Le cancer de la prostate (CaP) est la pathologie tumorale la plus fréquente chez les hommes dans les pays occidentaux. L’âge avancé, les origines ethno-géographiques et la présence d’antécédents familiaux de CaP sont les principaux facteurs de risque clairement établis. Les expositions aux substances chimiques issues de l’activité humaine, en particuliers ceux présentant des propriétés hormonales (perturbateurs endocriniens), sont suspectées. L’objectif général cette thèse est d’étudier le rôle de certains polluants universels présentant des propriétés hormonales, tels que le DDE (principal métabolite du DDT) et les PCBs, ainsi que celui des polymorphismes de gènes codant pour des enzymes intervenant dans le métabolisme des xénobiotiques (GSTM1, GSTT1) et des œstrogènes (CYP17, CYP19, CYP1B1, COMT, UGT1A1) dans la survenue du CaP ou de sa récidive après traitement par prostatectomie radicale. Ce projet s’appuie sur les données obtenues lors de l’étude cas-témoins en population générale en Guadeloupe (KARUPROSTATE) et de la file active des cas traités par prostatectomie radicale. / Prostate cancer (PCa) is the most frequent type of cancer in Western countries. Advanced age, ethno-geographic origin and the presence of a family history of CaP are the main clearly established risk factors. The effects of exposure to synthetic chemicals with hormonal properties, also called endocrine disruptors (EDCs), on PCa are also are suspected. The main objective of this thesis is to evaluate the relationships between plasma concentration of persistent organochlorine pollutants with hormonal properties, such as DDE (the main metabolite of DDT) and PCBs as well polymorphisms of selected genes involved in xenobiotic (GSTM1, GSTT1) and estrogens (CYP17, CYP19, CYP1B1, COMT, UGT1A1) metabolism, and the occurrence of PCa or its recurrence after treatment with radical prostatectomy. This project is based on data obtained from the population-based case-control study (KARUPROSTATE) in Guadeloupe and from cases treated by radical prostatectomy.

<p>The effects of environmental contaminants in humans and animals are of great concern. Some contaminants are endocrine disruptors that may interfere with the endogenous hormonal signalling and disturb, for example, reproductive organs and functions.</p><p>Primary uterine myometrial cells originating from women and Baltic grey seals were exposed to some polychlorinated biphenyls (PCBs) and their metabolites. Even though human and Baltic grey seal myometrial cells responded differently to the tested PCBs, the results indicate that PCBs can influence myometrial cell proliferation <i>in vitro</i>.</p><p>The prevalence of uterine leiomyomas was investigated among 257 Baltic grey seals. Leiomyomas were only present in females older than 22 years, at a prevalence of 65%. Proliferation in leiomyoma cells was detected in individuals lacking ovarian proliferation support, suggesting the presence of an exogenous stimulant. By taking into account temporal alterations in the contaminant burden of the seals, PCB exposure was found to be associated with leiomyoma prevalence. In conclusion, PCB exposure may be related to uterine leiomyoma development and proliferation in Baltic grey seals <i>in vivo</i>.</p><p>Human endometrial endothelial cells (HEECs) were exposed to some endocrine disruptors, and the effects of the endocrine disruptors on cell proliferation and viability were studied. All evaluated endocrine disruptors decreased HEEC proliferation and most also decreased HEEC viability. Further studies revealed that the reduction in HEEC proliferation after exposure to o,p’-DDT was associated with differential expression of mRNA involved in proliferation, defence response, and lipid and cholesterol metabolism compared to untreated HEEC. </p><p>In conclusion, these studies suggest that endocrine disruptors affect cultured cells from the female reproductive tract of humans and grey seals, and may have deleterious effects on proliferation, viability, and genes involved in defence response, and lipid or cholesterol metabolism.</p>

The effects of environmental contaminants in humans and animals are of great concern. Some contaminants are endocrine disruptors that may interfere with the endogenous hormonal signalling and disturb, for example, reproductive organs and functions. Primary uterine myometrial cells originating from women and Baltic grey seals were exposed to some polychlorinated biphenyls (PCBs) and their metabolites. Even though human and Baltic grey seal myometrial cells responded differently to the tested PCBs, the results indicate that PCBs can influence myometrial cell proliferation in vitro. The prevalence of uterine leiomyomas was investigated among 257 Baltic grey seals. Leiomyomas were only present in females older than 22 years, at a prevalence of 65%. Proliferation in leiomyoma cells was detected in individuals lacking ovarian proliferation support, suggesting the presence of an exogenous stimulant. By taking into account temporal alterations in the contaminant burden of the seals, PCB exposure was found to be associated with leiomyoma prevalence. In conclusion, PCB exposure may be related to uterine leiomyoma development and proliferation in Baltic grey seals in vivo. Human endometrial endothelial cells (HEECs) were exposed to some endocrine disruptors, and the effects of the endocrine disruptors on cell proliferation and viability were studied. All evaluated endocrine disruptors decreased HEEC proliferation and most also decreased HEEC viability. Further studies revealed that the reduction in HEEC proliferation after exposure to o,p’-DDT was associated with differential expression of mRNA involved in proliferation, defence response, and lipid and cholesterol metabolism compared to untreated HEEC. In conclusion, these studies suggest that endocrine disruptors affect cultured cells from the female reproductive tract of humans and grey seals, and may have deleterious effects on proliferation, viability, and genes involved in defence response, and lipid or cholesterol metabolism.

No description available.

abstract: Endocrine disruptors are chemicals that interact with the hormone system to negative effect. They ‘disrupt’ normal processes to cause diseases like vaginal cancer and obesity, reproductive issues like t-shaped uteri and infertility, and developmental abnormalities like spina bifida and cleft palate. These chemicals are ubiquitous in our daily lives, components in everything from toothpaste to microwave popcorn to plastic water bottles. My dissertation looks at the history, science, and regulation of these impactful substances in order to answer the question of how endocrine disruptors appeared, got interpreted by different groups, and what role science played in the process. My analysis reveals that endocrine disruptors followed a unique science policy trajectory in the US, rapidly going from their proposal in 1991 to their federal regulation in 1996, even amid intense and majority scientific disagreement over whether the substances existed at all. That trajectory resulted from the work of a small number of scientist-activists who constructed a concept and category as scientific, social, and regulatory. By playing actors from each sphere against each other and advancing a very specific scientific narrative that fit into a regulatory and social window of opportunity in the 1990s, those scientist-activists made endocrine disruptors a national issue that few could ignore. Those actions resulted in the Endocrine Disruptor Screening Program, a heavily-criticized and ineffective regulatory program. My dissertation tells a story of the past that informs the present. In 2018, the work of researchers, public media, and policymakers in the 1990s continues to play out, evident in the deep scientific division over endocrine disrupting effects and the inability of the European Union to settle on even a definition of endocrine disruptors for regulation purposes. / Dissertation/Thesis / Doctoral Dissertation Biology 2018

Para o desenvolvimento dos sensores aqui descritos foram utilizados materiais inovadores considerando relatos atuais da literatura, materiais estes: óxido de grafeno, óxido de grafeno reduzido, nanocompósitos de grafeno e nanopartículas (ródio, antimônio e sílica mesoporosa desordenada), materiais híbridos a base de grafeno e quantum dots de CdTe, além de biossensores incorporando a enzima lacase. Estes materiais foram sintetizados utilizando metodologias específicas e caracterizados por diversas técnicas analíticas como microscopia eletrônica de transmissão de alta resolução, microscopia de força atômica, espectroscopia Raman, difração de raios-X, espectroscopias de UV-Vis e fotoluminescência, e técnicas eletroquímicas. Posteriormente, os materiais foram utilizados para modificação em eletrodos de carbono vítreo e utilizados na determinação de interferentes endócrinos (os hormônios estriol e 17&beta;-estradiol) como sensores eletroquímicos em amostras ambientais e clínicas. Em essência, os eletrodos desenvolvidos apresentaram importantes vantagens, tais como alta sensibilidade, boa reprodutibilidade, simples instrumentação, fácil preparação e procedimentos analíticos rápidos, apresentando baixos limites de detecção, na ordem de picomolar e nanomolar, com baixa taxa de interferência de outras espécies na mesma matriz da amostra. Concluindo assim que as técnicas eletroquímicas podem ser facilmente aplicadas na determinação de interferentes endócrinos em amostras reais. / For the development of the sensors described here innovators materials were used considering current literature reports, these materials: Graphene oxide, reduced graphene oxide, nanocomposites graphene and nanoparticles (rhodium and antimony), hybrid materials of graphene and CdTe quantum dots, and biosensors incorporating the laccase enzyme. These materials were synthesized using specific methodologies and characterized by several analytical techniques such as transmission electron microscopy, high resolution transmission electron microscopy, atomic force microscopy, Raman spectroscopy, X-ray diffraction, UV-Vis and photoluminescence spectroscopy and electrochemical techniques. Subsequently, the materials were used for modification of glassy carbon electrodes to the determination of endocrine disruptors (estriol and 17&beta;-estradiol hormone) as electrochemical sensors for environmental and clinical samples. In essence, developed electrodes showed important advantages such as high sensitivity, good reproducibility, simple instrumentation, easy preparation and quick analytical procedures, with low detection limits in the range of picomolar and nanomolar, low interference rate of other species in same matrix sample. Finally, electrochemical techniques can be easily applied in the determination of endocrine disruptors in real samples.

Contexte : Les phtalates et les phénols sont des perturbateurs endocriniens. Les données concernant leurs effets sur la croissance fœtale et durant l'enfance sont limitées et suggèrent un effet dépendant du sexe de certains phénols sur le poids de naissance. Une des limites de ces études est l'estimation de l'exposition, basée sur la mesure de leurs concentrations dans un petit nombre d'échantillons d'urine maternelle. En raison de la faible persistance de ces composés chimiques dans l'organisme, les concentrations urinaires varient dans le temps. Les concentrations dosées dans d'autres matrices comme le liquide amniotique pourraient être pertinentes pour estimer l'exposition fœtale.Objectifs : Les objectifs de la thèse étaient : 1) d'étudier les impacts potentiels de l'exposition prénatale aux phénols et aux phtalates sur la croissance du fœtus et de l'enfant ; 2) de caractériser la variabilité des concentrations urinaires de phénols au long de la grossesse et de comparer les concentrations de phénols dosées dans le liquide amniotique et l'urine maternelle recueillis le même jour ; 3) de caractériser le biais et l'impact sur la puissance statistique de l'utilisation d'un faible nombre d'échantillons urinaires pour estimer les expositions. Méthodes : Les associations entre les phénols, les phtalates et la croissance ont été étudiées parmi un sous-effectif de la cohorte mère-enfant EDEN ayant accouché de garçons (n =520). La croissance fœtale a été estimée à l'aide d'échographies réalisées pendant la grossesse et de mesures à la naissance. La croissance postnatale a été modélisée à partir de mesures répétées normalisées, réalisées entre la naissance et 3 ans. Les biomarqueurs d'exposition aux phtalates et phénols ont été dosés dans les urines maternelles recueillies une fois pendant la grossesse. La variabilité des concentrations urinaires de phénols et la correspondance avec les concentrations mesurées dans le liquide amniotique ont été étudiées chez 71 femmes enceintes recevant une amniocentèse au centre médical Mount Sinaï (NY, États-Unis). Un échantillon d'urine maternelle a été recueilli le jour de l'amniocentèse, et à deux autres reprises pendant la grossesse. L'étude concernant les biais est basée sur des données simulées. Résultats : Les concentrations de triclosan étaient négativement associées à tous les paramètres de croissance mesurés à la troisième échographie (p ≤ 0,16) et avec la périmètre crânien à la naissance (β = - 1,4 mm, IC 95%; -2.8; 0.0). Les parabènes étaient associés positivement avec le poids à la naissance (p < 0,05). Le méthyle et propyle parabènes étaient aussi positivement associés au poids et à la circonférence abdominale à 3 ans (p-valeurs comprises entre 0,02 et 0,14). En ce qui concerne la variabilité des concentrations urinaires pendant la grossesse, les coefficients de corrélation intra-classe (ICC) variaient entre 0,48 et 0,62 pour l'ensemble des phénols sauf le bisphénol A (ICC = 0,11). Seuls la benzophénone-3 et le propyle parabène ont été détectés dans au moins 50 % des échantillons de liquide amniotique. Pour ces composés les concentrations dosées dans l'urine maternelle et le liquide amniotique, recueillis le même jour, étaient positivement associés. Dans le cadre d'une simulation, nous avons estimé que 5 échantillons d’urine étaient nécessaires pour estimer correctement l’exposition aux produits chimiques ayant un ICC de 0,6, tandis que pour des produits chimiques avec un ICC de 0,15, environ 25 échantillons étaient nécessaires.Conclusion : Un seul échantillon d'urine était disponible pour évaluer les expositions des femmes de la cohorte EDEN et nos résultats peuvent être affectés d'un biais résultant d'erreurs de classification des expositions, notamment pour le bisphenol A pour lequel nous avons observé une variabilité importante des concentrations. Néanmoins, notre étude suggérait un effet de l'exposition prénatale à certains phénols sur la croissance pré- et post-natale. / Background: Phthalates and phenols belong to the family of short half-life endocrine disruptors. Data regarding their effects on fetal and early post-natal growth in Human are sparse and suggest a sex-specific effect of some phenols on birth weight. One of the limitations of these studies is exposure assessment usually based on the measurement of their concentrations in a small number of maternal urine samples collected during pregnancy. Because of their low persistence in the organisms and the likely episodic nature of the exposures, urinary concentrations of these chemicals are likely to vary. Chemical concentrations measured in alternative matrix, such as amniotic fluid, might be a relevant dosimeter of fetal exposure.Objectives: Objectives of the thesis were: to study the potential effects of prenatal exposures to phenols and phthalates on pre- and early post-natal growth; to characterize variability in maternal urine concentrations of phenols throughout pregnancy and to compare phenol concentrations in amniotic fluid to those measured in maternal urine collected same day; to characterize the impact of increasing the number of measurements to estimate exposure on bias and statistical power of epidemiological studies.Methods: Associations between phenols, phthalates and growth were studied among a subsample of pregnant women of the French EDEN cohort delivered boys (n =520). We measured fetal growth with ultrasound (three times during pregnancy) and birth measurements. We used standardized measures acquired between birth and 3 years of age to model postnatal growth. We measured biomarkers of phthalates and phenols in maternal urines collected once during pregnancy: 191 women were assessed in 2008 and 410 other women in 2012 (ntot = 601). Variability in phenol urine concentrations and relationship between concentrations measured in amniotic fluid and maternal urine collected on the same day were studied among 71 pregnant women presenting for an amniocentesis at the Mount Sinai Medical Center (NY, USA). Maternal urine was collected at the time of the amniocentesis appointment, and on two subsequent occasions. Urine and amniotic fluid were analyzed for nine phenols.The study aiming at characterizing bias was based on simulated data. Results: Among the subsample of 191 pregnant women from the EDEN cohort, we observed a negative association between dichlorophenols and birth weight and a positive association between benzophenone-3 and birth weight. The associations with dichlorophenols were not replicated in the larger subsample of the EDEN cohort (n = 520). Triclosan concentration was negatively associated with all of the growth parameters measured at the third ultrasound examination (p ≤ 0.16) and with head circumference measured at birth (β = - 1.4 mm, 95% CI; -2.8; 0.0). All of the parabens were positively associated with weight at birth (p < 0.05). These associations remained in childhood for methyl- and propyl-parabens. Regarding the variability in phenol urinary concentrations during pregnancy, the intraclass correlation coefficients (ICC) ranged between 0.48 and 0.62 for all phenols except bisphenol A (ICC = 0.11). Only benzophenone-3 and propylparaben were detectable in at least half of the amniotic fluid samples; for these phenols, concentrations in maternal urine and amniotic fluid were positively associated. In a simulation study, we estimated that 5 samples will be needed to correctly estimate exposure to chemicals with ICC of 0.6, while for chemicals with ICC of 0.15 around 25 samples would be needed.Conclusion: We only had spot urine sample to assess exposure in the EDEN cohort and findings may be affected by exposure misclassification, especially for bisphenol A for which we observed high variability in urine concentrations. Nevertheless, our study lends support to a potential effect of prenatal exposure to some phenols on pre- and early post-natal growth.

Submitted by Maike Costa (maiksebas@gmail.com) on 2016-05-05T13:54:43Z No. of bitstreams: 1 arquivo total.pdf: 4535008 bytes, checksum: 35f2a65a445c1e8219acb5615d951d72 (MD5) / Made available in DSpace on 2016-05-05T13:54:43Z (GMT). No. of bitstreams: 1 arquivo total.pdf: 4535008 bytes, checksum: 35f2a65a445c1e8219acb5615d951d72 (MD5) Previous issue date: 2015-07-01 / Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPq / In this work were developed and validated two analytical methodologies using solid phase extraction and High Performance Liquid Chromatography (HPLC), for identification and quantification of endocrine disruptors in surface water. A methodology was used to analyze four estrogens: 17 β-estradiol, ethinyl estradiol, estrone and estriol, and the other methodology was used to analyze six phytoestrogens: biochanin A, genistin, genistein, daidzin, daidzein and formononetin. In the sample preparation step we developed an extraction method using solid phase extraction (SPE).The used cartridges were effective in the extraction for both estrogens and phytoestrogens using 1000 ml of river sample, and reached a pre-concentration factor of 2,857 times and recoveries above 90%. The proposed method uses fluorescence detector for estrogens, while the one for the phytoestrogens uses diode array detector. On methods validation were evaluated analytical performances for both methods. The selectivity shows that there was no presence of interfering peaks in both evaluated methods. The generated calibration curves presented good linearity and good correlation coefficients (above 0.99) for all studied analytes. The curves linearity was evaluated by an ANOVA and analysis of graphical residue which showed that the model shows no lack of fit. The limit of detection (LOD) and of quantification (LOQ) for estrogens and phytoestrogens determined in this study were similar to the observed values in other studies and therefore were considered appropriate for the evaluated matrix type. The accuracy of the methods was assessed by the repeatability and intermediate precision, which presented CV <13%. The accuracy was assessed using the recovery test, which was in the range of 72.9 -113%). In the evaluated stability, standard solutions of both methods were stable for a period of 30 days under refrigeration. The results showed that the proposed methods are reliable and have been validated successfully. After validated the methods were applied in the analysis of water samples from the Cuiá River, located in João Pessoa, Paraíba (Brazil), on different collection points, and three sampling campaigns. In all campaigns it was observed the presence of the four estrogens and phytoestrogens six in concentrations ranging from 1.40 to 4754 ng L-1 for estrogens and 3.58 to 2210 μg. L-1 to phytoestrogens in the aquatic studied system. / Neste trabalho foram desenvolvidas e validadas duas metodologias analíticas, utilizando extração em fase sólida e cromatografia líquida de alta eficiência (do inglês: High Performance Liquid Chromatography – HPLC), para identificação e quantificação de interferentes endócrinos em águas superficiais. Uma metodologia foi utilizada para analisar quatro estrógenos: 17 β-estradiol, 17 α-etinilestradiol, estrona e estriol, e a outra metodologia usada para analisar seis fitoestrógenos: biochanin A, genistina, genisteína, daidizina, daidizeína e formononetina. Na etapa de preparo das amostras foi desenvolvido um método de extração empregando extração em fase sólida (SPE). Os cartuchos utilizados foram eficazes na extração dos analitos, tanto dos estrógenos como dos fitoestrógenos, utilizando 1.000 mL de amostra de rio, sendo atingido um fator de pré-concentração de 2.857 vezes e recuperações acima de 90%. O método para os estrógenos utilizou detector de fluorescência, enquanto o método para os fitoestrógenos utilizou o detector de arranjo de diodos. Na validação dos métodos foram avaliadas as figuras de desempenho analítico para ambos os métodos. A avaliação da seletividade demonstrou que não havia a presença de picos interferentes em ambos os métodos avaliados. As curvas analíticas geradas apresentaram linearidade satisfatória e coeficientes de correlação acima de 0,99, para todos os analitos estudados. A linearidade das curvas foi avaliada com os testes de ANOVA e análise dos gráficos de resíduos os quais demonstraram que os modelos não apresentaram falta de ajuste. Os LD’s e LQ’s estimados para os estrógenos mostraram-se similares aos valores apresentados em outros estudos, enquanto que os LD’s e LQ’s estimados para os fitoestrógenos tiveram valores mais altos. No entanto podem ser considerados satisfatórios para o tipo de matriz avaliada. A precisão dos métodos foi avaliada pela repetitividade e pela precisão intermediária, as quais apresentaram CV < 13 %. A exatidão do método foi avaliada através do teste de recuperação, que esteve na faixa de 72,9 a 113 %. Na avaliação da estabilidade, as soluções padrões de ambos os métodos se mostraram estáveis por um período de até 30 dias sob refrigeração. Os resultados demonstraram que os métodos propostos são confiáveis e que foram validados com sucesso. Depois de validados, os métodos foram aplicados nas análises das amostras de água do Rio Cuiá, situado na cidade de João Pessoa, Paraíba (Brasil), em diferentes pontos de coleta e, em três campanhas amostrais. Em todas as campanhas observou-se a ocorrência dos quatro estrógenos e dos seis fitoestrógenos, em concentrações que variaram de 1,40 a 4.754 ng L-1 para os estrógenos e de 3,58 a 2.210 μg L-1 para os fitoestrógenos.

CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior / As substÃncias denominadas desreguladores endÃcrinos (DE) sÃo uma categoria recente de poluentes ambientais que interferem nas funÃÃes do sistema endÃcrino, sendo encontradas no meio ambiente em concentraÃÃes na ordem de &#956;g L-1 e ng L-1. Os efluentes de ETEs sÃo importantes fontes de lanÃamento desses compostos no ambiente aquÃtico uma vez que os processos convencionais de tratamento de Ãgua e esgoto nÃo removem totalmente esses micropoluentes. Neste trabalho avaliou-se a eficiÃncia da argila pilarizada utilizando o diÃxido de estanho como agente pilarizante para remoÃÃo de DE (de diferentes classes) em matrizes ambientais. Foi utilizado o planejamento experimental para avaliaÃÃo dos fatores que afetaram o processo adsortivo. Para etapa de otimizaÃÃo do mÃtodo analÃtico anteriormente validado foi estudada a eficiÃncia de trÃs cartuchos SPE comerciais. Foram obtidas concentraÃÃes afluentes, efluentes e eficiÃncias de remoÃÃo em duas estaÃÃes de tratamento de esgotos que operavam em escala real (UASB + cloraÃÃo). Por fim, foram realizados experimentos de adsorÃÃo de DE em sistemas mono e multicomponentes, assim como de regeneraÃÃo do adsorvente. Os cartuchos Oasis e Strata-X mostraram elevada eficiÃncia e capacidade seletiva, entretanto apenas o cartucho Strata-X foi o selecionado neste trabalho, uma vez que o mesmo mostrou maiores valores de recuperaÃÃo (%) de 50 (Sulfamethoxazol); 83 (Trimetoprima); 171 (Diclofenaco); 183 (Estrona); 14 (17&#946;-estradiol) e 82 (Bisfenol-A). O mÃtodo cromatogrÃfico mostrou-se seletivo para todos os compostos estudados, exceto para o hormÃnio estriol. Os valores de limite de quantificaÃÃo (1,28-29,97 ng L-1) e limite de detecÃÃo (0,42-9,89 ng L-1) obtidos neste trabalho foram considerados baixos. A maioria dos valores de recuperaÃÃo encontrados foi menor que 100%. Foi possÃvel observar que o esgosto afluente Ãs ETEs estudadas ainda apresentam em seus efluentes quantidades considerÃveis de DE, com valores mÃdios efluentes entre 21,94-311,79 ng L-1 para ETE Aracapà e 4,41-123,47 ng L-1 para ETE Mondubim, o que evidencia a necessidade de uma etapa de pÃs-tratamento nas ETEs estudadas. Foram encontradas maiores eficiÃncias de tratamento para os compostos bisfenol A (90,8%) e 17&#945;-etinilestradiol (76,6%) na ETE Mondubim. Jà para os compostos sulfametoxazol e estrona foi observado um incremento nos valores efluentes de 18,9 e 28,6%, respectivamente para a ETE AracapÃ. A argila pilarizada mostrou maior capacidade de adsorÃÃo quando comparada à argila natural, devido ao alargamento do espaÃo interlamelar da argila e aumento no volume de mesoporos como comprovado pelas tÃcnicas de caracterizaÃÃo. ApÃs anÃlise dos resultados do planejamento fatorial foi fixado os valores Ãtimos encontrados das variÃveis no processo para compor os estudos de cinÃtica e isoterma de adsorÃÃo, os quais foram Temperatura â 25 ÂC; AgitaÃÃo â 300 rpm; Massa do adsorvente: 300 mg e pH â 3. O estudo cinÃtico indicou tempo de equilÃbrio de 1 hora, sendo o modelo de pseudo-segunda ordem o que melhor se ajustou aos dados. O mecanismo de difusÃo intrapartÃcula nÃo foi a etapa determinante da velocidade e no processo de transferÃncia de massa. A maioria dos compostos DE estudados obteve maior remoÃÃo em sistema multicomponente quando comparados aos estudos monocomponentes. Os dados experimentais de isoterma de adsorÃÃo melhor se ajustaram ao modelo de Freundlich com exceÃÃo aos referentes aos compostos TMP e BPA. Os testes de regeneraÃÃo do adsorvente indicaram significante reduÃÃo da capacidade de adsorÃÃo da argila pilarizada no 2 ciclo de adsorÃÃo para os compostos TMP e BPA, com reduÃÃo de 99,5 e 79,2 %, respectivamente. Para os compostos E2 e E1, a adsorÃÃo foi afetada apÃs o 3 ciclo. / The substances called endocrine disruptors (ED) are a new category of environmental pollutants that interfere in the functions of the endocrine system, being found in the environment at concentrations in the order ug L-1 and L-1 ng. The WWTP effluent release are important sources of such compounds in the aquatic environment since the conventional methods of water treatment and sewage not completely remove these micropollutants. In this study we assessed the efficiency of pillared clay using tin dioxide as an agent for removing pilarizante DE (of different classes) in environmental matrices. Experimental design was used to evaluate the factors affecting the adsorptive process. For optimization step of the previously validated analytical method it was studied the effectiveness of three commercial SPE cartridges. Tributaries concentrations were obtained, effluents and removal efficiencies of two sewage treatment plants operating in full scale (UASB + chlorination). Finally, DE adsorption experiments were performed in single and multicomponent systems as well as regenerating the adsorbent. The Oasis and Strata-X cartridge efficiency showed high and selective ability, however, only Strata-X cartridge was selected in this study, since it showed higher recovery values (%) 50 (Sulfamethoxazol); 83 (Trimethoprim); 171 (diclofenac); 183 (estrone); 14 (17&#946;-estradiol) and 82 (Bisphenol A). The chromatographic method was selective for all compounds studied, except for the hormone estriol. The quantification limit values (1.28 to 29.97 ng L-1) and detection limit (from 0.42 to 9.89 ng L-1) obtained in this study were low. Most of the recovery values was less than 100%. It was observed that the esgosto tributary of the studied WWTPs still present in their waste considerable amounts of DE, with average values of effluents from 21.94 to 311.79 ng L-1 for ETE Aracapà and 4.41 to 123.47 ng L 1 to ETE Mondubim, which highlights the need for a step of post-treatment in the studied WWTPs. They have found greater efficiencies treatment for compounds bisphenol A (90.8%) and 17&#945;-ethinylestradiol (76.6%) ETE Mondubim. As for the compounds sulfamethoxazole and estrone it was observed an increase in effluent values of 18.9 and 28.6% respectively for the ETE AracapÃ. The pillared clay showed higher adsorption capacity compared to the natural clay, due to enlargement of the interlayer space of the clay and increased volume of mesopores as evidenced by the characterization techniques. After analyzing the results of the factorial design was set optimum values of the variables found in the process to make the studies of kinetics and adsorption isotherm, which was temperature - 25  C; Agitation - 300 rpm; Mass of adsorbent: 300 mg and pH - 3. The kinetic study indicated 1 hour equilibration time, with the model of pseudo-second order which best fit to the data. The intraparticle diffusion mechanism was not the determining step of the speed and mass transfer process. The majority of the DE compounds obtained greater removal in multicomponent system when compared to single-component studies. The experimental data better adsorption isotherm set the model Freundlich except to refer to the TMP and BPA compounds. The sorbent regeneration tests indicated a significant reduction in the adsorption capacity of pillared clay in the 2nd adsorption cycle for TMP and compounds BPA, with a reduction of 99.5 and 79.2%, respectively. For E2 and E1 compounds, adsorption was affected after the 3rd cycle.

Pesticides are among the most important risk factors for the health of workers and the environment. Many are recognized for their actions as endocrine disruptors, leading to changes in thyroid function markers. The aim of the study was to investigate the association between occupational exposure to organophosphate pesticides and thyroid function markers growers. The study enrolled 208 rural workers involved in the orange culture Boquim municipality in April 2015 to April 2016. They answered the questionnaire containing demographic information, health profile and occupational risk. Blood samples were collected for analysis of thyroid function. A large part of the workers live in the countryside 131 (72.0%), belong to social classes D and E (50.8%) and are predominantly male 161 (77.4%). The health profile analysis showed the presence of characteristic symptoms often associated with organophosphate poisoning. Muscle weakness has been reported (45.9%), skin disorders (36.3%), tremor night (17.2%) and seizures (2.2%). With regard to occupational variables, most responders reported having some kind of long, direct or indirect, with the pesticide (92.3%) and were exposed to pesticides to a period longer than five years (66.1%). Biochemical markers of thyroid function were analysed: TSH (thyroid stimulating hormone) with 10.5% of changed values, free T4 (thyroxine) with 41.4% of the reduced values, total T3 (triiodothyronine) with 21.8% of altered values. Altered levels of anti-thyroid peroxidase (anti-TPO) and of anti-thyroglobulin (anti-Tg) were found in 14.7% and 9.3% of cases, respectively. TSH levels and altered T3 predominated in women, and reduced free T4 predominated in men; all had a higher frequency in the fifth decade of life. The presence of positive autoimmunity predominated in women and had a higher frequency in the fourth decade of life for Anti-TPO and fifth for Anti-Tg. Conclusion: The exposure variables to organophosphate pesticides evaluated in this population showed no association with changes in serum TSH, free T4 and total T3 and with overt hypothyroidism diagnosis, subclinical hypothyroidism and hyperthyroidism. / Os agrotóxicos estão entre os mais importantes fatores de risco para a saúde dos trabalhadores e para o meio ambiente. Muitos são reconhecidos por suas ações como disruptores endócrinos, levando a alterações nos marcadores de função tireoidiana. O objetivo do estudo foi investigar a associação entre a exposição ocupacional aos agrotóxicos organofosforados e os marcadores de função tireoidiana de citricultores. Participaram do estudo 208 trabalhadores rurais envolvidos na cultura de laranja do município de Boquim no período de abril 2015 a abril 2016. Responderam o questionário contendo informações sociodemográficas, perfil de saúde e de risco ocupacional. Foram colhidas amostras de sangue dos trabalhadores para a análise da função tireoidiana. A maior parte dos trabalhadores moram na zona rural 131 (72,0 %), pertencem às classes sociais D e E (50,8%) e são predominantemente homens 161 (77,4%). A análise do perfil de saúde demonstrou presença de sintomatologia característica frequentemente associada à intoxicação por organofosforados. Foi relatado fraqueza muscular (45,9%), alteração na pele (36,3%), tremor noturno (17,2%) e convulsões (2,2%). Com relação às variáveis ocupacionais, a maioria dos entrevistados relataram ter algum tipo de contanto, direto ou indireto, com o agrotóxico (92,3%) e estavam expostos aos pesticidas a um período superior a 5 anos (66,1%). Os marcadores bioquímicos da função tireoidiana analisados foram: TSH (hormônio tireoestimulante) com 10,5% dos valores alterados, T4 livre (tiroxina) com 41,4% dos valores reduzidos, T3 total (triiodotironina) com 3,2% de valores alterados. Níveis alterados de anticorpo anti-tireoperoxidase (Anti-TPO) de e anti-tireoglobulina (Anti-Tg) foram encontrados em 14,7% e em 9,3% dos casos, respectivamente. Os níveis de TSH e T3 total alterados predominaram nas mulheres e os de T4 livre reduzidos predominaram nos homens; todos tiveram uma frequência de valores alterados maior na quinta década de vida. Já a presença de autoimunidade positiva predominou nas mulheres e teve uma frequência maior na quarta década de vida para o Anti-TPO e quinta para o Anti-Tg. Conclusão: As variáveis de exposição aos pesticidas organofosforados avaliadas nessa população não demonstraram associação com alterações dos hormônios TSH, T4 livre e T3 Total e com os diagnósticos de hipotireoidismo franco, hipotireoidismo subclínico e hipertireoidismo. / Lagarto, SE