La cigarette électronique est installée sur le marché depuis plusieurs années et jouit aujourd’hui d’une forte notoriété. Les données scientifiques existantes tendent à considérer l’e-cigarette comme moins toxique que son homologue principal, la cigarette conventionnelle. Cependant, l’impact intrinsèque du vapotage sur la santé humaine, à court et long terme, n’est pas précisément connu et est actuellement au coeur de nombreux débats de Santé Publique.Depuis 2014, nous menons un projet dont l’objectif principal est d’étudier l’impact sanitaire de la cigarette électronique au moyen d’une approche pluridisciplinaire combinant entre autres l’analyse physicochimique et la toxicologie expérimentale. Dans le cadre de ce projet, mes travaux ont porté sur la caractérisation physicochimique des e-liquides, d’une marque commerciale, et de leurs e-vapeurs, basée en particulier sur l’identification et la quantification de composés potentiellement toxiques pour l’Homme. En l’absence de méthodes de référence, cette analyse requiert un niveau élevé de maîtrise et de robustesse de l’ensemble de la chaîne de mesure, allant de la génération à l’analyse, notamment pour les e-vapeurs.Les éléments traces métalliques (ETM) étant des composés à impact sanitaire potentiel, nos travaux ont débuté par le développement et la validation d’une méthode de dosage simultané de 15 ETM dans les e-liquides par ICP-MS. Il s’avère que l’e-liquide, matrice organique visqueuse, est source d’effets de matrice non négligeables qu’il est nécessaire de corriger par l’ajout de matrice dans le calibrant, en proportion adaptée. La méthode a été entièrement validée selon les recommandations du Comité français d’accréditation et de l’US Environmental Protection Agency et a démontré des paramètres de robustesse satisfaisants.Six e-liquides et leurs e-vapeurs respectives, générées par une machine à fumer/vapoter, ont été ensuite analysés pour la recherche et la quantification de leurs ingrédients principaux (propylène glycol, glycérol et nicotine) et de différents polluants potentiellement toxiques (15 ETM, 50 pesticides, 16 hydrocarbures aromatiques polycycliques (HAP) et 3 composés carbonylés). Les e-liquides avaient une composition conforme à celle annoncée par le fabricant et contenaient quelques rares polluants, à l’état de traces. Dans les e-vapeurs, 3 composés carbonylés, 2 HAP et 4 ETM (Sb, Cd, Cr et Pb) ont été retrouvés à des concentrations 7 à 6126 fois inférieures à celles mesurées dans la fumée de la cigarette de référence 3R4F, analysée dans des conditions comparables (à l’exception du Cr et du Sb non présents dans la fumée de la 3RF4).Le profil de vapotage, qui repose essentiellement sur le volume, la durée et la fréquence des bouffées, semble contribuer à la large variabilité de la composition chimique des e-vapeurs observée entre les différentes données de la littérature. En se focalisant sur l’analyse d’une seule famille de composés à impact sanitaire probable, nous avons montré, d’une part, que le profil de vapotage a une influence certaine sur la composition de l’e-vapeur en composés carbonylés et, d’autre part, que les profils de vapotage ne sont pas adaptés à tous les modèles d’e-cigarette.Les travaux de cette thèse ont participé à améliorer les connaissances actuelles sur la caractérisation physicochimique des émissions de cigarette électronique. Globalement, les e-cigarettes et e-liquides testés émettent et/ou génèrent quelques rares composés potentiellement toxiques, à des concentrations inférieures à celles observées dans la fumée de cigarette conventionnelle. Les résultats de nos travaux répondent en partie à l’urgente nécessité d’optimiser et d’harmoniser les pratiques analytiques dans le domaine de l’e-cigarette et de ses émissions. Ils devraient ainsi contribuer à l’établissement de méthodes de référence qui faciliteront et autoriseront l’interprétation et la comparaison des données, actuellement très disparates dans la littérature. / The electronic cigarette has been on the market for several years and enjoys a strong reputation. Existing scientific data tend to consider the e-cigarette as less toxic than its main counterpart, the conventional cigarette. However, the intrinsic impact of vaping on human health, in the short and long term, is not precisely known and is currently part of many Public Health debates.Since 2014, we have undertaken a project whose main objective is to study the health impact of the electronic cigarette using a multidisciplinary approach comprising physicochemical analysis and experimental toxicology. As part of this project, my work focused on the physicochemical characterization of e-liquids, from a unique commercial source, and their e-vapors, mainly based on the identification and quantification of potentially-toxic compounds. Regarding the current lack of reference methods, this analysis requires a high level of control and robustness of the entire measurement chain, from generation to analysis methods, especially for e-vapor study.Considering the potential health impact of metallic trace elements (MTEs), we first developed and validated a method allowing the simultaneous dosage of 15 MTEs in e-liquids by ICP-MS. The e-liquid, a viscous organic matrix, is a source of significant matrix effects which must be corrected by the addition of matrix in the calibration step, in a suitable proportion. The method was fully validated according to the recommendations of the French Accreditation Committee and the US Environmental Protection Agency and demonstrated satisfactory robustness parameters.Six e-liquids and their respective e-vapors, generated via a smoking/vaping machine, were then analysed to detect and quantify their main ingredients (propylene glycol, glycerol and nicotine) and various potentially-toxic pollutants (15 MTEs, 50 pesticides, 16 polycyclic aromatic hydrocarbons and 3 carbonyl compounds). Each e-liquid composition was in accordance with that announced by the manufacturer and contained few pollutants, at trace levels. In the e-vapors, 3 carbonyl compounds, 2 polycyclic aromatic hydrocarbons and 4 MTEs (Sb, Cd, Cr and Pb) were found at concentrations 7 to 6126-fold lower than those measured in the mainstream smoke of the reference cigarette 3R4F, analysed under comparable conditions (except for chromium and antimony which were not detectable in the 3R4F smoke).The vaping regimen, that is mainly based on the volume, the duration and the frequency of puffs, is strongly suspected to participate to the large observed variability of the e-vapor chemical composition between different published data. Through focusing on the analysis of a unique family of compounds with health impact, we demonstrated, on the one hand, that the vaping regimen has some influence on the carbonyl composition of e-vapors and, on the other hand, that vaping regimens are not all suitable for any type of e-cigarette models.This work has contributed to improve the current knowledge on the physicochemical characterization of e-cigarette emissions. Globally, the e-cigarettes and e-liquids tested emit and/or generate few potentially-toxic compounds, at concentrations lower than those observed in conventional cigarette smoke. Our findings satisfy partly the urgent need of optimization and harmonization of the analytical practices used to study e-cigarettes and their emissions. They should thus contribute to the establishment of reference methods that will allow and facilitate the interpretation and comparison of data, which vary significantly across the literature.

Le bassin d’Arcachon est une lagune semi-fermée qui concentre de forts enjeux économiques grâce à la pratique de l’ostréiculture. Cette activité est affectée depuis une trentaine d’années par des phénomènes de mortalités estivales, et plus récemment par des surmortalités du naissain. Ces travaux se sont intéressés au rôle des polluants majeurs du bassin d’Arcachon dans ce contexte de crise en étudiant leurs effets sur la biologie de Crassostrea gigas. Une approche in situ a d’abord été adoptée afin d’identifier les contaminants les plus présents dans le milieu naturel. Des opérations de transplantation d’huîtres et des prélèvements de sédiments ont permis de quantifier divers contaminants et d’associer leur présence à des réponses biologiques. Les polluants ainsi identifiés ont ensuite été employés en conditions contrôlées au laboratoire. Trois expérimentations ont été réalisées : la première concerne l’étude des voies de contamination par le tributylétain ; la seconde concerne les effets des pesticides et du cuivre ; la troisième concerne l’effet des HAP sur des huîtres diploïdes et triploïdes. Nos résultats indiquent que les organismes transplantés au coeur de la lagune sont plus exposés aux polluants, en lien avec les caractéristiques hydrodynamiques du système. La plupart des paramètres biologiques étudiés sur le terrain ont par ailleurs montré une saisonnalité liée aux processus de gamétogenèse. Au laboratoire, la plupart des contaminants testés ont induit une réponse adaptative chez les huîtres exposées. Notre étude souligne l’importance de coupler approche de terrain et approche expérimentale pour comprendre le fonctionnement des écosystèmes côtiers. / The Arcachon Bay is a semi-enclosed lagoon and represents the core of strong economic stakes through the practice of oyster-farming. This activity has been affected for around thirty years by summer mortality events, and more recently by abnormally high death rates of juveniles. This work focused on the role of the Arcachon Bay’s main contaminants in this crisis, by studying their effects on the cupped oyster’s biology. Firstly, an in situ approach was adopted in order to identify the major pollutants of the bay: caged oysters were transplanted and sediments were sampled. The presence of contaminants in the samples was associated to biological responses. Secondly, the contaminants identified in situ were used in controlled conditions at the laboratory. Three experimentations were performed; the first dealt with the contamination pathways of tributyltin; the second focused on the biological effects of pesticides and copper; the third concerned the effects of PAH towards diploid and triploid oysters. Our results indicate that the inner stations present higher accumulation of metals and PAH, in accordance with the hydrodynamic features of the bay. The bioindicators used in situ exhibited seasonal trends related to the oysters’ gametogenesis. In the laboratory, most of the contaminants used at environmental levels induced an adaptive response of the exposed oysters. Our study highlights the importance of coupling in situ and laboratory approaches in order to understand the functioning of coastal ecosystems.

Three ionic liquids (ILs), trihexyltetradecylphosphonium tetrafluoroborate (TTPT), N-butyl-4-methylpyridinium tetrafluoroborate (BMPT), and 1-methyl-3- octylimidazolium tetrafluoroborate (MOIC), were utilized to prepare sol- gel sorbent coatings. Non-polar polydimethylsiloxane (PDMS) and polar poly(ethylene glycol) (PEG), poly(tetrahydrofuran) (PolyTHF) and bis[(3-methyldimethoxy-silyl)propyl] polypropylene oxide (BMPO) polymers were employed to develop novel ionic liquidmediated sol- gel hybrid organic- inorganic sorbents. The novel sorbents were first tested as coatings for capillary microextraction off-line hyphenated to gas chromatography. To gain an understanding of the role of the ionic liquids in the sol-gel process, the preconcentration abilities of these novel coatings were investigated for several classes of compounds utilizing CME-GC. This was accomplished by comparing GC peak areas of a series of analytes extracted on the ionic liquid mediated sol-gel CME coatings with that of analogous peak areas obtained on sol- gel coatings prepared without the ionic liquid. The morphology of these coatings was compared using scanning electron microscopy (SEM) imaging data. Overall, the ionic liquid-mediated sol- gel coatings had more porous morphologies than the sol-gel coatings prepared without ionic liquid. The PDMS andBMPO sol-gel coatings prepared with ionic liquid in the sol solution provided enhanced extraction sensitivity reflected in higher preconcentration effects and lower detection limits than the sol- gel coatings prepared without the ionic liquid. The polar IL-mediated BMPO sol- gel sorbent was further investigated by exploring the extraction profile and thermal stability of these coatings. A further application of ionic liquid-mediated sol-gel sorbents could be as stationary phases in a microchip-based separation system. Towards this goal, microfluidic channels were fabricated in glass substrates using microelectromechanical engineering. Spiral and serpentine channels were etched in Pyrex and fused silica wafers using wet and deep reactive ion etching (DRIE) techniques. Microfabrication protocols such as the use of hard mask and etching times were investigated for both techniques. DRIE produced microfluidic channels that had an etch quality that was superior to wet etched channels. Thus, the ultimate microchip-based separation system should by fabricated using DRIE.

Environmental toxicologists and public health officials are responsible for assisting in the identification, management, and mitigation of public health hazards. As a result, there is a continued need for robust analytical tools that can aid in the rapid quantification and characterization of chemical exposure. In the first research phase, we demonstrated that a current tool for estimating human organophosphate pesticide exposure, measuring dialkyl phosphate (DAPs) metabolites in urine as chemical biomarkers of pesticide exposure, could represent exposure to DAPs themselves and not to pesticides. We showed that DAPs are metabolically stable, have high oral bioavailability, and are rapidly excreted in the urine following oral exposure. Results suggest that DAP measurements may lead to overestimates of human organophosphate pesticide exposure. In the second phase of research, a quick, easy, cheap, effective, rugged, and safe (QuEChERS) based analytical method was developed and validated for quantifying polycyclic aromatic hydrocarbons (PAHs) in biotic matrices with fat contents that ranged from 3 to 11%. Our method improved PAH recoveries 50 to 200% compared to traditional QuEChERS methods, performed as well or better than state of the art Soxhlet and accelerated solvent extraction methods, had sensitivity useful for chemical exposure assessments, and reduced sample preparation costs by 10 fold. The validated QuEChERS method was subsequently employed in a human exposure assessment. Little is known about how traditional Native American fish smoke-preserving methods impact PAH loads in smoked foods, Tribal PAH exposure, or health risks. Differences in smoked salmon PAH loads were not observed between Tribal smoking methods, where smoking methods were controlled for smoking structure and smoke source. PAH loads in Tribally smoked fish were up to 430 times greater than those measured in commercially available smoked fish. It is not likely that dietary exposure to non-carcinogenic PAHs at heritage ingestion rates of 300 grams per day poses an appreciable risk to human health. However, levels of PAHs in traditionally smoked fish may pose and elevated of risk of cancer if consumed at high rates over a life time. Accurately estimating PAH exposure in cases where aquatic foods become contaminated is often hindered by sample availability. To overcome this challenge, we developed a novel analytical approach to predict PAH loads in resident crustacean tissues based on passive sampling device (PSD) PAH measurements and partial least squares regression. PSDs and crayfish collected from 9 sites within, and outside of, the Portland Harbor Superfund site captured a wide range of PAH concentrations in a matrix specific manner. Partial least squares regression of crayfish PAH concentrations on freely dissolved PAH concentrations measured by PSDs lead to predictions that generally differed by less than 12 parts per billion from measured values. Additionally, most predictions (> 90%) were within 3-fold of measured values, while state of the art bioaccumulation factor approaches typically differ by 5 to 15-fold compared to measured values. In order to accurately characterize chemical exposure, new analytical approaches are needed that can simulate chemical changes in bioavailable PAH mixtures resulting from natural and/or remediation processes. An approach based on environmental passive sampling and in-laboratory UVB irradiation was developed to meet this need. Standard PAH mixtures prepared in-lab and passive sampling device extracts collected from PAH contaminated environments were used as model test solutions. UV irradiation of solutions reduced PAH levels 20 to 100% and lead to the formation of several toxic oxygenated-PAHs that have been previously measured in the environment. Site specific differences in oxygenated-PAH formation were also observed. The research presented in this dissertation can be used to advance chemical exposure estimation techniques, rapidly and cost-effectively quantify a suite of PAHs in biotic tissues, and simulate the effect of abiotic transformation processes on the bioavailable fraction of environmental contaminants. / Graduation date: 2013 / Access restricted to the OSU Community at author's request from April 3, 2013 - April 3, 2014

More than half of all cases of breast cancer occur among women without any known risk factors. More research is needed on suspected risk factors in order to refine current breast cancer screening tools. The objectives of this thesis were: to determine the breast cancer risk associated with known risk factors (ethnicity, family history, breast biopsy, age at menarche, age at first birth, alcohol, HRT, and BMI), suspected risk factors (smoking, second-hand smoke exposure, smoked/grilled foods, and NSAID use), and to examine the above associations according to tumour receptor status, histologic grade, and menopausal status, with potential confounders also considered. This thesis project was conducted within the framework of the Molecular Epidemiology of Breast Cancer study, a case-control study of women in Vancouver, BC and Kingston, ON, with 1140 cases and 1169 controls recruited from 2005-2010. Information was collected from a detailed questionnaire. Cases and controls were similar in terms of age at menarche, age at first birth, smoking history, second-hand smoke exposure, lifetime smoked/grilled food consumption, HRT, and BMI. Among cases, there were significantly less Europeans and more Chinese, Japanese, and Filipino subjects compared to controls. Cases were more likely to have a first degree relative with breast cancer, as well as a previous benign breast biopsy. Alcohol consumption and past NSAID usage was higher among controls. The level of education completed was higher among controls. Cases were also more likely to be postmenopausal. Family history was associated with breast cancer risk (OR=1.59, CI=1.30-1.94), as was BMI (OR=1.28, CI=1.05-1.58 for overweight and OR=2.28, CI=1.35-3.86 for obese class II). Second-hand smoke was also found to be associated with breast cancer risk (OR=1.42, CI=1.02-1.97 for individuals with a less than 10 pack-year smoking history). Due to reduced sample size with stratification and marginally significant results, it is not possible to draw definitive conclusions regarding pathology sub-types. In summary, these results provide support for the association between several risk factors and breast cancer risk. More research is needed to ascertain how receptor status, histologic grade, and menopausal status affect these associations. / Thesis (Master, Community Health & Epidemiology) -- Queen's University, 2011-08-15 19:43:06.689

Made available in DSpace on 2014-12-17T14:08:43Z (GMT). No. of bitstreams: 1 MariaSMQ_DISSERT_1-36.pdf: 5283210 bytes, checksum: e75f1aa1d6f8e40607338226667f1b0d (MD5) Previous issue date: 2011-02-07 / Estuaries are environments prone to the input of chemical pollutants of various kinds and origins, including polycyclic aromatic hydrocarbons (PAHs). Anthropogenic PAHs may have two possible sources: pyrolytic (with four or more aromatic rings and low degree of alkylation) and petrogenic (with two and three aromatic rings and high degree of alkylation). This study aimed to evaluate the levels, distribution and possible sources of polycyclic aromatic hydrocarbons in the estuary of the Potengi river, Natal, Brazil. Samples of bottom sediments were collected in the final 12 km of the estuary until its mouth to the sea, where the urbanization of the Great Natal is more concentrated. Sampling was performed on 12 cross sections, with three stations each, totaling 36 samples, identified as T1 to T36. The non alkylated and alkylated PAHs were analyzed by gas chromatography coupled to mass spectrometry (GC / MS). PAHs were detected in all 36 stations with total concentration on each varying 174-109407 ng g-1. These values are comparable to those of several estuarine regions worldwide with high anthropogenic influence, suggesting the record of diffuse contamination installed in the estuary. PAHs profiles were similar for most stations. In 32 of the 36 stations, low molecular weight PAHs (with 2 and 3 ring: naphthalene, phenanthrene and their alkylated homologues) prevailed, which ranged from 54% to 100% of the total PAH, indicating that leaks, spills and combustion fuels are the dominant source of PAH pollution in the estuary. The level of contamination by PAHs in most stations suggests that there is potential risk of occasional adverse biological effects, but in some stations adverse impacts on the biota may occur frequently. The diagnostic ratios could differentiate sources of PAHs in sediments of the estuary, which were divided into three groups: petrogenic, pyrolytic and mixing of sources. The urban concentration of the Great Natal and the various industrial activities associated with it can be blamed as potential sources of PAHs in bottom sediments of the estuary studied. The data presented highlight the need to control the causes of existing pollution in the estuary / Os estu?rios s?o ambientes prop?cios ao aporte de poluentes qu?micos de diversas naturezas e origens, incluindo Hidrocarbonetos Polic?clicos Arom?ticos (HPA). Os HPA antr?picos s?o de duas fontes poss?veis: pirol?tica (com quatro ou mais an?is arom?ticos e baixo grau de alquila??o) e petrog?nica (com dois e tr?s an?is arom?ticos e alto grau de alquila??o). O presente trabalho teve como objetivo avaliar os n?veis, distribui??o e poss?veis fontes de Hidrocarbonetos Polic?clicos Arom?ticos no estu?rio do rio Potengi, Natal-RN. Amostras de sedimentos de fundo foram coletadas nos 12 km finais do estu?rio at? a sua foz, onde a urbaniza??o da Grande Natal ? mais concentrada. A amostragem foi realizada em 12 se??es transversais, com tr?s esta??es em cada uma, totalizando 36 amostras, identificadas de T1 a T36. Os HPA alquilados e n?o alquilados foram analisados por cromatografia gasosa acoplada a um detector seletivo de massas (CG/EM). Foram detectados HPA em todas as 36 esta??es, com concentra??o total em cada uma variando de 174 a 109407 ng g-1. Esses valores s?o compar?veis aos de v?rias regi?es estuarinas mundiais com grande influ?ncia antr?pica, o que sugere o registro de contamina??es difusas instaladas no estu?rio. O perfil de HPA foi similar para a maioria das esta??es. Em 32 das 36 esta??es predominaram HPA de baixo peso molecular (com 2 e 3 an?is: naftaleno, fenantreno e seus hom?logos alquilados), que variaram de 54% a 100% em rela??o ao total de HPA, indicando que vazamentos, derramamentos e queima de combust?veis s?o a fonte dominante de polui??o por HPA no estu?rio. O n?vel de contamina??o por HPA na maioria das esta??es sugere que h? risco potencial de ocasionais efeitos biol?gicos adversos serem observados, por?m em algumas esta??es se confirmam que impactos adversos sobre a biota ocorrem com freq??ncia. As raz?es diagn?sticas permitiram diferenciar as fontes de HPA nos sedimentos do estu?rio, que foram divididos em tr?s grupos: sedimentos com padr?es de introdu??o de hidrocarbonetos petrog?nicos, pirol?ticos e de mistura de fontes. A concentra??o urbana da Grande Natal e as atividades industriais diversas a ela associadas podem ser responsabilizadas como fontes potenciais dos HPA nos sedimentos de fundo do estu?rio estudado. Os dados apresentados evidenciam a necessidade de se controlar as causas da polui??o existente no estu?rio

Les sources d’émissions de polluants organiques persistants (POP) dans l’atmosphère sont relativement bien connues. Une fois dans ce compartiment sous formes gazeuse et/ou particulaire, ces composés sont transportés à plus ou moins longue distance puis éliminés en fonction des conditions météorologiques par dépôts secs (aérosols) ou humides (pluie et neige). L’impact des POP est planétaire, tous les milieux de l’environnement sont touchés et les milieux aquatiques de montagne ne sont pas épargnés. Plusieurs études ont rapportées la présence de Polychlorobiphényles (PCB) et d’Hydrocarbures Aromatiques Polycycliques (HAP) sur des lacs d’altitude européens où l’atmosphère est l’unique source de pollution. A ce jour, très peu d’études ont été menées en milieux de montagne pour comprendre et identifier les mécanismes de transfert à l’interface entre l’air et l’eau. Ces travaux de thèse sont ainsi focalisés sur les échanges de POP à l’interface air-eau en milieu aquatique de montagne. Dans le but de définir le rôle de l’atmosphère sur ces milieux et de calculer des flux de POP, deux systèmes hydriques distincts ont été étudiés : un lac d’altitude (Lac de la Muzelle, Oisans) et une rivière alpine (Arc, vallée de la Maurienne). Deux familles de POP ont été ciblées pour leurs différentes propriétés physico-chimiques : les HAP et les PCB. Pour l’étude de ces milieux de montagne parfois difficile d’accès, une stratégie d’échantillonnage passive a été choisie. Les systèmes d’échantillonnage employé ont été améliorés, développés au laboratoire ou utilisés tel quel pour échantillonner distinctement toutes les formes de POP dans l’air (gaz, particules, dépôts secs et humides) et dans l’eau (phase dissoute et particulaire). Une comparaison des systèmes d’échantillonneurs atmosphériques passifs a été réalisée pour définir le plus fiable et représentatif. Ces études de transferts air-eau ont été conduites sur le lac d’altitude pendant deux périodes estivales (2014 et 2015) et un suivi de deux ans a été réalisé (2014 à 2016) sur la rivière alpine.Le rôle de l’atmosphère en période estivale a pu être ainsi défini sur le lac d’altitude et des flux d’échanges de polluants à l’interface ont pu être calculés. La rivière alpine étant un système hydrique dynamique plus complexe pour l’étude des transferts air-eau et la quantification de flux, un suivi spatio-temporel de la contamination a tout d’abord été réalisé le long de la rivière et une première approche de calcul de flux de polluants à l’interface a été appliquée. / Atmospheric sources of persistent organic pollutants (POPs) are relatively well known. Once in this compartment under both gas and particulate forms, these compounds are carried on more or less long range. Then, pollutants are eliminated by dry (aerosol) or wet (rain, snow) depositions according to meteorological conditions. The global planetary distribution of POPs affects all environments and mountain aquatic environments are not spared. Several studies on European high altitude mountain lakes have reported the presence of Polychlorinated Biphenyls (PCBs) and Polycyclic Aromatic Hydrocarbons (PAHs). In these remote areas, the atmospheric compartment is the unique source of pollution. Few studies were conducted in order to understand and identify transfer mechanisms at the air-water interface in mountain. So, this thesis focused on POP exchanges at the air-water interface. In order to characterize atmospheric influence on aquatic compartment and calculate pollutant fluxes, two separate water systems were studied: a high altitude lake (Muzelle lake, Oisans) and an alpine river (Arc, Maurienne valley). Two POP families were targeted for their different physicochemical properties: PAHs and PCBs.In these mountain environments with limited access and energy, passive sampling strategy was chosen. Samplers were improved, developed in the lab or used to distinctly collect all POP forms in the air (gas, particulate, dry and wet depositions) and water (dissolved, particulate). A comparison of different atmospheric passive samplers was conducted to define the most reliable and representative. The air-water transfer studies were realized on the high altitude lake over two summer periods (2014 and 2015) and over a two years monitoring (2014 to 2016) in the alpine river. So, the atmospheric role on the alpine lake in summer was defined and air-water flux exchanges were calculated. As the alpine river is a more complex water system for the air-water transfers study and quantification, in a first time a space-time contamination monitoring was conducted along the river and a first approach was applied to calculate pollutant fluxes at the interface.

Les hydrocarbures aromatiques monocycliques (BTEX) et polycycliques (HAP) sont pour la plupart reconnus pour leur toxicité via ingestion. Le suivi de leur contenu dans les matrices alimentaires est donc indispensable. Plusieurs approches sensibles et complémentaires ont été établies, avec la pomme comme modèle d’étude, pour la double détermination de ces hydrocarbures aromatiques volatils et semi-volatils au niveau du µg/kg.Une micro-extraction en phase solide dans l’espace de tête (HS-SPME) a été utilisée pour l'extraction des hydrocarbures aromatiques les plus légers (MM entre 78 et 178 g/mol). La récupération des composés les plus lourds (MM entre 202 et 278 g/mol) a quant à elle été permise par une méthodologie basée sur l'extraction assistée par les ultrasons (UAE) suivie d'une extraction en phase solide (SPE). Une alternative plus sensible à cette stratégie combinant l’HS-SPME et l’UAE/SPE pour la détermination globale des hydrocarbures aromatiques a également été développée. Le remplacement de l’étape de SPE par une micro-extraction sur solide compacté (MEPS) a permis une récupération plus rapide, sensible et plus large des HAP (MM entre 152 et 278 g/mol).L’ensemble des stratégies d'extraction, associées à des analyses en chromatographie gazeuse couplée à la spectrométrie de masse, a ensuite pu être appliqué à la détermination des 20 composés aromatiques ciblés dans des pommes récoltées en Normandie ou des fruits provenant du commerce contaminés ou non par des gaz d’échappement ou des fumées de combustion de biomasse. Ces applications ont révélé la faible contamination des pommes normandes étudiées, l’adsorption prédominante des composés aromatiques au niveau de la peau des fruits et leur faible transfert vers la chair. / Monocyclic aromatic hydrocarbons (BTEX) and polycyclic aromatic hydrocarbons (PAHs) are considered and recognized as toxic compounds via ingestion. Their monitoring in food product is thus a significant concern. Sensitive and complementary experimental approaches were investigated with apple as model for the dual determination of volatile and semi-volatile aromatic hydrocarbons at the ppb level.A solid-phase micro-extraction in the headspace of samples (HS-SPME) was used for the most volatile aromatic hydrocarbons (MW between 78 and 178 g/mol). The recovery of the least volatile aromatic hydrocarbons (MW between 202 and 278 g/mol) was implemented with an ultrasound assisted extraction (UAE) followed by a purification step using a solid phase extraction (SPE). The methodology consisting in HS-SPME and UAE/SPE enabled the global determination of BTEX and PAHs. The SPE step was then substituted by a micro-extraction with a packed sorbent (MEPS) to elaborate a most sensitive and rapid methodology for the quantification of a wider range of PAHs (MW between 152 and 278 g/mol).Extraction procedures associated with analyses using gas chromatography and mass spectrometry were then applied to the determination of 20 targeted aromatic compounds in apples harvested in Normandy or in commercial fruits exposed or not exposed to exhaust gas or to wood smoke. These applications revealed low levels of contaminants in the studied apples from Normandy. A predominant adsorption of aromatic compounds occurs on the skin of fruits and the transfer to the pulp is almost inexistent.

Différentes études ont montré que les facteurs liés au mode de vie, de même que le vieillissement ou l’amélioration des tests de diagnostic et de screening, ne peuvent à eux seuls expliquer l’incidence croissante des cancers dans les pays dits industrialisés. Bien que des changements de comportements aient conduit à une diminution du nombre de cancers en France, l’incidence des carcinomes hépatocellulaires est toujours en augmentation. D’autres facteurs oncogéniques, tels que l’exposition à des cancérogènes de l’environnement pourraient intervenir. Parmi ceux-ci, les hydrocarbures aromatiques polycycliques (HAP), dont le benzo[a]pyrène (B[a]P) est le chef de file, et qui sont retrouvés notamment dans la fumée de cigarette, les gaz d’échappements ou les aliments grillés, constituent une priorité en termes de santé publique du fait de leurs effets cancérogènes. Une caractéristique-clé commune à tous les cancers a trait à leur métabolisme énergétique particulier, basé sur la glycolyse. Cependant, rien n’est connu quant à une possible reprogrammation métabolique due aux HAP. L’objectif global de mon projet de thèse a donc été d’étudier l’impact in vitro du B[a]P, utilisé à faible concentration, sur le métabolisme énergétique, de préciser le rôle de la reprogrammation métabolique dans le contrôle de la balance survie/apoptose par le B[a]P et de caractériser les mécanismes cellulaires et moléculaires impliqués. Nous avons d’abord identifié une production de monoxyde d’azote (NO) résultant de l’activation de la iNOS par le B[a]P, et agissant comme un signal de survie, possiblement via une hyperpolarisation mitochondriale. Nous avons ensuite démontré que le B[a]P induit une reprogrammation métabolique des cellules en favorisant un métabolisme glycolytique au détriment de la phosphorylation oxydative. Enfin, nous avons identifié IF1, l’inhibiteur physiologique de la F0F1ATPase, comme une nouvelle cible des HAP, participant à la reprogrammation métabolique et capable de promouvoir la survie sous l’effet du B[a]P. Au total, nous montrons que ces altérations du métabolisme mitochondrial promues par le B[a]P, sont à l’origine de signaux de survie dans notre modèle de cellules épithéliales hépatiques F258. Ces mécanismes pourraient ainsi contribuer à la progression tumorale sous l’effet des HAP. / Various studies have shown that factors related to lifestyle (smoking, diet, etc.), as well as aging or even the improved efficiency of diagnostic and screening tests, cannot explain by themselves the rising incidence of cancers in the industrialized countries. Although evolution of behaviors has helped reducing the number of cancers in France, the incidence of hepatocellular carcinomas is still increasing. This alarming result could be related to other oncogenic factors such as chronic exposure to environmental carcinogens. Among these compounds, polycyclic aromatic hydrocarbons (PAHs), including benzo[a]pyrene (B[a]P), the prototype carcinogen of this family, especially found in cigarette smoke, exhaust fumes or grilled food, are a priority in terms of public health due to their high carcinogenic potential. A key feature of cancer cells is related to their predominant glycolytic metabolism. However, nothing is known yet about a possible metabolic reprogramming upon PAH exposure. My PhD project has aimed at characterizing the impact of a low B[a]P concentration on energy metabolism, at clarifying the role of such a metabolic reprogramming in cell fate determination, and at elucidating the cellular and molecular basis of this phenomenon. We first identify a production of nitric oxide (NO), involving the activation of iNOS by B[a]P, and acting as a survival signal. We then demonstrate that B[a]P induces a metabolic reprogramming, thus promoting a glycolytic metabolism at the expense of oxidative phosphorylation. Finally, we identify IF1, the physiological inhibitor of the F0F1ATPase as a new target of PAHs, which participates in the B[a]P-elicited metabolic reprogramming and survival. To sum up, we identify new alterations of mitochondrial metabolism, acting as survival signals in B[a]P-treated rat hepatic epithelial F258 cells. These mechanism could therefore contribute to tumor progression.

De nombreux sites pollués par des hydrocarbures aromatiques polycycliques (HAP) sont recensés dans les pays industrialisés. Associés aux 16 HAP US-EPA réglementaires, d’autres composés aromatiques polycycliques (CAP), notamment les CAP polaires (oxygénés et azotés) sont présents. Ils proviennent des mêmes sources que les HAP et peuvent être également formés par des processus biotiques ou abiotiques de transformation des HAP (atténuation naturelle ou procédés de dépollution). Ces CAP, plus polaires que les 16 HAP US EPA, sont plus solubles dans l’eau, induisant potentiellement une mobilité accrue dans les sols et de ce fait un risque pour l’Homme et l’environnement. Il est donc indispensable d’enrichir nos connaissances sur la mobilité des CAP polaires dans les sols et leur transfert vers les eaux souterraines. Ainsi l’objectif de ce projet était d’identifier les mécanismes contrôlant la mobilisation des CAP polaires dans les sols en relation avec les 16 HAP US EPA, et leurs modes de transfert en combinant approches laboratoire et in situ. Nos travaux confirment une mobilisation préférentielle des CAP polaires par rapport aux HAP. La mobilisation dans les sols des CAP polaires ainsi que celle des HAP de faible poids moléculaire est essentiellement pilotée par des processus de dissolution des goudrons (loi de Raoult). Néanmoins, alors que les prédictions de mobilisation des CAP polaires sont satisfaisantes dans le cadre de pollutions « fraiches », un paramètre fondamental doit être pris en compte pour les pollutions historiques ayant subi un effet d’aging : la disponibilité. En effet, quelles que soient les conditions de mobilisation (statique-batch ou dynamique-colonne) la teneur en CAP dans les eaux est fortement dépendante de la disponibilité de la pollution. De plus, pour une forte disponibilité des CAP, les autres paramètres testés (force ionique, température) ont une influence limitée sur la mobilisation alors que pour une faible disponibilité, ils peuvent avoir une influence notable. Par ailleurs, la mobilisation des CAP polaires par les colloïdes semble limitée alors qu’elle est prépondérante pour les HAP de hauts poids moléculaires notamment dans le cas d’une eau présentant une force ionique faible. Les essais réalisés sur une colonne lysimétrique (2 m3) remplie avec une terre de cokerie contaminée au 2/3 supérieure et avec une terre prélevée sur le même site mais non contaminée pour le 1/3 inferieur confirment une mobilisation des CAP selon un mécanisme de dissolution des goudrons avec toutefois des concentrations largement inférieures à celles prédites par la loi de Raoult. Aux différentes échelles expérimentales utilisées (batch, colonnes de laboratoire et lysimétrique), il a été clairement mis en évidence que la composante biologique a une influence très forte. Ainsi, une fois sous forme dissoute, les HAP mais également les CAP polaires sont fortement biodégradés sans que des sous-produits (notamment CAP oxygénés) n’aient pu être détectés / In industrial countries, many sites have been diagnosed polluted by polycyclic aromatic hydrocarbons (PAHs). In addition to the regulated 16 US-EPA PAHs, other polycyclic aromatic compounds (PACs), especially polar PACs (oxygenated and nitrogenated) occur. They come from the same sources as PAHs but they may also be formed due to PAH degradation under biotic or abiotic processes (natural attenuation or remediation treatment). These PACs, more polar than the 16 US-EPA PAHs, are more soluble in water, resulting in a potentially increased mobility in soils and a higher risk for Humans and Environment. Thus, there is a need to increase our knowledge on polar PAC mobility in soils and their transfer to the groundwater. Combining laboratory and in situ works, this project aimed at identifying the mechanisms involved in the release and transfer mode of polar PACs in soils compared to the 16 US-EPA PAHs. Our works confirm a preferential release of polar PACs compared with PAHs. Polar PACs and low molecular weight PAHs (LMW-PAHs) are mainly released according to a coal tar dissolution mechanism (Raoult law). While satisfactory predictions are obtained for polar PAC release when the pollution is “fresh”, availability is a major parameter that needs to be taken into account for historical contamination impacted by aging. Indeed, whatever the leaching conditions (static-batch and dynamic-column), the PAC concentration in water is highly dependent on the availability level of the pollution. In addition, for a high level of PAC availability, the other parameters studied in the project (ionic strength and temperature) have a limited impact on the PAC release whereas at low availability level, these parameters can show a greater influence. Moreover, the PAC release in association with colloids seems limited for polar PACs but dominating for high molecular weight PAHs (HMW-PAHs), especially under low ionic strength conditions. Leaching tests performed on a lysimeter column (2 m3) filled with a contaminated soil in the 2/3 upper part and with a non-contaminated soil in the 1/3 lower part, both soils being sampled on a former coking plant site, confirm a release of PACs according to a coal tar dissolution mechanism although PAC concentrations are widely lower compared to those predicted by the Raoult law. Whatever the experimental scale studied (batch, laboratory or lysimeter column), a clear influence of the biological compartment has been evidenced. Once the PAHs and polar PACs are dissolved into water, they are highly biodegraded. No by-products - especially oxygenated PACs - were detected