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.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Polychlorinated biphenyls (PCBs) are toxic, non-biodegradable, and lipophilic chemical compounds of industrial origin. In Brazil, PCBs are still used in old electrical transformers and capacitors which were installed up to 1981 when their use and commercialization were banned. However, the permission to use devices with PCBs installed up to the early 80s was maintained up to the moment that their dielectric fluids or the entire device be fully replaced for products free of PCBs. Currently, PCBs are classified as persistent organic pollutants (POPs) because they pollute and accumulate in the environment affecting all organisms in the food chain. The main form of human intake is the ingestion of contaminated food, especially food of animal origin. Fish are the main means of transmission of PCB congeners to the human body. The concern about PCBs is centered on their toxicological potential, especially as inducers of cancer. Thus, the aim of this study was to investigate the possible contamination by residues of 11 individual PCB congeners in fresh marine fish from the state of Rio Grande do Sul (RS), Brazil. The methodology for the analysis of PCBs in fish included sampling on the coast of RS, the extraction and purification of these compounds by the use of acidified silica gel and solvents, as well as their identification and quantification using gas chromatography coupled to a micro electron capture detector (GC - μECD). Results were confirmed by gas chromatography coupled to mass spectrometry (GC - MS). PCBs investigated were not found in all samples. PCBs 28 and 52 were not detected. PCBs 153, 138, 180, 118, 101, 77, and 81 were found in 98.33 %, 95%, 93.33%, 60%, 33.33 %, and 31.67 % of the samples, respectively. PCBs 126 and 169 were found at lower frequencies, 18.33% and 15%, respectively. The individual congeners found in higher mean concentrations were PCB 153 (184.36 ng/g fat), followed by PCB 138 (159.27 ng/g fat), PCB 118 (98.16 ng/g fat), PCB 180 (69.04 ng/g fat), PCB 101 (32.99 ng/g fat), and PCB 77 (12.95 ng/g fat). PCBs 81, 126 and 169 were found in lower concentrations (4.97 ng/g, 4.49 ng/g and 2.08 ng/g fat, respectively). Results confirm the contamination by PCBs of all marine species of consumption analyzed and can be used as indicators of environmental contamination by these compounds in the coast of RS. / Bifenilos policlorados (PCBs) são compostos químicos de origem industrial, tóxicos, não biodegradáveis, lipofílicos, e que foram produzidos a partir da década de 30 até os anos 70, quando foram proibidos. No Brasil, PCBs estão presentes, por exemplo, em transformadores e capacitores elétricos instalados até 1981, quando a comercialização e utilização desses compostos foram proibidas no país. Porém, manteve-se a permissão de utilização desses equipamentos contendo PCBs e instalados até o início dos anos 80, até que ocorra a substituição integral dos mesmos ou a troca de seus respectivos fluidos dielétricos por produtos isentos de PCBs. Atualmente, PCBs são classificados como poluentes orgânicos persistentes (POPs), pois poluem e se acumulam no meio ambiente, influenciando todos os organismos da cadeia alimentar. A principal forma de contaminação humana é a ingestão de alimentos contaminados, principalmente alimentos de origem animal. Dentre esses, os pescados constituem-se no principal meio de veiculação de congêneres de PCBs até o organismo humano. A preocupação acerca dos PCBs está centrada no seu potencial toxicológico, principalmente como indutores de câncer. Diante disso, o objetivo desse trabalho foi investigar a possível contaminação, por resíduos de 11 congêneres individuais de PCBs, em pescados marinhos in natura do estado do Rio Grande do Sul, Brasil. A metodologia empregada para análise de PCBs nos pescados incluiu a coleta de amostras do litoral do RS, a extração e purificação desses compostos com a utilização de sílica gel acidificada, solventes e, finalmente, a identificação e quantificação dos mesmos utilizando-se cromatografia gasosa acoplada a um micro detector de captura de elétrons (GC-μECD). Os resultados obtidos foram confirmados por cromatógrafo gasoso acoplado à espectrometria de massas (GC-MS). Os PCBs investigados não foram encontrados em todas as amostras analisadas. Os PCBs 28 e 52 não foram detectados. O PCB 153 foi encontrado em 98,33% das amostras analisadas, seguido pelos PCBs 138 e 180 encontrados em 95% das amostras, pelo PCB 118 encontrado em 93,33% das amostras, pelo PCB 101 encontrado em 60% das amostras, pelo PCB 77 e PCB 81, encontrados em 33,33% e 31, 67% das amostras, respectivamente. Os PCBs 126 e 169 foram encontrados com menores freqüências, 18,33% e 15%, respectivamente. Os congêneres individuais encontrados em maiores concentrações médias foram o PCB 153 (184,36 ng/g de gordura), seguido pelo PCB 138 (159,27 ng/g de gordura), PCB 118 (98,16 ng/g de gordura), PCB 180 (69,04 ng/g de gordura), PCB 101 (32,99 ng/g de gordura) e PCB 77 (12,95 ng/g de gordura). Os PCBs 81, 126 e 169 foram encontrados nas menores concentrações (4,97 ng/g, 4,49 ng/g e 2,08 ng/g de gordura, respectivamente). Os resultados obtidos confirmam a contaminação por PCBs de todas as espécies marinhas de consumo analisadas e podem ser utilizados como indicativos da contaminação ambiental, por esses compostos, no litoral do RS.

This work includes two unrelated areas of research. The first portion of this work involved combusting densified refuse derived fuel (dRDF) with coal and studying the effect that Ca(0H)2 binder had on reducing polycyclic aromatic hydrocarbon (PAH) and polychlorinated biphenyl (PCB) emissions. The second area of work was directed at developing nondestructive infrared techniques in order to aid in the analysis of postage stamp adhesives. With Americans generating 150-200 million tons a year of Municipal Solid Waste (MSW) and disposing of nearly ninety percent of it in landfills, it is easy to understand why American landfills are approaching capacity. One alternative to landfilling is to process the MSW into RDF. There are technical and environmental problems associated with RDF. This work provides some answers concerning the amount of PAH and PCB emissions generated via the combustion of RDF with coal. It was found that the Ca(OH)2 binder greatly reduced both the PAH and the PCB emissions. In fact, PAH emissions at the ten-percent level were reduced more by using the binder than by the pollution control equipment. If the Ca(0H)2 binder can reduce not only PAH and PCB emissions, but also other noxious emissions, such as acid gases or dioxin, RDF technology could soon be the answer to the current landfill problems. The second portion of this work focused on developing a method to analyze stamp adhesives nondestructively. Using this method, it was fairly easy to differentiate among the three different types of adhesives that have been used by the United States Postal Service: gum arabic, dextrin, and polyvinyl alcohol. Differences caused by changes in chemicals added to the adhesives were also detected. Also, forgeries were detected with as much success, if not more, than by conventional methods. This work also led to the construction of equipment that allows large samples to be analyzed by reflectance infrared methods.

Im ersten Teil der Arbeit wird die Synthese neopentyl- und neosilylsubstituierter Phosphane zur Verwendung als Liganden in katalytisch aktiven Palladiumkomplexen beschrieben. Die Aktivität wurde in der Suzuki-Miyaura Kreuzkupplungsreaktion getestet. Während die neosilylsubstituierten Phosphane 2:1 Addukte (5b und 5d) mit geeigneten Palladiumsalzen bilden, welche moderate Katalyseaktivität zeigen, untergehen die neopentylsubstituierten Komplexe schnelle Cyclometalierungsreaktionen in Gegenwart von Basen und bilden die katalytisch wenig aktiven Palladacyclen (6a, 6e, and 6g). Die deaktivierende Cylometallierung konnte durch Darstellung der Palladiumcomplexe ausgehend von Pd(cod)Cl2 in Abwesenheit von Basen vermieden werden. Die erhaltenen 2:1 Phosphaneaddukte zeigten deutlich verbesserte Aktivität. Daraus wurde geschlossen, dass die Cyclomettalierung als Nebenreaktion eine wichtige Deaktiverungsmöglichkeit darstellt, diese Überlegung veranlasste uns Trialkylphosphane mittlerer Größe, mit Substituenten die nur schwer eine Cyclometallierungen eingehen können zu testen. Die Verwendung der Phosphoniumsalze 4h (R = Cy, R‘ = neopentyl) und 4m (R = iPr, R‘ = CH2Cy) führt zu höheren Aktivitäten in der Suzuki-Miyaura Kreuzkupplung, als bestes Katalysatorsystem hat sich die Kombination aus Pd2(dba)3 oder Pd(OAc)2 und entsprechendem Phosphoniumsalz ergeben. Im zweiten Teil dieser Arbeit werden Synthesen zu neuen biphenylbasierten Diphosphanen (70, 71, 76, and 77) vorgestellt. Die Palladiumkomplexe wurden ebenfalls auf ihre Eignung als Katalysatoren in palladiumkatalysierten Suzuki-Miyaura Kreuzkupplungen getestet und zeigen für diese Klasse von Komplexen gute Aktivität. Das Tetraphosphan 82 wurde für die Synthese des zweikernigen Palladium(II)-komplex 83 eingesetzt. Durch die Koordination des D2h-symmetrischen Tetraphosphanes an die Palladiumatome wird die Symmetrie des Moleküls erniedrigt und folglich erhält man den formal D2-symmetrischen Komplex 83. / In the first part of this thesis, the synthesis and catalytic activity of neopentyl and neosilyl substituted phosphine palladium complexes is described. The complexes have been tested in the Suzuki-Miyaura cross-coupling reaction. Whereas the neosilyl substituted phosphines form 2:1 adducts (5b and 5d) with Palladium salts which showed moderate activity, the neopentyl complexes quickly undergo cyclometallation in presence of bases to form Palladacycles (6a, 6e, and 6g) which showed only moderate catalytic activity. Cyclometallation could be avoided by the preparation starting from Pd(cod)Cl2 in the absence of bases. The obtained 2:1 phosphine adducts showed superior activity. We concluded that cyclometallation process is an important deactivation pathway, this prompted us to test trialkyl phosphine ligands with medium size but substituents not reliable to cyclometallation. We have been pleased to find that 4h (R = Cy, R‘ = neopentyl) and 4m (R = iPr, R‘ = CH2Cy) showed good activity in the Suzuki-Miyaura cross-coupling reaction. The best results have been obtained by in situ preparation of active catalyst from Pd2(dba)3 or Pd(OAc)2 and the appropriate phosphonium salt. In the second part of this thesis, the first synthesis of a new family of biphenyl based bisphosphine ligands (70, 71, 76, and 77) has been reported. Their palladium complexes were successfully tested as catalyst in the Suzuki cross-coupling reaction. Within the class of bisphosphine based palladium complexes they show good activity in Suzuki-Miyaura cross-coupling reaction. Systematically, was expanded our synthesis strategy and we were able to introduce the first synthesis of a highly symmetric 2,2',6,6'-tetraphosphinobiphenyl. Tetraphosphine 82 was used as ligand in a dinuclear palladium(II) complex 83. Upon complexation the D2h symmetric 2,2’,6,6’-tetraphosphine lead to a chiral D2 symmetric complex 83.

No description available.

No description available.

Polyklorerade bifeneyler (PCB) är en problematisk organisk förorening och består av 209 olikakongener, som sorteras beroende på antal kloratomer och dess position i bifenylmolekylen. Syftet idetta arbete har varit att utveckla studier kring de förhöjda halterna av PCB i två områden med hjälpav kongenmönster för sju av kongenerna - indikatorkongenerna (∑PCB7) - som används som enindikation av totalhalten PCB. Med hjälp av kongenmönster med de olika halterna från dataunderlaggjordes statistiska analyser med PCA och MFA i Rstudio för Oxundaområdet och Stockholmsområdet,och den statistiska analysen PMF i EPA PMF 5.0 samt en undersökning av gradienter för PCB iOxundaområdet. Ett av områdena som studeras är kring Oxundasjön, en sjö norr om Upplands Väsby som sedan år2013, efter miljöövervakning, kunnat konstateras vara ett av de mest förorenade områdena när detkommer till PCB i Sverige. Oxundaområdet har sedan dess haft ett aktivt arbete av provtagningar,undersökningar och analyser kring den troliga geografiska källan men även vad det kan tänkas varaför ursprungliga produkter och är därför ett av områdena som undersöks i detta arbete. Närmareundersökningar har visat att källan med största sannolikhet är ett före detta industriområde iUpplands Väsby, så kallade Messingen, men frågetecken finns fortfarande kring när, hur och vilkaprodukter av PCB som använts i detta område. Det andra området som undersökts ärStockholmsområdet (inklusive dess skärgård, Mälaren och närliggande insjöar), där förhöjda halter avPCB framför allt påvisats i områdena närmast Stockholms stad. Resultat visar en tydlig gradient i Oxundaområdet, med höga PCB-halter i olika undersökta matriser(sediment, biota, ytvatten) i Oxundasjön, Marängsån och Rosersbergviken, som gradvis klingar avnedströms i Mälaren. PCB-halterna uppströms Oxundasjön är betydligt lägre och en tydlig ökning avhalterna syns i Väsbyån i höjd med Upplands Väsby tätort. Därtill visades att EU:s gränsvärden försaluförd fisk överstegs i Oxundasjön, Rosersbergviken och i ett fall även Borgudden. Med hjälp av PCA kunde konstateras de ytliga sedimentproverna främst hade korrelation med delägre kongenerna (PCB28 och PCB52) men även att högklorerade PCB:er (PCB138, PCB153 ochPCB180) hade högre relativ andel i vissa djupare sediment, dessa har dock med stor sannolikhetmycket låga halter. För vattenprover visade platser också nära Messingen (Väsbyån, Ladbrodammen)mer korrelation till högklorerade PCB:er. Platser längre nedströms (Marängsån, Oxundasjön och Rosersbergviken) hade mer korrelation med lägre kongenerna för vatten, likt matrisen biota, somhade en stor majoritetkorrelation med lägre kongenerna. En trolig anledning till detta är läckage frånsediment i Oxundasjöomtrådet. I Stockholmsområdet visade biota (abborre, gädda och strömming) istället en stor blandning av kongenerna, men alla platser visade korrelation högklorerade PCB:ermedan främst platser i centrala Stockholm, innerskärgård och enstaka insjöar visade flerakorrelationer till lägre kongener. För sediment visades främst korrelation med lägre kongener i Stockholmsområdet. PMF (positiv matrisfaktorisering) användes för att närmare se korrelationer med matriserna vattenoch sediment i Oxundaområdet till sju kongensammansättningar av Aroclor. För vatten visades starkkorrelation till Aroclor 1242 (och 1016) medan flertalet sediment (uppströms och i Oxundasjön)visade störst korrelation till Aroclor1260. Aroclor1242 och 1016 är de vanligaste Aroclor (64% av allproduktion av Aroclor) medan Aroclor1260 i tidigare har setts vara en av den mest persistentaAroclor i naturen, vilket kan vara förklaring till dessa resultat i Oxundaområdet. Vidare efterforskningar behöver göras för att säkerhetsställa vilka produkter som utgör källor till PCB-kontamineringen av Oxundaområdet, med fler produkter att jämföra med samt med fler kongenerän indikatorkongenerna, framför allt i vidare studier med PMF. För Stockholmsområdet behövs flerstudier där områdena delas upp, och jämföra potentiella geografiska källor till olika kongenmönster.För bättre förståelse av PCB och dess kongenmönster hade PMF för båda områdena varit lämpligmed ett större kongenuppsättning, speciellt för biota som är en av de mesta komplexa matriserna förföroreningar på grund olika faktorer av den här typen av analyser.

Caspian terns (Hydroprogne caspia) and double-crested cormorants (Phalacrocorax auritus) nest in large colonies on East Sand Island in the Columbia River estuary, the largest known colonies for the two species in the world. Both species of piscivorous colonial waterbirds have been identified as predators with a significant impact on the survival of juvenile salmonids (Oncorhynchus spp.) listed under the U.S. Endangered Species Act. To better understand and address issues related to seabird-fisheries interactions in the Columbia River estuary, I conducted studies related to the ecology, conservation, and management of these two species of piscivorous waterbirds. I evaluated the demographics and inter-colony movements of Caspian terns belonging to the Pacific Coast metapopulation, with special emphasis on two breeding colonies, one on East Sand Island in the Columbia River estuary and the other on Crescent Island in the mid-Columbia River, based on re-sightings of color-banded individuals. Apparent annual adult survival at both colonies was high, and age at first reproduction was greater than previously reported for the species. Colony site philopatry of breeding adults at both colonies was high; however, some individuals prospected for breeding colonies over much of the Pacific Coast region and moved to other colonies over distances of up to 3,000 km. Some terns from the large colony in the Columbia River estuary responded quickly to the availability of new colony sites as distant as 550 km from the estuary, and established successful breeding colonies within less than a year of the new sites becoming available. The Caspian tern colony on East Sand Island appears to be an important source colony for a number of smaller, less productive colonies distributed over an extensive area from the Salton Sea, California to the Copper River Delta, Alaska, an area with limited and ephemeral nesting opportunities. Environmental contaminants have been a conservation concern for wildlife in the Columbia River estuary, especially species that consume fish and are therefore likely to bioaccumulate persistent organic pollutants. I measured and compared levels of polychlorinated biphenyls (PCBs) in eggs and chicks of Caspian terns and doublecrested cormorants, as well as their primary prey fish types, at colonies on East Sand Island and farther up-river. Based on differences in tern and cormorant diet composition at the various study colonies, higher PCB levels in eggs and chicks were associated with diets dominated by resident freshwater and estuarine fishes. PCB levels in prey fish were positively correlated with lipid content; however, PCB levels in the livers of chicks were negatively correlated with chick fat scores, suggesting that chick fat reserves are a sink for ingested PCBs. Lower PCB levels in terns and cormorants from East Sand Island compared to colonies farther up-river reflected diets with a higher proportion of marine forage fishes at East Sand Island; marine forage fishes had lower average levels of PCBs than their resident freshwater and estuarine counterparts. In order to explore non-destructive techniques for managing nesting colonies of double-crested cormorants, I evaluated habitat enhancement and social attraction, two techniques that have proven effective for relocating Caspian tern colonies to sites where impacts on fish stocks of conservation concern would be minimal. Cormorants were attracted to nest and successfully raised young at test plots on East Sand Island and on islands in the estuary with a previous history of cormorant nesting or unsuccessful nesting attempts. On an island with no history of cormorant nesting or prospecting, however, no cormorants were attracted to nest. My results suggest that attraction of nesting cormorants using these techniques is dependent on the previous history of cormorant nesting or nesting attempts, the frequency and intensity of disturbance by potential predators, and the presence of breeding cormorants nearby. While habitat enhancement and social attraction have potential as methods for redistributing nesting cormorants away from areas where fish stocks of concern are highly susceptible to predation, successful establishment of new colonies using these techniques will likely require a focus on sites with a history of cormorant nesting. Findings from this dissertation raise some concerns over the management of Caspian tern and double-crested cormorant colonies on East Sand Island in order to redistribute parts of these colonies to alternative sites and mitigate the impact of those piscivorous colonial waterbirds on ESA-listed salmonids. East Sand Island has supported source colonies of piscivorous colonial waterbirds for many smaller colonies throughout the region and is close to an abundant and relatively uncontaminated food supply. Also, alternative colony sites that can substitute for East Sand Island are not readily apparent, especially for double-crested cormorants. Therefore, management of Caspian tern and double-crested cormorant colonies on East Sand Island to benefit Columbia Basin salmonids needs to proceed cautiously and reversibly because of the implications for the region-wide populations of these piscivorous colonial waterbirds. / Graduation date: 2012

Les biphényles polychlorés (BPC) sont des contaminants de l’environnement, omniprésents dans la chaîne alimentaire, qui ont une propension à la bioaccumulation dans le corps humain. Ils traversent la barrière placentaire et sont suspectés d’induire des altérations du développement mental ou moteur chez des enfants exposés aux BPC pendant la vie intrautérine. Ces effets s’expliqueraient notamment par la capacité des BPC à perturber l’homéostasie de la fonction thyroïdienne chez la femme enceinte ou le nouveau-né. Malgré le nombre considérable d’études épidémiologiques réalisées, la relation entre l’exposition prénatale aux BPC et les altérations du développement mental et moteur ou de la fonction thyroïdienne n’a pas encore été clairement établie ; d’une part, différents bioindicateurs de l’exposition ont été employés (différents congénères de BPC mesurés et différentes matrices biologiques ou unités de mesure) limitant la comparaison directe entre les études et, d’autre part, le lien de causalité entre les BPC et les effets ciblés n’a pas été vérifié avec des critères épidémiologiques reconnus. Cette étude a été réalisée afin d’analyser la relation « concentration biologique de BPC – effet » entre l'exposition aux BPC de la mère pendant la grossesse et le développement mental et moteur de l’enfant ainsi que les paramètres de la fonction thyroïdienne chez la femme enceinte et le nouveau-né à partir d’une analyse systématique des études épidémiologiques disponibles en standardisant les données biologiques entre les études. Sur la base de considérations toxicocinétiques et en appliquant des facteurs de conversion établis à partir de la littérature épidémiologique publiée, les concentrations des BPC rapportées dans les différentes études revues ont été standardisées en termes d’équivalent de BPC totaux par kilogramme de lipides dans le plasma maternel (µg PCBMPEQ/kg de lipides). Afin d’analyser la possibilité d’une association causale entre l’exposition aux BPC et les effets d’intérêt, les critères de Hill ont été appliqués systématiquement à l’ensemble des associations « concentrations biologiques standardisées – effet ciblés ». En appliquant cette approche aux données publiées de 20 études épidémiologiques sur la relation entre les BPC et le poids à la naissance, l’exposition prénatale aux BPC, aux niveaux décrits (moyenne < 1920 µg PCBMPEQ/kg de lipides), n’apparaît pas associée de manière significative à un poids à la naissance inférieur à 2500 g dans les populations étudiées. Par ailleurs, en considérant des études menées sur le suivi de neuf cohortes d’enfants, la probabilité qu’une altération cognitive ou motrice cliniquement significative, qui persiste entre la naissance et l’âge scolaire, soit observée à des concentrations de BPC totaux inférieures à 1000 µg PCBMPEQ/kg de lipides semble faible. Aussi, à partir de l’analyse systématique des données de 17 études épidémiologiques, l’exposition aux BPC aux niveaux standardisés décrits (moyenne < 1000 µg PCBMPEQ/kg de lipides) ne semble pas induire de variation des hormones thyroïdiennes ou de TSH en dehors des intervalles physiologiques reconnus chez la femme enceinte et le nouveau-né. Ainsi, la valeur biologique de référence établie à 1000 µg PCBMPEQ/kg de lipides pour prévenir les effets sur le développement devrait aussi prévenir les effets sur le poids à la naissance et la fonction thyroïdienne chez la femme enceinte ou le nouveau-né. Les résultats présentés dans cette thèse fournissent aux autorités de santé publique responsables de l’établissement de directives et des normes de l’information utile à la révision des critères sanitaires visant à protéger des effets des BPC sur le développement de l’enfant et la fonction thyroïdienne chez la femme enceinte et le nouveau-né. / Polychlorinated biphenyls (PCBs) are persistent organic pollutants (POPs) ubiquitously present in the food chain, and with a propensity to bioaccumulate in the human body. They can cross the placental barrier and are suspected of inducing mental and motor development alterations in children prenatally exposed to PCBs. These contaminants could injure brain development by disrupting thyroid homeostasis in pregnant women or newborns. Despite the large number of epidemiological publications on PCBs, “biological concentration – response” relationships between PCB exposure and mental and motor development or thyroid function in pregnant women and newborns are not well established; a direct comparison of biological levels between published studies is limited by the heterogeneous biological PCB measurements (different PCB congeners or groups of congeners measured, variations in biological matrices sampled or units chosen to express biological results), and causal relationship between PCBs and a studied effect has not been verified with recognized epidemiological criteria. This research was performed to analyze “biological PCB concentration – effect” relationship between prenatal PCB exposure and children mental and motor development as well as parameters of thyroid function in pregnant women and newborns by conducting a systematic analysis of available epidemiological studies and by standardizing biological data between studies. Reported PCB concentrations in the different reviewed studies were standardized in terms of total PCB equivalent per kilogram of lipids in maternal plasma (µg PCBMPEQ/kg of lipids), by taking into account PCB toxicokinetics and using conversion factors based on published epidemiological data. To analyze a possible causal association between PCB exposure and studied effects, Hill criteria were consistently applied to all “standardized biological concentrations – response” associations. The systematic analysis of “standardized biological concentration – birth weight” relationship across 20 reviewed studies did not show any association between prenatal exposure to PCBs at the described levels (mean < 1920 µg PCBMPEQ/kg de lipids) and abnormal birth weight (< 2500 g). Furthermore, combining data from nine children cohorts to assess the “standardized biological concentration – development” relationship during follow-up of each cohort showed that risk of mental or motor development should be negligible for prenatal PCB concentrations below ≈ 1000 µg/kg of lipids in maternal plasma. Also, the systematic analysis of data from 17 epidemiological studies indicated that the weight of evidence of a significant impact of PCB exposure on TSH and thyroid hormone levels was low at reported levels in pregnant women and newborns (mean < 1000 µg PCBMPEQ/kg de lipids). The PCBMPEQ biological reference value of 1000 µg/kg lipids that should prevent neurodevelopmental effects should also prevent effects on birth weight and on thyroid function in pregnant women or newborns. Results presented in this thesis should provide useful information to public health authorities for the revision of guidelines and standards ensuring protection from PCB effects on child development and thyroid function in pregnant women and newborns.

Le cancer du sein est le plus fréquent des cancers de la femme. Son incidence n’est expliquée que partiellement par les facteurs de risque bien établis comme les facteurs reproductifs, hormonaux ou génétiques. Plusieurs éléments suggèrent l’existence de facteurs de risque environnementaux, tels que les polluants organochlorés persistants connus comme perturbateurs endocriniens. Les objectifs de ce travail sont : d’étudier les niveaux d’exposition, et leurs déterminants, au DDE (principal métabolite de l’insecticide DDT) et aux polychlorobiphényles (PCB) ; d’estimer par une modélisation pharmacocinétique à base physiologique (PBPK) les niveaux d’exposition au PCB-153 à la période péri-pubertaire qui constitue une fenêtre de susceptibilité accrue de la glande mammaire aux agents environnementaux ; d’étudier le rôle du DDE et du PCB-153 dans le risque de cancer du sein, à la fois à partir de prélèvements sanguins actuels et, pour le PCB-153, à partir de niveaux estimés à la période péri-pubertaire.Ce travail a été effectué à partir de l’étude CECILE, étude cas-témoins en population générale incluant 1055 témoins et 1080 cas de cancer du sein diagnostiqués de février 2005 à mars 2008 dans les départements d’Ille-et-Vilaine et de Côte d’Or chez lesquels un prélèvement sanguin a permis d’effectuer des dosages de p,p’-DDE et de PCB-153. La modélisation PBPK mise en place en coopération avec une équipe de toxicologues canadiens a permis de simuler des profils toxicocinétiques vie entière de PCB-153 et d’estimer les niveaux d’exposition au cours de la puberté. Cette modélisation est basée sur les niveaux mesurés au moment de l’enquête, les facteurs individuels de variation (poids, taille, grossesses, allaitement) connus d’après le questionnaire et la courbe de contamination environnementale au cours du temps.Les niveaux de contamination biologique observés sont plus faibles que ceux rapportés précédemment dans les populations occidentales. Nous montrons également que les principaux facteurs prédictifs des niveaux sériques de p,p’-DDE et de PCB-153 chez les femmes incluent l’âge, les habitudes alimentaires, le poids et ses variations au cours du temps, les grossesses et l’allaitement, et le lieu de résidence. Nous n’observons pas d’association entre les niveaux de p,p’-DDE et le risque de cancer du sein, mais une association inverse apparaît pour les cancers du sein de type négatifs pour les récepteurs hormonaux. Nous observons également une association inverse avec les niveaux de PCB-153 chez les femmes de 50 ans et plus. L’association inverse est renforcée lorsque les niveaux sont estimés pour la période péri-pubertaire à l’aide des modèles PBPK chez les femmes de la génération 1951-1960, correspondant à la cohorte de naissance des femmes de plus de 50 ans ayant connu les expositions aux PCB les plus élevées durant leur puberté.Plusieurs mécanismes biologiques pourraient expliquer l’association inverse observée entre le cancer du sein et l’exposition aux PCB. Ces résultats doivent être confirmés par des études tenant compte des fenêtres de susceptibilité de la glande mammaire et constituent une piste intéressante à approfondir. / Breast cancer is the most frequent cancer in women. Its incidence is only partially explained by well-established risk factors as reproductive, hormonal or genetic factors. It has been suggested that endocrine disrupting chemicals such as persistent organochlorine pollutants also play a role in breast cancer. The objectives of this study were: to assess exposure levels to DDE (main metabolite of DDT) and to polychlorobiphenyls (PCBs), and to explore their determinants; to estimate PCB-153 levels during the puberty using physiologically-based pharmacokinetic (PBPK) models, as this period of life constitutes a critical exposure window with increased susceptibility to carcinogens; to study the associations between breast cancer risk and separately DDE, PCB-153 measured at the time of diagnosis, and PCB-153 levels estimated during puberty.The analyses were based on data from the CECILE study, a population-based case-control study including 1055 controls and 1080 breast cancer cases who gave a blood specimen. The cases were diagnosed from February 2005 to March 2008 in two French administrative areas (Ille-et-Vilaine and Côte d’Or). p,p’-DDE and PCB-153 serum levels were measured. PBPK modeling allowed simulating PCB-153 lifetime toxicokinetic profiles and estimating exposure levels during puberty. These PBPK models were based on blood measurements at the time of recruitment in the study, on individual characteristics elicited from the questionnaire (weight, height, pregnancies, breastfeeding) and on the curve of environmental contamination by PCBs estimated since the 1930’s. The levels of biological contamination were lower than those previouly reported in Western populations in earlier periods. The main predictive factors of p,p’-DDE and PCB-153 serum levels included age; dietary habits; weight and its variations; pregnancies and breastfeeding; and residence area. We did not observed any association between p,p’-DDE levels and the risk of breast cancer, but an inverse association was observed for estrogen receptor-negative breast cancers. We also observed an inverse association of breast cancer with PCB-153 among women above 50 years. This inverse association was reinforced when considering PCB-153 levels estimated during peripubertal period from PBPK models, particularly among women born in 1951-1960, a birth cohort with peak exposure to PCB-153 during puberty. Biological mechanisms explaining the observed inverse association between breast cancer and PCB exposure are considered. These findings should be confirmed by further studies.