Per- and polyfluorinated compounds (PFCs) are known to be toxic, bioaccumulative, and persistent. However, exposure routes and toxic effects in humans are still widely unknown. The concentrations of 17 PFCs were measured in newborn cord blood plasma and plasma from pre- and postnatal women from Winnipeg, Manitoba using online solid phase extraction coupled with liquid chromatography mass spectrometry. Median concentrations (with standard deviation) were 2.2 ng/mL (1.8 ng/mL) for perfluorooctanesulfonic acid (PFOS) and 0.89 ng/mL (0.75 ng/mL) for perfluorooctanoic acid (PFOA) in prenatal maternal plasma and 1.8 ng/mL (1.8 ng/mL) for PFOS and 0.55 ng/mL (0.46 ng/mL) for PFOA in postnatal maternal plasma. Multiple linear regression and principal component analysis were used to evaluate possible associations of maternal and infant characteristics with PFC concentrations. In general, concentrations of PFCs in plasma were associated with maternal characteristics, but not home characteristics, wheezing, or developmental effects.

Per- and polyfluorinated compounds (PFCs) are known to be toxic, bioaccumulative, and persistent. However, exposure routes and toxic effects in humans are still widely unknown. The concentrations of 17 PFCs were measured in newborn cord blood plasma and plasma from pre- and postnatal women from Winnipeg, Manitoba using online solid phase extraction coupled with liquid chromatography mass spectrometry. Median concentrations (with standard deviation) were 2.2 ng/mL (1.8 ng/mL) for perfluorooctanesulfonic acid (PFOS) and 0.89 ng/mL (0.75 ng/mL) for perfluorooctanoic acid (PFOA) in prenatal maternal plasma and 1.8 ng/mL (1.8 ng/mL) for PFOS and 0.55 ng/mL (0.46 ng/mL) for PFOA in postnatal maternal plasma. Multiple linear regression and principal component analysis were used to evaluate possible associations of maternal and infant characteristics with PFC concentrations. In general, concentrations of PFCs in plasma were associated with maternal characteristics, but not home characteristics, wheezing, or developmental effects.

None

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Contamination of water resources has been caused great impact to the environment. The water constitutes the greatest source of food, and its value for health is incalculable. Despite this, the presence of contaminants in water for consumption in Brazil is a topic with few researches and sources of information. The main contamination of drinking water takes place directly by man, by the abusive use of pesticides or environmental contaminants, with high bioaccumulation potential in the environment, such as perfluorinated and organochlorine compounds. These compounds are present in water in trace levels, and appropriate analytical methods in order to demonstrate the suitability of method, ensuring the reliability of the results are needed. This study presents two multi-residue methods for determination of perfluorinated compounds (PFCs) and for the determination of pesticides in samples of tap water, bottled water and groundwater collected in Brazil, Spain and France. For PFCs was used solid phase extraction automated "in line" method with direct injection of the sample coupled to mass spectrometry with detection limits between 0.15 and 8.76 ng/L, and the determination of pesticides has been carried out by solid phase extraction and analysed using different techniques of separation and ionization LC-ESI-MS/MS, GC-MS/EI and GC-MS/NCI, with detection limits between 1.02 and 48.21 ng/L. The obtained results showed that the tap water have high concentrations of PFCs, especially in Brazil, with an average of 15.83 ng/L, followed by Spain and France with 15.33 and 7.73 ng/L, respectively. For pesticide analyzes, the data found demonstrate that the groundwater obtained in Brazil showed the highest concentrations of investigated contaminants in comparison with tap and bottled water. Regarding the risk of exposure by ingestion through drinking water, PFCs represent greater danger (estimated at 54.8, 58.0 and 75.6 ng/person per day in Spain, France and Brazil) in relation to pesticides (10.23, 29.40, 30.11 ng/person per day in Spain, France and Brazil, respectively). However, despite the levels found in the investigated countries, the consumption of drinking water does not poses imminent risks to contamination associated with PFCs and pesticides. / A contaminação dos recursos hídricos tem causado grande impacto para o meio ambiente. A água constitui-se na maior fonte de alimentação humana, e seu valor para a saúde é incalculável. Apesar disso, a presença de contaminantes em águas para o consumo no Brasil é um tema pouco pesquisado e com escassas fontes de informação. As principais contaminações nas águas potáveis ocorrem diretamente pela ação do homem, através do uso abusivo de agrotóxicos ou por contaminantes ambientais, com alta capacidade de bioacumulação no meio ambiente, como os compostos perfluorados e organoclorados. Estes compostos estão presentes nas águas em níveis de traços, portanto, metodologias analíticas adequadas, a fim de demonstrar que o método é apropriado, garantindo a confiabilidade dos resultados são necessários. Este estudo apresenta dois métodos multirresiduais para determinação de compostos perfluorados (PFCs) e para determinação de agrotóxicos em amostras de água de torneira, água engarrafada e água subterrânea coletadas no Brasil, Espanha e França. Para os PFCs foi utilizado o método de extração em fase sólida automatizada em linha com a injeção direta da amostra acoplada a espectrometria de massas, com limites de detecção entre 0,15 e 8,76 ng/L. Já a determinação de agrotóxicos foi realizada a partir de extração em fase sólida e análise por técnicas distintas de separação e ionização, LC-ESI-MS/MS, GC-MS/EI e GC-MS/NCI, com limites de detecção entre 1,02 e 48,21 ng/L. Os resultados obtidos demonstraram que as águas de torneira apresentam alta concentração de PFCs, especialmente no Brasil, com média de 15.83 ng/L, seguidos pela Espanha e França com 15,33 e 7,73 ng/L, respectivamente. Para as análises de agrotóxicos, os dados encontrados evidenciam que as águas subterrâneas obtidas no Brasil apresentaram as maiores concentrações dos contaminantes investigados, em comparação com as águas de torneira e águas engarrafadas. Em relação ao risco de exposição pela ingestão através do consumo de água, os PFCs representam um perigo maior (estimado em 54,8, 58,0 and 75,6 ng/indivíduo por dia na Espanha, França e Brasil) em relação aos agrotóxicos (23,10, 29,40, 30,11 ng/indivíduo por dia na Espanha, França e Brasil, respectivamente). Contudo, apesar dos níveis encontrados, em nenhum dos países investigados, o consumo de água potável coloca em risco iminente a contaminação associada a PFCs e agrotóxicos.

Les matériaux à faible énergie de surface (LSEMs) sont conçus pour différentes applications. Parmi celle-ci, les applications sur un support solide pour l’élaboration de surfaces superhydro/oléophobes ainsi qu’à l'interface de 2 milieux distincts pour la synthèse de nouveaux tensioactifs éco-responsables. Actuellement, ces matériaux sont constitués essentiellement de composés fluorés pour leurs propriétés uniques leur conférant à la fois l’hydro- et oléo-phobie ainsi que pour leur stabilité thermique et chimique dans des milieux corrosifs. Ce projet montre que l’élaboration des surfaces superhydro/oléophobes peut être réalisée sans utiliser nécessairement des chaînes perfluorées. Deux approches sont adoptées dans ce processus. La première stratégie est d'étudier l'influence de la longueur de la chaîne fluorée sur la structuration et la mouillabilité de la surface des dérivés du ProDOT. La seconde est d'explorer l'influence d'une chaine hydrocarbonée incorporée au coeur des monomères et d'étudier l'effet du type et de la longueur de ces chaînes sur les propriétés de surface. Dans le cadre de l'application des LSEMs sur les ‘matériaux mous’, deux études ont été réalisées : la première se focalisant sur l'effet de la longueur des chaînes hydrocarbonées sur les tensioactifs hybrides à courte chaine fluorée et la deuxième étudiant l'effet de la tête polaire. Deux séries de sulfates et bisulfates hybrides ont donc été synthétisées et leurs propriétés physico-chimiques étudiées. Ce travail a abouti à des résultats intéressants. / Two types of Low surface energy materials LSEMs can be recognized; those which are firstly applied on solid surfaces to elaborate superhydro/oleophobic surfaces that are micro and nano structured, and secondly at the water/air interface to synthesize new ecofriendly surfactants. LSEMs are essentially made from fluorinated compounds due to their unique properties of being both hydro and oleophobic as well as, their thermal and chemical stability in corrosive media. This project shows that the creation of superhydrophobic materials with high oleophobic properties does not necessarily require the utilization of long and bioaccumulative perfluorocarbon chains. Two approaches were adopted in this field. The first strategy was to develop ProDOT derivatives bearing short fluorinated chains to study the influence of the fluorinated chain length on the surface wettability. The proceeding part was to explore the effect of the introduction of a hydrocarbon tail and study the effect of their type and chain length on the surface properties. Another important aspect of this research involves the application of LSEMs on soft materials like surfactants as alternatives to toxic perfluorinated homologues. This study was done to explore the effect of the variant hydrocarbon chains with a short fluorinated tail of hybrid surfactants as well as the effect of the polar head. In this area, two families of hybrid sulfate and bisulfates were synthesized. Their physico-chemical properties were investigated and interesting results were obtained.

There is a growing interest in assessing the neurotoxic potential and endocrine disrupting properties of perfluoroalkyl compounds (PFCs). Several studies have reported in vitro and in vivo effects related to neuronal development, neural cell differentiation, pre- and post- natal development and behaviour. PFC exposure altered hormone levels (e.g. thyroid hormone, estrogen, and testosterone) and the expression of hormone-responsive genes in mammalian and aquatic species. Hormone-mediated events are critical in central nervous system development and function, especially those controlled by thyroid hormones (THs). The studies presented in this thesis are the first to assess the effects of PFCs on primary cultures of neuronal cells in two avian species; the domestic chicken (Gallus domesticus) and herring gull (Larus argentatus). The following TH-responsive genes were examined using real-time RT-PCR: type II iodothyronine 5’-deiodinase (D2), D3, transthyretin (TTR), neurogranin (RC3), octamer motif binding factor (Oct-1), and myelin basic protein (MBP). Several PFCs were shown to alter mRNA expression levels of genes associated with the TH pathway in avian neuronal cells. It was determined that short-chained PFCs (<8 carbons) altered the expression of TH-responsive genes to a greater extent than long-chained PFCs (≥8 carbons). Although several significant changes in mRNA expression were observed in TH-responsive genes following PFC exposure in chicken embryonic neuronal (CEN) cells (Chapter 2), there were fewer changes in herring gull embryonic neuronal (HGEN) cells (Chapter 3). The mRNA levels of D2, D3, TTR, and RC3 were altered following treatment with several short-chained PFCs in CEN cells. Oct-1 and RC3 expression were induced following treatment with several short-chained PFCs in HGEN cells. These studies are the first to report that PFC exposure alters mRNA expression in primary cultures of avian neuronal cells and provide insight into the possible mechanisms of action of PFCs in the avian brain.

There is a growing interest in assessing the neurotoxic potential and endocrine disrupting properties of perfluoroalkyl compounds (PFCs). Several studies have reported in vitro and in vivo effects related to neuronal development, neural cell differentiation, pre- and post- natal development and behaviour. PFC exposure altered hormone levels (e.g. thyroid hormone, estrogen, and testosterone) and the expression of hormone-responsive genes in mammalian and aquatic species. Hormone-mediated events are critical in central nervous system development and function, especially those controlled by thyroid hormones (THs). The studies presented in this thesis are the first to assess the effects of PFCs on primary cultures of neuronal cells in two avian species; the domestic chicken (Gallus domesticus) and herring gull (Larus argentatus). The following TH-responsive genes were examined using real-time RT-PCR: type II iodothyronine 5’-deiodinase (D2), D3, transthyretin (TTR), neurogranin (RC3), octamer motif binding factor (Oct-1), and myelin basic protein (MBP). Several PFCs were shown to alter mRNA expression levels of genes associated with the TH pathway in avian neuronal cells. It was determined that short-chained PFCs (<8 carbons) altered the expression of TH-responsive genes to a greater extent than long-chained PFCs (≥8 carbons). Although several significant changes in mRNA expression were observed in TH-responsive genes following PFC exposure in chicken embryonic neuronal (CEN) cells (Chapter 2), there were fewer changes in herring gull embryonic neuronal (HGEN) cells (Chapter 3). The mRNA levels of D2, D3, TTR, and RC3 were altered following treatment with several short-chained PFCs in CEN cells. Oct-1 and RC3 expression were induced following treatment with several short-chained PFCs in HGEN cells. These studies are the first to report that PFC exposure alters mRNA expression in primary cultures of avian neuronal cells and provide insight into the possible mechanisms of action of PFCs in the avian brain.

There is a growing interest in assessing the neurotoxic potential and endocrine disrupting properties of perfluoroalkyl compounds (PFCs). Several studies have reported in vitro and in vivo effects related to neuronal development, neural cell differentiation, pre- and post- natal development and behaviour. PFC exposure altered hormone levels (e.g. thyroid hormone, estrogen, and testosterone) and the expression of hormone-responsive genes in mammalian and aquatic species. Hormone-mediated events are critical in central nervous system development and function, especially those controlled by thyroid hormones (THs). The studies presented in this thesis are the first to assess the effects of PFCs on primary cultures of neuronal cells in two avian species; the domestic chicken (Gallus domesticus) and herring gull (Larus argentatus). The following TH-responsive genes were examined using real-time RT-PCR: type II iodothyronine 5’-deiodinase (D2), D3, transthyretin (TTR), neurogranin (RC3), octamer motif binding factor (Oct-1), and myelin basic protein (MBP). Several PFCs were shown to alter mRNA expression levels of genes associated with the TH pathway in avian neuronal cells. It was determined that short-chained PFCs (<8 carbons) altered the expression of TH-responsive genes to a greater extent than long-chained PFCs (≥8 carbons). Although several significant changes in mRNA expression were observed in TH-responsive genes following PFC exposure in chicken embryonic neuronal (CEN) cells (Chapter 2), there were fewer changes in herring gull embryonic neuronal (HGEN) cells (Chapter 3). The mRNA levels of D2, D3, TTR, and RC3 were altered following treatment with several short-chained PFCs in CEN cells. Oct-1 and RC3 expression were induced following treatment with several short-chained PFCs in HGEN cells. These studies are the first to report that PFC exposure alters mRNA expression in primary cultures of avian neuronal cells and provide insight into the possible mechanisms of action of PFCs in the avian brain.

There is a growing interest in assessing the neurotoxic potential and endocrine disrupting properties of perfluoroalkyl compounds (PFCs). Several studies have reported in vitro and in vivo effects related to neuronal development, neural cell differentiation, pre- and post- natal development and behaviour. PFC exposure altered hormone levels (e.g. thyroid hormone, estrogen, and testosterone) and the expression of hormone-responsive genes in mammalian and aquatic species. Hormone-mediated events are critical in central nervous system development and function, especially those controlled by thyroid hormones (THs). The studies presented in this thesis are the first to assess the effects of PFCs on primary cultures of neuronal cells in two avian species; the domestic chicken (Gallus domesticus) and herring gull (Larus argentatus). The following TH-responsive genes were examined using real-time RT-PCR: type II iodothyronine 5’-deiodinase (D2), D3, transthyretin (TTR), neurogranin (RC3), octamer motif binding factor (Oct-1), and myelin basic protein (MBP). Several PFCs were shown to alter mRNA expression levels of genes associated with the TH pathway in avian neuronal cells. It was determined that short-chained PFCs (<8 carbons) altered the expression of TH-responsive genes to a greater extent than long-chained PFCs (≥8 carbons). Although several significant changes in mRNA expression were observed in TH-responsive genes following PFC exposure in chicken embryonic neuronal (CEN) cells (Chapter 2), there were fewer changes in herring gull embryonic neuronal (HGEN) cells (Chapter 3). The mRNA levels of D2, D3, TTR, and RC3 were altered following treatment with several short-chained PFCs in CEN cells. Oct-1 and RC3 expression were induced following treatment with several short-chained PFCs in HGEN cells. These studies are the first to report that PFC exposure alters mRNA expression in primary cultures of avian neuronal cells and provide insight into the possible mechanisms of action of PFCs in the avian brain.

京都大学 / 0048 / 新制・課程博士 / 博士(地球環境学) / 甲第17932号 / 地環博第111号 / 新制||地環||22(附属図書館) / 30752 / 京都大学大学院地球環境学舎環境マネジメント専攻 / (主査)教授 藤井 滋穂, 教授 伊藤 禎彦, 准教授 田中 周平 / 学位規則第4条第1項該当 / Doctor of Global Environmental Studies / Kyoto University / DFAM