Éditeur(s) : HAL CCSD American Chemical Society
Résumé : International audience
2-Amino-9H-pyrido[2,3-b]indole (AalphaC) is the most abundant carcinogenic heterocyclic aromatic amine (HAA) formed in mainstream tobacco smoke. AalphaC is a liver carcinogen in rodents, but its carcinogenic potential in humans is not known. To obtain a better understanding of the genotoxicity of AalphaC in humans, we have investigated its metabolism and its ability to form DNA adducts in human hepatocytes. Primary human hepatocytes were treated with AalphaC at doses ranging from 0.1-50 muM, and the metabolites were characterized by ultra-performance LC/ion trap multistage mass spectrometry (UPLC/MSn). Six major metabolites were identified: a ring-oxidized doubly conjugated metabolite, N2-acetyl-2-amino-9H-pyrido[2,3-b]indole-6-yl-oxo-(beta-d-glucuronic acid) (N2-acetyl-AalphaC-6-O-Gluc); two ring-oxidized glucuronide (Gluc) conjugates: 2-amino-9H-pyrido[2,3-b]indol-3-yl-oxo-(beta-d-glucuronic acid) (AalphaC-3-O-Gluc) and 2-amino-9H-pyrido[2,3-b]indol-6-yl-oxo-(beta-d-glucuronic acid) (AalphaC-6-O-Gluc); two sulfate conjugates, 2-amino-9H-pyrido[2,3-b]indol-3-yl sulfate (AalphaC-3-O-SO3H) and 2-amino-9H-pyrido[2,3-b]indol-6-yl sulfate (AalphaC-6-O-SO3H); and the Gluc conjugate, N2-(beta-d-glucosidurony1)-2-amino-9H-pyrido[2,3-b]indole (AalphaC-N2-Gluc). In addition, four minor metabolites were identified: N2-acetyl-9H-pyrido[2,3-b]indol-3-yl sulfate (N2-acetyl-AalphaC-3-O-SO3H), N2-acetyl-9H-pyrido[2,3-b]indol-6-yl sulfate (N2-acetyl-AalphaC-6-O-SO3H), N2-acetyl-2-amino-9H-pyrido[2,3-b]indol-3-yl-oxo-(beta-d-glucuronic acid) (N2-acetyl-AalphaC-3-O-Gluc), and O-(beta-d-glucosidurony1)-2-hydroxyamino-9H-pyrido[2,3-b]indole (AalphaC-HN2-O-Gluc). The latter metabolite, AalphaC-HN2-O-Gluc is a reactive intermediate that binds to DNA to form the covalent adduct N-(2'-deoxyguanosin-8-yl)-2-amino-9H-pyrido[2,3-b]indole (dG-C8-AalphaC). Preincubation of hepatocytes with furafylline, a selective mechanism-based inhibitor of P450 1A2, resulted in a strong decrease in the formation of AalphaC-HN2-O-Gluc and a concomitant decrease in DNA adduct formation. Our findings describe the major pathways of metabolism of AalphaC in primary human hepatocytes and reveal the importance of N-acetylation and glucuronidation in metabolism of AalphaC. P450 1A2 is a major isoform involved in the bioactivation of AalphaC to form the reactive AalphaC-HN2-O-Gluc conjugate and AalphaC-DNA adducts.
ISSN: 0893-228X

anses-01419468
https://hal-anses.archives-ouvertes.fr/anses-01419468
https://hal-anses.archives-ouvertes.fr/anses-01419468/document
https://hal-anses.archives-ouvertes.fr/anses-01419468/file/Bellamri%20et%20al.%20-%202016%20-%20Metabolism%20of%20the%20Tobacco%20Carcinogen%202-Amino-9H-py.pdf
DOI : 10.1021/acs.chemrestox.6b00394

Éditeur(s) : HAL CCSD American Chemical Society
Résumé : International audience
The HIWATE (Health Impacts of long-term exposure to disinfection byproducts in drinking WATEr) project was a systematic analysis that combined the epidemiology on adverse pregnancy outcomes and other health effects with long-term exposure to low levels of drinking water disinfection byproducts (DBPs) in the European Union. The present study focused on the relationship of the occurrence and concentration of DBPs with in vitro mammalian cell toxicity. Eleven drinking water samples were collected from five European countries. Each sampling location corresponded with an epidemiological study for the HIWATE program. Over 90 DBPs were identified; the range in the number of DBPs and their levels reflected the diverse collection sites, different disinfection processes, and the different characteristics of the source waters. For each sampling site, chronic mammalian cell cytotoxicity correlated highly with the numbers of DBPs identified and the levels of DBP chemical classes. Although there was a clear difference in the genotoxic responses among the drinking waters, these data did not correlate as well with the chemical analyses. Thus, the agents responsible for the genomic DNA damage observed in the HIWATE samples may be due to unresolved associations of combinations of identified DBPs, unknown emerging DBPs that were not identified, or other toxic water contaminants. This study represents the first to integrate quantitative in vitro toxicological data with analytical chemistry and human epidemiologic outcomes for drinking water DBPs.
ISSN: 0013-936X

hal-00875923
https://hal.archives-ouvertes.fr/hal-00875923
DOI : 10.1021/es3024226
PUBMED : 22958121

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Meconium is the first fecal excretion of newborns. This complex accumulative matrix allows assessing the exposure of the fetus to xenobiotics during the last 6 months of pregnancy. To determine the eventual effect of fetal exposure to micropollutants in this matrix, robust and sensitive analytical methods must be developed. This article describes the method development of liquid chromatography methods coupled to triple quadrupole mass spectrometry for relevant pollutants. The 28 selected target compounds had different physico-chemical properties from very polar (glyphosate) to non-polar molecules (pyrethroids). Tests were performed with three different types of columns: reversed phase, ion exchange and HILIC. As a unique method could not be determined for the simultaneous analysis of all compounds, three columns were selected and suitable chromatographic methods were optimized. Similar results were noticed for the separation of the target compounds dissolved in either meconium extract or solvent for reversed phase and ion exchange columns. However, for HILIC, the matrix had a significant influence on the peak shape and robustness of the method. Finally, the analytical methods were applied to “real” meconium samples.
ISSN: 0039-9140

hal-01141722
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01141722
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01141722/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01141722/file/Development%20of%20liquid%20chromatography%20%281%29.pdf
PUBMED : 25863396

Éditeur(s) : HAL CCSD Taylor & Francis
Résumé : International audience
Introduction: Drug transporters are now recognized as major players involved in pharmacokinetics and toxicology. Methods for assessing their activity are important to consider, particularly owing to regulatory requirements with respect to inhibition of drug transporter activity and prediction of drug–drug interactions. In this context, the use of fluorescent-dye-based transport assays is likely to deserve attention.Areas covered: This review provides an overview of the nature of fluorescent dye substrates for ATP-binding cassette and solute carrier drug transporters. Their use for investigating drug transporter activity in cultured cells and clinical hematological samples, drug transporter inhibition, drug transporter imaging and drug transport at the organ level are summarized.Expert opinion: A wide range of fluorescent dyes is now available for use in various aspects of drug transporter studies. The use of these dyes for transporter analyses may, however, be hampered by classic pitfalls of fluorescence technology, such as quenching. Transporter-independent processes such as passive diffusion of dyes through plasma membrane or dye sequestration into subcellular compartments must also be considered, as well as the redundant handling by various distinct transporters of some fluorescent probes. Finally, standardization of dye-based transport assays remains an important on-going issue
ISSN: 1742-5255

hal-01162381
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01162381
DOI : 10.1517/17425255.2015.1053462
PUBMED : 26050735

Éditeur(s) : HAL CCSD Springer Verlag
Résumé : International audience
ISSN: 0944-1344

hal-01231841
https://hal.univ-antilles.fr/hal-01231841
DOI : 10.1007/s11356-014-3134-y

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Risk assessment related to the exposure of humans to chemicals released into the environment is a major concern of our modern societies. In this context, toxicology plays a crucial role to characterize the effects of this exposure on health and identify the targets of these molecules. MALDI imaging mass spectrometry (IMS) is an enabling technology for biodistribution studies of chemicals. Although the majority of published studies are presented in a pharmacological context, the concepts discussed in this review can be applied to the toxicological evaluation of chemicals released into the environment. The major asset of IMS is the simultaneous localization and identification of a parent molecule and its metabolites without labeling and without any prior knowledge. Quantification methods developed in IMS are presented with application to an environmental pollutant. IMS is effective in the localization of chemicals and endogenous species. This opens unique perspectives for the discovery of molecular alterations in metabolites and protein biomarkers that could help for a better understanding of toxicity mechanisms. Distribution studies of agrochemicals in plants by IMS can contribute to a better understanding of their mode of action and to a more effective use of these chemicals, avoiding the current concern of environmental damage.
ISSN: 1874-3919

hal-01367141
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01367141
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01367141/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01367141/file/Potential%20of%20MALDI%20imaging.pdf
DOI : 10.1016/j.jprot.2016.05.008

Éditeur(s) : HAL CCSD
47. European Congress of Toxicology (EUROTOX 2011)
Paris, France

ineris-00970856
https://hal-ineris.archives-ouvertes.fr/ineris-00970856
INERIS : EN-2011-261

Éditeur(s) : HAL CCSD Springer Verlag
Résumé : International audience
Chlordecone (Kepone) is an organochlorine insecticide that has been used as insecticide and fungicide. In the French West Indies, Guadeloupe and Martinique, it was intensively applied to banana fields from 1973 to 1993 to control root borers. This pesticide undergoes no significant biotic or abiotic degradation in the environment and is still present in soils where it was applied. It was only in 1999 that health and environmental authorities became aware of the extent of the chlordecone pollution of environmental media, including soils, waterways, and the food chain. Earlier observations and toxicological studies have demonstrated that chlordecone is a reproductive and developmental toxicant, neurotoxic and carcinogenic in rodents, and is an endocrine-disrupting chemical because of its estrogenic properties both in vitro and in vivo. Several surveys have confirmed that the French West Indian population continues to be exposed to this chemical though consumption of contaminated foodstuffs. Here, we report the findings of various epidemiological studies conducted in the French West Indies to assess the impact of environmental exposure to chlordecone on the health of the population.
ISSN: 0944-1344

hal-01150382
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01150382
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01150382/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01150382/file/Chlordecone%20exposure%20and%20adverse%20effects%20in%20French%20West.pdf
DOI : 10.1007/s11356-015-4621-5

Éditeur(s) : HAL CCSD Springer Verlag
Résumé : International audience
ISSN: 0944-1344

hal-01680552
https://hal.univ-antilles.fr/hal-01680552
DOI : 10.1007/s11356-015-5682-1

Éditeur(s) : HAL CCSD Instituto Oswaldo Cruz, Ministério da Saúde
Résumé : International audience
Leishmania are protozoan parasites that show remarkable diversity, as revealed by the various clinical forms of leishmaniasis, which can range from mild skin lesions to severe metastatic cutaneous/mucosal lesions. The exact nature and extent of Leishmania phenotypic diversity in establishing infection is not fully understood. In order to try to understand some aspects of this diversity, we subcutaneously infected BALB/c mice with first and second generation subclones of a L. amazonensis strain isolated from a patient (BA125) and examined in vivo lesion growth rate and antimony susceptibility. In vivo fast-, medium- and slow-growing subclones were obtained; moreover, fast-growing subclones could generate slow-growing subclones and inversely, revealing the continuous generation of diversity after passage into mice. No antimony-resistant subclone appeared, probably a rare occurrence. By tagging subclone cells with a L. amazonensis genomic cosmid library, we found that only a very small number of founding cells could produce lesions. Leishmania clones transfected with in vivo selected individual cosmids were also diverse in terms of lesion growth rate, revealing the cosmid-independent intrinsic characteristics of each clone. Our results suggest that only a few of the infecting parasites are able to grow and produce lesions; later, within the cell mixture of each lesion, there coexist several parasite populations with different potentialities to grow lesions during the next infection round. This may reflect a sort of programmed heterogeneity of individual parasites, favoring the survival of some individuals in various environmental conditions.
ISSN: 0074-0276

hal-01489009
https://hal-univ-perp.archives-ouvertes.fr/hal-01489009

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Humans are exposed to a large number of contaminants, many of which may have similar health effects. This paper presents a framework for identifying pollutants to be included in a cumulative risk assessment approach. To account for the possibility of simultaneous exposure to chemicals with common toxic modes of action, the first step of the traditional risk assessment process, i.e. hazard identification, is structured in three sub-steps: (1a) Identification of pollutants people are exposed to, (1b) identification of effects and mechanisms of action of these pollutants, (1c) grouping of pollutants according to similarity of their mechanism of action and health effects. Based on this exposure-based grouping we can derive "multi-pollutant" toxicity reference values, in the "dose-response assessment" step. The approach proposed in this work is original in that it is based on real exposures instead of a limited number of pollutants from a unique chemical family, as traditionally performed. This framework is illustrated by the case study of semi-volatile organic compounds in French dwellings, providing insights into practical considerations regarding the accuracy of the available toxicological information. This case study illustrates the value of the exposure-based approach as opposed to the traditional cumulative framework, in which chemicals with similar health effects were not always included in the same chemical class.
ISSN: 0013-9351

hal-00982315
https://hal-univ-rennes1.archives-ouvertes.fr/hal-00982315
https://hal-univ-rennes1.archives-ouvertes.fr/hal-00982315/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-00982315/file/An_exposure-based_framework_for_grouping_pollutants_accepted.pdf
DOI : 10.1016/j.envres.2014.01.007

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
The easy-to-use in vivo model, zebrafish larva, is being increasingly used to screen chemical-induced hepatotoxicity, with a good predictivity for various mechanisms of liver injury. However, nothing is known about its applicability in exploring the mechanism called membrane remodeling, depicted as changes in membrane fluidity or lipid raft properties. The aim of this study was, therefore, to substantiate the zebrafish larva as a suitable in vivo model in this context. Ethanol was chosen as a prototype toxicant because it is largely described, both in hepatocyte cultures and in rodents, as capable of inducing a membrane remodeling leading to hepatocyte death and liver injury. The zebrafish larva model was demonstrated to be fully relevant as membrane remodeling was maintained even after a 1-week exposure without any adaptation as usually reported in rodents and hepatocyte cultures. It was also proven to exhibit a high sensitivity as it discriminated various levels of cytotoxicity depending on the extent of changes in membrane remodeling. In this context, its sensitivity appeared higher than that of WIF-B9 hepatic cells, which is suited for analyzing this kind of hepatotoxicity. Finally, the protection afforded by a membrane stabilizer, ursodeoxycholic acid (UDCA), or by a lipid raft disrupter, pravastatin, definitely validated zebrafish larva as a reliable model to quickly assess membrane remodeling involvement in chemical-induced hepatotoxicity. In conclusion, this model, compatible with a high throughput screening, might be adapted to seek hepatotoxicants via membrane remodeling, and also drugs targeting membrane features to propose new preventive or therapeutic strategies in chemical-induced liver diseases.
ISSN: 0260-437X

hal-01526425
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01526425
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01526425/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01526425/file/Zebrafish%20larva%20as%20a%20reliable%20model-Podechard%20JAT%202016%20revised.pdf
DOI : 10.1002/jat.3421

Éditeur(s) : HAL CCSD Elsevier Masson
Résumé : National audience
Objectifs Évaluer les connaissances des médecins généralistes et des pharmaciens d'officine en matière de dopage sportif, Populations et méthodes Deux études descriptives transversales par questionnaire anonyme ont été menées en 2006 et 2009 respectivement chez 280 pharmaciens et 992 médecins. Résultats Ils estiment que la plupart des records sont battus grâce au dopage et que les champions y recourent. Selon eux, les sports les plus touchés sont le cyclisme, l'athlétisme, le football, l'haltérophilie et la natation. Ils méconnaissent la liste des produits interdits. Pour eux, les personnes proches des sportifs et Internet sont les principales sources d'approvisionnement en dopants. Seuls 42 % des médecins et 35 % des pharmaciens pensent informer un patient sportif sur les produits pouvant positiver un contrôle antidopage. On note que 51,5 % des médecins ne connaissent pas les autorisations d'usage à des fins thérapeutiques et 90 % ignorent l'existence des antennes médicales de prévention du dopage. Ils déclarent ne pas avoir reçu d'enseignement universitaire spécifique sur le dopage et s'estiment mal informés. Conclusion Les médecins généralistes et les pharmaciens d'officine ne semblent pas disposer de connaissances suffisantes pour assurer leurs missions et pour prendre conscience de leurs responsabilités dans la lutte antidopage.
ISSN: 0765-1597

hal-01010769
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01010769
DOI : 10.1016/j.scispo.2013.10.004

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Mixtures of polybrominated diphenyl ethers (PBDEs) are present in indoor environments. Studies of the developmental effects of exposure to these chemicals in large prospective mother-child cohorts are required, with data on prenatal exposure and long-term follow-up of the children. We aimed to investigate the relationship between prenatal and childhood exposure to PBDEs and neurodevelopment at the age of six years. We determined the levels of PBDEs and other neurotoxicants in cord blood and dust collected from the homes of children for 246 families included in the PELAGIE mother-child cohort in France. We assessed two cognitive domains of the six-year-old children using the Wechsler Intelligence Scale for Children-IV. Verbal comprehension scores were lower in children from homes with higher concentrations of BDE99 (βDetects < median_vs_NonDetects = −1.6; 95% CI: −6.1, 2.9; βDetects≥median_vs_NonDetects = −5.4; −9.9, −1.0; ptrend = 0.02) and of BDE209 (β2nd_vs₁st_tertile = −1.8; 95% CI: −6.1, 2.5; β3rd_vs₁st_tertile = −3.2; −7.5, 1.2; ptrend = 0.15) in dust, particularly for boys (ptrend = 0.02 and 0.04, respectively). Working memory scores seemed to be lower in children with higher BDE99 concentrations in dust (ptrend = 0.10). No association was observed with cord blood levels of BDE209. Our findings are in agreement with those of four previous studies suggesting adverse cognitive outcomes among children associated with early-life exposure to penta-BDE mixtures, and provide new evidence for the potential neurotoxicity of BDE209. Several countries are in the process of banning the use of PBDE mixtures as flame-retardants. However, these compounds are likely to remain present in the environment for a long time to come
ISSN: 0161-813X

hal-01286255
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01286255
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01286255/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01286255/file/Childhood%20exposure%20to%20polybrominated%20diphenyl-accepted.pdf
DOI : 10.1016/j.neuro.2016.03.002

Éditeur(s) : HAL CCSD
Résumé : Benzophenone derivatives (BPs) are used as UV filters in many different products. These lipophilic compounds were recently described as ubiquitous contaminant of different compartiments of aquatic systems, including fish. In this study, we evaluated estrogenic activity of ten BPs in a model fish species, the zebrafish (Danio rerio), by combining newly developed in vitro and in vivo models. In vitro, three specific zebrafish reporter gene models expressing zebrafish estrogen receptors (ZfERs) in zebrafish hepatic cell line (ZFL) were used.Estrogenic activity of BPs was quantify in vivo by using a newly developed transgenic zebrafish line that expresses green fluorescent protein (GFP) under the control of the cyp19a1b promoter. The cyp19a1b gene codes for the brain aromatase B that is under the control of estrogens. Vitellogenin (Vtg), a marker of estrogenic compound, was used to assess the potential estrogenic effect of certain BPs in male fish. Five of 10 BPs induced an estrogenic activity on the three models: BP2, THB, BP1, 4BP, while BP and 234 BP were non active. We noted diffrence in BPs ranking depending on the zfER subtypes suggesting ?/? receptor selectivity by certain BPs. By quantifying GFP expression in live zebrafish, we confirm the estrogenic activity of some BP, i.e., BP1, THB, 4BP and 44'BP, as shown by their ability to induce GFP in a concentration-dependent manner. However, the ranking of BPs as a function of their estrogenic activity assay is different between models. For instance, 4BP was the most estrogenic compound in vivo but not in vitro. Differences were also noticed regarding the estrogenic activity of BP2. In vitro, BP2 has strong activity but had no effect on GFP in cyp19a1b-GFP embryo. However, BP2 induced strongly Vtg in male. The lack of estrogenic activity of BP2 in embryo may be related to difference of biodisponibility and/or metabolisation of this compound between embryo and adult fish. Our approach allows to characterize the estrogenic potency of emerging pollutants, using innovative in vitro and in vivo assays within a unique model fish species. The differences observed between assays deserve further studies to characterize the behavior of compounds in the different biological models in term of biodisponibility and metabolism.
1. European Conference on the Replacement, Reduction and Refinement of Animal Experiments in Ecotoxicology
Dübendorf, Switzerland

ineris-00971019
https://hal-ineris.archives-ouvertes.fr/ineris-00971019
INERIS : EN-2012-243

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Experimental studies have demonstrated that the antileukemic trivalent inorganic arsenic prevents the development of severe pro-inflammatory diseases mediated by excessive Th1 and Th17 cell responses. Differentiation of Th1 and Th17 subsets is mainly regulated by interleukins (ILs) secreted from dendritic cells (DCs) and the ability of inorganic arsenic to impair interferon-γ and IL-17 secretion by interfering with the physiology of DCs is unknown. In the present study, we demonstrate that high concentrations of sodium arsenite (As(III), 1-2 μM) clinically achievable in plasma of arsenic-treated patients, block differentiation of human peripheral blood monocytes into immature DCs (iDCs) by inducing their necrosis. Differentiation of monocytes in the presence of non-cytotoxic concentrations of As(III) (0.1 to 0.5 μM) only slightly impacts endocytotic activity of iDCs or expression of co-stimulatory molecules in cells activated with lipopolysaccharide. However, this differentiation in the presence of As(III) strongly represses secretion of IL-12p70 and IL-23, two major regulators of Th1 and Th17 activities, from iDCs stimulated with different toll-like receptor (TLR) agonists in metalloid-free medium. Such As(III)-exposed DCs also exhibit reduced mRNA levels of IL12A and/or IL12B genes when activated with TLR agonists. Finally, differentiation of monocytes with non-cytotoxic concentrations of As(III) subsequently reduces the ability of activated DCs to stimulate the release of interferon-γ and IL-17 from Th cells. In conclusion, our results demonstrate that clinically relevant concentrations of inorganic arsenic markedly impair in vitro differentiation and functions of DCs, which may contribute to the putative beneficial effects of the metalloid towards inflammatory autoimmune diseases.
ISSN: 0041-008X

inserm-00813758
http://www.hal.inserm.fr/inserm-00813758
DOI : 10.1016/j.taap.2012.11.008
PUBMED : 23164666

Éditeur(s) : HAL CCSD Elsevier Masson
Résumé : Le cancer de la prostate est le cancer le plus fréquent chez l'homme dans la majorité des pays occidentaux. Certains facteurs de risque sont bien identifiés (âge, antécédents familiaux, origine ethnique) mais son étiologie reste largement méconnue. Les substances chimiques d'origine anthropique suscitent de nombreuses interrogations quant à leur rôle dans la survenue de la maladie. Divers travaux ont montré, de manière consistante, la présence d'un excès de risque de cancer de la prostate chez les populations agricoles par rapport à la population générale. Cependant, l'hypothèse qu'un tel excès de risque soit relié à l'utilisation de pesticides n'a pas encore été formellement démontrée.
ISSN: 1166-7087

hal-00671956
https://hal.archives-ouvertes.fr/hal-00671956

Éditeur(s) : HAL CCSD Springer Verlag
Résumé : International audience
Chlordecone (CLD) was an organochlorine insecticide whose previous use resulted in an extensive pollution of the environment with severe health effects and social consequences. A closely related compound, 5b-hydrochlordecone (5b-hydroCLD), has been searched for and often detected in environmental matrices from the geographical area where CLD was applied. The current consensus considered that its presence was not the result of a biotic or abiotic dechlorination of CLD in these matrices but rather the consequence of its presence as impurity (synthesis by-product) in the CLD released into the environment. The aim of the present study was to determine if and to what extent degradation of CLD into 5b-hydroCLD occurred in the field. To test this hypothesis, the ratios of 5b-hydroCLD and CLD concentrations in a dataset of 810 soils collected between 2006 and 2012 in Martinique were compared to the ratios measured in 3 samples of the CLD dust commercial formulations applied in the banana fields of French West Indies (FWI) and 1 sample of the technical-grade CLD corresponding to the active ingredient used in such formulations. Soil data were processed with a hierarchical Bayesian model to account for random measurement errors and data censoring. Any pathway of CLD transformation into 5b-hydroCLD occurring over the long term in FWI soils would indeed change the ratio of 5b-hydroCLD/CLD compared to what it was in the initially applied formulations. Results showed a significant increase of the 5b-hydroCLD/CLD ratio in the soils-25 times greater in soil than in commercial formulations-which suggested that natural CLD transformation into 5b-hydroCLD over the long term occurred in these soils. Results from this study may impact future decisions for the remediation of the polluted areas.
ISSN: 0944-1344

hal-01347150
https://hal.archives-ouvertes.fr/hal-01347150
https://hal.archives-ouvertes.fr/hal-01347150/document
https://hal.archives-ouvertes.fr/hal-01347150/file/Devault_15973.pdf
DOI : 10.1007/s11356-015-4865-0

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
Exposure to solvents during pregnancy has long been suspected to increase the risk of congenital malformations. Glutathione S-transferases (GSTs) are enzymes essential for the detoxification of various chemicals. Our objective here was to assess whether GST polymorphisms might modify the association between maternal solvent exposure and the risk of birth defects. A prospective cohort included 3421 pregnant women in Brittany, France (2002-2006). Occupational exposure to solvents was assessed from a job-exposure matrix. Congenital malformations were diagnosed among livebirths, stillbirths, and medical pregnancy terminations. Using a nested case-control design, 32 babies with major birth defects were compared to 348 normal births for babies' cord blood genotypes (at GSTT1 and GSTM1) and maternal occupational solvent exposure. Logistic models were used to adjust for potential confounders. The risk of major defects increased significantly in women with solvent exposure (20% of controls and 34% of cases). Frequencies of the null genotype of both the GSTT1 and GSTM1 genes were similar among controls and cases. There was a significantly increased risk of birth defects in GSTM1 not-null cord-blood genotype in pregnancies exposed to solvents (odds ratio [OR], 1.0 for not-null, not-exposed; OR, 4.0 for not-null, exposed; 95% confidence interval [CI], 1.4-11.2; OR, 1.6 for null, not-exposed; 95% CI, 0.6-3.9; OR, 1.0 for null, exposed; 95% CI, 0.2-4.7; p = 0.05). This nested case-control study suggests that the child's GSTM1 genotype modifies the risk of major birth defects among offspring of solvent-exposed women. Replication and additional investigations are necessary to confirm and elucidate these findings.
ISSN: 1542-0752

hal-00875957
https://hal.archives-ouvertes.fr/hal-00875957
DOI : 10.1002/bdra.23018
PUBMED : 22570144

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Human exposure to dechloranes has been evaluated in Western Europe (France) with the analysis of Dechlorane Plus (DP), Dechloranes (Dec) 602, 603 and 604, Chlordene Plus (CP) and Mirex in 48 serum samples collected between 2003 and 2005. While no production source has been identified in Europe until now, detection frequencies for all investigated dechloranes were high, except for Dec 604 which was below detection limit for all samples. The mean DP concentration was 1.40±1.40ng/g lipid weight (lw), lower than levels reported in serum from Chinese population, but higher than levels reported in Canadian human milk. To the best of our knowledge, this is the first time that ∑5dechlorane levels are reported for human serum. A specific pattern of contamination was found (Dec 603>DP>Mirex>Dec 602>CP) compared to other biota samples that have been analyzed from Europe, with Dec 603 as the most abundant dechlorane (mean level: 2.61±2.63ng/g lw). Dec 603 and CP levels were correlated with age and with levels of some bioaccumulative organochlorine pesticides (OCPs). These results indicate that bioaccumulation properties should be further investigated and taken in consideration when assessing human exposure to dechloranes. For comparison purposes, polybrominated diphenyl ether (PBDE) levels were also measured for BDE-47, -99, -100, -153 and -154 in the serum samples. As expected, BDE-47 and BDE-153 were the major congeners with mean levels of 2.06±1.80ng/g lw and 1.39±0.97ng/g lw, respectively. The mean ∑5PBDE levels (4.32±2.99ng/g lw) were in the range typical of Western Europe levels, but lower than the mean ∑5dechlorane levels (6.24±4.16ng/g lw). These results indicate that the attention to dechloranes should be continued if research indicates toxicological concerns.
ISSN: 0160-4120

hal-01004642
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01004642
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01004642/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01004642/file/Levelssur dechloranes_and_polybrominated_diphenyl_ethers_accepted.pdf
DOI : 10.1016/j.envint.2013.12.014