published_or_final_version / abstract / Ecology and Biodiversity / Master / Master of Philosophy

Testicular germ cell apoptosis is a process that begins in early development and continues in the adult testis. It is important during spermatogenesis for maintaining homeostasis of different types of germ cells. The number of sperm produced depends on the supportive capacity of surrounding Sertoli cells, which provide nutrition and an adaptive environment for growth and development of the germ cells. There are two major pathways that regulate germ cell apoptosis: extrinsic and intrinsic. We hypothesize that Sertoli cells use the extrinsic pathway to eliminate germ cells when exposed to phthalates, a common Sertoli cell toxicant. Death ligands, which are involved in the extrinsic pathway, were used in this research to test this hypothesis. Here, we demonstrate that: 1) the loss of FasL and TRAIL protein expression results in decreased production of mature spermatids in the adult testis, likely as a result of alterations in germ cell homeostatsis during the first wave of spermatogenesis. 2) The high baseline incidence of germ cell apoptosis in peripubertal FasL-/- and TRAIL-/- mice is correlated with increases in levels of TRAIL and FasL, respectively. 3) The decline in germ cell apoptosis observed after MEHP treatment in FasL-/- mice closely corresponds to the occurrence of increased levels of c-FLIP. 4) A more predominant role of FasL occurs in controlling the proper number of germ cells during the first wave of spermatogenesis in peri-pubertal mice. TRAIL is more critical for maintaining long-term homeostasis of the germ cell population in adult testis as well as in the reproductive function. 5) Several possible genes are involved in the altered spermatogenesis and development in the testis of gene-deficient mice. 6) Findings described in Chapter 6 indicate cellular mechanisms triggered by MEHP exposure that act to enhance tumor progression/metastasis in testicular embryonal carcinoma cells (NT2/D1). Taken together, these novel findings provide important mechanistic insights into the functional roles of FasL in the testis at distinct developmental periods and further indicate that FasL itself is required for the regulation of c-FLIP levels in the testis. Additionally, exposure to environmental toxicants, such as the phthalates, can enhance testicular cancer metastasis and invasion. / text

Not available / text

published_or_final_version / abstract / toc / Ecology and Biodiversity / Master / Master of Philosophy

Thesis (Ph. D.)--University of Hong Kong, 2005. / Title proper from title frame. Also available in printed format.

Orientadores: Helena Teixeira Godoy, Marisa Padula / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Engenharia de Alimentos / Made available in DSpace on 2018-08-23T04:09:43Z (GMT). No. of bitstreams: 1 Oliveira_WellingtondaSilva_M.pdf: 956439 bytes, checksum: 3f0a6d0735f71f0d97e159bbf8fce38f (MD5) Previous issue date: 2013 / Resumo: No Brasil, mais de 50% da população utiliza mamadeiras durante a amamentação de crianças. Após a proibição do uso do bisfenol A em mamadeiras de policarbonato, outros polímeros como o polipropileno e o Tritan® passaram a ser utilizados com essa finalidade. Embora estes materiais sejam liberados para uso como material de contato com alimentos há uma lacuna no que diz respeito à migração de compostos oriundos do plástico utilizado na fabricação de mamadeiras. Estudos voltados para a identificação de substâncias não intencionalmente adicionadas e migrantes, em mamadeiras, são necessários para avaliar a segurança no uso destes materiais. Diante disso, o objetivo deste estudo foi avaliar o potencial de migração dos materiais utilizados na confecção de mamadeiras. Foram avaliadas 32 mamadeiras, de 3 marcas diferentes, feitas de Tritan (A) e polipropileno (B, CT e CP). Entre as marcas, três eram transparentes e com desenhos (A, B, CT), e uma era completamente pigmentada (CP). Inicialmente, foi feito a caracterização das mamadeiras e confirmação do material por espectroscopia no infravermelho por transformada de Fourier (FT-IR). Na caracterização foram avaliadas a espessura mínima, o diâmetro, o volume, a massa e altura das mamadeiras. Em seguida, foram realizados ensaios de migração de acordo com a RDC 51/2010 da Agência Nacional de Vigilância Sanitária (ANVSA), que recomenda a utilização de etanol 50% como simulante de leite. A simulação foi realizada mantendo a mamadeira em contato com o simulante a 70°C por 2h. Neste ensaio foi feita a identificação dos migrantes com base na biblioteca de espectros de massas do National Institute of Standards and Technology (NIST). Um método para determinação de di(2-etilhexil) ftalato (DEHP) e dibutil ftalato foi validado para os parâmetros limite de detecção (LD) e quantificação (LQ), linearidade, repetitividade e precisão intemediária. O perfil de antioxiandantes foi determinado utilizando um cromatógrafo líquido com detector de arranjo de diodos. Com base na caracterização, foi observado que as mamadeiras das marcas B, CT e CP apresentaram maior uniformidade nos parâmetros avaliados que as mamadeiras da marca A, que apresentaram dimensões com coeficientes de variação maiores que 20%, indicando falta de padrão em mamadeiras de um mesmo lote. Na seleção e identificação de migrantes foi observada a migração de mais de 20 compostos, dentre eles o DEHP e o DBP. O método validado apresentou limites de detecção e quantificação de 16 µg/L e 52 µg/L para o DBP e 10 µg/L e 30 µg/L para o DEHP. O método mostrou-se linear nas faixas de 52-660 µg/L para o DBP e 52-1100 µg/L para o DEHP, com boa repetitividade e precisão intemediária com CV abaixo de 20%. Todas as mamadeiras apresentavam concentrações de DEHP abaixo do LQ. Em relação ao DBP, somente as mamadeiras da marca CP apresentaram migrações acima do limite de migração específa (0,3 mg/kg) recomendado pela ANVISA. Em todas as mamadeiras foram encontrados os antioxidantes Irganox 1010 e Irgafos 168. Estes compostos não têm restrição de uso, podendo ser usados em materiais de contato com alimentos. Das três marcas de mamadeiras analisadas, somente as marcas B e CT apresentaram resultados satisfatórios para utilização em contato com o leite. As mamadeiras da marca A deformaram após o ensaio de simulação. As mamadeiras da marca CP apresentaram níveis de migração acima do limite de migração especifica (0,3 mg/kg) preconizado pela ANVISA / Abstract: In Brazil, more than 50% of the population uses baby bottles to feed children. After banning the use of bisphenol A in polycarbonate baby bottles, other polymers such as polypropylene and Tritan® have been used for this purpose. Although these materials were approved for using as food contact material, there is a vacuity with regard to the migration of plastic derived compounds used in the manufacture of baby bottles. Studies aimed at the identification of non-intentionally added substances and migrants, in baby bottles, are needed to assess the safety of these materials. Thus, the aim of this study was to evaluate the migration potential of materials used in the baby bottles manufacture . Thirty-two baby bottles of three different brands made of Tritan (A) and polypropylene (B, CT, and CP) were evaluated. Among the brands, three were transparent and drawings (A, B, CT), and one was completely pigmented (CP). Initially, were made a characterization the material baby bottles and then its materials were confirmed by infrared spectroscopy Fourier transform (FT-IR). The characterization was based on minimum thickness, diameter, volume, mass and height of the baby bottles. Then, migration assays were performed according to the RDC 51/2010 of the National Agency for Sanitary Vigilance (ANVISA), which recommends the use of 50% ethanol as a milk simulant. The simulation was done by putting the baby bottles in contact with the simulant at 70 ° C for 2 h. In this assay the identication of the migrant was done based on the mass spectra library of the National Institute of Standards and Technology (NIST). A method for the determination of di (2-ethylhexyl) phthalate (DEHP) and dibutyl phthalate (DBP) was validated for the parameters detection (LOD) and quantification (LOQ) limit, linearity, repeatability and accuracy-intermediate. The antioxiandants profile was determined using a liquid chromatograph with a diode array detector. The materials used in the baby bottles manufacture, as declared on the labels were confirmed. Based on characterization, it was observed that the baby bottles of brands B, CT, and CP showed greater uniformity in the parameters evaluated than brand A, which had dimensions with variation coefficients (CV) greater than 20%, indicating the lack of standard in the same lot of baby bottles. The selection and identification of migrants showed the migration of more than 20 compounds, including DEHP and DBP. The method validated in this study showed a detection and quantification limits of 16 µg/L and 52 µg/L for DBP and 10 µg/L and 30 µg/L for DEHP. The method was linear in the range of 52-660 µg/L for DBP and 52-1100 µg/L for DEHP, with good repeatability and accuracy-intermediate with CV below 20%. All baby bottles had concentrations of DEHP below the LOQ. Regarding DBP, only the baby bottles of brand CP showed migration above specific migration limit (0.3 mg / kg) recommended by ANVISA. In all bottles were found the antioxidants Irganox 1010 and Irgafos 168. These compounds have no use restriction and can be used in food contact materials. Taking into account the brands of baby bottles analyzed, only the brands B and CT showed satisfactory results for use in contact with milk. The baby bottles of brand A deformed after the simulation test. The baby bottles of the brand CP showed migration levels above the specific migration limit (0.3 mg/kg) recommended by ANVISA / Mestrado / Ciência de Alimentos / Mestre em Ciência de Alimentos

Four in ten people in the US will be diagnosed with cancer during their lifetime. Environmental exposures are important determinants of cancer risk, causing as many as 19% of cancers worldwide. Phthalates are a group of chemicals used to increase the flexibility of plastics and vinyl in household materials such as food packaging, plastic toys, wood finishes and adhesives. Some phthalates may act as endocrine disruptors with hypothesized links to endometriosis, breast cancer, and reproductive outcomes. However, no research yet exists on phthalate exposure and all-cancer mortality. We investigated the relationship between seven urinary phthalate metabolites among 5,205 adults in National Health and Nutrition Examination Survey (NHANES), from 1999 to 2006 with mortality data through 2011. Urinary phthalate metabolites were measured in spot urine samples using HPLC-MS/MS and HPLC-ESI-MS/MS. Cox proportional hazard regressions were conducted to calculate hazard ratios and 95 percent confidence intervals for all-cancer mortality, stratified by gender. Mean creatinine adjusted metabolite concentrations ranged from 0.03 – 3.86 ug/mg in males and 0.07 – 4.37 ug/mg in females. Age-adjusted and multivariate Cox proportional hazard models did not yield statistically significant results for any metabolites. Hazard ratios in the multivariate model for continuous, creatinine adjusted, log transformed metabolite concentrations, ranged from 0.90 to 1.27 in men and 0.86 to 1.07 in women. There was no evidence for a dose-response relationship in the quartile analyses, with p-values for trend above 0.12. This research contributes to the limited cancer literature on phthalate exposure that helps direct future regulations on plasticizers in consumer products.

by Chan Chui Man. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2006. / Includes bibliographical references (leaves 83-94). / Abstracts in English and Chinese. / Acknowledgements --- p.i / Abstract --- p.ii / 摘要 --- p.iii / Contents --- p.iv / List of Figures --- p.ix / List of Plates --- p.xi / List of Tables --- p.xii / List of Abbreviations --- p.xiv / Chapter 1 --- Introduction --- p.1 / Chapter 1.1 --- Di(2-ethylhexyl)phthalate (DEHP) --- p.1 / Chapter 1.1.1 --- The chemical class of DEHP: Phthalate ester --- p.1 / Chapter 1.1.2 --- Characteristics of DEHP --- p.3 / Chapter 1.1.3 --- Sources of releases and environmental concentration --- p.4 / Chapter 1.1.4 --- Persistence of DEHP --- p.5 / Chapter 1.1.5 --- Routes of exposure --- p.6 / Chapter 1.1.6 --- Toxicity of DEHP --- p.7 / Chapter 1.1.6.1 --- Acute toxicity --- p.7 / Chapter 1.1.6.2 --- Chronic toxicity --- p.8 / Chapter 1.1.6.2.1 --- Adverse effects on reproduction system --- p.8 / Chapter 1.1.6.2.2 --- Carcinogenicity --- p.9 / Chapter 1.1.6.2.3 --- Developmental toxicity --- p.9 / Chapter 1.1.6.2.4 --- Endocrine disruption --- p.10 / Chapter 1.1.6.2.5 --- Hepatotoxicity --- p.10 / Chapter 1.1.7 --- Regulations --- p.10 / Chapter 1.2 --- Treatment of DEHP --- p.11 / Chapter 1.2.1 --- Conventional treatment technologies --- p.11 / Chapter 1.2.1.1 --- Physical method --- p.11 / Chapter 1.2.1.1.1 --- Adsorption --- p.11 / Chapter 1.2.1.1.2 --- Sonolysis --- p.12 / Chapter 1.2.1.2 --- Photochemical method --- p.13 / Chapter 1.2.1.2.1 --- Photocatalytic oxidation (PCO) --- p.13 / Chapter 1.2.1.3 --- Biological method --- p.13 / Chapter 1.2.1.3.1 --- Biodegradation --- p.13 / Chapter 1.2.1.3.2 --- Sewage treatment process --- p.14 / Chapter 1.2.2 --- Integrated treatment method in the present study --- p.15 / Chapter 1.2.2.1 --- Biosorption --- p.15 / Chapter 1.2.2.1.1 --- Definition of biosorption --- p.15 / Chapter 1.2.2.1.2 --- Advantages of biosorption --- p.16 / Chapter 1.2.2.1.3 --- Chitinous materials as biosorbents --- p.16 / Chapter 1.2.2.1.4 --- Advantages of using chitinous materials as biosorbents --- p.17 / Chapter 1.2.2.1.5 --- Modeling of biosorption --- p.19 / Chapter 1.2.2.2 --- PCO --- p.21 / Chapter 1.2.2.2.1 --- Definition of PCO --- p.21 / Chapter 1.2.2.2.2 --- Mechanism of PCO --- p.23 / Chapter 1.2.2.2.3 --- Advantages of PCO --- p.25 / Chapter 2 --- Objectives --- p.27 / Chapter 3 --- Materials and methods --- p.28 / Chapter 3.1 --- Materials --- p.28 / Chapter 3.1.1 --- Adsorbate --- p.28 / Chapter 3.1.2 --- Biosorbents --- p.28 / Chapter 3.1.2.1 --- Pretreatment of biosorbents --- p.29 / Chapter 3.1.3 --- Photocatalytic reactor --- p.29 / Chapter 3.1.4 --- Photocatalyst --- p.30 / Chapter 3.1.5 --- Electron scavenger --- p.31 / Chapter 3.2 --- Methods --- p.31 / Chapter 3.2.1 --- Determination of DEHP concentration --- p.31 / Chapter 3.2.2 --- Batch biosorption experiment --- p.32 / Chapter 3.2.2.1 --- Screening of biosorbents --- p.33 / Chapter 3.2.2.2 --- Optimization of biosorption conditions --- p.33 / Chapter 3.2.2.2.1 --- Effect of biosorbent concentration --- p.33 / Chapter 3.2.2.2.2 --- Effect of initial pH --- p.33 / Chapter 3.2.2.2.3 --- Effect of biosorption time --- p.34 / Chapter 3.2.2.2.4 --- Effect of temperature --- p.34 / Chapter 3.2.2.2.5 --- Effect of agitation rate --- p.34 / Chapter 3.2.2.2.6 --- Effect of initial DEHP concentration --- p.34 / Chapter 3.2.2.2.7 --- "Combinational effect of initial pH, chitin A concentration and initial DEHP concentration" --- p.35 / Chapter 3.2.3 --- Extraction of adsorbed DEHP from chitin A --- p.35 / Chapter 3.2.3.1 --- Screening of extraction agents --- p.36 / Chapter 3.2.3.2 --- Determination of extraction time --- p.36 / Chapter 3.2.4 --- Batch PCO experiment --- p.36 / Chapter 3.2.4.1 --- Optimization of PCO conditions --- p.38 / Chapter 3.2.4.1.1 --- Effect of reaction time --- p.38 / Chapter 3.2.4.1.2 --- Effect of UV-A intensity --- p.38 / Chapter 3.2.4.1.3 --- Effect of TiO2 concentration --- p.38 / Chapter 3.2.4.1.4 --- Effect of H2O2 concentration --- p.38 / Chapter 3.2.4.1.5 --- Effect of initial pH --- p.39 / Chapter 3.2.4.1.6 --- Combinational effect of H2O2 concentration and initial pH --- p.39 / Chapter 3.2.4.1.7 --- Effect of concentration factor --- p.39 / Chapter 3.2.4.2 --- Identification of intermediates/products of DEHP --- p.39 / Chapter 3.2.4.3 --- Evaluation for the toxicity of DEHP and the intermediates/products by the Microtox® test --- p.40 / Chapter 4 --- Results --- p.42 / Chapter 4.1 --- Batch biosorption experiment --- p.42 / Chapter 4.1.1 --- Screening of biosorbents --- p.42 / Chapter 4.1.2 --- Optimization of biosorption conditions --- p.42 / Chapter 4.1.2.1 --- Effect of biosorbent concentration --- p.42 / Chapter 4.1.2.2 --- Effect of initial pH --- p.42 / Chapter 4.1.2.3 --- Effect of biosorption time --- p.46 / Chapter 4.1.2.4 --- Effect of temperature --- p.46 / Chapter 4.1.2.5 --- Effect of agitation rate --- p.46 / Chapter 4.1.2.6 --- Effect of initial DEHP concentration --- p.46 / Chapter 4.1.2.7 --- "Combinational effect of initial pH, chitin A concentration and initial DEHP concentration" --- p.51 / Chapter 4.1.2.8 --- Summary of biosorption conditions before and after optimization --- p.54 / Chapter 4.2 --- Extraction of adsorbed DEHP from chitin A --- p.54 / Chapter 4.2.1 --- Screening of extraction agents --- p.54 / Chapter 4.2.2 --- Determination of extraction time --- p.55 / Chapter 4.3 --- Batch PCO experiment --- p.56 / Chapter 4.3.1 --- Optimization of PCO conditions --- p.56 / Chapter 4.3.1.1 --- Effect of reaction time --- p.56 / Chapter 4.3.1.2 --- Effect of UV-A intensity --- p.57 / Chapter 4.3.1.3 --- Effect of TiO2 concentration --- p.59 / Chapter 4.3.1.4 --- Effect of H2O2 concentration --- p.60 / Chapter 4.3.1.5 --- Effect of initial pH --- p.61 / Chapter 4.3.1.6 --- Combinational effect of H2O2 concentration and initial pH --- p.62 / Chapter 4.3.1.7 --- Effect of CF --- p.63 / Chapter 4.3.1.8 --- Summary of PCO conditions before and after optimization --- p.63 / Chapter 4.3.2 --- Identification of intermediates/products of DEHP --- p.64 / Chapter 4.3.3 --- Evaluation for the toxicity of DEHP and the intermediates/products by the Microtox® test --- p.66 / Chapter 5 --- Discussion --- p.68 / Chapter 5.1 --- Batch biosorption experiment --- p.68 / Chapter 5.1.1 --- Screening of biosorbents --- p.68 / Chapter 5.1.2 --- Optimization of biosorption conditions --- p.69 / Chapter 5.1.2.1 --- Effect of biosorbent concentration --- p.69 / Chapter 5.1.2.2 --- Effect of initial pH --- p.69 / Chapter 5.1.2.3 --- Effect of biosorption time --- p.70 / Chapter 5.1.2.4 --- Effect of temperature --- p.71 / Chapter 5.1.2.5 --- Effect of agitation rate --- p.71 / Chapter 5.1.2.6 --- Effect of initial DEHP concentration --- p.71 / Chapter 5.1.2.7 --- "Combinational effect of initial pH, chitin A concentration and initial DEHP concentration" --- p.73 / Chapter 5.2 --- Extraction of adsorbed DEHP from chitin A --- p.74 / Chapter 5.2.1 --- Screening of extraction agents --- p.74 / Chapter 5.2.2. --- Determination of extraction time --- p.74 / Chapter 5.3 --- Batch PCO experiment --- p.74 / Chapter 5.3.1 --- Optimization of PCO conditions --- p.74 / Chapter 5.3.1.1 --- Effect of reaction time --- p.74 / Chapter 5.3.1.2 --- Effect of UV-A intensity --- p.74 / Chapter 5.3.1.3 --- Effect of TiO2 concentration --- p.75 / Chapter 5.3.1.4 --- Effect of H2O2 concentration --- p.75 / Chapter 5.3.1.5 --- Effect of initial pH --- p.76 / Chapter 5.3.1.6 --- Combinational effect of H2O2 concentration and initial pH --- p.77 / Chapter 5.3.1.7 --- Effect of CF --- p.77 / Chapter 5.3.2 --- Identification of intermediates/products of DEHP --- p.78 / Chapter 5.3.3 --- Evaluation for the toxicity of DEHP and the intermediates/products by the Microtox test --- p.79 / Chapter 6 --- Conclusions --- p.80 / Chapter 7 --- References --- p.83

A key trend in the PVC market is to replace or decrease the amount of phthalate plasticisers used due to increasing health concerns. Therefore, the demand for non-phthalate based plasticisers is growing rapidly. Mineral oils are used in a variety of rubber and polymer applications as plasticisers; however, due to the lower polarity their applicability in PVC compounds is limited. Therefore, these materials are typically used as secondary plasticiser along with a primary for the purpose of improved properties and cost reduction. Some of the non-phthalate based solutions are fast fusing plasticisers, which act like solvents and have too rapid and too high plasticizing effect. This makes the compounding difficult and could cause problems in production. These substances have good compatibility with mineral oils, and using them together in PVC compounds can help the compounding issue by reducing the solvent power and increasing the fusion time to a level where the production parameters are similar to compounding with phthalates.   The aim of this study was to evaluate the use of mineral oils as a secondary plasticiser in a non-phthalate system for PVC. Four different grades of mineral oil and three non-phthalate plasticisers were used in compounding and compression moulding of PVC sample films. Mechanical, physical and chemical testing were done to assess the properties in a comparative study with phthalate plasticized PVC.   Tensile testing and hardness measurements showed that the mineral oils did not contribute with any plasticizing effect for the non-phthalate plasticisers tested in the study. The hardness was instead slightly increased for all the sample films that contained mineral oil. This indicates that the mineral oil either is less efficient than the primary plasticiser or that it affects the primary plasticisers intramolecular shielding between the PVC chains.       The shrinkage test showed that the migration of mineral oil was acceptable, especially the thicker grades of mineral oils had low migration. Colour stability test showed that the thicker mineral oil grades had some problems with discolouration. The discolouration is probably related to content of polyaromatics and oxidation stability.

published_or_final_version / abstract / Ecology and Biodiversity / Doctoral / Doctor of Philosophy