Bisfenol A (BPA) är ett propanderivat med två fenolgrupper. Det syntetiserades för första gången år 1905 av Thomas Zincke vid Marburgs universitet. När en polymerkemist upptäckte att det kunde användas för att bilda polykarbonatplaster växte dess popularitet. Idag är BPA-industrin en miljardindustri och många av oss använder dagligen plaster där denna kemikalie ingår. Nu har det gjorts nya toxikologiska undersökningar som visar att BPA kanske inte är så ofarligt som man tidigare trott. Vårt största intag av föreningen sker via mag-tarmkanalen genom att det kan läcka från olika slags plastföremål i kontakt med livsmedel. Enligt en panel sammansatt av USA:s National Institutes of Health finns det en risk för negativa effekter på hjärna och beteende hos barn. Reaktionerna på riskbedömningarna har varierat och detta examensarbete vill presentera några argument för vikten av att undersöka BPA: s hälsorisker mer. Syftet med detta examensarbete är att med en litteraturstudie undersöka en del av vad som finns dokumenterat om BPA: s hälsorisker för människan, typ av genomförda toxikologiska undersökningar och hur dessa resultat har påverkat företag och länder. Denna litteraturstudie visar att det finns stor bredd på tolkningen av de toxikologiska studiernas resultat och därmed är det osäkert om det finns hälsorisker eller inte. Det finns omdebatterade resultat som tyder på en ökad risk av toxikologiska effekter, till exempel skada på hjärta hos barn men det finns ingen fastställd hälsorisk för människor. Mer standardisering behövs i forskningen för att ge den en högre kvalitet och göra studier mer jämförbara. / Bisphenol-A (BPA) is a propane derivative with two phenol groups. It was synthetisized for the first time in the year of 1905 by Thomas Zincke at the Marburg University. When a polymer chemist discovered that it could be used to form polycarbonate plastics its popularity grew. Today the chemistry of BPA is a billion industry and many of us use daily plastics in which this chemical is used for. Many new toxicological studies have shown that BPA maybe is not as friendly as before thought. Our biggest exposure to it is orally because it can leak from different plastics with contact to food. According to a panel assembled by USA’s National Institutes of Health there is a risk of negative effects on brain and behaviour on children. The reactions of the risk assessment have been different and this thesis wants to show some arguments for the importance of exploring the health risks of BPA more. The purpose of this thesis is to use a literature study to investigate a part of what is documented about the health effects of BPA on humans, the kind of toxicological studies performed and how their results have affected companies and countries. The literature study shows that the width of interpretation of the toxicological studies’ results is big and thus that it is uncertain if there are health effects or not. There are some uncertain results facts funded on conflict that show a heightened risk for toxicological effects, for example damage on heart and changes in behavior in infants but there is no empirically stated health risk in humans. More standardization in research is needed for giving it a higher quality and thus making it more comparable.

Philosophiae Doctor - PhD / Emerging micropollutants such as bisphenol-A and 2-nitrophenol present a great threat in drinking water due to their adverse effects. Most conventional technologies in water and wastewater treatment are not designed to eliminate these xenobiotics; instead pollutants are merely transferred from one phase to another. Advanced oxidation technologies (AOTs) however, have been identified as suitable routes for the degradation of these potential damaging substances based on free radical mechanisms and use of less expensive chemicals. Moreover, due to the structural complexity of wastewater and the existence of pollutants as mixtures, no single advanced oxidation technology can convincingly remove all forms of contaminants and then most often than not, a combination of treatment processes is required for an effective purification process. Besides, the problem of adequate degradation of emerging contaminants in the environment, when AOT(s) are used individually, they present inherent problems. For instance, powder TiO₂ photocatalysts obstruct light penetration, thus prevent effective interaction of UV light with the target pollutants, and particulates present problems of post-filtration and recovery of catalyst particles after treatment. Additionally, TiO₂ has a high band gap energy, high electron-hole recombination rate, and is prone to aggregation of the suspended particles. Similarly, the dielectric barrier discharge (DBD) system produces ultra violet light and hydrogen peroxide within the plasma zone which is not fully maximised for the mineralization of persistent organic pollutants. Rapid oxidation and aggregation of nano zero valent iron particles in photo-Fentons process reduce the particles mobility and affect its performance. In the same vein, the jet loop reactor (JLR) system is characterised by low impingement yield, which is responsible for low mineralization rate. In light of this background, this research investigated the degradation of bisphenol-A and 2- nitrophenol in aqueous solution using the following combined advanced oxidation methods: DBD/supported TiO₂ or Ag doped TiO₂ photocatalysts, DBD/photo-Fenton induced process and JLR/UV/H₂O₂. The target was to assess the performance of each single system and then identify the best combined AOTs capable of significantly mineralizing the target compounds. Firstly, two materials were developed namely supported TiO₂ and stabilized nano zero valent Fe. The TiO₂ photocatalyst supported on a stainless steel mesh was synthesised using sol-gel solution of 8 % PAN/DMF/TiCl₄. The influence of calcination temperature and holding time on the formation of nanocrystals was investigated. Afterwards, various amounts of metallic silver were deposited on the (optimum) supported TiO₂ photocatalyst using thermal evaporation. The catalysts were characterized by several analytical methods; HRSEM, HRTEM, EDS, SAED, FTIR, TGA-DSC, UV-vis/diffuse reflectance spectroscopy, XRD, BET, and XPS. The photocatalytic activity of the prepared catalysts was determined using methylene blue as a model pollutant under ultra-violet light irradiation. Secondly, the TiO2 photocatalyst and 2.4 % Ag doped TiO₂ nanocomposites obtained as optimums (in section 1) were combined with the DBD to decompose BPA or 2-NP in aqueous solution. Moreover, the photo-Fenton process was applied for degradation of the model pollutants, and different dosages of stabilized nZVI (in the range of 0.02 -1.00 g) were added to the DBD system to induce the photo-Fenton process and improve BPA or 2-NP degradation efficiency. Finally, a jet loop reactor (JLR) presenting advanced mixing by the “impinging effect” was explored to decompose BPA or 2-NP in aqueous solution as a function of inlet applied pressure, solution pH, and initial concentration of BPA or 2-NP. Subsequently, different concentrations of hydrogen peroxide (H₂O₂) were added to the JLR to enhance the mineralization process. Furthermore, a combination of JLR with in-line UV light and H₂O₂ were further utilised to decompose BPA or 2-NP in aqueous solution. The residual concentration of the model compounds and intermediates were analysed using high performance liquid chromatography (HPLC) and liquid chromatography mass spectrometry (LCMS). The concentration of the ozone, hydrogen peroxide and hydroxyl radicals generated by the DBD in the presence or absence of a catalyst was monitored using Ultraviolet-visible spectroscopy and Photoluminescence spectroscopy. The results revealed that the optimal thermal conditions to obtain well supported uniformly grown, highly active crystalline TiO₂ catalysts with high specific surface area was 350 ºC at a 3 h holding time in N2 atmosphere with a flow rate of 20 mL/min. Pyrolysis temperature and holding time played an important role on the crystalline nature and photocatalytic activity of the catalyst. Moreover, 2.4 % Ag doped TiO₂ nanocomposites exhibited higher photocatalytic activity for methylene blue degradation than the undoped supported TiO₂ nanocrystals. The results indicated that combining DBD with 2.4 % Ag doped TiO₂ nanocomposites achieved 89 % and 81 % removal efficiency for BPA or 2-NP compared to 67.22 % or 56.8 % obtain when using the DBD system alone. The 2.4 % Ag doped TiO₂ nanocomposites demonstrated excellent activity and offered photochemical stability after four repeated applications.In the case of the photo-Fenton induced process, nano zero valent iron particles (nZVI) stabilized with polyethylene glycol were synthesised using a modified borohydride reduction method. The HRSEM, BET, XRD, and XPS analysis confirmed the formation of filamentous, high surface area iron nanoparticles in the zero valent state. Unlike combined DBD/Ag doped TiO2 nanocomposites, 100 % or complete removal of BPA or 2-NP in aqueous solution was achieved with DBD/nZVI system within 30 minutes compared to 67.9 % (BPA) or 56.8 % (2-NP) with DBD alone after 80 minutes. The removal efficiency was attributable to the production of an increased concentration of OH radicals as well as existence of a synergetic effect in the combined DBD/nZVI system. Five new transformation products namely: 4-nitrophenol (C₆H₅NO₃), 4-nitrosophenolate (C₆H₄NO₂), 4-(prop-1-en-2-yl) cyclohexa-3,5-diene-1,2-dione, (C₉H₈O₂), 4-(2- hydroxylpropan-2-yl)cyclohexane-3,5-diene-1,2-dione (C₉H₁₀O₃), and 1,2-dimethyl-4-(2- nitropropan-2-yl)benzene (C₉H₁₀NO₄) were identified during the degradation of BPA. While, three aromatic intermediate compounds such as 2-nitro-1,3,5-benzenetriolate (C₆H₂NO₅), 2- nitro-1,4-benzoquinone (C₆H₃NO₄), and 2,5-dihydroxyl-1,4-benzoquinone (C₆H₄O₄) respectively were identified during the degradation of 2-NP for the first time in the DBD with JT14 or JT17 using LC-MS. These intermediate compounds have never been reported in the literature, thereby expanding the number of BPA or 2-NP intermediates in the data base in the DBD/JT14 or DBD/nZVI system. BPA degradation proceeded via ozonation, hydroxylation, dimerization, and decarboxylation and nitration step, while 2-NP proceeded via hydroxylation, nitration and denitration respectively. Furthermore, maximum removal efficiency of BPA or 2-NP in aqueous solution using JLR alone under the optimum solution pH (3), inlet pressure (4 bar), flow rate (0.0007 m3/s) was 14.0 % and 13.2 % respectively after 80 minutes. A removal efficiency of 34.9 % was recorded for BPA while 33.2 % was achieved for 2-NP using combined JLR/UV under the same conditions as JLR alone. For the combined JLR/H₂O₂ under optimum conditions of inlet pressure (4 bar), solution pH (3) and peroxide dosage (0.34 g/L), a 51.3 % and 50.1 % removal efficiency was achieved for BPA and 2-NP respectively under same conditions relative to JLR alone. Combination of JLR/UV/H₂O₂ achieved 77.7 % (BPA) or 76.6 % (2- NP) removal efficiency under the same conditions. The combined JLR/UV/H₂O₂ process was found to be most effective combination under the optimized operating parameters due to existence of a synergetic index value of 6.42 or 6.84. This implies that JLR should be coupled with UV and H₂O₂ to achieve greater mineralization efficiency instead of using the system individually. The obtained experimental data of these combined treatment processes fitted the pseudo-first order kinetic models. The combination of the JLR/UV/H₂O₂ was found to be energy efficient and could effectively degrade BPA or 2-NP in aqueous solution to a greater extent than the JLR, JLR/UV or JLR/H₂O₂ system. However, the total organic carbon (TOC) reduction value by all combined DBD and JLR system recorded was not completely achieved due to the formation of recalcitrant intermediate compounds under the applied conditions. In conclusion, this study is reporting for the first time a combination of supported 2.4 % Ag doped TiO₂ nanocomposites with dielectric barrier discharge system for BPA/2-NP degradation in aqueous solution; a combination jet loop reactor based on impingement with in-line UV lamp and H2O2 for successfully decomposing BPA or 2-NP in aqueous solution; as well as a combination of dielectric barrier discharge system and stabilised nano zero valent iron particles, which induced a photo-Fenton process for highly effective removal of BPA or 2-NP in aqueous solution. This study conclusively supports the hypothesis that combined advanced oxidation technologies offer a sustainable and highly efficient means of achieving partial or complete removal of BPA or 2-NP in aqueous solutions. Considering all the combinations of AOTs investigated in this study, the novel DBD/photo-Fenton-induced process under optimised operating parameters was found to be the most efficient in the elimination of BPA or 2-NP in aqueous solutions. The combination of DBD with photo- Fenton like process offers a promising advanced waste water purification technology in the immediate future. Based on these findings, it is recommended that DBD should be redesigned to prevent loss of ozone and JLR system reconfigured to increase impingement and cavitational yield in order to have an effective combination treatment strategy for waste water purification especially in large scale waste water management. / National Research Foundation (NRF) and Water Research Commission, South Africa

The overall objective of the research presented in this dissertation was to assess exposure to endocrine disrupting chemicals (EDCs), polychlorinated biphenyls (PCBs), phthalates, and bisphenol A (BPA) in the general population and evaluate their associations with adverse reproductive health effects, including cancers, in women. Given the proven contribution of unopposed estrogens to the risk for endometrial neoplasia or breast cancer, renewed health concerns have aroused about estrogen mimicking EDCs found in food, personal care products or as environmental contaminants. Our meta-analysis showed that exposure to estrogen mimicking PCBs increased summary risk of breast cancer and endometriosis. We further evaluated the relationship between endometriosis and breast cancer, and EDCs using a bioinformatics method. Our bioinformatics approach was able to identify genes with the potential to be involved in interaction with PCB, phthalates and BPA that may be important to the development of breast cancer and endometriosis. Therefore, we hypothesized that exposure to EDCs such as PCBs, phthalates, and BPA, results in adverse reproductive health effects in women. Using subject data and biomarkers available from the Center for Disease Controls National Health and Nutrition Examination Survey database we conducted a cross-sectional study of EDCs in relation to self-reported history of endometriosis, uterine leiomyomas, breast cancer, cervical cancer, ovarian cancer, and uterine cancer. Significantly higher body burdens of PCBs were found in women diagnosed with breast cancer, ovarian cancer, and uterine cancer compared to women without cancer. PCB 138 was significantly associated with breast cancer, cervical cancer, and uterine cancer, while PCBs 74 and 118 were significantly associated with ovarian cancer. The sum of dioxin-like PCBs were significantly associated with ovarian cancer (OR of 2.02, 95% CI: 1.06-3.85) and the sum of non-dioxin-like PCBs were significantly associated with uterine cancer (OR of 1.12, 95%CI: 1.03-1.23). Significantly higher body burdens of PCBs were also found in women diagnosed with endometriosis and uterine leiomyomas. Documenting the exposure to EDCs among the general U.S. population, and identifying agents associated with reproductive toxicity have the potential to fill research gaps and facilitate our understanding of the complex role environmental chemicals play in producing toxicity in reproductive organs.

Endocrine Disrupting Chemicals (EDC) are exogenous agents that mimic endogenous hormone activity in the body. EDC exposure during the critical period of neonatal development can potentially cause life-long neurological, behavioural and physiological disease. This thesis focuses on the EDC Bisphenol A (BPA), a synthetic xenoestrogen widely prevalent in everyday materials that has significant environmental relevance given its ubiquitous presence in humans around the world. The central research question of my thesis is: Does perinatal exposure to BPA affect rat pup development? A rodent model was selected to study the effects of BPA on the adrenal component of the hypothalamic-pituitary-adrenal axis (HPA axis) stress pathway, which has not been extensively studied. Rat dams were divided into five groups (vehicle control (VEH), positive control diethylstilbestrol (DES), BPA 5, BPA 50 and BPA 500 μg/kg bw/day) and dosed daily throughout gestation and for four days of lactation. Rat pups were sacrificed at two time-points at the beginning and the end of the stress hyporesponsive period (SHRP), at postnatal day (PND) 5 and PND 15. Changes in three morphometric parameters (bodyweight, crown-rump (CR) length and anogenital distance (AGD) were assessed based on the factors of Treatment and Sex. Adrenal gland glucocorticoid receptor (GR) and 18SrRNA expression was determined by qPCR in male pups at PND 5 and PND 15. At PND 5, compared to the VEH group, the BPA 50 pups were significantly heavier (ANOVA, Dunnett’s post-hoc) and the DES and BPA 50 pups had significantly longer CR lengths (ANOVA, Dunnetts’ post-hoc). At PND 15, xenoestrogen treatment significantly influenced CR length (ANOVA). At both time-points, males had significantly longer AGD than females, as physiologically expected (ANOVA). Adrenal gland GR expression in male pups was not significantly affected by treatment, but there was an effect of treatment in18SrRNA gene expression at PND 5 (Kruskal-Wallis). Using the Ct method to determine GR and 18SrRNA fold changes, we cautiously suggest that our experimental doses resulted in a non-monotonic dose response to BPA in the PND 5 animals and a monotonic dose response to BPA exposure in the PND 15 animals. This study highly values the importance of investigating the effects of environmentally relevant, low dose BPA exposure during the critical window of development, given the little that is known about potentially permanent alterations to the stress pathway due to exposure during this delicate period of development.

Nanofiltration (NF) is an attractive option for the treatment of wastewater e.g. municipal wastewater and landfill leachate. However, membrane fouling can be a major obstacle in the implementation of this technology. Fouling of nanofiltration membranes by hu-mic acids (HA) was investigated using bisphenol A (BPA) as an indicator chemical to dif-ferentiate between various mechanisms that may lead to a change in solute rejection. Three commercially available NF membranes were investigated and an accelerated foul-ing condition was achieved with a foulant mixture containing humic acids in an electro-lyte matrix. The effects of membrane fouling on the rejection of BPA were interpreted with respect to the membrane pore sizes and the fouling characteristics. Results report-ed here indicate that calcium concentration in the feed solution could be a major factor governing the humic acid fouling process. Moreover, a critical concentration of calcium in the feed solution was observed, at which membrane fouling was most severe. Mem-brane fouling characteristics were observed by their influence on BPA rejection. Such influence could result in either an increase or decrease in rejection of BPA by the three different membranes depending on the rejection mechanisms involved. It is hypothe-sised that these mechanisms could occur simultaneously and that the effects of each might not be easily distinguished. However, it was observed that their relative contribu-tion was largely dependent upon membrane pore size. Pore blocking, which resulted in a considerable improvement in rejection, was prominent for the more open pore size TFC-SR2 membrane. In contrast, the cake-enhanced concentration polarisation (CECP) effect was more severe for the tighter NF270 and NF90 membranes. For hydrophobic solutes such as BPA, the formation of the fouling layer could also interfere with the so-lute-membrane interaction, and therefore, exert considerable influence on the separa-tion process. The combined impact of humic acid fouling and CaCO3 scaling on the rejection of trace organic contaminants by a commercially available nanofiltration membrane was inves-tigated in this study. Due to the presence of humic acid in the feed solution, CaCO3 scal-ing behaviour differed substantially from that of a pure CaCO3 solution. A prolonged induction period was consistently observed prior to the onset of membrane scaling. In addition, membrane scaling following humic acid fouling did not result in a complete loss of permeate flux. This is consistent with the absence of any large CaCO3 crystals. In fact, the CaCO3 crystals on the membrane surface were quite small and similar in size, which would result in a relatively porous cake layer. At the onset of CaCO3 scaling the rejection of all three trace organic contaminants started to decrease dramatically. The observed decrease in rejection of the trace organic contaminants was much more se-vere than that reported previously with a single layer of either organic or colloidal foul-ing. Such severe decrease in rejection can be attributed to the extended cake-enhanced concentration polarisation effect occurring as a result of the combination of membrane fouling and scaling. The porous CaCO3 scaling layer could lead to a substantial cake-enhanced concentration polarisation effect. In addition, the top CaCO3 scaling layer could reduce the wall shear rate within the underlying humic acid fouling layer, causing an additional concentration polarisation (CP) effect.:1 INTRODUCTION 1 1.1 Fundamentals of NF/RO 1 1.1.1 Solute transport through NF/RO membranes 2 1.1.2 Separation mechanisms 3 1.1.2.1 Steric size exclusion 3 1.1.2.2 Donnan effect 3 1.1.2.3 Electrostatic repulsion 4 1.1.2.4 Adsorption 4 1.1.3 Environmental applications of NF/RO 5 1.1.4 Drinking water treatment from groundwater and surface water sources 5 1.1.5 Water/Wastewater reclamation 7 1.2 Classification and materials of NF/RO membranes 7 1.2.1 Membrane classes 7 1.2.2 Membrane materials 8 1.2.3 Organic membrane materials 9 1.2.3.1 Polyamide membranes 9 1.2.3.2 Cellulose acetate membranes 9 1.2.4 Inorganic membrane materials 10 1.3 Removal of trace organic contaminants 11 1.3.1 Impact of membrane characteristics 14 1.3.1.1 Molecular weight cut-off/pore size 14 1.3.1.2 Surface charge 14 1.3.1.3 Hydrophobicity/hydrophilicity 15 1.3.1.4 Surface morphology 15 1.3.2 Impact of feed characteristics 17 1.3.2.1 pH value 17 1.3.2.2 Ionic strength 18 1.3.2.3 Organic matter 19 1.3.2.4 Presence of divalent ions 20 1.3.2.5 Presence of foulants 20 1.3.2.6 Temperature 20 1.3.3 Impact of solute characteristics 22 1.3.3.1 Molecular weight 22 1.3.3.2 Molecular size (length and width)/molecular volume 22 1.3.3.3 Minimum projection area/Equivalent width 23 1.3.3.4 Charge 23 1.3.3.5 Hydrophobicity/hydrophilicity 24 1.3.4 Impact of operational characteristics 25 1.3.4.1 Transmembrane pressure/permeate or transmembrane flux 25 1.3.4.2 Cross-flow velocity/recovery/concentration polarisation 25 1.3.5 Impact of fouling on rejection 26 1.3.5.1 Organic fouling 28 1.3.5.2 Colloidal fouling 30 1.3.5.3 Inorganic fouling (scaling) 31 1.3.5.4 Biological fouling 32 1.3.6 Impact of membrane cleaning on rejection 32 1.3.6.1 Changes of membrane morphology due to cleaning 32 1.3.6.2 Impact on rejection of TrOCs due to cleaning 33 1.3.7 Validation at pilot and full scale systems 35 2 MEMBRANE FOULING IN THE NANOFILTRATION OF LANDFILL LEACHATE AND ITS IMPACT ON TRACE CONTAMINANT REMOVAL 37 2.1 Introduction 37 2.2 Materials and Methods 40 2.2.1 Analytical reagents and chemicals 40 2.2.2 Nanofiltration membrane 40 2.2.3 Membrane filtration set-up and protocol 41 2.2.4 Analytical technique 42 2.3 Results and discussion 42 2.3.1 Landfill leachate characterisation 42 2.3.2 Physico-chemical properties of bisphenol A 43 2.3.3 Influence of the calcium concentration on the flux 44 2.3.4 Influence of fouling on the rejection of organic contaminants 46 2.4 Conclusions 48 3 CHARACTERISING HUMIC ACID FOULING OF NANOFILTRATION MEMBRANES USING BISPHENOL A AS A MOLECULAR INDICATOR 50 3.1 Introduction 50 3.2 Materials and methods 52 3.2.1 Model NF membranes and membrane characterisation 52 3.2.2 Model trace organic contaminant 52 3.2.3 Organic foulant 53 3.2.4 Membrane filtration set-up 54 3.2.5 Filtration protocol 55 3.2.6 Analytical technique 56 3.3 Results and discussions 56 3.3.1 Membrane characteristics 56 3.3.2 Membrane fouling behaviour 58 3.3.3 Change of membrane hydrophobicity 61 3.3.4 Effects of organic fouling on the nanofiltration of BPA 63 3.3.5 Effects of organic fouling on rejection: the mechanisms 65 3.4 Conclusions 67 4 EFFECTS OF FOULING AND SCALING ON THE REJECTION OF TRACE ORGANIC CONTAMINANTS BY A NANOFILTRATION MEMBRANE: THE ROLE OF CAKE-ENHANCED CONCENTRATION POLARISATION 69 4.1 Introduction 69 4.2 Materials and methods 71 4.2.1 Nanofiltration membrane 71 4.2.2 Chemicals and reagents 71 4.2.3 Crossflow membrane filtration system 72 4.2.4 Experimental protocol 73 4.2.5 SEM-EDS analysis 74 4.2.6 Analytical methods 75 4.3 Results and discussion 75 4.3.1 Membrane characteristics 75 4.3.2 Membrane fouling and scaling development 76 4.3.3 Effects of fouling/scaling on the membrane rejection behaviour 79 4.3.4 Cake-enhanced concentration polarisation 85 4.4 Conclusions 87 5 SUMMARY AND CONCLUSIONS 88 6 REFERENCES 94 7 ACKNOWLEDGEMENTS 112

Steroid hormones in testis play an important role in spermatogenesis, maintenance of the male reproductive tract, production of semen and the maintenance of secondary sex characteristics and libido. They are also discussed as a target for substances called endocrine disruptors (EDs). No complex study was conducted on evaluation of relationships between EDs and steroid spectrum in 2 biological fluids; seminal plasma and plasma. The aim of the PhD. thesis was to develop and validate a method for determination of bisphenol A (BPA) and steroid spectrum in plasma and seminal plasma and to shed more light into mechanisms of ED action and effects of BPA and polychlorinated biphenyls (PCBs) on human spermatogenesis and steroidogenesis. Two new liquid-chromatography mass spectrometry methods for determination of BPA and 11 steroids in plasma and seminal plasma were developed and validated. The methods were used for estimation of analyte concentrations in 191 men with a different degree of fertility. Concurrently, the levels of six congeners of PCBs, gonadotropins, selenium and zinc in plasma were estimated. Partial correlations adjusted for age and BMI were calculated to evaluate relationships between these analytes. Seminal BPA, but not plasma BPA, was negatively associated with sperm concentration...

Le milieu aquatique est le réceptacle ultime de la pollution environnementale. De nombreux micropolluants y sont présents et montrent des effets toxiques envers les systèmes aquatiques. La Directive Cadre Eau (DCE) a comme objectif la restauration du bon état écologique et chimique des milieux aquatiques d’ici 2015. Pour cela, elle impose des Normes de Qualités Environnementales (NQE) faibles et une surveillance accrue des masses d’eau. Au-delà des micropolluants réglementés, certains dits « émergents » ont été détectés à de faibles concentrations (ng.L-1) dans les systèmes aquatiques. Sous ce terme, sont regroupés les composés pharmaceutiques, certains pesticides, les hormones, etc. L’ensemble de ces micropolluants sont introduits dans l’environnement par plusieurs sources : dépôts atmosphériques, lessivage des sols, lixiviation et rejets industriels et/ou domestiques. Ces travaux de thèse ont porté plus précisément sur les alkylphénols, présents sur la liste des contaminants prioritaires dangereux de la DCE, leurs dérivés éthoxylés, le bisphénol A et les composés pharmaceutiques. Dans un premier temps, une attention particulière a été portée à l’analyse de ces composés. Les méthodes analytiques de chromatographie liquide couplée à la spectrométrie de masse simple (LC-MS) et en tandem (LC-MS/MS) pour les alkylphénols ont été optimisées en améliorant les contrôles qualités et en portant une attention particulière à l’extraction des composés sensibles aux contaminations extérieures (manipulateur, ambiance, etc.). Pour pallier aux problèmes liés à la contamination des échantillons par ces composés lors de l’extraction, la microextraction sur phase solide (SPME) et une méthode d’analyse par chromatographie en phase gazeuse couplée à la spectrométrie de masse simple (GC-MS) ont été dévelopées. Dans un second temps, le devenir et le comportement des alkylphénols, de leurs dérivés éthoxylés et des composés pharmaceutiques dans les stations d’épuration (STEP), sources d’introduction dans les systèmes aquatiques avérées, ont été étudiés. Cette étude a permis de mettre en évidence que les concentrations diminuent au cours des traitements dans les STEP pour tous les composés étudiés sauf pour l’acide alkylphénoxy acétique (NP1EC) qui est formé au cours des traitements secondaires ; la carbamazépine et dans une moindre mesure le diclofénac restent stables. Seuls les traitements tertiaires permettent une élimination significative de ces composés. La présence à plus de 50% des alkylphénols et de leurs dérivés éthoxylés dans la phase particulaire entraînent une adsorption non négligeable de ces composés dans les boues. Dans le but d’améliorer le suivi environnemental, les POCISTM standard (« Polar Organic chemical Integrative SamplersTM ») de configuration « pharmaceutiques » ont été développés lors d’expérimentations menées en laboratoire pour l’échantillonnage des alkylphénols, de leurs dérivés éthoxylés, du bisphénol A et des composés pharmaceutiques. Les alkylphénols et leurs dérivés éthoxylés sont accumulés avec un temps de latence dans les POCISTM standard montrant l’influence de la membrane sur le transfert de masse de ces composés. Les POCISTM standards ont été optimisés en changeant la nature des membranes pour l’échantillonnage des alkylphénols et de leurs dérivés éthoxylés. Ces nouveaux outils sont nommés POCISTM-like. Les POCISTM-Nylon 0,1 µm et 30 µm sont les POCISTM-like montrant un fort pouvoir concentrateur des alkylphénols, de leurs dérivés éthoxylés et du Bisphénol A tout en éliminant le temps de latence observé dans leur accumulation dans les POCISTM standards. Ces POCISTM-like ont par la suite été validés en mésocosmes puis dans le milieu naturel afin de mettre en évidence leur caractère intégratif, permettant ainsi de s’affranchir de l’effet matriciel et de détecter certains composés à des concentrations inférieures aux limites de quantification. / The aquatic environment is the ultimate receptacle of environmental pollution. Many micro-pollutants are present and show toxic effects to aquatic systems (bioaccumulation in tissues, inhibition of growth, endocrine dysfunction, etc.). The Water Framework Directive (WFD) aims to restore the good ecological and chemical quality of aquatic environments by 2015. For this, it imposes low Environmental quality standards (EQS) and increased monitoring of water bodies. Beyond regulated micro-pollutants, some "emerging" have been detected at low concentrations (ng L-1) in aquatic systems. Under this term are grouped pharmaceutical compounds, some pesticides, hormones, etc. All of these micro-pollutants are introduced into the environment through several sources: atmospheric deposition, soil leaching and industrial or domestic discharges.This work is specifically focused on alkylphenols, present on the list of priority hazardous compounds in the WFD, their ethoxylated derivatives, bisphenol A and pharmaceutical compounds. As a first step, particular attention was paid to the analysis of these compounds. Analytical methods of liquid chromatography coupled to mass spectrometry (LC / MS) and tandem mass spectrometry (LC-MS/MS) for alkylphenols were optimized by improving quality controls and paying attention to the extraction of sensitive compounds toward contamination (manipulator, atmosphere, etc.). To overcome the problems associated with sample contamination by these compounds during the extraction, solid phase microextraction (SPME) and a method of analysis by gas chromatography coupled to mass spectrometry (GC-MS) was developed. In a second step, the fate and behavior of alkylphenols, their ethoxylated derivatives and pharmaceutical compounds in sewage treatment plants (WWTPs), sources of introduction into aquatic systems proved, were studied. This study has allowed showing the decrease of concentrations during treatment in WWTPs for all compounds studied except for alkylphenoxy acetic acid (NP1EC) which is formed during secondary treatment, carbamazepine, and to a lesser extent diclofenac remain stable. Only tertiary treatments allow significant removal of these compounds. The presence of more than 50% of alkylphenols and ethoxylated derivatives in the particulate phase lead to significant adsorption of these compounds into sludges. In order to improve environmental monitoring, during experiments conducted in the laboratory POCISTM standard (Polar Organic Chemical Integrative Samplers), "pharmaceuticals" configuration, have been developed for sampling alkylphenols, their ethoxylated derivates, bisphenol A and pharmaceutical compounds. Alkylphenols and their ethoxylated derivatives are accumulated with a lag phase in standard POCISTM showing the influence of the membrane on the mass transfer of these compounds. The standard POCISTM were optimized by changing the nature of the membranes for sampling alkylphenols and their ethoxylated derivatives. These new tools are named POCISTM-like. The POCISTM-Nylon 0.1 µm and 30 µm are POCISTM-like showing a strong power concentrator for alkylphénols, their ethoxylated derivatives and BPA while eliminating the lag phase observed in standard POCISTM. These POCISTM-like were subsequently validated in mesocosms and in the environment in order to highlight their integrative nature, allowing to overcome the matrix effect and to detect some compounds at concentrations below the limits of quantification.

The utilization of renewable sources as alternatives for petroleum and natural gas products has immense commercial, health and global warming significance. D-Isosorbide (2) is a bifunctional, polar, chiral and rigid molecule, which is produced from renewable sources. Synthesis of new polymers containing 2 is of interest for polymers and in drug delivery. The aim of the present work is to synthesize various polymers (homo- and copolymers) containing 2 via the olefin metathesis routes, ring-opening metathesis polymerization (ROMP) and acyclic-diene metathesis polymerization (ADMET). N-Phenyl-7-oxanorbornene-dicarboximide, and norbornene functionalized onto 2 were used as the monomers for ROMP. These monomers were polymerized using Grubbs’ catalysts to generate a series of homo-, co-, block and cross-linked-polymers. These polymers were characterized using GPC, NMR, and IR. In addition, ADMET polymerization of a terminal diolefinunctionalized D-isosorbide (2) was also conducted to produce ADMET polymers.

Detta examensarbete beskriver optimering av ett katalytiskt protokoll för framställning av bisguaiacol F, ett ofarligt alternativ till bisphenol A. Lewissyrliga grupp IV metallkomplex med triflatligander användes som katalysatorer under milda betingelser och kinetisk analys användes för att underlätta optimeringen av reaktionsprotokollet för att öka utbyte och selektivitet för transformationen. Dessutom bidrog kinetiken med mekanistiska insikter och avslöjade att den nukleofila attacken starkt påverkar reaktionens selektivitet och utbyte. / This thesis describes the optimization of catalytic protocol for the formation of bisguaiacol F, a benign alternative to bisphenol A. Lewis acidic group IV metal complexes bearing triflate ligands were used as catalysts under mild conditions and kinetic analysis was used to aid optimization of the reaction protocol to increase the yield and selectivity of the transformation. In addition, the kinetics shed light on the operating mechanisms and revealed that competition of nucleophiles greatly impact selectivity and yield of the reaction.

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