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1
Malheiro, Ana Cristina Calhabeutt Gabriel da Costa. "Determinação espectrofotométrica da caboxiemoglobinemia em indivíduos expostos ocupacionalmente ao monóxido de carbono". Universidade de São Paulo, 1991. http://www.teses.usp.br/teses/disponiveis/9/9137/tde-03032015-160133/.
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O monóxido de carbono (CO) constitui sério risco à saúde de indivíduos expostos a este gás. Os efeitos nocivos aparecem como conseqüência de sua combinação com a hemoglobina formando a carboxiemoglobina(COHb). A avaliação da exposição ao CO pela monitorização biológica é realizada, preferencialmente, pela determinação da carboxiemoglobinemia. O método espectrofotométrico proposto, para a determinação de COHb, utiliza a leitura na região Soret (420 e 432 nm) e fatores de calibração do espectrofotômetro. É realizado estudo comparativo entre o uso do CO obtido por reação química e o de cilindro de gás no preparo de solução 100% de COHb. O método apresenta boa precisão (coeficiente de variação de 2 e 6% para 4,98 e 1,01 % de COHb, respectivamente) e sensibilidade (0,50 % de COHb) adequadas à avaliação da exposição ao monóxido de carbono. A quantificação da COHb não é comprometida pelo teor hemoglobínico nem pela opalescência (lipemia) da amostra colhida no período pós-prandial. É apresentada a carboxiemoglobinemia em fumantes (n= 119) e não-fumantes (n= 189) que constituem 4 grupos de indivíduos expostos ocupacionalmente ao CO (n=209) e um grupo controle (n=99); e a análise estatística dos resultados (teste não-paramétrico).Carbon monoxide (CO) is recognized as a high risk hazard to the health of exposed workers. Combining with hemoglobin it reduces the oxigen carrying capacity of the blood. The individual overall exposure may be assessed through the carboxyhemoglobin (COHb) content of blood samples, as a biological exposure index. A spectrophotometric method is proposed using measurements in the region Soret (420 - 432 nrn) together with calibration factors of the instrument. A comparative study is made between the use of CO from compressed gas cilinders and the CO delivered by a chemical reaction in preparing the saturated COHb solution. The method presents precision (coefficient of variation is 2 and 6% to 4,98 and 1,01% of COHb, respectively) and sensitivity (0,5% of COHb), which are adequate to the purpose. Hemoglobin and lipidic content of samples showed no effect in the COHb measurement. Carboxyhiemoglobin level of four groups of exposed workers (n = 209) and a control group (n = 99) among smokers (n = 115) and non-smokers (n = 189) were determinated using the method. The statistical analysis of the results are presented (non-parametric test).
2
Oliveira, Ricardo Jorge Dinis. "Toxicity of Paraquat in Isolated Rat Lung. Search for Efficient Antidotes". Doctoral thesis, Faculdade de Farmácia da Universidade do Porto, 2006. http://hdl.handle.net/10216/7369.
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DoutoramentoPhD Degree
The immune evasion mechanisms of pathogenic trypanosomatids involve a multitude of phenomena such as the polyclonal activation of lymphocytes, cytokine modulation and the enhanced detoxification of oxygen reactive species. A trypanothione-cascade seems to be involved in the detoxification process. We have recently described and characterized a tryparedoxin (LiTXN1) involved in the Leishmania infantum cytoplasmatic hydroperoxide metabolism. LiTXN1 is a secreted protein upregulated in the infectious form of the parasite, suggesting that it can play an important role during infection. In the present study, we investigated whether the recombinant LiTXN1 (rLiTXN1) would affect T and B cell functions in a murine model. We observed a significant increase of CD69 surface marker on the B-cell population in total spleen and on isolated B-cells from BALB/c mice after in vitro rLiTXN1 stimulus. Activated Bcells underwent further proliferation, as measured by an increased [3H]-thymidine incorporation. Cytokine quantification showed a dose-dependent upregulation of IL-10 secretion. B-cells were identified as a source. Furthermore, intraperitoneal injection of rLiTXN1 into BALB/c mice triggered the production of elevated levels of rLiTXN1 specific antibodies, predominantly of the IgM, IgG1 and IgG3 isotypes, with a minimum reactivity against other heterologous antigens. Taken together, our data suggest that rLiTXN1 could participate in the immunopathological processes by targeting the B-cells effector functions with subsequent IL-10 secretion and specific antibodies production.
3
Costa, Vera Marisa Freitas. "Role of catecholamines and reactive oxygen species in the mechanism of oxidative stress-induced heart disease:in vitro studies using fresly isolated rat cardiomyocytes". Doctoral thesis, Faculdade de Farmácia da Universidade do Porto, 2008. http://hdl.handle.net/10216/20812.
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Pontes, Helena de Oliveira. "Toxicological and Toxicokinetic Interactions Between Ethanol and Ecstasy. In Vivo and In Vitro Studies". Doctoral thesis, Faculdade de Farmácia da Universidade do Porto, 2008. http://hdl.handle.net/10216/9486.
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Alves, Ema Luís Pereira Gomes. "Neurotoxicity of Methylenedioxymethamphetamine (MDMA; Ecstasy) and its Main Metabolites, on Rat Brain Mitochondria In Vitro and In Vivo - Behavioral Consequences". Doctoral thesis, Faculdade de Farmácia da Universidade do Porto, 2007. http://hdl.handle.net/10216/7499.
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Monteagudo, Maykel Cruz. "Multi-Objective Optimization Based on Desirability Estimation of Several Interrelated Responses (MOOp-DESIRe): A Computer-Aided Methodology for Multi-Criteria Drug Discovery". Doctoral thesis, Faculdade de Farmácia da Universidade do Porto, 2009. http://hdl.handle.net/10216/63799.
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Monteagudo, Maykel Cruz. "Multi-Objective Optimization Based on Desirability Estimation of Several Interrelated Responses (MOOp-DESIRe): A Computer-Aided Methodology for Multi-Criteria Drug Discovery". Tese, Faculdade de Farmácia da Universidade do Porto, 2009. http://hdl.handle.net/10216/63799.
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Alves, Ema Luís Pereira Gomes. "Neurotoxicity of Methylenedioxymethamphetamine (MDMA; Ecstasy) and its Main Metabolites, on Rat Brain Mitochondria In Vitro and In Vivo - Behavioral Consequences". Tese, Faculdade de Farmácia da Universidade do Porto, 2007. http://hdl.handle.net/10216/7499.
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Costa, Vera Marisa Freitas. "Role of catecholamines and reactive oxygen species in the mechanism of oxidative stress-induced heart disease:in vitro studies using fresly isolated rat cardiomyocytes". Tese, Faculdade de Farmácia da Universidade do Porto, 2008. http://hdl.handle.net/10216/20812.
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Oliveira, Ricardo Jorge Dinis. "Toxicity of Paraquat in Isolated Rat Lung. Search for Efficient Antidotes". Tese, Faculdade de Farmácia da Universidade do Porto, 2006. http://hdl.handle.net/10216/7369.
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DoutoramentoPhD Degree
The immune evasion mechanisms of pathogenic trypanosomatids involve a multitude of phenomena such as the polyclonal activation of lymphocytes, cytokine modulation and the enhanced detoxification of oxygen reactive species. A trypanothione-cascade seems to be involved in the detoxification process. We have recently described and characterized a tryparedoxin (LiTXN1) involved in the Leishmania infantum cytoplasmatic hydroperoxide metabolism. LiTXN1 is a secreted protein upregulated in the infectious form of the parasite, suggesting that it can play an important role during infection. In the present study, we investigated whether the recombinant LiTXN1 (rLiTXN1) would affect T and B cell functions in a murine model. We observed a significant increase of CD69 surface marker on the B-cell population in total spleen and on isolated B-cells from BALB/c mice after in vitro rLiTXN1 stimulus. Activated Bcells underwent further proliferation, as measured by an increased [3H]-thymidine incorporation. Cytokine quantification showed a dose-dependent upregulation of IL-10 secretion. B-cells were identified as a source. Furthermore, intraperitoneal injection of rLiTXN1 into BALB/c mice triggered the production of elevated levels of rLiTXN1 specific antibodies, predominantly of the IgM, IgG1 and IgG3 isotypes, with a minimum reactivity against other heterologous antigens. Taken together, our data suggest that rLiTXN1 could participate in the immunopathological processes by targeting the B-cells effector functions with subsequent IL-10 secretion and specific antibodies production.
11
Pontes, Helena de Oliveira. "Toxicological and Toxicokinetic Interactions Between Ethanol and Ecstasy. In Vivo and In Vitro Studies". Tese, Faculdade de Farmácia da Universidade do Porto, 2008. http://hdl.handle.net/10216/9486.
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Hoffmann, Sebastian. "Evidence-based in vitro toxicology". [S.l.] : [s.n.], 2005. http://deposit.ddb.de/cgi-bin/dokserv?idn=975776207.
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Holmgren, Per. "Postmortem toxicology : aspects on interpretation /". Linköping : Univ, 2004. http://www.bibl.liu.se/liupubl/disp/disp2004/med862s.pdf.
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Wilson, Joanne Patricia. "The molecular toxicology of butadiene". Thesis, University of Newcastle Upon Tyne, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.287826.
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Crouch, David G. "A political sociology of toxicology". Thesis, University of Sussex, 1989. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.694645.
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Kim, Hea-Young. "Molecular Toxicology of Pyrrolizidine Alkaloids". DigitalCommons@USU, 1994. https://digitalcommons.usu.edu/etd/3910.
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Pyrrolizidine alkaloids are cytotoxic, carcinogenic, and anti-carcinogenic in vivo and in vitro, and they produce many hazardous effects in humans and animals. Pyrrolizidine alkaloids (PAs) also cross-link with DNA and/or protein. However, whether such cross-linking is important to the toxic action of PAs is not known. In addition, the exact mechanism underlying these DNA cross-links or cytotoxicity is also not clear.
In three separate studies, I characterized the nature of PA-induced DNA cross-links and the relationships between PA structures and cross-linking potency. In the first study (Chapter II), I found that cross-linking potency of PA congeners coincided with their abilities to cause cytopathologic effects. Macrocyclic a,p-unsaturated diesters PAs and their pyrrolic metabolites were the most potent inhibitors of colony formation, and inducers of cytopathologic changes and megalocyte formation. The macrocyclic α, β-saturated diester PA and open diesters PAs slightly inhibited colony formation, and slightly changed cell morphology. Retronecine and indicine N-oxide were completely inactive. In the next study (Chapter Ill), I found that pyrrolic macrocyclic metabolites were more potent DNA cross-linkers than their parent compounds as determined by alkaline elution. The pyrroles of the macrocyclic diester PAs were potent DNADNA (inter- and/or intra) cross-linkers in BstEll-digested λ-phage DNA or pBR322 plasmid DNA but dehydroretronecine and indicine N-oxide were not. I also examined which DNA sequences were more susceptible to PA-induced cross-links by using a series of restriction endonucleases to determine sequence specificity. The most favorable cross-linking site for PAs appeared to be 5'd(GG) and 5'-d(GA) although other sites, 5'-d(CC) or 5'-d(CG), might be also preferable cross-linking targets. In the next study (Chapter IV), I characterized the nature of DNA-protein interactions induced by PAs, because I found in previous studies that PA-induced cross-links are largely protein associated. In PA or pyrrolic PA exposed cells, cross-linked proteins with molecular weights 40 - 60 kD were detected. Two-dimensional electrophoretic analysis revealed that these proteins were probably acidic in nature. In an in vitro system utilizing pBR322 or Bst Ell-digested λ-phage DNA. dehydrosenecionine induced DNAprotein cross-links with BSA, indicating that such interactions might be related to amino acid composition of protein.
These results confirmed that PA-induced DNA cross-links (DNA-DNA, DNA-protein cross-links) are influenced by three structural features: the C1 ,2 unsaturation of pyrrolizidine ring, α, β-unsaturation, and size of the macrocyclic diester ring. The ability to form cross-links was closely related to the known toxic potencies of these PAs. From this research, I also conclude that DNA crosslinking is the most critical event leading to PA-related diseases and that crosslinking is due to pyrrolic metabolites of PAs, not via a common metabolite as was once thought.
17
Neagu, Daniel, i A.-N. Richarz. "Big data in predictive toxicology". Royal Society of Chemistry, 2019. http://hdl.handle.net/10454/17603.
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NoThe rate at which toxicological data is generated is continually becoming more rapid and the volume of data generated is growing dramatically. This is due in part to advances in software solutions and cheminformatics approaches which increase the availability of open data from chemical, biological and toxicological and high throughput screening resources. However, the amplified pace and capacity of data generation achieved by these novel techniques presents challenges for organising and analysing data output. Big Data in Predictive Toxicology discusses these challenges as well as the opportunities of new techniques encountered in data science. It addresses the nature of toxicological big data, their storage, analysis and interpretation. It also details how these data can be applied in toxicity prediction, modelling and risk assessment.
18
Frank, Evan A. "Toxicology and Mechanisms of Lung Responses to Carbon Nanotube Exposures". University of Cincinnati / OhioLINK, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1448037426.
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Ouchi, Rejane Yuriko [UNESP]. "Avaliação dos efeitos do brometo de etídio em Drosophila melanogaster (Diptera-Drosophilidae)". Universidade Estadual Paulista (UNESP), 2011. http://hdl.handle.net/11449/100512.
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ouchi_ry_dr_sjrp.pdf: 1860080 bytes, checksum: 6ea294f1febce43f75eaaecd7bef2497 (MD5)A cada ano, milhares de novos compostos químicos entram no mercado, e um volume enorme de resíduos é gerado pela atividade humana, existindo uma grande preocupação com relação aos seus efeitos a curto e longo prazo sobre a saúde e o ambiente. Um grande número dessas substâncias químicas é potencialmente perigoso e pode acarretar efeitos biológicos deletérios, sendo que mudanças a nível molecular são usualmente as primeiras respostas detectáveis da perturbação ambiental. Para avaliar os efeitos em sistemas biológicos, são utilizados bioindicadores, organismos sensíveis a agentes tóxicos. O presente trabalho teve por objetivo analisar os efeitos do Brometo de Etídio (BE), substância potencialmente mutagênica, na mosca da fruta (Drosophila melanogaster), realizando-se sempre comparações com o controle positivo, etilmetanosulfonato (EMS). Escolhemos o brometo de etídio por se tratar de uma substância usada frequentemente em métodos de biologia molecular, sendo tida como mutagênica, apesar de não constar como carcinogênico nas listagens da Agência Internacional para Pesquisa de Câncer (IARC). A pesquisa foi feita ao longo de 25 gerações, e em seis gerações (1ª, 5ª, 10ª, 15ª, 20ª, 25ª gerações) foram analisados: (1) os efeitos sobre padrões morfológicos, (2) a produtividade diária ao longo de 15 dias. Além disso, foram analisadas também: (3) alterações bioquímicas em enzimas do sistema oxidativo, acarretadas pela exposição a diferentes concentrações de brometo de etídio e EMS, (4) alterações gênicas: em nível de transposição do elemento transponível Bari-1 e na expressão dos genes que codificam as proteínas catalase, hsp 70 (heat shock protein), superóxido dismutase...
Each year thousands of new chemicals enter the market, and an enormous volume of waste is generated by human activity. Accordingly, there is a great concern regarding their short and long term health and environmental effects. A large number of these chemicals is potentially dangerous and can cause harmful biological effects, and changes at the molecular level are usually the first detectable responses of environmental disturbance. To evaluate the effects on biological systems, are used bioindicators, organisms sensitive to toxic agents. This study aimed to analyze the effects of Ethidium Bromide (EB), a potentially mutagenic substance, in the fruit fly (Drosophila melanogaster), comparing with a positive control, ethylmethanesulfonate (EMS). We chose ethidium bromide because it is a chemical frequently used in molecular biology techniques, and considered as a mutagenic although it is not included in the lists of the International Agency for Research on Cancer (IARC). The survey was conducted over 25 generations, and in six generations (1st, 5th, 10th, 15th, 20th, 25th generations) were analyzed: (1) the effects on morphological patterns, (2) the daily productivity over 15 days. In addition, we also analyzed: (3) biochemical changes in enzymes of the oxidative system brought about by exposure to different concentrations of ethidium bromide and EMS, (4) genetic alterations: level of transposition of the transposable element Bari-1 and expression genes that encode proteins catalase, hsp 70 (heat shock protein), superoxide dismutase 1 and esterase-6 and (5) longevity. Concerning daily productivity, five replicates were done, involving negative and positive controls (not exposed to any mutagen and with EMS, respectively), and three groups exposed to 1, 5 and 30 µM of EB. The results show that there were... (Complete abstract click electronic access below)
20
Farina, Massimo. "Metallomics in in vitro toxicology research". Doctoral thesis, Universitat Autònoma de Barcelona, 2008. http://hdl.handle.net/10803/3924.
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Los metales son ubicuos y su acumulación cada vez mayor en el ambiente conduce a serias preocupaciones en términos de seguridad ambiental, ocupacional y del consumidor. Entre otros efectos potenciales sobre la salud, la carcinogenicidad y la neurotoxicidad inducidas por los metales representan un riesgo importante para la sociedad humana y, por lo tanto, merecen ser determinadas completamente. En este contexto, se necesita llevar a cabo un amplio proyecto de investigación in vitro en estas áreas en compuestos metálicos seleccionados. El trabajo se refiere a investigaciones en metalómica destinadas a estudiar las rutas metabólicas de compuestos caracterizados de As, Cd, Cr, Pt, Mn y V mediante modelos experimentales desarrollados en ECVAM, como las líneas celulares de fibroblasto de ratón (Balb/3T3), las variedades de células del feocromocitoma de la rata (PC12) y reagregados de cerebro de rata y sus tipos celulares individuales. Los estudios se han realizado usando técnicas nucleares y radioanalíticas (análisis por activación de neutrones (NAA), radiotrazadores con alta radiactividad específica) y técnicas espectrométricas avanzadas (HPLC-ICPMS y GFAAS). Incluyen la especiación en relación al comportamiento de los compuestos metálicos en los medios de cultivo celular, su absorción, distribución intracelular del metal, y unión con los componentes celulares.Etapas del proyecto de investigación:
(i) preparación de los radiotrazadores para etiquetar las diferentes concentraciones de los compuestos metálicos
(ii) exposición de modelos in vitro estandardizados a los compuestos estables y/o metales marcados radioactivamente para diferentes periodos de tiempo y rango de concentración
(iii) estudios mecanísticos que permitan establecer la relación dosis-efecto en cuanto a la absorción del metal estudiado por todos los compartimentos celulares, como se obtiene por centrifugación diferencial y por técnicas de filtración de gel. Determinación del estado de oxidación del metaloma en los compartimentos de la célula
(iv) tratamiento estadístico de los datos y desarrollo de modelos metabólicos.
Metals are ubiquitous and increasing accumulation in the environment raises serious concerns in terms of environmental, occupational and consumer safety. Among other potential health effects, metal-induced carcinogenicity and neurotoxicity represent a major risk to the human society and therefore deserves to be fully assessed. In this context, a comprehensive in vitro research project in these areas needs to be conducted on selected metal compounds.
The work concern in vitro metallomics investigations concerning metabolic pathways of chemically-characterized As, Cd, Cr, Pt, Mn and V compounds by experimental models developed at ECVAM, such as mouse fibroblast (Balb/3T3), rat pheochromocytoma (PC12) cell lines and rat brain re-aggregates and their individual cell types. The studies will be carried out by using nuclear, radioanalytical (neutron activation analysis (NAA) and use of radiotracers with high specific radioactivity) and advanced spectrochemical (HPLC-ICPMS and GFAAS) techniques. They will include metal speciation concerning behaviour of test metal compounds in cell culture media, uptake, intracellular distribution, binding with cell components.
Steps of the research project:
(i) preparation of radiotracers for labelling of different concentrations of metal compounds
(ii) exposure of standardised in vitro models to stable and/or radiolabelled metal compounds for different time periods and range of concentration
(iii) mechanistic studies involving the establishment of dose-effect relationship in relation to uptake of metal tested by whole cell compartments as obtained by differential centrifugation as well as gel filtration techniques. Determination of the oxidation state of metallome in cell compartments
(iv) statistical treatment of the data and development of metabolic models.
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Sharma, Raju Prasad. "Integrative Systems Toxicology For Human Health". Doctoral thesis, Universitat Rovira i Virgili, 2018. http://hdl.handle.net/10803/665621.
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Els disruptors endocrins (DE) són substàncies naturals o antropogèniques presents el ambient, aliments o productes de consum que poden alterar els equilibris hormonals en humans i animals i produir efectes adversos per a la salut fins i tot a dosis baixes. S'han desenvolupat nombrosos mètodes, sota l'orientació de la UE i OCD, amb l'objectiu de realitzar avaluacions de riscos quantitatius per a aquests substàncies, tanmateix, aquests mètodes encara no tenen la confiança en el nivell de seguretat per a l'exposició humana. La predicció quantitativa dels efectes adversos dels DE en la salut humana planteja diversos reptes associats a la seva complexa exposició, cinètica no lineal, metabolisme(s) i mecanisme complex o la resposta complexa d'organismes en diferents etapes de vida o escales de temps. L'anàlisi d'alta capacitat emergent ,(OMICS), in-silico, com la farmacocinética-dinàmica fisiològica (PBPK /PD), la biologia de sistemes i les vies d'èxit adverses (AOPs) faciliten la comprensió de la complexitat biològica i la seva connectivitat multinivell. L'objectiu d'aquesta tesi és construir un model de toxicologia de sistemes integradors per predir els efectes adversos induïts a la salut humana per exposició a DE. La primera part d'aquest treball es centra en el desenvolupament i la validació del model detallat de dosimetria tisular que integra espècies i dades fisiològiques específiques de la població, dades in vitro i in-silico. La segona part es centra en el desenvolupament i la validació del model de toxicologia de sistemes integradors que inclou la biologia de sistemes, la senyalització del desenvolupament i la validació del model de la ruta de la xarxa / AOP, i l'acoblament d'aquests amb el model PBPK detallat. Aquest model de toxicologia de sistemes integrat proporcionarà així una plataforma de models predictius robusta per a productes químics / DE qualificats per donar suport als requisits regulatoris.Los disruptores endocrinos (DE) son sustancias naturales o antropogénicas presentes en el ambiente, alimentos o productos de consumo que pueden alterar los equilibrios hormonales en los humanos y animales, y producir efectos adversos a la salud incluso a bajas dosis. Se han desarrollado numerosos métodos bajo la guía de la UE y la OCDE con el objeto de realizar Evaluaciones Cuantitativas de Riesgos para estas sustancias, sin embargo, estos métodos aún carecen de la confianza en el nivel de seguridad de exposición a humanos. La predicción cuantitativa de los efectos adversos de los DC en la salud plantea desafíos que están asociados a: su compleja exposición, cinética no lineal, metabolito (s) y complejas respuestas de organismos en su ciclo de vida o en escalas de tiempo. El análisis de alto rendimiento emergente (OMICS) y herramientas in silico como la farmacocinética-dinamia basada en fisiología (PBPK/PD), la biología de los sistemas y las vías de resultados adversas (AOP), facilitan la compresión de la complejidad biológica y su conectividad multinivel. El objetivo de esta tesis es construir un modelo de toxicología de sistemas integrados para predecir los efectos adversos a la salud por la exposición a los DE. La primera parte de este trabajo se centra en el desarrollo y la validación del modelo detallado de dosimetría tisular que integra especies y datos fisiológicos específicos de la población, datos in vitro e in silico. La segunda parte se centra en el desarrollo y validación del modelo de toxicología de sistemas integrados que incluye: la biología, red de señalización/desarrollo y validación del modelo vía AOPs, y el acoplamiento de éstos con el modelo detallado de PBPK. Este modelo de toxicología de sistemas integrados proporcionará una sólida plataforma de modelos predictivos para compuestos químicos/DC calificados para el respaldo de los requisitos reglamentarios.
Endocrine disrupting chemicals (EDCs) are natural or anthropogenic substances in the environment, food, or consumer products that can disrupt hormonal balances in humans and wildlife, and result in adverse health effects even at low dosages. To date, many test methods have been developed under EU and OECD guidance with the aim to perform Quantitative Risk Assessments for these chemicals. However, these methods still lack the confidence on their safety level of exposure to human. Quantitative Prediction of EDCs' adverse effect on human health poses several challenges associated with their complex exposure, nonlinear kinetics, metabolite (s), and complex mechanism or the complex response of organisms over different life stages or time scales. Emerging high-throughput analysis (OMICS) and in-silico tools such as physiologically based pharmacokinetic/pharmacodynamics (PBPK/PD), Systems biology and Adverse Outcome Pathways (AOPs) offer an opportunity to understand the biological complexity and their multilevel connectivity. The objective of this thesis is to build an integrative systems toxicology model for predicting EDCs-induced adverse effects on human health. The first part of this work focuses on the development and the validation of the detailed tissue-dosimetry model integrating species and population specific physiological data, in-vitro and in-silico derived data. The second part focuses on the development and validation of integrative systems toxicology model that includes Systems biology, signalling network/AOPs pathway model development and validation, and coupling of these models with detailed PBPK model. This integrative systems toxicology model will thereby provide a robust predictive models platform for chemicals/EDCs qualified to support regulatory requirements.
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Cheng, Crystal. "Toxicology of nanoparticles after cellular uptake". Thesis, University of Cambridge, 2010. https://www.repository.cam.ac.uk/handle/1810/245264.
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Nanoscience is a multi-disciplinary field with the potential to both create new applications and understand existent systems, but its materials may be sources of toxicological concern. Understanding their toxic potential becomes essential to prevent any occupational, environmental, and consumer hazards. In this study, the toxicity of three different nanoparticles (NPs) was assessed: multi-walled carbon nanotubes (MWNTs), single-walled carbon nanotubes (SWNTs), and zinc oxide (ZnO) nanopowders. A combination of cell viability assays—NR, MTT, LDH, live dead—and microscopy—TEM, SEM, confocal—was used. No direct interactions occurred with any of the assays except the NR and ZnO nanopowders at > 50 µg/mL. The overall cytotoxic trend was ZnO > MWNT > SWNT. Both uncoated and PVA-coated ZnO nanopowders exhibited dose dependent toxicity with a sudden rate of increase between 12.5 and 25 µg/mL. Zn²+ cations appeared to be the major toxic source. Cytotoxic curves of ZnO nanopowders were similar to ZnCl2, a chemical known to dissociate into Zn²+ + Cl-, and a stereological analysis indicated specific mitochondrial damage, a condition associated with Zn²+ neurotoxicity. Zinc dissolution also increased with decreasing cell pH. Unpurified and purified MWNTs exhibited dose and time dependent toxicity with necrosis as the main mechanism of cell death. The residual iron Fe2O3 yielded no toxicity suggesting the nanotubes themselves as the toxic source. MWNTs entered cells both actively and passively and were found in the cytoplasm and nuclei. Only HiPco SWNTs caused significant cell death; none was observed for the unpurified and purified SWNTs. At the concentrations tested, this study found that both ZnO nanopowders and MWNTs caused acute toxicity while SWNTs were not acutely toxic. All three NPs should remain in the research and development stage until further studies can fully characterise their relationship with cells.
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Rogerson, Jonathan G. "Biosensor technology : applications in microbial toxicology". Thesis, University of Bedfordshire, 1997. http://hdl.handle.net/10547/621817.
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This work describes the development of mediated amperometric biosensors that are able to monitor the metabolic activity of both single and mixed microbial populations, with applications in toxicity assessment and wastewater treatment plant protection. Biosensor systems have been constructed incorporating either the single-species eubacteria Escherichia coli or Pseudomonas putida, Bioseed®, or a mixture of activated sludge organisms from wastewater treatment plants, as the sensing components immobilised on disposable screen printed electrodes in stirred reaction vials. The biosensor approach is generic allowing for a wide range of microbial cell types to be employed. Appropriate bacterial species can be selected for specific sensor applications in order to confer validity and relevance to the test, hence the biosensor can be tailor-made to assess the toxicity in a particular environment and provide diagnostically valid and relevant results. The biosensors have been used to assess the toxicity of a standard toxicant and toxicant formulations and in blind testing of a range of industrial effluents, in parallel with a number of bioassays including Microtox® and activated sludge respiration inhibition. The biosensor results generally show significant correlation to the appropriate conventional toxicity tests. In this study, an activated sludge based biosensor assay was developed and used to assess the toxicity of industrial process and site effluents with the specific purpose of wastewater treatment plant protection. Data generated compared significantly with those from an activated sludge respiration inhibition test, with added advantages of rapidity, safety and ease of use.
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Dempsey, R. "The genetic toxicology of carcinogenic compounds". Thesis, Swansea University, 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.636437.
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This thesis involved the development of a range of assay systems for the detection of environmental mutagens and carcinogens. Initially a protocol was optimised for the induction of mitotic gene conversion in stationary-phase cultures of the yeast Saccharomyces cerevisiae, strain JD1 following exposure to compounds which require exogenous metabolic activation, which involved an initial incubation at 37oC for 2 hours followed by a 16 hour incubation at 28oC. This protocol was found to be effective for the detection of cyclophosphamide and sterigmatocystin. In two separate studies, the activities of a total of 14 different compounds were then investigated in yeast using this, and other protocols involving exponential-phase cultures. In the first study, benzidine and diaminoterphenyl were detected, although, despite being structural analogues, their metabolic requirements differed. Dimethylaminoazobenzene and cyanodimethylaniline could not be detected under any of the conditions examined. In the second of these studies 8 carcinogens and 2 non-carcinogens were examined. Only one of the carcinogens, Acrylonitrile, was detected. The inactivity of the other 7 carcinogens was considered to be due to their ineffectiveness at inducing mitotic gene conversion. A third study indicated that respiratory status of the yeast strain used, had both quantitative and qualitative effects on the detection of sterigmatocystin, benzidine and diaminoterphenyl. Further studies were performed on two additional assays, chromosomal aberration induction and mammalian cell transformation, as these endpoints had proved very successful for detecting chemicals which were not readily detected in assays for other genetic endpoints. BZD was found to induce chromosomal abberrations in peripheral human lymphocyte cultures, in the absence of S9, which was in contrast to the activity detected in the yeast system. It was suggested that this was due to metabolic competence of the human lymphocyte cells. Studies on the stepwise transformation of Syrian hamster dermal cells, led to the suggestion of a model for the occurrence of aneuploidy events during this process, and their fixation at completion of transformation. The significance of this with respect to the observed occurrence of aneuploidy with cancer is discussed.
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Winstanley, Peter Andrew. "The pharmacology and toxicology of amodiaquine". Thesis, University of Liverpool, 1988. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.237571.
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Nassr, Azize Cristina Capelli. "Desenvolvimento reprodutivo de ratos machos expostos ao fenvalerato in utero e lactação". [s.n.], 2005. http://repositorio.unicamp.br/jspui/handle/REPOSIP/318041.
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Orientador: Wilma De Grava KempinasDissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia
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Resumo: o fenvalerato é um inseticida piretróide sintético usado na agricultura, pecuária e no controle de insetos domésticos, e seus efeitos reprodutivos são pouco conhecidos. Algunsestudos têm proposto que o fenvaleratoseja um desregulador endócrino,atuando como um estrógeno ambiental. Estudos realizados com ratos adultos expostos a determinados piretróides mostraram a redução do número de espermatozóides e das concentrações plasmáticas de testosterona. Sabendo-se que o sistema reprodutor masculino de ratos é mais sensível ao efeito de substâncias tóxicas durante as fases fetal e neonatal, o objetivo deste trabalho foi avaliar os possíveis efeitos tardios sobre o desenvolvimento reprodutivo na pré-puberdade (40 dias de idade), puberdade (60 dias) e maturidadesexual (90 dias), em ratos machos cujas mães foram expostas ao fenvalerato durante a prenhez e lactação. Adicionalmente,investigou-seo comportamentosexual, a fertilidadedos ratos adultos,a transferênciado fenvaleratodas mães para a prole,e a sua persistência no organismo dos descendentes machos. Para este estudo ratas prenhes (n=8) foram tratadas com fenvalerato técnico (96% de pureza), na dose diária de 40 mg/Kg, do 12° dia de prenhez até o final da lactação (período crítico de diferenciação do sistema reprodutor masculino da prole). Ratas controles (n=8) receberam óleo de milho (veículo), nas mesmas condições experimentais. O desenvolvimento reprodutivo foi avaliado através da idade da descida testiculare da separação prepucial,pesos dos órgãos reprodutores, concentração plasmática de testosterona, contagem de células germinativas no testículo e epidídimo, morfologia espermática, estudo do processo espermatogênico, número de células de Sertoli, do diâmetro dos túbulos seminíferos e altura de epitélio germinativo. Tambémfo~m avaliados o comportamentosexual e a fertilidadedos ratos adultos após acasalamentos naturais. A quantificação de resíduos de fenvalerato foi realizada por Cromatografia Líquida de Alta Precisão (CLAP) em amostras de órgãos e tecidos das mães, fetos e filhotes. Os resultados da quantificação de fenvalerato revelaram que o piretróide foi transferido das mães para os fetos, pela placenta, e para os filhotes, pelo leito matemo, respectivamente. O piretróide permaneceu no organismo dos filhotes até, pelo menos, 40 dias de idade, com destaque para o testículo e epidídimo. A exposição in utero e lactacional ao fenvalerato foi tóxica para o testículo, conforme mostrado pela diminuição dos pesos deste órgão nos grupos tratados e pela redução da produção espermática na puberdade, sem que tenha havido depleção androgênica ou diminuição da população de células de Sertoli. Os estudos morfológicos e morfométricos não mostraram danos sobre o aspecto histológico do testículo e o processo espermatogênico, sugerindo a ação do fenvalerato sobre a formação dos cordões seminíferos nos testículos fetais. Na idade adulta houve aumento significativo do peso da vesícula seminal e do número de ejaculações, embora os resultados dos testes de fertilidade tenham sido semelhantes entre os grupos controle e tratado. Esses achados podem ter sido uma conseqüência tardia de um desequilíbrio neuroendócrino durante o período crítico de diferenciação do sistema reprodutor masculino, quando ocorreu a exposição ao fenvalerato. Concluiu-se que o fenvalerato, diluído em óleo de milho, na dose de 40 mg/Kg, administrado para ratas do 12°. dia de prenhez até o final da lactação, foi transferido pela placenta e pelo leite matemo, provocando efeitos tardios no desenvolvimento reprodutivo da prole masculina
Abstract: Fenvalerate is a synthetic pyrethroid insecticide used in agriculture, cattle raising and in the control of domestic insects, and its reproductive effects are little-known.Some studies already have proposed that fenvalerate is an endocrine disruptor, acting as an environmentalestrogen. Studies done with rats exposed to some pyrethroids showed reduction of sperm number and plasmatic testosterone concentration. Knowingthat the male reproductive system of rats is more sensitive to the effects of toxic substances during fetal and neonatal phases, the objective of this work was to evaluate the possible Iate effects on the reproductive development at pre-puberty (aged 40 days), puberty (aged 60 days) and sexual maturity(aged 90 days) in male rats whose mothers were exposed to fenvalerate during gestation and lactation. Additionally,sexual behavior, fertilityof adult rats, transference of fenvalerate from the mothers to the offspringand its persistence in the organism of the male descendents were investigated. For this study pregnant rats (n=8) were treated with technical fenvalerate (96% purity), in the dose of 40 mglKg, from gestational day 12 until the end of lactation (critical period for differentiation of the male reproductive system of the offspring). Control rats (n=8) received com oil (vehicle), irí the same experimental conditions. The reproductive development was evaluated through of the age when testicular descent and preputial separation occurred, weight of reproductive organs, plasmatictestosterone levels, numbers of germ cells in the testis and epididymis and sperm morphology. The spermatogenic process, the number of Sertoli cells, seminiferous tubule diameter and height of the germinative epithelium were also evaluated. The sexual behavior and fertilityof adult rats were also evaluated by natural matings. Fenvalerate -residues were quantified using High Performance Liquid Chromatography (HPLC)in samples of organs and tissues of mothers,fetuses and pups. The results of the fenvalerate quantification revealed that the pyrethroid was transferred from the mothersto the fetuses through the placenta, and to the pups by maternal milk, respectively. The pyrethroid remained in the organism of the pups until at least 40 days of age, especially in the testis and epididymis. In utero and lactational exposure to fenvalerate was toxic for the testis, as shown by the diminished weight of this organ in the treated groups and reduction of the sperm production at puberty, without androgen depletion or decrease of the Sertoli cell population. The morphological and morphometrical studies did not show injuries in the histological aspect of the testis or the spermatogenic process, suggesting the action of fenvalerate on the formation of seminiferous cords in the fetal testicJe. At adult age there was a significant increase of the seminal vesicJe weight and in the number of ejaculations, although the fertilitytest results were similarbetween control and treated groups. These effects can be a Iate consequence of a neuroendocrinedysregulationduringthe critical period of differentiation of the male reproductive system, when the exposure to fenvalerate occurred. It was concluded that fenvalerate, diluted in com oil at the dose of 40 mg/Kg, administered to rats from the gestational day 12 until the end of lactation was transferred through the placenta and milk, provoking Iate effects in the reproductive development of the male offspring
Mestrado
Biologia Celular
Mestre em Biologia Celular e Estrutural
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Ouchi, Rejane Yuriko. "Avaliação dos efeitos do brometo de etídio em Drosophila melanogaster (Diptera-Drosophilidae) /". São José do Rio Preto : [s.n.], 2011. http://hdl.handle.net/11449/100512.
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Orientador: Gustavo Orlando Bonilla RodriguezCoorientador: Carlos Roberto Ceron
Banca: Eduardo Alves Almeida
Banca: Lucilene Regina Maschio
Banca: Lilian Castiglione
Banca: Rogério Pincela Mateus
Resumo: A cada ano, milhares de novos compostos químicos entram no mercado, e um volume enorme de resíduos é gerado pela atividade humana, existindo uma grande preocupação com relação aos seus efeitos a curto e longo prazo sobre a saúde e o ambiente. Um grande número dessas substâncias químicas é potencialmente perigoso e pode acarretar efeitos biológicos deletérios, sendo que mudanças a nível molecular são usualmente as primeiras respostas detectáveis da perturbação ambiental. Para avaliar os efeitos em sistemas biológicos, são utilizados bioindicadores, organismos sensíveis a agentes tóxicos. O presente trabalho teve por objetivo analisar os efeitos do Brometo de Etídio (BE), substância potencialmente mutagênica, na mosca da fruta (Drosophila melanogaster), realizando-se sempre comparações com o controle positivo, etilmetanosulfonato (EMS). Escolhemos o brometo de etídio por se tratar de uma substância usada frequentemente em métodos de biologia molecular, sendo tida como mutagênica, apesar de não constar como carcinogênico nas listagens da Agência Internacional para Pesquisa de Câncer (IARC). A pesquisa foi feita ao longo de 25 gerações, e em seis gerações (1ª, 5ª, 10ª, 15ª, 20ª, 25ª gerações) foram analisados: (1) os efeitos sobre padrões morfológicos, (2) a produtividade diária ao longo de 15 dias. Além disso, foram analisadas também: (3) alterações bioquímicas em enzimas do sistema oxidativo, acarretadas pela exposição a diferentes concentrações de brometo de etídio e EMS, (4) alterações gênicas: em nível de transposição do elemento transponível Bari-1 e na expressão dos genes que codificam as proteínas catalase, hsp 70 (heat shock protein), superóxido dismutase... (Resumo completo, clicar acesso eletrônico abaixo)
Abstract: Each year thousands of new chemicals enter the market, and an enormous volume of waste is generated by human activity. Accordingly, there is a great concern regarding their short and long term health and environmental effects. A large number of these chemicals is potentially dangerous and can cause harmful biological effects, and changes at the molecular level are usually the first detectable responses of environmental disturbance. To evaluate the effects on biological systems, are used bioindicators, organisms sensitive to toxic agents. This study aimed to analyze the effects of Ethidium Bromide (EB), a potentially mutagenic substance, in the fruit fly (Drosophila melanogaster), comparing with a positive control, ethylmethanesulfonate (EMS). We chose ethidium bromide because it is a chemical frequently used in molecular biology techniques, and considered as a mutagenic although it is not included in the lists of the International Agency for Research on Cancer (IARC). The survey was conducted over 25 generations, and in six generations (1st, 5th, 10th, 15th, 20th, 25th generations) were analyzed: (1) the effects on morphological patterns, (2) the daily productivity over 15 days. In addition, we also analyzed: (3) biochemical changes in enzymes of the oxidative system brought about by exposure to different concentrations of ethidium bromide and EMS, (4) genetic alterations: level of transposition of the transposable element Bari-1 and expression genes that encode proteins catalase, hsp 70 (heat shock protein), superoxide dismutase 1 and esterase-6 and (5) longevity. Concerning daily productivity, five replicates were done, involving negative and positive controls (not exposed to any mutagen and with EMS, respectively), and three groups exposed to 1, 5 and 30 µM of EB. The results show that there were... (Complete abstract click electronic access below)
Doutor
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Tanamachi, Amanda Rodrigues A. R. "Potencial toxicogenômico do contaminante ambiental 2-fenilbenzotriazol-9 não clorado (non-Cl PBTA-9) in vivo". Botucatu, 2020. http://hdl.handle.net/11449/192455.
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Orientador: Daisy Maria Fávero SalvadoriResumo: O setor industrial, em constante expansão, gera, diariamente, resíduos com elevado potencial tóxico ao ambiente. Nesse contexto, a indústria têxtil apresenta grande impacto poluidor para a hidrosfera, devido aos compostos e processos químicos utilizados na coloração de tecidos. A literatura mostra que não há eficiência na remoção desses compostos, tanto por parte das fábricas, como em Estações de Tratamento de Água (ETAs) para o abastecimento humano. Pelo contrário, o processo de descontaminação pode tornar corantes do grupo azo, por exemplo, ainda mais tóxicos. Portanto, a poluição ambiental por essa classe de corantes vem sendo alvo de inúmeros estudos para a caracterização química e toxicológica, sobretudo dos subprodutos e intermediários gerados, dentre os quais os 2-fenilbenzotraizóis não clorados (non-Cl PBTA). Dentre eles, o non-Cl PBTA-9 tem recebido especial atenção por ser derivado do corante Disperse Violet 93, que tem sido detectado em maior quantidade nos corpos fluviais sob influência de atividades têxteis. Com base nesse cenário, o presente estudo objetivou investigar o potencial toxicogenômico do non-Cl PBTA-9 em camundongos. Foram testadas três concentrações do composto, 5, 50 e 500 μg/kg p.c., administradas aos animais por via gástrica (gavage) em dose única. Foram analisadas as frequências de micronúcleo em células de medula óssea, o nível de danos primários no DNA em células do sangue, fígado e cólon, além do padrão de expressão dos genes TP53, CYP1A1, NAT... (Resumo completo, clicar acesso eletrônico abaixo)
Abstract: The constantly expanding industrial sector has been generating residues with high toxic potential to the environment. The textile industry has a heavily impact, polluting the hydrosphere due to chemical processes used. Literature shows that even after effluent treatment, toxic compounds are still present in the wastewater and in rivers. Moreover, the water decontamination can make some dyes compounds even more toxics. Currently, environmental pollution caused by azo dyes, their byproducts and intermediates, has been widely investigated. In this sense, the non-chlorinated 2-phenilbenzotriazole 9 (non-Cl PBTA 9) has received attention because it is derived from the dye Disperse Violet 93, which is detected in high quantity in surface waters under influence of textile activities. Thus, the aim of this study was to investigate the toxicogenomic potential of acute exposure to the non-chlorinated PBTA-9 in mice. The three doses tested (5, 50 and 500 μg/kg body weight) of the compound were orally (gavage) administered to the animals. Micronucleus frequency in bone marrow cells, primary DNA damage in blood, liver and colon cells, and gene (TP53, CYP1A1, NAT2 and CDKN1A) expression profiling in liver cells were analyzed. The results showed that the non-Cl PBTA 9 was genotoxic in blood and liver cells at the highest dose (500 μg/kg b.w.) and at doses of 5, 50 and 500 μg/kg b.w. in colon cells. Mutagenic effect in bone marrow cells was observed at 5 and 50 μg/kg b.w.. No histological al... (Complete abstract click electronic access below)
Mestre
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Phelps, Jennifer Suzanne 1960. "CISPLATIN NEPHROTOXICITY: IN VITRO STUDIES (KIDNEY, TOXICOLOGY, PLATINUM)". Thesis, The University of Arizona, 1986. http://hdl.handle.net/10150/291243.
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Kultima, Kim. "Transcriptomics and Proteomics Applied to Developmental Toxicology". Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis, 2007. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-7921.
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Smith, Catherine Clare. "The genetic toxicology of DNA-based products". Thesis, Imperial College London, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.406671.
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Gal, Aharon. "The toxicology of nitric oxide In vitro". Thesis, Massachusetts Institute of Technology, 1996. http://hdl.handle.net/1721.1/39614.
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Alzeer, Samar Adnan. "Forensic toxicology of gamma hydroxybutyrate (GHB) metabolism". Thesis, University of Strathclyde, 2011. http://oleg.lib.strath.ac.uk:80/R/?func=dbin-jump-full&object_id=16779.
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Lourens, Denise. "The epidemiology, pathology and toxicology of suicide". Master's thesis, University of Cape Town, 1998. http://hdl.handle.net/11427/26780.
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Complete suicides and parasuicides are a major cause of death and disability in South Africa and the rest of the world. The epidemiology, pathology and toxicology of complete suicides were investigated in this study. All the complete suicide cases, which were presented to Salt River Medicolegal Laboratory over a period of one year (1 January 1997 - 31 December 1997), were analysed. The candidate personally conducted 148 of the alleged 180 suicide cases that presented in this time period (82%). The candidate did all the follow up investigations herself. The main findings were: 1. The male to female ratio was 5: 1. (131: 26) 2. Shooting and hanging were the most commonly used methods. 3. The racial distribution of violent deaths showed a high rate of suicides amongst the White population. 4. Suicides accounted for the Joss of young lives, the average age being 37,8 years. The mean age was 34 years. 5. Most victims committed suicide in and around their own homes. 6. The majority did not leave suicide notes. 7. Psychiatric disorders, poor health, arguments with close family members and friends, financial problems and long-standing relationship problems were the most common reasons for the suicides. 8. Suicides by prisoners accounted for 3,8% of the study (6 cases). 9. Two cases of double suicide (group suicide) were identified. 10. Five cases of homicide-suicide were identified in the study material. 11. One case of an attempted suicide by means of a high-speed motor vehicle accident, followed by the successful suicide by other means, was identified.
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Kristovich, Robert Lee. "Chemistry and toxicology of respirable airborne particulates". Connect to this title online, 2004. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1100898370.
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Thesis (Ph. D.)--Ohio State University, 2004.Title from first page of PDF file. Document formatted into pages; contains xvii, 260 p.; also includes graphics (some col.). Includes bibliographical references (p. 242-260).
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Duffin, Roger. "Molecular toxicology studies on the quartz hazard". Thesis, Edinburgh Napier University, 2003. http://researchrepository.napier.ac.uk/Output/2777.
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Silicon makes up almost 28% of the Earth's crust and within that crust, quartz (crystalline silica) is one of the most abundant minerals. Exposure to quartz can occur in a number of occupations, including the mining and construction industries in which respirable quartz particles are generated and become airborne. Inhalation of quartz can lead to the fibrosing lung disease silicosis and cancer. Silicosis has been recognised for many decades as one of the most prevalent occupational lung diseases. In 1997, an IARC working Group classified quartz as a class 1 lung carcinogen, but only in some industries, suggesting that the quartz hazard is a variable entity. The reactivity of the quartz surface may underlie its ability to cause inflammation and treatments that ameliorate this reactivity would then reduce the quartz hazard. In the present study the effect of treating quartz with aluminium lactate, a procedure reported to decrease the quartz hazard, on the highly reactive quartz surface and on proinflammatory events in the rat lung were explored. Aluminium lactate-treated quartz showed a reduced surface reactivity as measured by electron spin resonance. Eighteen hours post-instillation of quartz into the rat lung, there was massive inflammation as indicated by the number of neutrophils in the bronchoalveolar lavage (BAL) and an increase in BAL macrophage inflammatory protein-2 (MIP-2). However, aluminium lactate-treated quartz had no significant effect when compared to control. Epithelial damage as indicated by BAL protein and gamma glutamyl transpeptidasea lso increased with quartz instillation but not with aluminium lactate-treated quartz and furthermore, quartz induced an increase in MIP-2 mRNA content of BAL cells while aluminium lactate-treated quartz had no effect compared to controls. There was an increase in nuclear binding of the transcription factor nuclear factor-kappa B (NF-xB) in the quartz exposed BAL cells and again, no effect on nuclear NF-xB binding in BAL cells from aluminium lactate-treated quartz instilled rats. In addition, the effect of aluminium lactate and PVNO quartz treatment on DNA damage, cell cytotoxicity and particle uptake by A549 cells was assessed. DNA strand breakage, as produced by quartz at non-toxic concentrations, could be completely prevented by both coating materials. Particle uptake by A549 cells appeared to be significantly inhibited by the PVNO coating, and to a lesser extent by the aluminium lactate coating, demonstrating that respirable quartz particles induce oxidative DNA damage in human lung epithelial cells and indicating that the surface properties of the quartz as well as particle uptake by these target cells are important in the cytotoxic and genotoxic effects of quartz in vitro. Finally, the role played by surface area and specific reactivity in the acute inflammatory response to particles was investigated. Acute inflammatory response following instillation of particles has been used to evaluate hazard but has been criticised because of the non-physiological delivery and the problems of local overload. Here, a number of low toxicity dusts of various particle sizes were instilled and the neutrophil influx into the lung 18-24 hours post-instillation assessed. The extent of inflammation was shown to be a function of the surface area instilled and ultrafine particles, which present a case of high surface area per unit mass, were inflammogenic pro rata with their surface area. There is no evidence that ultrafine particles of carbon black, titanium dioxide or polystyrene have any special reactivity in addition to their large surface area. We further tested whether this approach could be used to model the reactivity of highly toxic dusts. Rats were instilled with either quartz or aluminium lactate-treated quartz and, as anticipated, the high specific surface reactivity of quartz meant that it was much more inflammogenic than was predicted using the relationship described for `low toxicity' dusts. This approach represents the possibility of modelling potential toxicity for nuisance dusts based on the inflammatory response of a given instilled surface area dose.
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Bordin, Diana Lilian. "Avaliação da genotoxicidade e estresse oxidativo em planárias aquáticas (Dugesia schubarti) tratadas com formulações do herbicida glifosato". reponame:Repositório Institucional da UCS, 2007. https://repositorio.ucs.br/handle/11338/480.
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Atualmente, diversas formulações de herbicidas a base de glifosato estão disponíveis no mercado. No entanto, diferentes surfactantes são também adicionados às formulações a fim de aumentar a eficácia do produto, o que pode contribuir significativamente para o aumento da toxicidade do herbicida aos organismos não alvos. Este estudo avaliou a genotoxicidade e o estresse oxidativo em planárias aquáticas (Dugesia schubarti) expostas às formulações de glifosato Roundup Original, Roundup Transorb e Roundup Ready. As planárias foram expostas à soluções de 0.5 mg/L de equivalente ácido de glifosato das três formulações durante 4, 8 e 16h. A genotoxicidade foi avaliada através do ensaio cometa e o estresse oxidativo foi medido através da atividade das enzimas superóxido dismutase (Sod) e catalase (Cat) e pelas substâncias reativas com o ácido tiobarbitúrico (TBARS). Todas as formulações foram capazes de induzir danos ao DNA e estresse oxidativo. A atividade de Sod aumentou entre 4 e 16h, enquanto os níveis de TBARS diminuíram entre 4 e 16h de tratamento. A atividade de Cat permaneceu diminuída em todos os tempos de exposição para as três formulações testadas. Esses resultados demonstram que formulações de herbicida contendo glifosato são capazes de causar dano ao DNA e alterar o balanço oxidativo em planárias indicando que a toxicidade deste herbicida não está restrita às plantas.Submitted by Marcelo Teixeira (mvteixeira@ucs.br) on 2014-05-30T16:17:08Z No. of bitstreams: 1 Dissertacao Diana Lilian Bordin.pdf: 300600 bytes, checksum: 95ba8b94d9994115a4d1aaa7a0f08bc0 (MD5)
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Currently, several glyphosate-based herbicide formulations are available in the market. However, different surfactants are also added to the formulation in order to increase the effectiveness of the product, what it can contribute significantly to the toxic effect exerted by the herbicide to the non target organisms. This study evaluated the genotoxicity and the oxidative stress in freshwater planarians exposed to the glyphosate formulations Roundup Original, Roundup Transorb and Roundup Ready. The planarians were submitted to 0.5 mg/L of glyphosate formulations during 4, 8, and 16h. The genotoxicity was evaluated through comet assay, and the oxidative stress was measured through the superoxide dismutase (Sod) and catalase (Cat) activity and by thiobarbituric acid reactive substances (TBARS). All three formulations were able to induce genotoxicity and to disturb the antioxidants activity in different ways. While Sod increased between 4 and 16h, TBARS decreased between 4 and 16h, and Cat stayed depressed during all time-points tested. These results demonstrate that herbicide formulations which contend glyphosate can induce damage to the DNA and to modify the oxidative balance in planarians, indicating that the toxicity of this herbicide is not restricted to the plants.
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Ferreira, Rafael Alexandre Costa [UNESP]. "Análise morfológica e histoquímica do corpo gorduroso e dos túbulos de Malpighi de operárias adultas de Scaptotrigona postica (Latreille, 1807) (Hymenoptera, Apidae) tratadas com fipronil e ácido bórico". Universidade Estadual Paulista (UNESP), 2010. http://hdl.handle.net/11449/87724.
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ferreira_rac_me_rcla.pdf: 739935 bytes, checksum: 50907a1ee0174b4ffcbc2dde8cbd2c71 (MD5)As abelhas contribuem para a manutenção das espécies vegetais no nicho ecológico onde vivem. Alguns compostos químicos encontrados em inseticidas utilizados na agricultura (fipronil), ou lançados no meio com resíduos industriais (ácido bórico) são tóxicos para as abelhas. Assim, objetivou-se avaliar a atividade tóxica desses compostos em doses subletais, bem como, analisar as alterações morfológicas (citoplasmáticas e nucleares) do corpo gorduroso e túbulos de Malpighi. As análises estatísticas para o experimento realizado com ácido bórico (0,75% m/m) e fipronil (0,1 ng/abelha/dia) mostraram que os perfis de sobrevivência das abelhas que ingeriram a dieta contaminada foram significativamente diferentes ao perfil de sobrevivência apresentado pelo grupo controle (p<0,0001). As análises morfologicas confirmam que os inseticidas fipronil e ácido bórico, apresentam citotoxicidade em doses subletais, dentre essas alterações, destaca-se: nos túbulos de Malpighi aparente liberação de material celular para o lúmen, alguns núcleos picnóticos e bordo em escova que em alguns casos bloquearam o lúmen do órgão, em algumas células notou-se características morfológicas de degeneração. No corpo gorduroso de abelhas destacam-se intensa atividade de coalescência vacuolar, núcleos picnóticos e alguns núcleos dos trofócitos com aparente ramificação. Ultraestruturalmente destaca-se o aumento da porção apical das microvilosidades, dilatações das cisternas dos retículos endoplasmáticos rugoso, presença de vesículas e acúmulo de polirribossomos no citoplasma para os túbulos de Malpighi dos grupos experimentais tratados com fipronil e ácido bórico. As análises do corpo gorduroso mostram o aumento da quantidade, coalescência, depósitos lipídicos e protéicos nos vacúolos nos trofócitos do corpo gorduroso. Os resultados apresentados mostram que as doses...
Bees help to maintain the plant species in the ecological niche where they live. Some chemicals found in pesticides used in agriculture (fipronil), or thrown in the ambient with industrial waste (boric acid) are toxic to bees. The objective was to evaluate the toxic activity of these compounds at sublethal doses, as well as analyze the morphological (cytoplasmic and nuclear) of the fat body and Malpighian tubules. In the experimental groups, the compounds were added to the diet (Candi). The concentration of fipronil used in the experiment was 0.1 g/kg of candi and the concentration of boric acid was 0.75% (m/m). Statistical analysis for the experiment conducted with fipronil and boric acid profiles showed that the survival of bees that ingested the contaminated diet were significantly different to the profile of survival made by the control group (p <0.0001). Morphologically, in control group, changes found in Malpighian tubules of bees treated with boric acid and fipronil were subtle, showing apparent release of cellular material into the lumen, some pyknotic nuclei and, in some cases, brush border blocking the lumen organ, in some cells we observed morphological features of degeneration. Morphological changes are evident in the fat body of bees treated with fipronil and boric acid compared to control group. Among these changes, stand out intense activity of vacuolar coalescence, pyknotic nuclei and some nuclei of trophocytes with apparent branching. Histochemically, the cells of the Malpighian tubules showed, by the reaction of Bromophenol Blue, proteic activity more apparent in the treated groups compared to controls. The reaction of the PAS-Alcian Blue revealed the presence of glycoproteins in the apical portion of the cells of the Malpighian tubules of the treated groups. For the Feulgen reaction, we observed a high degree of chromatin compaction... (Complete abstract click electronic access below)
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Von, Woff Marya Anne. "Avaliação ecotoxicológica do antidepressivo cloridrato de fluoxetina". [s.n.], 2011. http://repositorio.unicamp.br/jspui/handle/REPOSIP/267796.
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Orientador: Cassiana Maria Reganhan ConeglianDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Tecnologia
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Resumo: Fármacos para tratamento de distúrbios psíquicos estão entre as substancias ativas mais prescritas no mundo. A ocorrência destes em matrizes ambientais torna-se cada vez mais freqüente. Estudos recentes indicam que o fármaco cloridrato de fluoxetina, um inibidor seletivo da recaptação da serotonina, esta presente em estações de tratamento de efluentes e em águas de superfície. O aumento nas pesquisas ambientais acerca dos fármacos está ligado a sua baixa biodegradabilidade e sua persistência no ambiente. Este trabalho revisa os dados da literatura relacionados à ocorrência ambiental e dados de toxicidade para os organismos não-alvo do medicamento cloridrato de fluoxetina e contribui para a literatura cientifica com testes de toxicidade do fármaco com os organismos-testes Daphnia similis e Pseudokirchneriella subcaptata. Com base em resultados obtidos, realizou-se a estimativa de impacto ambiental para a Estação de Tratamento de Esgotos do rio Piracicamirim. No entanto, não existem padrões estabelecidos para a concentração de fármacos no ambiente, pois não são totalmente conhecidos seus efeitos ecotoxicologicos. Os dados compilados têm o intuito de contribuir para a priorização e determinação da necessidade de estudos que indiquem a ocorrência, destino, transporte, saúde e elucidação dos efeitos causados por fármacos, para a contínua melhoria dos padrões de água no Brasil e no mundo
Abstract: Drugs for treating mental disorders are among the most active substances prescribed in the world. The occurrence of these in environmental matrices is becoming increasingly common. Recent studies indicate that the drug fluoxetine hydrochloride, a selective inhibitor of serotonin, is present in sewage treatment effluents and in surface waters. The large increase in environmental research about the drug is linked to its low biodegradability and its persistence in the environment. This paper reviews the literature related to the occurrence and environmental toxicity data for the non-target organisms of the drug fluoxetine hydrochloride. An increase in contributions from the scientific literature is done on the species Daphnia similis and Pseudokirchneriella subcaptata exposure to fluoxetine hydrochloride. Based on results obtained, we carried out the environmental impact assessment for the Sewage Treatment Station Piracicamirim River. However, there are no established standards for the concentration of pharmaceuticals in the environment because they are not fully known ecotoxicological effects. The data collected are intended to help prioritize and determine the need for studies that indicate the occurrence, destiny, transport, health and elucidation of the effects caused by drugs, for the continuous improvement of standards of water in Brazil and worldwide
Mestrado
Tecnologia e Inovação
Mestre em Tecnologia
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Maruo, Viviane Mayumi. "Estudo dos possíveis efeitos tóxicos da exposição à Solanum lycocarpum em ratos adultos e em sua prole". Universidade de São Paulo, 2002. http://www.teses.usp.br/teses/disponiveis/10/10133/tde-05022004-155718/.
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Solanum lycocarpum St. Hill é uma planta comum no cerrado brasileiro e possui um alcalóide com configuração estereoespecífica para a síntese de hormônios esteróides. O presente estudo foi desenvolvido para determinar os possíveis efeitos tóxicos da ingestão dos frutos de S. lycocarpum (3% adicionados à dieta) em ratos adultos machos (60 dias de administração), fêmeas (37 dias) e fêmeas prenhes (nos períodos de pré-implantação e organogênese). Poucas diferenças significantes no peso corpóreo e no consumo de água e ração foram observadas. Nenhuma diferença significante foi detectada no ganho de peso dos animais e no ciclo estral. Ratas tratadas apresentaram redução significante nos pesos do útero e do fígado. Porém, nenhuma diferença significante foi observada nos pesos de outros órgãos (adrenal, fígado, vesícula seminal, testículo e ovário) e na avaliação de enzimas e proteínas sangüíneas de ratos fêmeas e machos. Ao estudo anatomopatológico as fêmeas apresentaram maior incidência de hiperplasia do epitélio endometrial, cistos foliculares, proliferação de ductos biliares, congestão hepática e renal. A administração da planta no período de pré-implantação causou poucas alterações nos consumos de água e comida das fêmeas e sua prole apresentou aumento de hemorragia do bulbo olfatório. O consumo da planta durante a organogênese aumentou a média de filhotes fêmeas, reduziu o peso da placenta e aumentou o número de fetos com esternébrios assimétricos. Tomando estes dados em conjunto, pode-se sugerir que a administração da S. lycocarpum à 3% na ração causa efeitos tóxicos em ratas adultas e na prole, principalmente quando exposta durante o período de organogênese.Solanum lycocarpum St. Hill is a common plant in Brazilian savanna. This plant has an alkaloid with stereospecific configuration to the synthesis of steroid hormones. Since the plant may be long-term consumed, the present study was undertaken to determine the possible toxic effects of S. lycocarpum fruit ingestion (3% added to the diet) on male (60 days of administration), female (37 days) adult rats and pregnant female (during preimplantation and organogenesis). Few significant differences in the body weight and consumption of food and water were observed. No significant differences were detected in the male and female weight gain and the estrous cycle. Female treated rats showed a significant reduction in the uterus and liver weights. However, no significant differences were observed in other organ (adrenal, liver, seminal vesicle, testicle and ovary) weights and in the evaluation of blood enzimes and proteins of the female and male rats. The anatomopathological study showed a higher incidence of endometrial epithely hiperplasy, pholicular cysts, biliary ducts proliferation, hepatic and renal congestion in female rats. Plant administration during preimplantation caused few alterations in food and water consumption in female and their offspring showed increase in olfactory bulb hemorragy. Plant consumption during organogenesis increased the media of female pups, reduced placental weight and increased the number of fetuses with assimetric sternebrae. These data suggest that the S. lycocarpum administration at 3% causes toxic effects in adult female rats and in the offspring, specially when exposed to the plant during organogenesis.
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Button, Mark. "Arsenic contaminated soils : human exposure and environmental toxicology". Thesis, University of Leicester, 2009. http://hdl.handle.net/2381/7797.
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Burgess, Vanessa Anne, i n/a. "Toxicology Investigations With The Pectenotoxin-2 Seco Acids". Griffith University. School of Public Health, 2003. http://www4.gu.edu.au:8080/adt-root/public/adt-QGU20030905.090222.
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Pectenotoxins (PTXs) are a group of large cyclic polyether compounds associated with diarrhetic shellfish poisoning (DSP) as they are often found in combination with other DSPs such as okadaic acid (OA) and dinophysis toxins (DTXs) in shellfish. Although classified and regulated with the DSPs, there is debate over whether these toxins should be classified with DSP toxins. To date, ten different analogues of PTXs have been identified from shellfish and algae, and of these, the pectenotoxin-2 seco acids (PTX2-SAs) are of particular interest as they have previously been implicated in a shellfish poisoning incident in Australia, but relatively little was known of their toxicology. One such incident occurred in December 1997, when approximately 200 people were reported with severe diarrhoetic shellfish poisoning in Northern New South Wales (NSW). Analysis of the shellfish associated with this incident revealed relatively high PTX2-SA concentrations (approx. 300 micrograms/kg shellfish meat), with only trace amounts of pectenotoxin-2 (PTX2) and OA. Following this incident, PTX2-SAs were considered a health threat and guidelines were implemented in the absence of toxicological data, which has caused a great economic burden to shellfish industries around the globe, in particular to Australia, New Zealand and Ireland. Such regulation created in the absence of scientific data demonstrated the need to determine the toxicology of PTX2-SAs in commercial shellfish. Thus a comprehensive study on the toxicology and possible health implications of the PTX2-SAs in Australian shellfish was conducted. PTX2-SAs were isolated in different batches from shellfish (pipis, oysters and mussels) and from algal bloom samples of Dinophysis caudata. Toxin extraction was conducted with several purification stages and chemical analysis was performed with high-performance liquid chromatography coupled to a tandem mass spectrometer (HPLC-MS/MS). The chemical stability of the PTX2-SAs was investigated to ensure consistency of doses between toxicology experiments. Acute dosing studies with mice were then performed and included toxicopathology investigations with light microscopy and electron microscopy, in addition to toxin distribution studies and investigation of in vivo lipid peroxidation. In vitro studies with HepG2 cells included cytotoxicity assays, cell cycle investigations using flow cytometry and gene expression profiling of cells exposed to PTX2-SAs employing cDNA microarray technology. Acute pathology studies demonstrated that the PTX2-SAs do not cause the characteristic symptoms or lesions associated with DSP toxins. No diarrhoea was observed at any dose level in mice and no deaths occurred up to the maximum dosing level of 1.6mg/kg PTX2-SA. Only one batch of PTX2-SA extract produced toxic lesions characteristic of a DSP toxin (batch 1-pilot study) but after follow up studies, it was determined that this first batch of shellfish most likely contained an additional unidentified shellfish toxin or contaminant that co-extracted with PTX2-SAs during toxin isolation and purification procedures. This finding highlighted the importance of supporting the inclusion of the mice bioassay in procedures for shellfish toxin testing to enable detection of new toxins, and also highlighted the importance of toxin purification for toxicology studies. A significant rise in malondialdehyde excretion was observed within 24 hours of dosing mice, indicating that the PTX2-SAs may cause damage by lipid peroxidation in vivo. In vitro studies showed HepG2 cells to have cell cycle and gene expression changes within 24 hours of a dose of 800ng/mL PTX2-SAs. Cell cycle arrest was observed at the G2/M checkpoint and gene expression changes included alterations in genes involved in cell cycle control, lipid metabolism and transport, lipid genesis and trace metal transport. Many genes involved in DNA repair processes were moderated at the 24 hour point, but as no apoptosis was observed up to 72 hours post dosing it is a promising indication that any DNA damage that may have been caused by the administration of PTX2-SAs was not lethal, and was able to be repaired. In light of the information provided by toxicology investigations in this PhD, with particular reference to evidence of in vivo lipid peroxidation by raised levels of MDA in mouse urine, and changes in cell cycle distribution and gene expression in a cultured human cell line, it is concluded that there is potential for these toxins to induce biological changes in mammalian cells in vivo and in vitro, and hence potential for PTX2-SAs to cause health effects in humans. During the course of this three-year study, developments in techniques for shellfish toxin identification within our laboratories have revealed that the shellfish responsible for the 1997 NSW poisoning incident contained significant concentrations of okadaic acid acyl esters that were not detected at the time of the NSW incident. Although reportedly less toxic than okadaic acid itself, the OA ester concentrations present may have been sufficient to cause the observed symptoms. It is also theorized that these esters could be hydrolyzed in the human gastro-intestinal tract to release okadaic acid. In the light of this new evidence and with no pathology lesions or symptoms of diarrhoea being observed in PTX2-SA dosing studies with mice, we now believe these OA acyl esters to be the causative agent in the 1997 NSW DSP incident and not the PTX2-SAs. Nothing is currently known of the chronic toxicology of PTX2-SAs and thus their potential implications to public health in the long term cannot determined. The toxicology investigations in this thesis were acute studies, and it has not been established if the observed changes could be repaired or returned within normal limits without the manifestation of illness or disease occurring. Utilizing the acute toxicology information in this thesis, a health risk assessment for consumption of PTX2-SA contaminated shellfish was performed. This risk assessment, employing numerous safety factors essential for an incomplete data set, produced guideline values that are lower than the current recommend concentrations. To date, there has been no solid evidence that PTX2-SAs cause illness in humans all documented incidents involving the PTX2-SAs have also included other DSP contaminants that are known to cause human illness. Pathology has not unequivocally been demonstrated in animal studies and thus, in consideration of the epidemiological evidence, PTX2-SAs cannot be considered as high a risk to public health as was previously thought. For the reasons discussed above, and weighing up risk-benefit considerations of the economic burden the current guideline values are causing to shellfish industries around the globe, it is recommended that levels of PTX2-SAs be monitored in recognition of the precautionary principle, but no longer regulated as tightly with other DSPs until such a time that toxicological or epidemiological evidence can prove that the PTX2-SAs are a DSP and are a more considerable threat to human health than has been indicated by toxicology studies in this thesis. This study has produced a substantial amount of acute toxicology data and has provided a good basis for future chronic toxicology investigations with the PTX2-SAs for regulatory purposes.
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Verhagen, Franciscus Johannes Josephus. "Toxicology of the food additives BHA and BHT". Maastricht : Maastricht : Universitaire Pers Maastricht ; University Library, Maastricht University [Host], 1989. http://arno.unimaas.nl/show.cgi?fid=5479.
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Eiselen, Sue Catherine. "Neuropsychological toxicology a theoretical overview of neuropsychological assessment /". Pretoria : [s.n.], 2007. http://upetd.up.ac.za/thesis/available/etd-10162007-133533.
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Small, Rowena Dianne. "The molecular toxicology of isoprene and its metabolites". Thesis, University of Newcastle Upon Tyne, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.363859.
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Allen, Christopher N. "Cultured human gastrointestinal cell lines for predictive toxicology". Thesis, University of Newcastle Upon Tyne, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.287261.
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Ismail, A. "Ecology and toxicology of arsenic in contaminated grassland". Thesis, University of Essex, 1986. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.376741.
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Antczak, Philipp. "Moving towards predictive toxicology - a systems biology approach". Thesis, University of Birmingham, 2012. http://etheses.bham.ac.uk//id/eprint/3342/.
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Human health and the environment are at risk of being exposed to a large number of hazardous chemicals each day. Unfortunately, many of these chemicals have no or little recorded toxicity information. Predictive toxicology aims to provide tools and methodologies to address this issue. In combination with systems biology approaches these can provide a powerful toolbox for understanding the impact of chemicals on biological species. The work presented within this thesis demonstrates the effectiveness of such approaches in the context of industrial and environmentally relevant species. More specifically we focus on characterization of a general toxicity mechanism in Rattus norvegius and Daphnia magna as well as for the first time demonstrate that the transcriptional response of D. magna is predictive not only of chemical class but also of measured toxicity. We also show that inclusion of pathway-level information can increase biological interpretability in non-model species. Lastly, we provide evidence supporting the application of reverse engineering methodologies in the context of identifying adverse outcome pathways in Pimephales promelas, an environmentally relevant species. Ultimately, our results have shown that these approaches can provide highly relevant information in model and non-model species. Further development building on these results could potentially lead to improvements in risk assessment and environmental monitoring.
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Hughes, Sarah Jane Murty. "Towards deep-sea toxicology : experimental approaches with echinoderms". Thesis, University of Southampton, 2010. https://eprints.soton.ac.uk/168893/.
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As anthropogenic activities expand into the deep sea, it is only recently that the importance of deep-sea ecosystems and processes to global biogeochemical systems has become clear. If the potential impact of human activity upon deep-sea organisms and ecosystems is to be understood and predicted, experimental studies are required to improve our knowledge of their sensitivity to contamination and disturbance. Echinoderms are integral components of deep-sea benthic communities and, by virtue of their abundance, they contribute significantly to deep-sea biogeochemical processes. As such, echinoderms can be considered relevant target organisms for deep-sea experimental studies. Three approaches to the investigation of deep-sea anthropogenic impact upon echinoderms were undertaken in this study. The first was based on contaminant exposure experiments with two species of shallow-water echinoid, the eurytopic Psammechinus miliaris and the stenotopic Brissopsis lyrifera. A range of biomarkers was used to assess the responses of the echinoids to contaminant exposure. Compared with the significant cytological and molecular (assess via qPCR) responses in P. miliaris, a reduced capacity to respond to contaminant exposure was found in B. lyrifera at these levels of biological organisation. Stenotopic species are hence recommended for future experimental studies as proxies for deep-sea echinoderms which, due to their adaptation to the stable environment of the deep sea, are also considered to have a reduced capacity for homeostasis in the face of environmental perturbation. The second experimental approach involved sediment burial experiments, simulating anthropogenic drilling disturbance, with the deep-water echinoderm species Echinus acutus. ROV technology was used to perform the burial experiments in situ at 114 m depth. The application of quantitative PCR molecular biomarker methodology revealed a significant increase in the expression of a stress-70 protein in response to sediment burial. These results demonstrate the sensitivity of the qPCR technique to assess an organism’s stress-response, and its relevance to deep-sea experimental studies. Finally, the development and successful deployment of an in situ respirometer, the benthic incubation chamber system (BICS) 2, made possible the acquisition of physiological measurements from deep-sea echinoderms at the abyssal sea floor at 3500 m. The results revealed similarities between the oxygen consumption rates of shallow-water and deep-sea echinoderms. The future performance of in situ deep-sea experimentation is dependent on the development of experimental equipment that confers the ability to perform experiments in situ with ROV technology and to obtain results without interference from recovery-related side effects.
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Grabinski, Christin M. "NANOPARTICLE DEPOSITION AND DOSIMETRY FOR IN VITRO TOXICOLOGY". Case Western Reserve University School of Graduate Studies / OhioLINK, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=case1428085283.
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