Environmental exposure levels are often sufficiently disparate between populations such that there is little or no overlap, complicating our ability to ascertain the full dose-response curve and as such create informed regulatory policy.I reviewed the literature on methods available to address non- and partially-overlapping exposure distributions, drawing from both epidemiology as well as other relevant disciplines to describe the universe of proposed solutions. I also used the case study of maternal PCB-153 exposure and birthweight, utilizing real-world and simulated data to explore our ability to ascertain “true” dose-response curves from observational data given the limited cohort-specific exposure ranges. I investigated the importance of controlled and uncontrolled confounding as well as the impact of sample size on our ability to ascertain a “true” underlying dose-response curve. Pooling and meta-analysis were useful to increase the heterogeneity of exposure distributions despite imperfect confounding control and heterogenous confounding structures across cohorts. The analyses also serve as continued evidence of the challenges of making population-wide inferences from study samples with restricted exposure ranges as well as the danger of pooling multisite data without sufficiently accounting for heterogeneity in both exposure level and distribution of confounders. These results highlight the limitations of using both individual studies and systematic reviews of environmental chemicals, and emphasize the need for pooling and meta-analysis to widen exposure distributions that in turn permit us to accurately capture the negative effects of these environmental chemicals.

The gut microbiota plays a major part in maintaining the health of a human host. Countless of crucial functions in the body, including immune responses, cell signaling and energy metabolism to name a few, are conducted by the gut microbiota and its metabolites. Accordingly, it is of interest to gain knowledge on what can alter the gut microbiota, as these alterations by extension can give rise to adverse health effects. In this study, the impact of polychlorinated biphenyl (PCB)- and organochlorine pesticide (OCP) exposure on tricarboxylic acid (TCA) cycle metabolites, short-chain fatty acids (SCFAs) and bile acids, as well as other polar and semi-polar metabolites, which are all related to the gut microbiota, were investigated. An in vitro fermentation of faecal samples exposed to a PCB/OCP mixture was performed, and liquid chromatography-time of flight mass spectrometry (LC-qToF-MS) targeted and non-targeted approaches were applied to the extracts. The results obtained suggested that PCBs and OCPs most likely have an effect on the levels of several features of the gut metabolome with either increased or decreased levels upon exposure. Bile acids and TCA metabolites appear to follow a trend of decreasing levels, while no apparent effects could be seen for the SCFAs. Furthermore, distinct concentrations of the PCB/OCP mixture appear to induce different changes in gut microbiota functioning, which highlights the importance of performing dose-response studies when exploring biological effects of these compounds. The identification of different metabolite profiles during fermentation also allows for the possibility of further investigation of potential biomarkers to assess PCB/OCP exposure.

No description available.

No description available.

The ability of Chromolaena odorata propagated by stem cuttings and grown for six weeks in the greenhouse to thrive in soil containing different concentrations of PCB congeners found in Aroclor and transformer oil, and to possibly remediate such soil was studied under greenhouse conditions. Chromolaena odorata plants were transplanted into soil containing 100, 200, and 500 ppm of Aroclor and transformer oil (T/O) in 1L pots. The experiments were watered daily at 70% moisture field capacity. Parameters such as mature leaves per plant, shoot length, leaf colour as well as the root length at harvest were measured. C. odorata growth was negatively affected by T/O in terms of shoot length and leaf numbers, but no growth inhibition was shown by Aroclor. At the end of six weeks of growth, Plants size was increased by 1.4 and 0.46%, but decreased at -1.0% in T/O, while increases of 45.9, 39.4 and 40.0% were observed in Aroclor treatments. Mean total PCB recoveries were 6.40, 11.7, and 55.8μg in plants tissues at Aroclor treated samples resulting in a percentage reduction of PCB from the soil to 2.10, 1.50, and 1.10 at 100, 200, and 500mg/kg Aroclor treatments respectively. There was no PCB recovery from plants in transformer oil treatments as a result of its inhibition to growth. Root uptake was found to be the probable means of remediation of PCB-contaminated soil by C. odorata, this was perhaps aided by microbes. This study has provided evidence on the ability of C. odorata to remediate PCB contaminated soil. However, the use of C. odorata for phytoremediation of PCB contaminated soil under field condition is therefore advised. / Environmental Sciences / M.Sc. (Environmental Science)

This thesis examines fatty acid (FA) and polychlorinated biphenyl (PCB) dynamics in a marine top predator, the grey seal (Halichoerus grypus,) and their transfer during lactation from mother to offspring. It examines regional and annual variations in FA composition and PCB loads, and also how the physical and chemical characteristics of these molecules (e.g. their polarity and size) can affect the rates of accumulation, mobilization and transfer of specific FAs or PCBs. Two UK grey seal colonies (North Rona (NR) and Isle of May (IOM) were studied during three consecutive years (1996-1998 and 2004-2006). Lactating grey seals and their pups were repeatedly captured during the lactation period and sampled for blubber, serum and milk and analysed for FAs and PCBs. Overall, the two colonies were clearly distinguished from each other, suggesting that the main prey species had different FA composition, and possibly that the seals from these colonies had different diets . These differences are probably a direct consequence of differences in prey community structure in the two regions where seals from these two colonies are thought to feed. Within each colony, annual differences could be detected between some years but not between others. During 1996-98, IOM seals showed a clear change in their FA profiles while NR seals did not. In contrast, during 2004-2006 NR seals showed a clear change while IOM seals did not. The changes observed in IOM during 1996-1998 are consistent with the large-scale regime shift that occurred in the North Sea during the 1990‟s. The relative proportions of each FA that were mobilized from blubber and transferred to the milk during lactation were very similar between colonies, and could be explained to a large degree by their physico-chemical properties. For a given carbon chain length the mobilization increased with increasing number of double bonds; and for a given number of double bonds the mobilization decrease with increasing carbon chain length. However, the mobilization also appeared to be influenced by the specific nutritional requirements of the growing pups. For instance, FAs that are considered essential for pup development or efficient energy storage (e.g. saturated FAs) were more highly mobilised than expected. This selectivity was also reflected in the FA composition of the different body compartments (maternal blubber and milk, pup blubber) that persisted throughout lactation. These changes were also similar between the colonies. Colonies could also be clearly distinguished by their blubber PCB profiles. IOM seals had higher total concentrations on average than NR seals (1327.9 vs. 680.2 ng/g lipid in 2005 and 1199.7 vs. 819.0 ng/g lipid in 2006). IOM seals also had higher total amounts in both years (79.2 vs. 38.0 mg in 2005 and 61.7 vs. 53.4 mg in 2006). One of the main differences between colonies was that females from IOM had higher concentrations of highly chlorinated congeners than NR seals. PCB concentrations in blubber increased towards the end of lactation. Serum and milk PCB concentrations also increased rapidly, especially for the highly chlorinated congeners. These results were consistent with other studies showing the increase in concentrations as a result of lipid loss. Serum concentrations stayed constant during the first part of lactation and increased at late lactation. This was also observed in milk PCB concentrations. The changes in the PCB profiles in the three body compartments were very similar between colonies. However IOM seals always had higher total concentrations of PCBs in all of the body compartments. The concentrations of individual congeners relative to PCB-153 showed that blubber contained higher proportions of the highly chlorinated PCBs relative to other tissues. There were no clear changes in these proportions in blubber during lactation, but the relative proportions of highly chlorinated PCB In serum and milk increased throughout lactation while the less chlorinated PCBs stayed constant. The highly chlorinated PCBs were found in lower concentration in the milk compared to the less chlorinated compounds suggesting a selective release from blubber to blood and a selective transfer of PCBs to the milk.

Depuis plusieurs dizaines d’années, la population des anguilles européennes a souffert d’un dramatique déclin et est classée parmi les espèces hors de leurs limites biologiques depuis 1998. Différents phénomènes, tels que la pêche, les obstacles aux migrations, ou le réchauffement climatique, en sont à l’origine. Cependant, les perturbations environnementales, telles que les contaminations métalliques et organiques ou les épisodes d’hypoxie, participent probablement à la vulnérabilité de cette espèce. Or, l’estuaire de la Gironde est soumis à des contaminations poly-métalliques historiques, ainsi qu’à des contaminations organiques de différentes origines, et à des épisodes hypoxiques réguliers. Les travaux menés au cours de cette thèse, se sont donc composés d’études de terrain visant à identifier les contaminants majeurs chez les anguilles jaunes de l’estuaire de la Gironde, ainsi que leur voie de bio-accumulation et leurs impacts au niveau physiologique, biochimique et moléculaire. Ces études ont nécessité la mise en place d’expériences préliminaires ayant pour objectifs de vérifier les impacts de certaines procédures, telles que l’anesthésie et la mise en cage des anguilles jaunes. D’autre part, les impacts des deux principaux contaminants métalliques et organiques des anguilles européennes de l’estuaire de la Gironde, ont été testés, de façon individuelle et combinée, ainsi que ceux de l'hypoxie sur des anguilles pré-contaminées ou non, lors d’une étude expérimentale.Ainsi, ces travaux ont mis en évidence que les anguilles européennes installées dans la zone avale de l’estuaire, étaient susceptibles d’être soumises à des contaminations poly-métalliques plus importantes, essentiellement d’origine trophique, responsables d’une croissance pondérale moins élevée et de perturbations transcriptionnelles hépatiques et cérébrales. De plus, bien que les contaminations métalliques de ces anguilles ne mettent pas ne danger la santé humaine, les contaminations en PCB sont, en revanche, supérieures aux normes de consommation. D’autre part, ces travaux ont également mis en évidence des dérèglements mitochondriaux ainsi qu’un stress oxydant, au niveau branchial et cérébral chez des anguilles contaminées au Cd, et au niveau cérébral, branchial, hépatique et rénal chez les anguilles contaminées aux PCB. Enfin, la concomitance de ces deux contaminants et/ou d’un épisode d’hypoxie, réduit et/ou retarde les capacités de réponses transcriptionnelles de ces anguilles. Il semble donc que les différentes perturbations chimiques subies par les anguilles européennes au stade jaune au sein de l’estuaire de la Gironde participent de façon non négligeable à la vulnérabilité de cette espèce. / For several decades, the European eel has been suffering from a dramatic decline and has been classified among species beyond their biological limit since 1998. Different phenomena, as fishing, migration barriers, or global warming, are to blame. Environmental perturbations, as metallic and organic contaminations, or hypoxic episodes, probably take part to the vulnerability of this species. The Gironde estuary has been submitted to historic poly-metallic contaminations, to organic contaminations from different origins, and to regular hypoxic episodes. This thesis work is composed of field studies aimed to identify the main contaminants in yellow eel living in the Gironde estuary, their major bioaccumulation way and impacts on physiological, biochemical and molecular parameters. These studies needed preliminary experiments aimed to verify whether some field and handling procedures are consistent with ecotoxicological analyses. Moreover, impacts of the two main contaminants in European eels from the Gironde estuary have been assessed individually or combined, with those of hypoxia on pre-contaminated eels.Thus, these studies have demonstrated that European eels installed in the downstream area of the estuary, were likely to be subject to largest poly-metallic contaminations, mostly by food web, and responsible for a less weight gain and high liver and brain transcriptional disturbances. Furthermore, although the metal contamination of eels does not endanger human health, PCB contaminations are higher than consumption standards. On the other hand, these studies have also revealed oxidative stress and mitochondrial disorders in gills and brain of Cd-contaminated eels, and in brain, gills, liver and kidneys of PCB-contaminated eels. The combination of these two contaminants and/or an episode of hypoxia, reduces and/or delays the transcriptional responses ability of these eels. It seems that the different chemical disturbances, suffered by the yellow eels in the estuary of the Gironde, participate significantly to this species vulnerability.

Actuellement, le public et surtout dans les pays industrialisés est de plus en plus conscient du fait que la dégradation de l’environnement peut dépasser les avantages du progrès rapide dans les domaines industriels et technologiques et que des dommages sérieux et irréversibles peuvent être imposés aux futures générations. L'occurrence des POPs dans l'environnement, qui résulte essentiellement des activités anthropogéniques, est l'une des préoccupations permanentes chez les scientifiques. Ces composés ont été trouvés dans toutes les matrices environnementales telles que l'air, le sol, l'eau et les sédiments et en raison de leurs propriétés lipophiles, ils risquent de rebondir dans la chaîne alimentaire humaine. Durant cette dernière décennie, le Liban a connu une grande explosion démographique qui a été accompagnée par des activités anthropogéniques diverses. La dégradation de la qualité de l’environnement est bien ressentie par la population locale et les conséquences sur la santé humaine sont lourdes et affreuses. Les travaux de cette thèse ont permis d’évaluer concrètement l’effet de POPs sur la qualité de l’environnement au Liban, ces travaux ont abouti à la détermination des niveaux de quelques POPs les plus globalement étudiés tels que les HAPs, les PCBs et les OCPs dans les différents compartiments environnementaux au Liban. A cette fin, des protocoles d'analyse comprenant une méthode GC/MS pour la séparation et la détection des HAPs, une méthode UAE pour l'extraction des HAPs à partir du sol et des sédiments et une méthode SPE pour l'extraction des HAPs à partir de l'eau ont été développés. Ces méthodes ont été ensuite appliquées pour évaluer les niveaux de 17 HAPs dans des sols de différents usages et pour étudier la distribution de HAPs dans la phase aqueuse et les sédiments sur les côtes libanais et dans des rivières côtières et internes. Les principaux résultats ont montré que les niveaux de contamination des sols par les HAPs décroissent dans l’ordre suivant: industriels, urbains, transport et agricoles et que les sols industriels et urbains étaient 777 et 256 fois plus toxiques que les sols ruraux de référence selon l'approche TEF. De plus, l'eau et les sédiments des sites côtiers affectés par l'industrie et le transport maritime ont montré une contamination plus élevée par les HAPs. Certains échantillons de sédiments ont montré des niveaux de quelques HAPs individuels supérieures à l'ERL, ce qui pourrait occasionnellement provoquer des effets écologiques négatifs. Les travaux de cette thèse incluent aussi la détermination des niveaux des PCBs et des OCPs dans les sédiments de la rivière Litani qui est une source d’une grande préoccupation environnementale actuelle au Liban. / Currently, the public and especially in industrialized countries is increasingly aware that environmental degradation can outweigh the benefits of rapid progress in the industrial and technological fields and that serious and irreversible damage can be imposed on the future generations. The occurrence of POPs in the environment, which results mainly from anthropogenic activities, is one of the permanent concerns of scientists. These compounds have been found in all environmental matrices such as air, soil, water and sediments and because of their lipophilic properties, they are likely to rebound in the human food chain. During the past decade, Lebanon has experienced a large population explosion that has been accompanied by various anthropogenic activities. The degradation of the quality of the environment is felt by the local population and the consequences for human health are heavy and horrendous. The work of this thesis allowed to evaluate concretely the effect of POPs on the quality of the environment in Lebanon, this work led to the determination of the levels of some POPs most widely studied such as PAHs, PCBs and OCPs in the different environmental compartments in Lebanon. To this end, analytical protocols including a GC/MS method for the separation and detection of PAHs, a UAE method for the extraction of PAHs from soil and sediments and an SPE method for the extraction of PAHs from water were developed. These methods were then applied to evaluate the levels of 17 PAHs in soils of different uses and study the distribution of PAHs in the aqueous phase and sediments on the Lebanese coasts and in coastal and inner rivers. The main results showed that soil contamination levels by PAHs decreased in the following order: industrial, urban, transport and agricultural and that industrial and urban soils were 777 and 256 times more toxic than rural reference soils according to the TEF approach. In addition, water and sediments from coastal sites affected by industry and shipping have shown higher contamination by PAHs. Some sediment samples showed concentrations of a few individual PAHs greater than the ERL, which could occasionally cause negative ecological effects. The work of this thesis also includes the determination of levels of PCBs and OCPs in the sediments of the Litani River which is a source of great environmental concern currently in Lebanon.

A exposição ambiental aos poluentes orgânicos persistentes tem recebido amplo destaque na literatura recentemente devido à extensa associação entre o desenvolvimento de doenças metabólicas, obesidade e/ou diabetes mellitus, e a presença destes poluentes, principalmente os organoclorados, como as bifenilas policloradas (PCBs), no organismo. Por outro lado, os mecanismos de ação destes poluentes é controverso devido à elevada quantidade de representantes destas classes, gerando diversidade de protocolos de exposição e escassez de estudos experimentais. Por isto, foi objetivo deste trabalho elucidar os mecanismos de ação tóxica do PCB126, nas doses de 0,1; 1 ou 10 µg/kg de massa corpórea, em ratos Wistar machos, durante quinze dias, expostos por instilação intranasal. O procotolo de exposição empregado foi caracterizado e considerado suficiente para causar toxicidade, uma vez que foram observadas alterações no sistema imune, metabolismo e em parâmetros relacionados à gênese do diabetes mellitus. A caracterização da exposição foi determinada pela quantificação da concentração de PCB126 no fígado e pulmão (CG/MS) e pelo aumento da expressão do receptor aril hidrocarboneto (AhR) no rim, fígado, pulmão e tecido adiposo (Western Blot). O efeito imunossupressor do PCB126 foi evidenciado pelo comprometimento da produção de células na medula óssea e, consequentemente, no número de células totais no sangue circulante. Adicionalmente, foi evidenciada a interferência do poluente na via de ativação mediada por receptores acoplados à proteína G (GPCRs), principalmente em neutrófilos, alterando importantes funções destas células, como a expressão de moléculas de adesão, geração de espécies reativas de oxigênio e migração. Entre as alterações metabólicas observadas, destacamos o aumento dos níveis de triglicerídeos e colesterol sérico, aumento da liberação de ácidos graxos livres; aumento da atividade da enzima hepática gama glutamil transferase; aumento da resistência à insulina e aumento da geração de óxido nítrico pelas ilhotas de Langerhans, dados estes, possivelmente relacionados ao comprometimento das células beta (β) pancreáticas, confirmados pelo aumento da expressão de GLUT4 no tecido adiposo, aumento da concentração de insulina sérica e aumento do estresse oxidativo nas ilhotas de Langerhans. Em conjunto, os dados obtidos destacam importantes alterações causadas pela exposição intranasal ao PCB126, evidenciando a participação do poluente na gênese do diabetes mellitus do tipo II. / The environmental exposure to persistent organic pollutants has been widely highlighted in recent literature due to the extensive association between the development of metabolic diseases, obesity and/or diabetes mellitus, and presence of these pollutants, especially organochlorines such as polychlorinated biphenyls (PCBs) in organism. Moreover, the mechanisms of action of these pollutants are controversial due to the high number of PCBs congeners, diversity of exposure protocols and lack of experimental studies. Therefore, the aim of this study was to elucidate the mechanisms of PCB126\'s toxic action at doses of 0.1; 1 or 10 µg/kg body weight in male Wistar rats exposed by intranasal instillation for 15 days. The established exposure procotol was characterized and considered sufficient to cause toxicity since changes were observed in the immune system, metabolism and in parameters related to the pathogenesis of diabetes mellitus. Characterization of exposure was determined by quantifying the concentration of PCB126 in liver and lung (GC-MS) and by the increased expression of aryl hydrocarbon receptor (AhR) in kidney, liver, lung, and adipose tissue (Western blot). The immunosuppressive effect of PCB126 was evidenced by impairment of cell production in the bone marrow and thus the total number of cells in the circulation. In addition, the interference of the pollutant in the activation pathway mediated by G-protein coupled receptors (GPCRs), in particular in neutrophils, was observed by changing important functions of these cells such as the expression of adhesion molecules, reactive oxygen species generation, and migration. Among the metabolic changes observed, we highlight the increased levels of triglycerides and serum cholesterol, increased release of free fatty acids; increased gamma glutamyl transferase hepatic enzyme activity; increased insulin resistance and increased generation of nitric oxide by the islets of Langerhans, these data possibly related to the impairment of beta cells (β) pancreatic function, suggested by the increased expression of GLUT4 in adipose tissue, increased serum insulin concentration and increased oxidative stress in the islets of Langerhans. Altogether, these results highlight important changes caused by intranasal exposure to PCB126, suggesting participation of the pollutant in the genesis of diabetes mellitus type II.

O Pinguim-de-Magalhães, Spheniscus magellanicus, é o mais abundante dos pinguins que vivem em regiões temperadas da América do Sul, sendo um bom indicador de poluição ambiental. Poluentes orgânicos persistentes (POPs) foram detectados em fígado de Pinguins-de-Magalhães encontrados debilitados ou mortos nas praias do Brasil (Rio de Janeiro, São Paulo, Santa Catarina e Rio Grande do Sul) entre 2008 - 2012 e, do Uruguai e do Chile, em 2011. Os bifenilos policlorados (PCBs) predominaram em relação aos pesticidas organoclorados (DDTs ∼ HCB ∼ Drins) e aos éteres difenilos polibromados (PBDEs). O contaminante emergente fipronil não foi detectado apesar de seu uso na América do Sul. Entre os PCBs predominaram os congeneres penta, hexa e heptaclorados. Concentrações de POPs foram similares entre as áreas de migração e reprodução exceto para os PCBs que foram relativamente maiores na área de reprodução. Avaliação temporal (2008 - 2012) de POPs apresentou constância para os pesticidas organoclorados e tendência ao declínio para os PCBs. A glândula uropigiana de Pinguim-de-Magalhães mostrou-se um tecido alternativo adequado para análise de POPs em aves debilitadas. No geral, as regiões de reprodução e migração dos pinguins na América do Sul apresentam baixas concentrações de POPs com tendência constante ou indícios de declínio. / The Magellanic Penguin , Spheniscus magellanicus, is the most abundant penguin that live in temperate regions of South America and a good indicator of environmental pollution in that region. Persistent organic pollutants (POPs) were detected in the liver of Magellanic penguins found debilitated or dead on the beaches of Brazil (Rio de Janeiro, Sao Paulo, Santa Catarina and Rio Grande do Sul) between 2008 - 2012, and in Uruguay and Chile in 2011. Polychlorinated biphenyls (PCBs) were more prevalent than organochlorine pesticides (DDTs ∼ HCB ∼ Drins) and polybrominated diphenyl ethers (PBDEs). Fipronil, an emerging contaminant, was not detected despite its use in South America. Among PCBs, the congeners penta, hexa and heptaclorados were predominant. Concentrations of POPs are similar between the migration and reproduction areas except for PCBs that are relatively higher in the breeding area. At this time point (2008 - 2012) POPs showed constancy for organochlorine pesticides and PCBs tendency to decline. The Magellanic penguin uropygian gland has proved to be a suitable alternative for POPs tissue analysis in debilitated birds. Overall, southern South America has low concentrations of POPs with constant trend or decline evidence.