A number of investigations during the last two decades describe adverse trends in male reproductive health, which have been proposed to be caused by environmental factors with endocrine disrupting properties. In contrast to many other toxicants, endocrine disruptors often do not show linear dose-response relationships typical of those found in traditional toxicological studies. For many compounds, low-dose exposure causes effects opposite to the ones seen after high-dose exposure. In addition, the timing of exposure has been found to be critical. Hence, to correctly assess the impact of endocrine disruptors on reproductive health requires in-depth knowledge of their mechanisms of action. This thesis aimed at identifying the mechanisms underlying the effects of cadmium (Cd), phthalates and phytoestrogens on testicular steroidogenesis. For this purpose, in vitro as well as in vivo models were used. Cd was found to inhibit testosterone synthesis in vivo by down-regulating LH receptor gene expression and reducing the testicular levels of cAMP and StAR protein. In addition, Cd caused a pronounced increase in testicular prostaglandin F2ɑ (PGF2ɑ), suggesting that Cd exerts its suppressive effect on steroidogenesis also by inducing the inhibitory PKC pathway. Pre-treatment with zinc (Zn) protected completely against Cd-induced effects on testosterone and PGF2ɑ. Furthermore, we observed that Cd exposure increased glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA expression in the testis. GAPDH is a potent coactivator of androgen receptor-mediated transcription and the up-regulation found in our study is probably a compensatory response to reduced testosterone concentrations. This finding is interesting since GAPDH has been proposed to have an important role in the regulation of apoptosis as well as sperm motility. We discovered that mono-(2-ethylhexyl) phthalate (MEHP), the active metabolite of the frequently used phthalate di-(2-ethylhexyl) phthalate (DEHP), stimulates Leydig cell steroidogenesis in vitro, by a cAMP- and StAR-independent mechanism. MEHP exposure caused a similar effect in granulosa cells. Gene expression analysis revealed that MEHP is likely to stimulate steroidogenesis by increasing the amount of cholesterol available for steroid synthesis. In the last investigation, we examined the effects of low-dose phytoestrogen exposure on testosterone synthesis during puberty in male goats. Isoflavones present in clover increased plasma concentrations of testosterone and free as well as total triiodothyronine (T3). T3 has previously been shown to induce testosterone synthesis and it is possible that an elevated T3 secretion underlies the increased plasma testosterone levels. Reduced fertility and reproductive tract malformations affect both the individual and the society. Hence, a sound knowledge of reproductive toxicants is of crucial importance. The findings presented in this thesis provide new insights into the reproductive toxicology of endocrine disruptors and may be valuable for risk assessment purposes.

The objective of this thesis was to assess the environmental fate and transport of chemicals emitted from consumer products through the development and application of modelling tools. The following hypotheses were tested: i) Multimedia fate models can be applied in a multistage assessment process to emerging chemicals when limited knowledge exists to identify the likely environmental fate and to direct further research; ii) the indoor environment acts as a source of anthropogenic substances in consumer products to the outdoor environment; and iii) chemical removal pathways in the indoor environment are important for the fate of organic chemicals in densely populated areas. The thesis shows that a structured chemical fate assessment strategy can and should be applied at early stages of the evaluation of emerging chemicals to assess their fate and to direct further research. Multimedia fate models play a key role in this strategy. The three‐solubility approach is a simple, rapid method that can be used to estimate physical‐chemical properties for use in early stage evaluation (Paper I). Emissions in the indoor environment affect the urban fate of hydrophobic organic chemicals by providing additional removal pathways and prolonging urban chemical residence times compared to outdoor emissions (Paper III). Emissions of BDE 209, DINP and DEHP to Stockholm indoor air were estimated to be 0.1, 3.4 and 290 mg/capita year, respectively (Paper IV). The contribution of emissions indoors to outdoor air pollution varies between substances. For BDE 209, emissions in the indoor environment added 38 % to the mass entering Stockholm city with inflowing air. For Sweden, the indoor environment was estimated to account for 80 % of BDE 209 emissions to outdoor air (Papers II and IV). For the phthalates, outdoor emissions and/or background inflow are the dominant sources to outdoor air pollution in Stockholm and the influence of the indoor environment is limited (Paper IV). / <p>At the time of the doctoral defense, the following paper was unpublished and had a status as follows: Paper 4: Manuscript</p>

Made available in DSpace on 2014-08-26T17:15:09Z (GMT). No. of bitstreams: 2 license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) 61.pdf: 1204647 bytes, checksum: 2820eae53e7d2294edaeedea563ab9b9 (MD5) Previous issue date: 2010 / Universidade do Estado do Rio de Janeiro. Instituto de Nutrição. Departamento de Nutrição Básica e Experimental / O poli-(cloreto de vinila) (PVC) necessita da adição de plastificantes, que são aditivos que conferem flexibilidade e maleabilidade para a sua transformação em filme flexível. Os mais utilizados são o adipato de di-(2-etil-hexila) (DEHA) e o ftalato de di-(2-etil-hexila) (DEHP). Para verificar a possível exposição do consumidor aos plastificantes DEHA e DEHP, adicionados a filmes de PVC utilizados no acondicionamento de alimentos gordurosos, utilizou-se o inquérito alimentar como ferramenta no estudo seccional, numa amostra populacional de conveniência, para determinar os cinco primeiros alimentos de maior freqüência de consumo, com no mínimo 3% (m/m) de gordura e com possibilidades de acondicionamento por filme de PVC. O resultado indicou os seguintes alimentos: peito de frango (96%); carne bovina magra (95%); pizza de mozarela (91%); coxa de frango (82%) e queijo mozarela (76%). A migração para os alimentos foi calculada pela diferença entre o teor inicial de DEHA e DEHP no filme de PVC e o teor no filme de PVC após o contato com os alimentos. Quando foi avaliada a pior situação, na amostra de queijo mozarela, os resultados de migração indicaram um nível excessivamente elevado quando comparados com o limite de migração específica (LME) de cada plastificante. Os valores encontrados foram, aproximadamente, 37 vezes mais do permitido para o DEHA (18 mg/kg) e 1.779 vezes mais para o DEHP (1,5 mg/kg). O cálculo de extrapolação da migração para 1 kg de alimento foi realizado com amostras alimentares menores, entre 26 a 270 g. Foi realizado um estudo cronológico com uma amostra de queijo-prato, para avaliar como a migração desses plastificantes ocorria durante 10 dias ininterruptos. Nesse estudo foi encontrada uma estabilidade de migração do DEHA para a amostra alimentar, quando comparada desde a primeira avaliação até a final. Esse estudo demonstrou a exposição do consumidor ao ingerir alimento que tenha sido previamente embalado com filme de PVC e utilizado sem um processo de cocção, onde se encontrou para o DEHA 28,83 mg/100g e 70,06 mg/100g para o DEHP. A presente pesquisa mostra a importância de quantificar a migração desses plastificantes nos alimentos, para uma atualização das leis quanto ao uso dos plastificantes utilizados nos filmes de PVC, quando os mesmos tenham a possibilidade de embalar os alimentos, possibilitando viabilizar a segurança dos alimentos, assegurar a saúde humana e, ainda, se os mesmos deveriam ou não continuar a serem utilizados no mercado para embalar alimentos. / The poly (vinyl chloride) (PVC) requires the addition of plasticizers that given flexibility and adaptability to flexible films. The most plasticizers are di-(2-ethyl-hexyl) adipate (DEHA) and di-(2-ethylhexyl) phthalate (DEHP). We used the food survey as a tool in cross-sectional study, a sample of convenience, to determine the top five foods higher frequency of consumption for at least 3% (w/w) fat and check the possible consumer exposure to the plasticizer DEHP and DEHA added to PVC films. The results indicated the following foods: chicken breast (96%), lean beef (95%); mozzarella pizza (91%), chicken thigh (82%) and mozzarella cheese (76%). The migration into food was calculated as the difference between the initial content of DEHP and DEHA in PVC film and PVC content in the film after contact with food. The migration results were too higher if compared with the specific migration limits (SMLs) for each plasticizer. In the worst case or mozzarella cheese sample, they corresponded at 1,779 times the DEHP limit (1.5 mg/kg). In regard to DEHP migration, these corresponded at 37 times about the limit (18 mg/kg). The extrapolation migration for 1 kg of food was carried out with smaller samples, between 26 to 270 g. A chronological study was conducted with a sample of cheese-dish, to evaluate how the migration of plasticizers occurred for 10 continuous days. In this study we found a stable for DEHA migration from the food sample, compared from the first to the final evaluation. This study demonstrated the exposure of consumers to eat food that has been previously packed with PVC film and used without a cooking process, was found for DEHA and DEHP, respectively, 28.83 mg/100g and 70.06 mg/100g. This research shows the importance of quantifying the migration of plasticizers into the food, for an update of the laws regarding the use of plasticizers in PVC films, when they have the ability to pack the food, allowing viable food safety, ensure human health and also whether they should or not continue to be used in food packaging market.

The thesis Phthalates in yoghurts during storage focuses on monitoring of phthalic acid esters in yogurt samples in relation to their storage period. The analyzed phthalates are di-2-(ethylhexyl)-phthalate (DEHP) and di-n-butyl-phthalate (DBP), which are among the most commonly used polymeric plasticizers, especially polyvinyl chloride. I analyzed samples of yoghurt with 1 % and 5 % chia and bamboo fiber and then subsequently compared them with natural yogurts. In total, I analyzed 120 samples of yoghurt, for which I measured DBP concentrations ranging from 0.2 mg.kg-1 to 7.7 mg.kg-1 of the original raw material and concentration of undetected values of DEHP in range up to 2.6 mg.kg-1 of the original raw material. While analyzing the yoghurt packaging, I measured average DBP values of 174.1 μg.dm-2 (68.0 μg.g-1 plastic) and DEHP values of 26.2 μg.dm-2 (10.2 μg.g-1 plastic). After prior preparation of samples, I used high performance liquid chromatography to do the phthalates analysis.

The thesis on the topic ''Monitoring of phthalic acid esters in agricultural soil'' is focused on the contamination of the agricultural soils by dibuthyl phtalate (DBP) and di (2-ethylhexyl) phthalate (DEHP). This thesis was created in cooperation with the Central Control and Testing Institute of Agriculture as a part of annual soil monitoring of organic contaminants. Forty soil samples were taken in February and March of 2017. The monitoring was carried in twelve regions of the Czech Republic. Samples were extracted using sonication and mixture of acetone-hexane (1:1). Samples were analyzed by liquid chromatography with UV detection. The measured concentrations ranged for DBP from 0,01 to 0,53 mg.kg-1 dry weight and for DEHP from 0,00 to 0,65 mg.kg-1 dry weight. None of these concentration levels exceeded the values set by the Ministry of Environment of the Czech Republic and stated in its Guideline, based on the RSL (Regional Screening Levels) published by the United States' Environmental Protection Agency (USEPA).

The increasing use of plastics has elevated the risk of exposure to environmental pollutants such as plasticisers in the general population, making it necessary to understand the possible long term health consequences of the same. In this study we aim to understand how DEHP affects the gene expression in mice models and if it causes disruptions to its cellular pathways. Two datasets, GSE18564 and GSE14920 comprising of 15 and 60 samples respectively were downloaded from GEO database for analysis. Quality control checks were done using Principal Component Analysis and quantile normalisation. Differentially expressed genes were found using LIMMA model, following which only top 20 genes were selected for pathway analysis using KEGG and Gene Ontology. DEHP was found to be associated with chemical carcinogenesis, including negative regulation of extrinsic apoptotic signaling pathway and fatty acid metabolism. Furthermore, it seems likely that PPAR-alpha might play a key role in DEHP related metabolic disruption. Further studies are required to better elucidate the effect of DEHP on individual metabolic pathway implicated in this thesis.

The diploma thesis is focused on the determination of the content of phthalates (PAE) in printed and non-printed plastic packaging materials for meat products. There were analyzed 30 package samples. The sample area was 1 dm2. Concentrations of dibutyl phthalate (DBP) ranged from undetectable values (< 0.1) to 72.6 ug.dm-2 of the sample surface in printed packaging materials. In non-printed wraps it was from undetectable values (< 0.1) to 67.7 ug.dm-2 of the sample surface. Concentrations of di-2-ethylhexyl phthalate (DEHP) ranged from undetectable values (< 0.1) to 98.7 ug.dm-2 of the sample surface in printed packaging materials. In non-printed wraps it was from undetectable values (< 0.1) to 60.3 ug.dm-2 of the sample surface.

The thesis on the topic Soil pollution by phthalic acid esters in Czech Republic solves the problem of soil pollution by dibutyl phthalate (DBP) and di (2-ethylhexyl) phthalate (DEHP). This thesis joined the annual monitoring conducted by Central Control and Testing Institute of Agriculture. The monitoring of contaminants was carried in twelve regions of the Czech Republic. The samples do represent different types of culture farmland. They were formed by arable land, permanent grassland and hop-garden. Before the analysis, the samples were extracted with acetone-hexane mixture with 1:1 ratio, and ultrasound. Samples were analyzed by liquid chromatography with UV detection. The measured concentrations for the year 2016 ranged in DBP from 0.07 to 0.21 mg.kg-1 dry weight, at DEHP from 0.19 to 1.08 mg.kg-1 dry weight, esters together from 0.13 to 0.65 mg.kg-1.

Les polymères électroactifs (PAE), sont des matériaux permettant de réaliser une conversion entre l'énergie électrique et mécanique. L'objet de ce travail est de proposer des procédés de modifications des terpolymères électrostrictifs par voies composites basés sur différentes approches dans le but d’améliorer les performances électromécaniques et de développer des applications à partir de ces matériaux modifiés. Dans un premier temps, un nano-composite à base de terpolymère et de noir de carbone a été préparé pour améliorer la permittivité diélectrique. Dans un deuxième temps, sur la base de la nature hétérogène de terpolymère semi-cristallin ainsi que du rôle important que la polarisation interfaciale joue sur la réponse diélectrique et électromécanique, une faible quantité d’agent plastifiant (bis (2-ethylhexyl) phalate (DEHP)) a été introduite dans le terpolymère électrostrictif afin de former un composite tout organique permettant l'amélioration des performances électromécaniques. Enfin, l’utilisation de ces matériaux modifiés dans deux applications spécifiques a été étudiée: La récupération de l'énergie mécanique et une pompe microfluidique sans valve. / Electroactive polymers (EAPs), which can realize the conversion between electrical and mechanical energy, have been emerging as one of the most interesting smart materials in the past two decades due to their low density, excellent mechanical properties, ease of processing, low price and potential applications in the fields of sensors, actuators, generators, biomimetic robots and so on. The object of this work is to modify electrostrictive terpolymers with different approaches to improve the electromechanical performances and to develop some applications based on modified terpolymers. Firstly, an organic/inorganic (terpolymer/carbon black) nanocomposite was prepared to improve the dielectric permittivity based on the percolation theory. Secondly, based on the heterogeneous nature of semi-crystalline terpolymer and the important role that interface polarization plays for dielectric and electromechanical response, small molecular plasticizer bis(2-ethylhexyl) phalate (DEHP) was introduced into electrostrictive terpolymer to form an all-organic polymer composite with improved electromechanical performances. Finally, two applications including mechanical energy harvesting and microfluidic pump based on DEHP modified terpolymers were investigated.

The thesis on the topic "The analysis of phthalic acid esters in agricultural soils in the Czech Republic" describes the properties of phthalic acid esters, the occurrence and the negative effects related to the environment and human health. The aim of this diploma thesis was to monitor phthalic acid esters, especially di-2- (ethylhexyl) phthalate (DEHP) and di-n-butyl phthalate (DBP) in agricultural soil samples. Monitoring of phthalates was carried out in cooperation with the Central Control and Testing Institute of Agriculture in Brno as part of their annual monitoring of phthalates and other organic contaminants in soils. During March 2018, a total of 40 soil samples were collected in 12 regions of the Czech republic. Before phthalate analysis, samples were extracted with a mixture of acetone-hexane (1:1). Using ultrasound was performed using high performance liquid chromatography with UV detection. Determined concentrations for DBP were from 0.13 to 1.07 mg.kg-1 dry weight and for DEHP from 0.13 to 1.02 mg.kg-1 dry weight.