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 National Institute of Environmental Health Sciences
Résumé : International audience
BACKGROUND: Women of reproductive age can be exposed to endocrine-disrupting chemicals (EDCs) at work, and exposure to EDCs in pregnancy may affect fetal growth. OBJECTIVES: We assessed whether maternal occupational exposure to EDCs during pregnancy as classified by application of a job exposure matrix was associated with birth weight, term low birth weight (LBW), length of gestation, and preterm delivery. METHODS: Using individual participant data from 133,957 mother-child pairs in 13 European cohorts spanning births from 1994 through 2011, we linked maternal job titles with exposure to 10 EDC groups as assessed through a job exposure matrix. For each group, we combined the two levels of exposure categories (possible and probable) and compared birth outcomes with the unexposed group (exposure unlikely). We performed meta-analyses of cohort-specific estimates. RESULTS: Eleven percent of pregnant women were classified as exposed to EDCs at work during pregnancy, based on job title. Classification of exposure to one or more EDC group was associated with an increased risk of term LBW [odds ratio (OR) = 1.25; 95% CI: 1.04, 1.49], as were most specific EDC groups; this association was consistent across cohorts. Further, the risk increased with increasing number of EDC groups (OR = 2.11; 95% CI: 1.10, 4.06 for exposure to four or more EDC groups). There were few associations (p < 0.05) with the other outcomes; women holding job titles classified as exposed to bisphenol A or brominated flame retardants were at higher risk for longer length of gestation. CONCLUSION: Results from our large population-based birth cohort design indicate that employment during pregnancy in occupations classified as possibly or probably exposed to EDCs was associated with an increased risk of term LBW.
ISSN: 0091-6765

hal-01405823
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01405823
DOI : 10.1289/EHP208
PUBMED : 27152464

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

Éditeur(s) : HAL CCSD
Résumé : International audience
The plastic component bisphenol A (BPA) is suspected to exert deleterious effects towards human health and targets various cellular and molecular pathways, including activity of ATP-binding cassette drug transporters. The present study was designed to determine whether BPA and some derivatives, like its substitutes bisphenol F (BPF) and bisphenol S (BPS) and the flame retardant tetrabromobisphenol A (TBBPA), may additionally interact with solute carrier (SLC) drug transporters. Activities of the various following SLC transporters were inhibited in a major way (by > 60%) by 100 μM bisphenols: OCT1 and MATE1 (by BPA and TBBPA), OATP1B1 (by BPA, BPF and TBBPA), OATP1B3 and NTCP (by TBBPA) and OAT3 (by BPA, BPF, BPS and TBBPA); by contrast, activities of other transporters were not impacted (MATE2-K) or were stimulated (notably OCT1 by BPS and OCT2 by BPF). Transporter inhibitions due to bisphenols were concentrations-dependent, with half maximal inhibitory concentrations (IC50) ranging from 0.5 μM to 73.5 μM. BPA was finally shown to be not transported by OAT3, although inhibiting this transporter in a competitive manner. Taken together, these data indicate that bisphenols interact with SLC transporters, at concentration levels however rather higher than those occurring in humans in response to environmental exposure. © 2016 Elsevier B.V.
Toxicology in Vitro

hal-01467545
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01467545
DOI : 10.1016/j.tiv.2016.12.009
PUBMED : 27989701

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
There are emerging concerns about potential effects on child health and development of early-life exposure to substances such as brominated flame retardants (BFRs), perfluorinated compounds (PFCs), phthalates and phenols (including bisphenol A (BPA)); pregnancy and birth cohort studies are ideally designed to study such concerns prospectively. As part of the ENRIECO project, we evaluated existing human biomonitoring data for these substances in European birth cohorts and develop recommendations for more harmonized methods that will enable combination and comparison of cohort data in the future. The ENRIECO inventory shows that 20 European birth cohorts have measured or are measuring BFRs (N=10), PFCs (N=11), phthalates (N=16) or phenols (N=8). Generally, samples were collected prenatally or at birth and measurements involved few subjects in each cohort (a few hundred maximum). Biological matrices, timing, and analytical methods of the measurements varied between cohorts. Few cohorts have measured at multiple time points or in children. In European cohorts, levels of BFRs were very low and at least 10-fold lower than in US; levels of PFCs and phthalates have decreased over the last decade since the phasing out of certain of these compounds; concentrations of phenols are comparable to those in the US. Although there is little published data in the cohorts now, many measurements are ongoing and we recommend that cohorts start working towards combined and comparison studies. Specific recommendations for use of existing data include the development of conversion models for the different media used for measurement of persistent chemicals, and inter-laboratory comparisons and calibrations. Recommendations for further data collection include more evaluation of exposure to these chemicals in children; repeated measurements of non-persistent chemicals; validation and harmonisation of questionnaires; and the development of mechanisms for fast European birth cohort response for the detection and prioritisation of new chemicals of concern.
ISSN: 1438-4639

hal-01118579
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01118579
DOI : 10.1016/j.ijheh.2012.05.009
PUBMED : 22795704

Éditeur(s) : HAL CCSD
Résumé : Semi-volatile organic compounds (SVOCs) refer to a broad spectrum of molecules from different chemical families that have numerous properties. They can be used as pesticides, plasticizers, flame retardants, surfactants, lubricants, etc. Consequently, they are introduced in numerous applications in buildings or used daily by the entire population. Once emitted through evaporation or abrasion in the indoor environment or introduced from the outdoors, their chemical or biological degradation is limited, and they persist indoors. This persistence also explains why some SVOCs that were banned a few years ago are still detected in the air and dust inside buildings. In indoor environments, SVOCs are divided between the gas phase, airborne particles, and dust settled on floors and surfaces. SVOCs are of concern due to their established or suspected health effects and their widespread exposure through different environmental media and pathways. The objective of the thesis was to study the concentrations of 66 SVOCs on airborne particles (PM10) and 48 SVOCs in settled dust in two samples of dwellings randomly selected across France. PM10 were sampled during the nationwide housing survey carried out by the French Observatory of indoor air quality in 2003-2005. The dust samples were collected from vacuum cleaner bags during a nationwide survey carried out in French dwellings where at least one child aged 6 months to 6 years lived (2008-2009). The SVOCs to be analyzed had prior been selected using a ranking method based on their toxicity and indoor concentrations. The data analysis focused in particular on the identification of French specificities in terms of detected molecules and measured concentrations. It highlighted some determinants of exposure, e.g., influence of particle size, type of dust collected, dust bioaccessibility, which are not always considered and limit the comparability of results. The measured concentrations were also used to assess the health ranking implemented prior to this work and to confirm its relevance. The concentrations measured both in the air and in settled dust were compared to study the similarities in terms of concentrations and SVOC mixtures. Finally, the exposure doses to SVOCs were calculated for both a child and an adult to assess the respective contributions of inhalation and ingestion to these compounds in particulate phase in dwellings.
Les composés organiques semi-volatils (COSV) font l’objet d’une attention croissante depuis une dizaine d’années. Utilisés dans de nombreux produits et matériaux du quotidien, ils sont émis dans les bâtiments par dispersion lors de l’usage, par évaporation ou abrasion. Du fait de leurs caractéristiques physico-chimiques, ces composés se répartissent à la fois dans l’air, en phases gazeuse et particulaire, et dans les poussières déposées au sol, sur le mobilier et les objets. Compte tenu du temps passé par la population dans les bâtiments, en particulier par les populations sensibles comme les enfants, les femmes enceintes et les personnes âgées, l’exposition à ces substances mérite d’être documentée, tenant compte des voies d’exposition en jeu : inhalation, ingestion et contact cutané. La thèse a porté sur les COSV présents en phase particulaire dans les logements. L’objectif de la thèse visait à exploiter les mesures de 66 COSV dans les particules en suspension de diamètre inférieur à 10 µm (PM10) et de 48 COSV dans les poussières au sol de taille inférieure à 100 µm considérées comme étant celles adhérant à la peau. Ces mesures ont été réalisées dans le cadre de deux campagnes nationales : la campagne « Logements » de l’Observatoire de la qualité de l’air intérieur conduite en 2003-2005 et l’enquête Plomb-Habitat dont les prélèvements ont eu lieu en 2008-2009. Une hiérarchisation des molécules jugées prioritaires au regard de leur impact sanitaire potentiel avait permis au préalable d’établir la liste des COSV à mesurer. L’exploitation de ces données de contamination a notamment porté sur l’identification d’éventuelles spécificités françaises au regard des molécules en présence et/ou des concentrations mesurées. Elle a permis de mettre en lumière un ensemble de facteurs déterminants de l’exposition (influence de la taille des particules, du type de poussières collectées, de leur bioaccessibilité), qui ne sont pas toujours considérés et qui limitent par ailleurs la comparabilité des résultats. Les concentrations mesurées ont aussi permis d’évaluer rétrospectivement la hiérarchisation sanitaire et d’en confirmer la pertinence. Les concentrations des COSV quantifiés à la fois dans l’air et au sol ont été mises en perspective afin d’examiner dans quelle mesure les particules en suspension et les poussières déposées sont similaires en termes de concentrations et de mélanges de COSV en présence. Enfin, l‘estimation des doses d’exposition aux COSV à partir d’équations simples, de variables humaines d’exposition et des données de contamination a permis une première évaluation des contributions respectives de l’inhalation et de l’ingestion aux expositions domestiques des enfants et adultes à ces composés en phase particulaire.
https://tel.archives-ouvertes.fr/tel-01308524

NNT : 2015REN1B033
tel-01308524
https://tel.archives-ouvertes.fr/tel-01308524
https://tel.archives-ouvertes.fr/tel-01308524/document
https://tel.archives-ouvertes.fr/tel-01308524/file/MANDINCorinne.pdf

Éditeur(s) : HAL CCSD
Résumé : International audience
BACKGROUND: Semi Volatile Organic Compounds (SVOCs) are contaminants commonly found in dwellings as a result of their use as plasticizers, flame retardants, or pesticides in building materials and consumer products. Many SVOCs are suspected of being neurotoxic, based on mammal experimentation (impairment of locomotor activity, spatial learning/memory or behavioral changes), raising the question of cumulative risk assessment. The aim of this work is to estimate the relative toxicity of such SVOCs, based on neuronal death. METHOD: SVOCs fulfilling the following conditions were included: detection frequency >10% in dwellings, availability of data on effects or mechanism of action for neurotoxicity, and availability of dose-response relationships based on cell viability assays as a proxy of neuronal death. Benchmark concentration values (BMC) were estimated using a Hill model, and compared to assess relative toxicity. RESULTS: Of the 58 SVOCs selected, 28 were suspected of being neurotoxic in mammals, and 21 have been documented as inducing a decrease in cell viability in vitro. 13 have at least one dose-response relationship that can be used to derive a BMC based on a 10% fall in neuronal viability. Based on this in vitro endpoint, PCB-153 appeared to be the most toxic compound, having the lowest BMC10 (0.072μM) and diazinon the least toxic compound, having the highest BMC10 (94.35μM). We showed that experimental designs (in particular choice of cell lines) had a significant influence on BMC calculation. CONCLUSION: For the first time, the relative in vitro toxicity of 13 indoor contaminants belonging to different chemical families has been assessed on the basis of neuronal cell viability. Lack of comparable toxicity datasets limits the number of SVOCs that can be included. More standardized protocols in terms of cell lines, species and exposure duration should be developed with a view to cumulative risk assessment.
Toxicology Letters

hal-01579605
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01579605
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01579605/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01579605/file/Fournier%20et%20al.%20-%20Relative%20toxicity%20for%20indoor%20semi%20volatile%20organic.pdf
DOI : 10.1016/j.toxlet.2017.07.875