brevetoxin metabolism and biomarkers as well as azaspiracid localisation and metabolism. Finally, the detection of novel compounds is a particularly challenging area. The interest in this area has risen over the past years following cases of unexplained mouse toxicity such as the UK cockle toxicity and the French atypical toxicity in mussels and oysters from the Atlantic and Mediterranean coasts. Some attention is given to immuno-, functional and cellular bio-assays for the identification of bioactive agents in shellfish.
Durant les sept dernières années, les méthodes disponibles pour la détection des phycotoxines ont été abondamment revues dans de nombreux groupes internationaux d’expertises, tels que les consultations organisées par FAO/IOC/WHO et EFSA ainsi que dans de nombreux articles scientifiques de synthèse. Ces revues ont démontré que, vis-à-vis des systèmes de régulations officiels, les méthodes disponibles présentent des limites d’utilisation importantes. Soit elles ont un périmètre réduit et des limites de détection trop élevées, soit il y a un manque d’étalons, de matériaux de référence ou d’efforts de validation. La présente revue focalise sur les développements récents dans la détection de phycotoxines en recherche appliquée. Sans vouloir décrire de manière exhaustive tous les développements récents, la revue examine trois domaines d’intérêt pour les auteurs : (i) la détection de quantités ultra-traces de toxines, (ii) la métabolisation et la localisation des toxines dans des tissus biologiques, et (iii) les approches pour la détection de toxines non-répertoriées ou des analogues de toxines connues. La miniaturisation en combinaison avec les techniques physico-chimiques constitue apparemment une approche efficace pour la détection de faibles traces d’analogues individuels des toxines. En particulier, la micro-filtration et des techniques de pré-concentration en ligne se sont montrées utiles pour la détection des azaspiracides et des toxines du groupe de l’acide okadaïque dans la caractérisation de diverses espèces d’algues et de coquillages. Dans le domaine des interactions des toxines avec les coquillages et des systèmes vivants de mammifères, nous avons noté que plusieurs études sur les bio-marqueurs révèlent soit des marqueurs protéiniques d’exposition aux toxines, soit des marqueurs du métabolisme des toxines elles-mêmes. Un intérêt spécifique a été trouvé dans les résultats d’étude sur le métabolisme des brévétoxines et des azaspiracides. La détection des composés bioactifs non-répertoriés constitue un défi particulièrement difficile. Ce domaine a trouvé plus d’intérêt dû à plusieurs cas de toxicités inexpliquées dans le test souris telles que les toxicités observées dans les coques en provenance de Grande-Bretagne ou encore dans les moules et huîtres des côtes méditerranéennes et atlantiques françaises. Une attention particulière a été consacrée à l’identification d’agents bioactifs par les essais cellulaires ou fonctionnels ou basés sur la détection immuno-chimique.

Droits : 2010 SFET
http://archimer.ifremer.fr/doc/00019/12975/9949.pdf
http://archimer.ifremer.fr/doc/00019/12975/

Éditeur(s) : HAL CCSD
Résumé : International audience
OBJECTIVES: To detect new hazards ("signals"), occupational health monitoring systems mostly rest on the description of exposures in the jobs held and on reports by medical doctors; these are subject to declarative bias. Our study aims to assess whether job-exposure matrices (JEMs) could be useful tools for signal detection by improving exposure reporting. METHODS: Using the French national occupational disease surveillance and prevention network (RNV3P) data from 2001 to 2011, we explored the associations between disease and exposure prevalence for 3 well-known pathology/exposure couples and for one debatable couple. We compared the associations measured when using physicians' reports or applying the JEMs, respectively, for these selected diseases and across non-selected RNV3P population or for cases with musculoskeletal disorders, used as two reference groups; the ratio of exposure prevalences according to the two sources of information were computed for each disease category. RESULTS: Our population contained 58,188 subjects referred with pathologies related to work. Mean age at diagnosis was 45.8 years (95% CI 45.7; 45.9), and 57.2% were men. For experts, exposure ratios increase with knowledge on exposure causality. As expected, JEMs retrieved more exposed cases than experts (exposure ratios between 12 and 194), except for the couple silica/silicosis, but not for the MSD control group (ratio between 0.2 and 0.8). CONCLUSIONS: JEMs enhanced the number of exposures possibly linked with some conditions, compared to experts' assessment, relative to the whole database or to a reference group; they are less likely to suffer from declarative bias than reports by occupational health professionals.
International Archives of Occupational and Environmental Health

hal-01560279
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01560279
DOI : 10.1007/s00420-017-1215-1
PUBMED : 28299449

Éditeur(s) : HAL CCSD Institute of Electrical and Electronics Engineers
Résumé : International audience
: A new set-up for exposure of human cells in vitro at 37°C to pulse-modulated 300 MHz and 500 MHz signals of future magnetic resonance imaging (MRI) systems is designed, built up, and characterized. Two dipole antennas, specifically designed for ultra high field MRI, are used as radiating structures. The electromagnetic (EM) field distribution inside the incubator containing the cells is computed, and it is shown to be in a good agreement with measurements. The electric field at the cell level is quantified numerically. Local, 1g average, and averaged over the culture medium volume SAR are provided along with the standard deviation values for each well. Temperature increments are measured inside the culture medium during the exposure using an optical fiber thermometer. Then we identify the pulse parameters corresponding to the thermal threshold of 1°C, usually considered as a threshold for thermally-induced biological effects. For these parameters, the induction of heat shock proteins is assessed to biologically verify a potential thermal response of cells. The data demonstrate that, under the considered experimental conditions, exposure to pulsemodulated radiations emulating typical ultra high field MRI signals, corresponding to temperature increments below 1°C, does not trigger any heat shock response in human brain cells.
ISSN: 0018-9294

hal-00874329
https://hal.archives-ouvertes.fr/hal-00874329
DOI : 10.1109/TBME.2013.2270371
PUBMED : 23799680

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Dietary exposure to pesticide residues may present a risk to public health, especially for sensitive populations such as pregnant women. To characterize this risk, this study assessed chronic dietary exposure to pesticide residues based on the French ELFE cohort. A self-administered food frequency questionnaire (FFQ) about the last three months of pregnancy filled in by pregnant women in 2011 was used in combination with occurrence data from French Total Diet Studies completed by the results of national monitoring programs on pesticide residues in food. The dietary intake of pesticides (μg/kg of body weight/day) was estimated for 14,099 pregnant women with a complete FFQ, for 317 substances under two occurrence scenarios to handle left-censored data: a lower-bound scenario (LB), where undetected results were set to zero, and an upper-bound scenario (UB), where undetected results were set to the detection limit if the substance was expected to be found in food and zero if it was not. The risk was assessed for 284 substances with a toxicological reference value (TRV) and a good coverage level of the diet potentially contributing to pesticide intake. The cumulative risk was also assessed for seven effects on nervous and thyroid systems using the hazard index and the Cumulative Assessment Groups defined by EFSA. Substances with the highest exposure levels under the LB scenario were, in decreasing order, imazalil, piperonyl butoxide, chlorpropham, thiabendazole, iprodione and propargite. Under the LB scenario, only for lindane did women have a statistically significant probability of exceeding the TRV (2.4%). Under the UB scenario, risk could not be excluded for nine other substances. A better management of left-censored data and more sensitive analyses of the main food contributors might help to refine the UB exposure and risk assessments. A statistically significant cumulative risk was found for neurochemical effects related to high intake levels of three organophosphate insecticides (chlorpyrifos, pirimiphos-methyl and dimethoate) mainly detected in fruits and cereals
ISSN: 0160-4120

hal-01319892
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01319892
DOI : 10.1016/j.envint.2016.04.007
PUBMED : 27187793

Éditeur(s) : HAL CCSD BMJ Publishing Group
Résumé : International audience
OBJECTIVES: Many women who work during pregnancy are occupationally exposed to toxicants. The developing central nervous system is highly vulnerable to neurotoxicants such as solvents. Although the neurotoxicity of solvents to adults is well established, very few studies have examined their effects on children's behaviour following prenatal exposure. METHODS: Women from the Perturbateurs endocriniens: Étude Longitudinale sur les Anomalies de la Grossesse, l'Infertilité et l'Enfance (PELAGIE) mother-child cohort (including 3005 working women) were recruited in Brittany (France) between 2002 and 2006, at the beginning of pregnancy, to assess occupational exposure to solvents at that time. Child behaviour was documented at age 2 by mothers (n=1278) assessing components of attention deficit/hyperactivity, aggression, opposition and emotionality. We used a multiple linear regression analysis to evaluate the association between occupational solvent exposure and children's behaviour. Complementary sensitivity analyses allowed us to handle missing data, due mostly to attrition. RESULTS: 20% of women reported occasional exposure and 31% regular exposure to solvents. Children prenatally exposed were more likely to have higher scores of attention deficit/hyperactivity and aggression, and dose-response relations were observed. CONCLUSIONS: The dose-response effect and the high prevalence of children potentially exposed to solvents from their mother's workplace exposure underline the public health relevance of this result. Our results should be replicated in further studies designed to identify which solvents are most deleterious and to assess child behaviour at school age.
ISSN: 1351-0711

inserm-00795043
http://www.hal.inserm.fr/inserm-00795043
http://www.hal.inserm.fr/inserm-00795043/document
http://www.hal.inserm.fr/inserm-00795043/file/Occupationnal_solvent_exposure_child_behavior_HAL.pdf
DOI : 10.1136/oemed-2012-100892

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
Selective serotonin reuptake inhibitor medication exposure during the perinatal period can have a long term impact in adult offspring on neuroplasticity and the serotonergic system, but the impact of these medications during early development is poorly understood. The aim of this study was to determine the effects of developmental exposure to the SSRI, fluoxetine, on the serotonergic system, dopaminergic system, and synaptophysin density in the prefrontal cortex and hippocampus, as well as number of immature neurons in the dentate gyrus, in juvenile rat offspring at weaning. To model aspects of maternal depression, prenatal restraint stress was used. Sprague-Dawley rat offspring were exposed to either prenatal stress and/or fluoxetine. Main findings show that developmental fluoxetine exposure to prenatally stressed offspring decreased 5-HT and 5-HIAA levels and altered the dopaminergic system in the hippocampus. Prenatal stress, regardless of fluoxetine, increased synaptophysin density in the PFC. This work indicates that early exposure to maternal stress and SSRI medication can alter brain monoamine levels and synaptophysin density in offspring at weaning. © 2015 Wiley Periodicals, Inc. Dev Psychobiol
ISSN: 0012-1630

hal-01237091
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01237091
DOI : 10.1002/dev.21372
PUBMED : 26477449

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 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 Wiley
Résumé : International audience
Background: Health care workers (HCWs) are occupationally exposed to various hazards, some associated with adverse pregnancy outcomes in previous reviews. This systematic review aims at synthesizing the recent literature on occupational exposures among HCWs related to fetal death, congenital anomalies, and fertility disorders. Methods: We searched the Medline database from 2000 to 2015 for articles about all potential occupational exposures of women and men working in this sector. Results: We retained 32 studies, most of them (n = 30) among women HCWs. Studies based on job title reported excess risks of some congenital anomalies (especially nervous and musculoskeletal systems) among HCWs compared to non-HCWs but no evidence about fetal death. Excess risks associated with specific exposures includes reports of some congenital anomalies forwomenexposed to anesthetic gases. Exposure to some sterilizing agents and, with less evidence, to antineoplastic drugs and to ionizing radiation, is associated with increased risks of miscarriage but not stillbirth. Strenuous work schedules appear to be associated with fertility disorders, but the evidence is limited. Only a few studies have been published since 2000 about non-ionizing radiation, or about fertility disorders related to chemical or physical agents, or about male HCWs. Conclusions: Despite the establishment of recommendations to limit exposures of HCWs, some excess risks of adverse pregnancy outcomes are still reported and need to be explained.
ISSN: 0271-3586

hal-01560148
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01560148
DOI : 10.1002/ajim.22711
PUBMED : 28514021

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
Radiofrequency radiations constitute a new form of environmental pollution. Among them, millimeter waves (MMW) will be widely used in the near future for high speed communication systems. This study aimed therefore to evaluate the biocompatibility of MMW at 60 GHz. For this purpose, we used a whole gene expression approach to assess the effect of acute 60 GHz exposure on primary cultures of human keratinocytes. Controls were performed to dissociate the electromagnetic from the thermal effect of MMW. Microarray data were validated by RT-PCR, in order to ensure the reproducibility of the results. MMW exposure at 20 mW/cm2, corresponding to the maximum incident power density authorized for public use (local exposure averaged over 1 cm2), led to an increase of temperature and to a strong modification of keratinocyte gene expression (665 genes differentially expressed). Nevertheless, when temperature is artificially maintained constant, no modification in gene expression was observed after MMW exposure. However, a heat shock control did not mimic exactly the MMW effect, suggesting a slight but specific electromagnetic effect under hyperthermia conditions (34 genes differentially expressed). By RT-PCR, we analyzed the time course of the transcriptomic response and 7 genes have been validated as differentially expressed: ADAMTS6, NOG, IL7R, FADD, JUNB, SNAI2 and HIST1H1A. Our data evidenced a specific electromagnetic effect of MMW, which is associated to the cellular response to hyperthermia. This study raises the question of co-exposures associating radiofrequencies and other environmental sources of cellular stress.
ISSN: 1932-6203

hal-01118066
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01118066
PUBMED : 25302706
DOI : 10.1371/journal.pone.0109435
PUBMEDCENTRAL : PMC4193780

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