Um dos grandes problemas da engenharia ambiental é a contaminação dos corpos hídricos. Os sanitaristas têm se preocupado com os hormônios sexuais, notadamente os estrógenos, compostos extremamente ativos biologicamente, que têm sido referidos como agentes etiológicos de feminilização e de vários tipos de cânceres. Os estrógenos naturais 17 \'beta\'-estradiol (E2), estriol (E3), estrona (E1) e o sintético 17 \'alfa\'-etinilestradiol (EE2), desenvolvidos para uso médico em terapias de reposição hormonal feminina e métodos contraceptivos, são os que despertam maiores preocupações, pela contínua introdução ao ambiente; hormônios que possuem a melhor conformação reconhecida pelos receptores que resultam respostas máximas, por isso são considerados responsáveis pela maioria dos efeitos disruptores desencadeados pela disposição de efluentes. A mudança de padrões quanto à atividade sexual dos jovens e a preocupação com o planejamento familiar, levaram ao grande consumo de contraceptivos que, através da urina, são levados pela rede coletora aos corpos de água. O indiscriminado uso desses hormônios na bovinocultura, suinocultura, avicultura e aqüicultura são responsáveis por parte considerável desse contaminante nos mananciais. Os hormônios excretados através da urina e fezes e agentes provenientes das indústrias de processamento de alimentos preocupam os sanitaristas porque o lançamento de efluentes in natura ou tratados, são as principais vias de contaminação do ambiente aquático, quer pelo déficit de infra-estrutura em saneamento, quer pela ineficiência tecnológica e/ou operacional na remoção desses compostos nas estações de tratamento de água ou de efluentes. Apesar de possuírem meia-vida relativamente curta, quando comparados a outros compostos orgânicos como praguicidas, os estrógenos naturais são continuamente introduzidos no ambiente, o que lhes confere caráter cumulativo. A proposta desta pesquisa foi verificar a presença de estrógenos na água bruta que chega à Estação de Tratamento de Água, após seu tratamento, em água tratada por osmose reversa e por tecnologia Milli Q (marca registrada). Para verificar e quantificar presença desses hormônios estrógenos em água de abastecimento de São Carlos-SP, foram realizadas exames através de imunoensaio quimiluminescente e radioimunoensaios. Os resultados apontaram que a ETA não possui solução eficiente para a remoção dos analitos de interesse dessa pesquisa, uma vez que na água tratada foram encontrados valores semelhantes aos da água bruta. / One of the major problems of environmental engineering is the water contamination. The sanitary persons have been concerned with the gonadal hormones, notably the estrogen, biologically active compounds extremely, which have been referred to as etiologic agents of feminization and several types of cancers. The natural estrogen 17 \'beta\'-estradiol (E2), estriol (E3), estrone (E1) and synthetic 17 \'alpha\'-ethinylestradiol (EE2), developed for medical use of hormone replacement therapy in women and contraceptive methods, are those that attract larger concerns by the continuous introduction into the environment; hormones that have the best conformation recognized by receptors that result answers maximum, so they are considered responsible for most of the effects disruptors triggered by the wastewater disposal. The change in patterns on the sexual activity of young people and the concern with family planning, led to the large consumption of contraceptives that, in the urine, are led by the distribution net to water. The indiscriminate use of these hormones in cattle, pigs, poultry and aquaculture are responsible for part of this contaminant in the source. The hormones excreted in the urine and feces and agents from the food processing industries in the sanitary concern that the launch of effluents in nature or treated, are the main routes of contamination of the aquatic environment, either by lack of infrastructure, sanitation, or by inefficiency technological and/or operating in the removal of these compounds in the treatment plants, water or effluent. Despite having relatively short stocking-lige when compared to other organics such as pesticides, natural estrogens are continuously released into the environment, which gives them character cumulative. The proposal of this research was to verify the presence of estrogen in the gross water that arrives at the water treatment plant, after the treatment, in water treated by reverse osmosis and by Milli Q technology. To verify and quantify presence of these hormones estrogen in water supply of San Carlos-SP, examinations were conducted through immunoassay chemiluminescent and radioimunoassays. The results showed that the ETA has no efficient solution for removal of interest analytes of this research, because in the treated water were found values similar to crude water.

Les perturbateurs endocriniens (PE) sont des polluants environnementaux naturels ou fabriqués par l'Homme capables d'interférer avec les systèmes hormonaux endogènes. Parmi ces molécules, le di(2-éthylhexyl) phtalate (DEHP) et le nonylphénol (NP) sont très répandus dans les produits du quotidien et figurent sur la liste des Substances Prioritaires de l'eau. Cependant, peu d'études s'intéressent au contrôle central de la reproduction suite à l'exposition adulte et à de faibles doses de ces PE. L'exposition chronique de souris mâles adultes à ces PE seuls ou combinés montre des altérations à des doses proches de l'exposition environnementale humaine et de la dose journalière tolérable. Nous avons constaté une diminution de l'émission des vocalisations ultrasonores (USV) et de l'attraction des femelles par les mâles exposés au DEHP. Ceci a pu être relié à une diminution de l'expression du récepteur des androgènes dans l'aire préoptique médiane, région clé dans l'expression du comportement sexuel mâle. Ces effets ont été inversés lors de l'arrêt de l'exposition au DEHP. L'exposition au NP augmente l'émission des USV et les nombres de montées, d'intromissions et de poussées pelviennes avant d'atteindre l'éjaculation. Par ailleurs, l'exposition au mélange provoque des altérations comportementales différentes de celles observées pour les molécules isolées. Ces résultats ont permis de mettre en évidence une vulnérabilité du circuit neural régulant l'expression du comportement sexuel à l'exposition à ces PE. Des cibles moléculaires ont également pu être identifiées, particulièrement pour le DEHP, aidant ainsi à la compréhension de leur mode d'action dans le système nerveux central / Endocrine disruptors are natural or man-made environmental pollutants capable of interfering with endogenous hormonal systems. Among these molecules, phthalates and particularly di(2-éthylhexyl) phtalate (DEHP) and nonylphenol are widely present in everyday products and classified as priority substances in the Water Framework Directive. These two molecules are highly studied but few publications address the neural control of reproductive behaviors following adult exposure to low doses of these molecules.Chronic exposure of adult male mice to these two molecules, alone or in combination, showed behavioral alterations at doses close to human environmental exposure and tolerable daily intake. We observed a decreased emission of ultrasonic vocalisations and attraction of receptive females by males exposed to DEHP. These behavioral alterations were related to down-regulation of the androgen receptor in the medial preoptic area, the key region involved in the expression of male sexual behavior. These behavioral and molecular effects were reversed by DEHP exposure arrest. Adult exposure to NP increased the emission of ultrasonic vocalisations and number of mounts, intromissions and pelvic thrusts, without any amelioration of sexual behavior. Interestingly, exposure to both molecules caused behavioral alterations, which are are different from those observed for each molecule alone.Altogether, these results highlight the vulnerability of the neural circuitry underlying sexual behavior to exposure to these molecules. Furthermore, molecular targets have been identified, particularly for DEHP, thereby helping to understand their mode of action in the central nervous system.

The normal operation of the endocrine (hormonal) system can be disrupted by a number of man-made and naturally-occurring chemicals, thereby affecting those physiological processes that are under hormonal control. Such substances are called endocrine disrupting compounds (EDCs). The endocrine disruption issue has alarmed the environmental authorities since the substances involved can hinder hormonal processes causing far-reaching effects on reproduction and development in current and future human and wildlife generations. Effects on some species of fish triggered worldwide concern and initiated a research scheme which is being undertaken by various organisations e.g. United States Environmental Protection Agency (USEPA), United Kingdom Environment Agency (UKEA), Oslo and Paris Commission (OSPAR), Japan Environment Agency (JEA) and World Wildlife Fund (WWF) in order to assess the effects (present and potential), point of generation, levels of contamination and exposure limits. The findings showed that most of the oestrogens are produced by humans and animals and get discharged into river streams mainly through sewage effluents. Fish in particular have been found to be affected the most even when the oestrogenic levels in water are very low. The probability of future European legislation to eliminate hormonally active compounds from wastewaters suggests that new and alternative methods should be developed for their removal. In this work, the adsorption of 17ß-oestradiol (E2) and 17a-ethinyl oestradiol (EE2) onto several granular activated carbons and Hypersol-Macronet hypercrosslinked polymers was investigated by batch experiments after a low level detection system had been developed using Gas Chromatography Mass Spectrometry (GC/MS). Equilibrium experiments were carried out for all adsorbents to quantify the sorption capacity for E2 and EE2. For better assessment of the sorbents performance, their physical properties such as surface area, average pore diameter and micropore volume and chemical structure were characterised by N2 adsorption experiments, scanning electron microscopy (SEM), FTIR spectroscopy, elemental analysis, sodium capacity determination, pH titration, proton binding curves and zeta potential measurements. Adsorption isotherm data were fitted to the Langmuir and Freundlich equations. Activated carbons were found to be preferable to Hypersol-Macronet hypercrosslinked polymers for adsorption purposes. The adsorption of oestrogens appears to be controlled by hydrophobic interactions. Kinetic experiments were performed with different size ranges of adsorbents at different concentrations and the results were analysed by a particle diffusion model. It was found that concentration did not seem to influence the kinetics of the oestrogen sorption whereas the particle size of the adsorbents influenced the adsorption rate of both molecules. The particle diffusion model seemed to fit the data collected for the adsorption rate of 17B-oestradiool onto the adsorbents but gave a poor fit for most of the data collected for 17a-ethinyl oestradiol.

Depuis le début des années 1990, de nombreuses équipes de recherche ont consacré leurs travaux à étudier les effets des perturbateurs endocriniens (PEs) sur l'homme et les espèces animales. Plusieurs polluants libérés dans l’environnement tels que les pesticides, les herbicides, les plastifiants industriels ou les résidus de médicaments ont ainsi le potentiel de perturber les équilibres hormonaux des organismes, induisant ainsi de graves conséquences sur leur développement et leur reproduction. Pour lutter contre ces dommages, diverses réglementations spécifiques et des systèmes de criblages se mettent en place pour détecter ces molécules. Ces systèmes doivent être rapides et fiables et les poissons téléostéens comme le medaka ou le poisson zèbre constituent d'excellents modèles pour détecter la présence de ces molécules et étudier leurs effets in vivo. Durant cette thèse nous avons étudié l’impact de certains PEs sur le développement embryonnaire en utilisant le poisson zèbre et le médaka comme modèle. Nous avons pu caractériser l'action du Bisphenol A sur la formation des otholites de l’oreille interne du poisson zèbre. En alliant des approches pharmacologiques et génétiques, nous avons identifié le récepteur nucléaire orphelin ERR comme une nouvelle cible in vivo de cette molécule. En parallèle, nous avons développé des lignées transgéniques rapportrices de médaka permettant de détecter la présence de polluants à activités androgénique ou anti-androgénique ce qui accroît ainsi la gamme des outils disponibles pour évaluer la présence des PEs dans les effluents liquides. / Since the early 1990s, many research teams have devoted their work to study the effects of endocrine disruptors (EDCs) in humans and animal species. Many pollutants released into the environment such as pesticides, herbicides, industrial plasticizers or drug residues have the potential to disrupt bodies’ hormonal balances, thus inducing a severe impact on their development and reproduction. To fight against these damages, various specific regulations and screening systems are setting up to detect these molecules. These systems must be fast, reliable. Teleost fish such as medaka and zebrafish are excellent models to detect the presence of these molecules and study their effects in vivo. In this thesis, we studied the impact of certain EDCs on the embryonic development using zebrafish and medaka as models. We characterized the action of Bisphenol A on the otoliths formation in the inner ear of zebrafish. By combining genetic and pharmacological approaches, we identified the orphan nuclear receptor ERRγas a new target of this molecule in vivo. In parallel, we have developed reporter transgenic lines of medaka to detect the presence of pollutants containing androgenic or anti-androgenic activities and thereby increasing the range of tools available to assess the presence of EDCs in liquid effluents.

Les produits phytosanitaires contiennent des molécules qui peuvent interférer avec le système endocrinien et induire des effets délétères sur les êtres vivants. Ce sont des perturbateurs endocriniens. Afin d’assurer un niveau de protection satisfaisant pour les mollusques aquatiques, une bonne compréhension des perturbations du système endocrinien est nécessaire. L’organisation pour le développement et la coopération économique s’est exprimée en faveur de la mise en place de protocoles standards d’écotoxicité chez les mollusques, notamment sur la reproduction, dans le cadre des processus d’évaluation du risque écologique et des autorisations de mise sur le marché de nouvelles molécules. Cette thèse vise à proposer des tests standards et des outils d’analyse afin d’évaluer les effets de substances chimiques chez un escargot d’eau douce, Lymnaea stagnalis. Une série de tests de toxicité a été conduite dans laquelle les limnées ont été exposées à des androgènes, des oestrogènes et dessolvants. Les effets observés ont été évalués à l’aide d’approches statistiques standards et d’un modèle de toxicokinétique-toxicodynamique (TKTD). Les limnées ont montré une sensibilité uniquement au tributyltin et triphényltin à des concentrations réalistes d’un point de vue environnemental. Le triéthylène glycol et l’acétone étaient les solvants les moins nocifs. De plus, le modèle TKTD suggère un mécanisme généraliste dans l’action du composé. La manifestation des perturbations endocriniennes chez L. Stagnalis restent évasives et nécessitent d’autres recherches. Enfin, la thèse a montré que / Plant protection products and biocides may contain chemicals that interfere with the endocrine system and consequently induce adverse effects on wildlife. Such chemicals are known as endocrine disruptors (EDs). To ensure a satisfactory protection level for aquatic molluscs a comprehensive understanding of endocrine disruption is needed. The Organisation for Economic Co-operation and Development supports the standardisation of toxicity tests guideline on mollusc reproductive toxicity, which is intended for environmental risk assessments purposes. This PhD thesis aimed at improving toxicity test protocols and data analysis tools to evaluate effects of chemicals on the great pond snail Lymnaea stagnalis. A suite of toxicity tests was conducted in which snails were exposed to putative androgens (tributyltin, triphenyltin, methyltestosterone), putative oestrogens (alkylphenols and ethynyloestradiol), and solvents. Resulting effects were evaluated using standard statistical approachesand/or a toxicokinetic-toxicodynamic (TKTD) model. Snails were sensitive to tributyltin and triphenyltin, while none of the oestrogenic chemicals and methyltestosterone significantly impacted animals at environmentally relevant concentrations. Triethylene glycol and acetone were the least harmful solvents. Further, the analysis of data from the tributyltin test with the TKTD model suggested a generic mechanism of action of the compound (i.e., not specific for EDs). The demonstration of endocrine disruption in L. stagnalis remained elusive and deserves further research. Finally, the thesis highlight

Orientador: Wilson de Figueiredo Jardim / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Quimica / Made available in DSpace on 2018-08-07T20:01:49Z (GMT). No. of bitstreams: 1 Ghiselli_Gislaine_D.pdf: 7893135 bytes, checksum: 77abd572fbade3721ea074ed0616e34b (MD5) Previous issue date: 2006 / Doutorado / Quimica Analitica / Doutor em Quimica

Orientador: Wilson de Figueiredo Jardim / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Química / Made available in DSpace on 2018-08-26T13:39:08Z (GMT). No. of bitstreams: 1 Pescara_IgorCardoso_D.pdf: 5286232 bytes, checksum: 74793adc4ea590e2eb8fdeb51a796399 (MD5) Previous issue date: 2014 / Resumo: Este trabalho teve como objetivo avaliar a eficiência dos tratamentos empregados em cinco estações de tratamento de esgoto (ETE) e duas estações de tratamento de água (ETA) na remoção dos hormônios endógenos estrona (E1), 17?-estradiol (E2), estriol (E3), testosterona (TTN) e progesterona (PROG), hormônios sintéticos 17a-etinilestradiol (EE2), dietilestilbestrol (DES), norgestrel (NGT) e mestranol (MEE), produtos de uso industrial bisfenol A (BPA), fenolftaleína (PhPh), n-nonilfenol (nNP), n-octilfenol (nOP) e triclosan (TCS), o fármaco cafeína (CAF) e o pesticida atrazina (ATZ). Foi possível quantificar BPA, E1, E3, CAF e ATZ em esgoto bruto e BPA, E1, CAF e ATZ em água bruta. Para cada composto, tanto os tratamentos realizados pelas ETE quanto os realizados pelas ETA apresentaram eficiências de remoção variáveis. A cafeína foi o composto-alvo mais frequentemente encontrado nas amostras, sendo escolhida como indicador químico para avaliar a eficiência dos tratamentos. Foi encontrada uma taxa média de 99% para a remoção de CAF pelas ETE, sendo as etapas com tratamentos biológicos as mais eficientes. Os tratamentos anaeróbios apresentaram remoções médias superiores a 80% na remoção de CAF, e os tratamentos aeróbios foram capazes de remover cerca de 20% da carga do composto. Nas ETE, os tratamentos de coagulação e desinfecção foram pouco eficientes nas remoções dos compostos-alvo. Já para as ETA, foram observadas remoções de até 80% de CAF pelos tratamentos empregados, sendo a etapa de coagulação a responsável pela maior remoção de CAF da água bruta. A etapa de filtração em carvão ativado apresentou eficiências de remoção menores que 10%, enquanto a desinfecção demonstrou baixa eficiência na remoção de CAF. Na cidade de São José do Rio Preto ¿ SP foi possível quantificar, ao menos uma vez, BPA, E1, E3, PhPh, CAF, TCS e ATZ em água superficial, BPA, TCS e CAF em água subterrânea e BPA, CAF e ATZ em água de abastecimento. / Abstract: Water and wastewater conventional treatments are often considered inefficient to remove micropollutants. The aim of this work was to evaluate the removal efficiency of the endogenous hormones estrone (E1), 17? estradiol (E2), estriol (E3), testosterone (TTN), and progesterone (PROG), the synthetic hormones 17a-ethinylestradiol (EE2), diethylstilbestrol (DES), norgestrel (NGT), and mestranol (MEE), the industrial chemicals bisphenol A (BPA), phenolphthalein (PhPh), n nonylphenol (nNP), n octylphenol (nOP), and triclosan (TCS), the pharmaceutical caffeine (CAF), and the pesticide atrazine (ATZ) by five wastewater treatment plants (WWTP) and two drinking water treatment plants (DWTP). The target compounds BPA, E1, E3, CAF, and ATZ were found in raw sewage, while BPA, E1, CAF, and ATZ in raw water. Both WWTP and DWTP treatments presented variable removal efficiency. Caffeine was the target compound more often detected in samples, thus it was chosen as a chemical indicator to evaluate treatment efficiencies. The average removal of CAF by WWTP was 99%, in which the biological treatment was more efficient. The anaerobic treatment presented an average removal of CAF above 80%, and around 20% for the aerobic treatments. Coagulation and disinfection treatments of WWTP showed low efficiency to remove the target compounds. DWTP treatment efficiency reached up to 80% removal, with coagulation step presenting highest removals of CAF. The activated carbon filtration showed removal efficiency under 10%, whereas the disinfection step presented low efficiency to remove CAF. At São José do Rio Preto city were found, at least once, BPA, E1, E3, PhPh, CAF, TCS, and ATZ in surface water; BPA, TCS, and CAF in groundwater, and BPA, CAF, and ATZ in drinking water / Doutorado / Quimica Analitica / Doutor em Ciências

<p>Nespu&scaron;teni testis predstavlja odsustvo testisa u skrotumu sa jedne ili obe strane. Faktori rizika za pojavu nespu&scaron;tenog testisa obuhvataju genetsku predispoziciju, prevremeno rođenje, nisku porođajnu masu i prenatalnu izloženost endokrinim disruptorima ili duvanskom dimu. Endokrini disruptori se defini&scaron;u kao egzogene supstance koje imaju uticaj na homeostazu organizma i proizvodnju reproduktivnih hormona. U ovoj grupi nalaze se organofosforni pesticidi koji se &scaron;iroko upotrebljavaju u poljoprivredi. Većina organofosfornih pesticida ima antiandrogeni uticaj i uz činjenicu da živimo u pretežno agrarnoj sredini predmet su na&scaron;eg interesovanja. Cilj istraživanja je da se utvrdi razlika u izloženosti organofosfornim pesticidima kori&scaron;ćenjem upitnika kreiranog po modelu standardizovanog Evropskog upitnika QLK 4-1999-01422 kod osoba koje su rodile zdravu mu&scaron;ku decu i osoba koje su rodile decu sa nespu&scaron;tenim testisom. Pored toga, cilj istraživanja je i da se odredi i uporedi vrednost metabolita organofosfornih pesticida (dimetilfosfat, dimetilditiofosfat, dietilfosfat, dietiltiofosfat i dietilditiofosfat) u urinu majki koje su rodile mu&scaron;ku decu sa nespu&scaron;tenim testisima i majki koje su rodile zdravu mu&scaron;ku decu. Metodologija: Rad je radomizovano, prospektivno, kliničko istraživanje sprovedeno na Klinici za ginekologiju i aku&scaron;erstvo Kliničkog centra Vojvodine i Katedri za farmakologiju i toksikologiju Medicinskog fakulteta, Univerziteta u Novom Sadu. U kliničko istraživanje uključeno je 50 porodilja koje su rodile mu&scaron;ku decu sa nespu&scaron;tenim testisima (eksperimentalna grupa) i 53 porodilje koje su rodile zdravu mu&scaron;ku decu (kontrolna grupa) u periodu od oktobra 2012. godine do aprila 2018. godine. Tokom boravka u porodili&scaron;tu ispitanice su popunjavale upitnik o navikama nakon čega im je uzet uzorak urina radi analiziranja nivoa metabolita OF pesticida. Uzorci urina su pripremljeni metodom koju su opisali Wu i saradnici 2010. godine, a potom analizirani na gasnom hromatografu masenom spektrofotometaru marke Agilent 7890A. Rezultati: Ispitivane grupe se ne razlikuju po starosti ispitanica (prosečna starost kontrolne grupe 29,41 &plusmn; 5,58 godina, a eksperimentalne 30,54 &plusmn; 4,87 godina). U obe grupe prosečno je ispitanicama ovo bila druga trudnoća. Ispitanice se nisu razlikovale ni po načinu porođaja. Prosečna gestacijska nedelja trudnoće na porođaju iznosila je 39,45 &plusmn; 1,38 nedelja za kontrolnu grupu i 39,20 &plusmn; 1,38 nedelja za eksperimentalnu grupu, a porođajna masa novorođenčeta 3527,30 &plusmn; 470,16 g u kontrolnoj grupi i 3404,37 &plusmn; 508,20 g u eksperimentalnoj grupi. Statistički značajna razlika postoji u odnosu na mesto stanovanja (50,9 % ispitanica kontrolne grupe i 77,6 % ispitanica eksperimentalne grupe žive u gradu), jedinicu stanovanja (67,9 % kontrolne i 45,7 % ispitanica eksperimentalne grupe žive u kući) i načinu začeća (6 % ispitanica eksperimentalne i 1,9 % ispitanica kontrolne grupe prijavilo je IVF kao način začeća). Skoro polovina ispitanica obe grupe su pu&scaron;ači, a njih 32,7 % kontrolne grupe i 38,8 % eksperimentalne pu&scaron;ile su i tokom trudnoće. Izloženost pesticidima prijavilo je 50,9 % ispitanica kontrolne i 44 % ispitanica eksperimentalne grupe, a profesionalnu izloženost prijavilo je 3 ispitanice kontrolne i 2 ispitanice eksperimentalne grupe. Ispitanice se ne razlikuju ni po poreklu voća i povrća koje konzumiraju, kao ni po vrsti voća koje su konzumirale tokom trudnoće. Prosečne izmerene vrednosti DMF u kontrolnoj grupi iznose 5,604 &plusmn; 6,103 ug/L, a u eksperimentalnoj 4,815 &plusmn; 6,729 ug/L. Izmerene vrednosti DEF u kontrolnoj grupi su 0,408 &plusmn; 0,447 ug/L, a u eksperimentalnoj 0,461 &plusmn; 0,593 ug/L. Nivo DMDTF u kontrolnoj grupi bio je 0,431 &plusmn; 0,508 ug/L, a u eksperimentalnoj 0,547 &plusmn; 0570 ug/L, a DETF 0,403 &plusmn; 0,606 ug/L u kontrolnoj i 0,529 &plusmn; 0,725 ug/L u eksperimentalnoj grupi. Ni jedan metabolit ne pokazuje statistički značajnu razliku u ispitivanim grupama. Slične vrednosti dobijene su i za vrednosti korigovane za nivo kreatinina. Univarijantna regresiona analiza pokazala je da ispitanice koje žive u gradu imaju 3,3 puta veće &scaron;anse da rode dete sa nespu&scaron;tenim testisom, a one koje žive u stanu imaju 2,5 puta veće &scaron;anse za isti ishod. Statistički značajna razlika primećena je u nivou DEDTF u zavisnosti od starosti ispitanica i jedinici stanovanja. Vi&scaron;e vrednosti DETF dobijene su kod ispitanica koje su bile na hormonskoj terapiji tokom trudnoće. Ispitanice koje su prijavile da su bile izložene pesticidima tokom trudnoće u urinu su imale statistički značajno vi&scaron;e vrednosti DMDTF u odnosu na ispitanice koje su se izjasnile da nisu bile izložene pesticidima. Slični rezultati za vrednost DEDTF dobijeni su kod ispitanica koje su se izjasnile da poseduju kućne ljubimce. Statistički vi&scaron;e vrednosti DEF i DETF korigovano za nivo kreatinina dobijene su kod ispitanica koje nisu konzumirale jabuke, a vi&scaron;e vrednosti DEF i DEDTF dobijene su kod ispitanica koje su konzumirale maline i kupine tokom trudnoće. Ostale grupe nisu pokazale statistički značajnu razliku među ispitivanim grupama. Zaključci: Izloženosti trudnica OF pesticidima nije značajno veća u grupi majki koje su rodile decu sa nespu&scaron;tenim testisom u odnosu na izloženost OF pesticidima kod majki zdrave mu&scaron;ke dece. Vrednosti metabolita OF pesticida (dimetilfosfat, dimetilditiofosfat, dietilfosfat, dietiltiofosfat, dietilditiofosfat) u urinu majki koje su rodile mu&scaron;ku decu sa nespu&scaron;tenim testisima nije vi&scaron;a u odnosu na vrednosti metabolita OF pesticida (dimetilfosfat, dimetilditiofosfat, dietilfosfat, dietiltiofosfat, dietilditiofosfat) izmerene u jutarnjem urinu majki koje su rodile zdravu mu&scaron;ku decu.</p> / <p>Undescended testis is the absence of testis in the scrotum on one or both sides. Risk factors for the occurrence of undescended testis include genetic predisposition, premature birth, low birth weight and prenatal exposure to endocrine disruptors or tobacco smoke. Endocrine disruptors are defined as exogenous substances that can affect homeostasis of the organism and the production of reproductive hormones. In this group are organophosphorus pesticides that are widely used in agriculture. Most of organophosphorus pesticides have anti-androgenic effect and with the fact that we live in a predominantly agricultural area, they are the focus of our interest. The aim of the research: The aim of this study is to determine the difference in exposure to organophosphorous pesticides using questionnaires created by standardized European model questionnaire QLK 4-1999-01422 in individuals who gave birth to a healthy male children and women who gave birth to children with undescended testis. In addition, the aim of this study is to determine and compare the value of metabolites of organophosphorus pesticides (dimethylphosphate, dimethyldithiophosphate, diethylphosphate, diethylthiophosphate and diethyldithiophosphate) in the urine of mothers who gave birth to male children with undescended testis and mothers who gave birth to healthy male children. Methodology: This work is randomized, prospective, clinical research conducted at the Clinic for gynaecology and obstetrics of the Clinical center of Vojvodina and the Department of Pharmacology and toxicology of the Faculty of Medicine, University of Novi Sad. This clinical research includes 50 new mothers that gave birth to male children with undescended testes (experimental group) and 53 new mothers that gave birth to healthy male children (control group) in the period from October 2012 to April 2018. During their stay at the maternity hospital the subjects were asked to fill out a questionnaire about habits and to give a urine sample for analyzing the level of metabolites of organophosphus pesticides. Urine samples were then prepared using the method described by Wu and associates 2010, and analyzed on gas chromatograph with a mass spectrophotometer Agilent 7890A brand. Results: Study groups do not differ according to the age of women (average age of control group is 29.41 &plusmn; 5.58 years, and experimental 30.54 &plusmn; 4.87 years). In both groups this was second pregnancy on average. The subjects did not distinguish either by the way of delivery. The average gestational weeks of pregnancy to childbirth was 39.45 &plusmn; 1.38 weeks for the control group and 39.20 &plusmn; 1.38 weeks for the experimental group, and birth weight of newborn was 3527.30 &plusmn; 470.16 g in control group and 3404.37 &plusmn; 508.20 g in the experimental group. There is no statistically significant difference in relation to the place of residence (50.9 % of the control group and 77.6 % of experimental live in the city), the living unit (67.9 % and 45.7 % of the control and experimental groups are living in the house) and the way of conception (6 % of experimental and 1.9 % of the control group reported IVF as a way of conception). Nearly half of both groups are smokers, and 32.7 % of women in the control group and 38.8 % in experimental smoked during pregnancy. Exposure to pesticides reported 50.9 % of mothers in control and 44 % of mothers in the experimental group. Professional exposure was reported by 3 control subjects and 2 subjects in experimental group. The subjects did not differ according to the origin of fruits and vegetables they were consuming, neither regarding the type of fruits they consumed during pregnancy. Average level of dimethylphosphate in control group was 5.604 &plusmn; 6.103 ug/L, and in experimental 4.815 &plusmn; 6.729 ug/l. Levels of diethylphosphate in control group were 0.408 &plusmn; 0.447 ug/L, and in experimental 0.461 &plusmn; 0.593 ug/l. DMDTP level in the control group was 0.431 &plusmn; 0.508 ug/L, and in experimental 0.547 &plusmn; 0570 ug/L, and the DETP was measured 0.403 &plusmn; 0.606 ug/L in control, and 0.725 &plusmn; 0.529 ug/L in the experimental group. These metabolites showed no statistically significant difference in the examined groups. Similar values are obtained for the adjusted values for creatinine level. Univariate regression analysis showed that the subjects who live in town are 3.3 times more likely to have child with undescended testis, and those who live in the apartment are 2.5 times more likely for the same outcome. Statistically significant difference was noticed in DEDTP level depending on the age of the subject and the living unit. Higher levels of DETP metabolites were detected in subjects that have been on hormonal therapy during pregnancy. The subjects who reported being exposed to pesticides during pregnancy had statistically significantly higher DMDTP values in relation to the subjects that were not exposed to pesticides. Similar results are obtained for the DEDTP level with higher levels in subjects owning pets. Statistically higher levels of DEP and DETP adjusted for creatinine were obtained in subjects that were not reporting eating apples, and higher levels of DEP and DEDTP were obtained in subjects that consumed raspberries and blackberries during pregnancy. Other groups showed no statistically significant difference between the study groups. Conclusion: Exposure of pregnant women to OP pesticides is not significantly greater in the group of mothers who gave birth to children with undescended testis in relation to exposure to OP pesticides in mothers of healthy male children. The level of OP metabolites (dimethylphosphate, dimethyldithiophosphate, diethylphosphate, diethylthiophosphate and diethyldithiophosphate) in the urine of mothers who gave birth to children with undescended testis is not higher in relation to the levels of OP metabolites (dimethylphosphate, dimethyldithiophosphate, diethylphosphate, diethylthiophosphate and diethyldithiophosphate) recorded in urine of mothers who gave birth to healthy male children.</p>

Abstract  Sellfrid, M. (2019) The occurrence of endocrine disruptors in objects on Swedish preschools: A quantitative study on the relationship between occurrence and self-rated knowledge and/or construction year. Bachelor thesis in Public Health Science. Department of Occupational and Public Health Science. Faculty of Health and Occupational Studies. University of Gävle, Sweden.  Objective: The aim of this study is to investigate the occurrence of items containing Bisphenol A, forbidden phthalates and brominated flame retardants in all preschools in a Swedish municipality. Furthermore, to study whether the occurrence may have a connection with the factors self-related knowledge of the staff and/or construction year.  Method: The study is an explorative quantitative study using questionnaires answered anonymously by 270 preschool teachers out of 354. An inventory of all 24 preschools in the municipality was performed to investigate the occurrence. The numeric data was analyzed using an analysis of variances (Anova) or a Chi Square test.  The Results showed that the presence of objects containing endocrine disruptors clearly differed between preschools. Furthermore, the study finds that there is a significant correlation between the occurrence and the preschool's construction year (p= &lt;0,001). On the other hand, there are no significant connections between the occurrence and the self-rated knowledge of the teachers (p=0,985).  Conclusion: the older a preschool is, the more likely it is to have a higher occurrence of items containing these chemicals. The most logical reasons for this are that older preschools have the same items now as decades ago and donated items occur in a greater extent. / Syftet med studien var att undersöka förekomsten av lösa föremål som innehåller de hormonstörande ämnena Bisfenol A, Ftalater och Bromerade flamskyddsmedel på samtliga förskolor i en svensk kommun. Vidare att studera om förekomsten kan ha ett samband med faktorerna byggnadsår och/eller förskolepersonalens självskattade kunskap.   Examensarbetet är en empirisk studie med en explorativ studiedesign. Metoden som använts är kvantitativ och all insamlade data är numerisk. En inventering av 24 förskolor genomfördes för att få reda på hur många föremål med potentiella hormonstörande effekter som fanns i respektive förskola. Utöver det fick all förskolepersonal (354st) möjlighet att besvara ett frågeformulär utformat så att respondenterna själva får uppskatta sina kunskaper inom ämnet miljögifter och hormonstörande ämnen, 270st valde att delta. Både fast anställda och vikarier inkluderades, medan köks- och städpersonal exkluderades. All data hanterades i IBM:s programvara SPSS Statistics, version 24. Beroende på vilken variabel som undersöktes genomfördes antingen Chi2-analyser eller envägs variansanalyser (Anova) för att besvara studiens frågeställningar.  Resultatet visade att förekomsten av föremål innehållande hormonstörande ämnen skiljde sig tydligt mellan förskolorna. Vidare kan studien konstatera att det finns ett signifikant samband mellan förekomsten och förskolans byggnadsår (p= &lt;.001). Äldre förskolor hade äldre leksaker och kemikalierna som undersöks återfinns i dessa föremål. I studien finns inga signifikanta samband mellan förekomsten och personalens självskattade kunskap (p=.985).   Slutsatsen blir att ju äldre förskolan är desto större sannolikhet är det att föremål med Bisfenol A, förbjudna ftalater och bromerade flamskyddsmedel förekommer. Anledningen till det är för att förskolorna har kvar samma föremål som för decennier sedan och har samlat på sig donerade föremål över tid.

Le bisphénol A (BPA) est une molécule dérivée du plastique, considéré comme un perturbateur endocrinien (PE) pour sa capacité de liaison aux récepteurs nucléaires (RNs). Il est associé à des troubles neurodéveloppementaux, probablement en raison de la présence de certains RNs dans le cerveau des vertébrés. Les PEs peuvent également affecter les invertébrés marins, dont les ascidies, mais leur mode d'action reste inconnu. Mon projet de thèse a pour but d’étudier la toxicité du BPA sur le développement embryonnaire de l'ascidie Phallusia mammillata. Tout d’abord, j’ai évalué l’expression des RNs de P. mammillata et j’ai trouvé que 5 d’entre eux (COUP, ERR, PPAR, PXR/VDR) sont exprimés dans le cerveau de l’ascidie (= vésicule sensorielle) ou à proximité (TR). Ils correspondent majoritairement aux orthologues humains connus pour lier le BPA. Puis, j’ai évalué la toxicité du BPA au cours du développement et constaté qu’il est toxique de façon dose-dépendante. En effet, j’ai montré que de faibles doses de BPA induisent une toxicité neurodéveloppementale en affectant la différenciation de l'organe sensoriel pigmenté de l’ascidie. Ce phénotype est spécifique aux bisphénols. Enfin, l’étude d’agonistes et d’antagonistes de l’estrogen-related receptor (ERR) a montré des phénotypes correspondant à ceux obtenus avec le BPA. J’ai trouvé que Pm-ERR est exprimé dans la vésicule sensorielle de la larve, autour de l'organe sensoriel pigmenté. Il semble donc que Pm-ERR est impliqué dans ce phénotype. Toutefois, la présence des autres RNs que j’ai identifiés soulève la possibilité de leur implication dans le développement de l’ascidie et/ou de la toxicité de PEs. Ils ne doivent donc pas être négligés. / Bisphenol A (BPA) is a plastic-derived molecule that is now considered an endocrine disruptor (ED). BPA impair hormonal systems via binding to nuclear receptors (NRs) and it has been linked to neurodevelopmental disorders, possibly due to the presence of some NRs in the vertebrate brain. BPA has been reported to affect marine invertebrates such as ascidians, but how is BPA acting is not known. My PhD project is aimed at deciphering the toxicity of BPA on embryonic development of the marine invertebrate chordate Phallusia mammillata (Tunicata). Firstly, I assessed the embryonic expression of P. mammillata NRs and found that 5 are expressed within the ascidian brain (also called sensory vesicle, SV) (COUP, ERR, PPAR, PXR/VDR) or nearby (TR). Interestingly, the human orthologues of most of these NRs are known to bind BPA. Secondly, I assessed BPA toxicity during P. mammillata embryonic development and found that BPA is toxic in a dose-dependent manner. I also show that at micromolar doses BPA induces neurodevelopmental toxicity by impairing differentiation of the ascidian pigmented sensory organ (PSO). I further show that this phenotype is specific to bisphenols. Finally, estrogen-related receptor (ERR) agonists and antagonists partially phenocopied BPA phenotype. Interestingly, I found that Pm-ERR is expressed in the larval SV close to the ascidian PSO, thus suggesting an involvement of Pm-ERR in the BPA phenotype. Furthermore, the complex pleiotropic action of BPA together with the presence of other NRs in the ascidian larval brain raises the possibility that these NRs are involved both in ascidian brain development and EDs toxicity, thus they should not be overlooked.