Dissertations / Theses on the topic 'Toxicity'
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Marcelová, Štěpánka. "Toxicita nitroderivátů toluenu a produktů jejich transformací." Master's thesis, Vysoké učení technické v Brně. Fakulta chemická, 2010. http://www.nusl.cz/ntk/nusl-216647.
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This work is focused on verification of p-Nitrotoluenu toxicity and compounds resulting from the aerobic transformation, and methyl group oxidation and reduction of nitro. Some of these products are not commercially available and had to be made soon. Toxicity of the substances was determined by toxicity tests. Were tested root growth inhibition Sinapis alba, which resulted in an inhibitory concentration IC50; test inhibition duckweed Lemna minor , which was also the determination of IC50 inhibitory concentration, and acute toxicity test Artemia salina, which was observed in mortality and immobility organisms and the test result was an efficient concentration EC50 value. Results of tests are compared in the conclusion of the work and is made evaluation of the toxicity of individual substances.
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Anderson, James Ainslie. "Interleukin-2 toxicity." Thesis, University of Southampton, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.245045.
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El-Daher, Marie-Thérèse. "Huntingtin proteolysis and toxicity." Thesis, Paris 11, 2013. http://www.theses.fr/2013PA11T029/document.
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La maladie de Huntington (MH) est une maladie neurodégénérative héréditaire autosomique dominante. Elle est due à l’expansion anormale de polyglutamine dans la partie N-terminal de la protéine huntingtine (HTT). Une des étapes clés de la pathologie est le clivage de la HTT pleine longueur en fragments N-terminaux plus petits, contenant l’expansion de polyglutamine, et qui sont toxiques pour les neurones. En effet, les clivages de la HTT mutée génère des fragments N-terminaux (N-ter) de tailles comprises entre les acides aminés 1-105 et 1-586 observés dans des extraits de cerveaux de patients MH post-mortem et dont l’implication dans la mort neuronal est bien caractérisée. Mes travaux de thèse ont visé à modéliser le clivage de la HTT et à évaluer les conséquences sur la survie neuronale.Au cours de ma thèse, j’ai développé un outil permettant de contrôler le clivage de la HTT dans le temps et à des sites spécifiques. J’ai étudié le clivage de la HTT à deux sites stratégiques : les positions clivées par la caspase-6 et par la bléomycine hydrolase/cathepsine Z. A l’aide de cet outil, j’ai montré que le clivage de la HTT confère une toxicité cellulaire qui dépend du profil du clivage. Plus précisément, J’ai décrit une interaction intramoléculaire au sein des domaines de la HTT. Mes résultats indiquent que cette interaction protège les cellules de la toxicité induite par le clivage de la HTT mutée. En effet, les clivages successifs de la HTT annulent cette interaction, ce qui induit la libération des fragments N-ter mutants et provoque la mort cellulaire à l’issue de leur translocation nucléaire. Pour conclure, au cours de ma thèse, j’ai montré que la protéolyse successive de la HTT induit des processus cytotoxiques différentsHuntington’s disease (HD) is an autosomal dominant inherited neurodegenerative disorder caused by an abnormal polyglutamine (polyQ) expansion in the N-terminus of the protein huntingtin (HTT). A crucial step in HD pathogenesis is the cleavage of full-length HTT into smaller N-terminal (N-ter) fragments that contain the polyQ stretch and that are toxic to neurons. HTT cleavage generates short N-ter fragments whose amino-acid positions range from 1-105 to 1-586. These fragments are observed in HD post mortem brain samples and their participation in neuronal death in HD is well characterized. During my PhD research, I investigated the consequences of full-length mutant HTT proteolysis by developing a time and site-specific controlled system for HTT proteolysis. I have assessed HTT cleavage on two sites caspase-6 and cathepsin Z. My results show that HTT cleavage induces neurotoxicity in vitro as well as in vivo, toxicity which depends on HTT proteolysis pattern. Briefly, we described an intramolecular interaction within the HTT domains which is impaired upon successive proteolysis of HTT. We found that HTT intramolecular interaction buffer mutant N-ter HTT-induced toxicity. Moreover, specific cleavages of the mutant HTT generated toxic N-ter fragments as they translocate into the nucleus. To conclude, my PhD work has shown that additional cleavage of mutant HTT induces cytotoxicity by different mechanisms
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Kratchman, Jessica. "Predicting Chronic Non-Cancer Toxicity Levels from Short-Term Toxicity Data." Thesis, The George Washington University, 2017. http://pqdtopen.proquest.com/#viewpdf?dispub=10263969.
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This dissertation includes three separate but related studies performed in partial fulfillment of the requirements for the degree of Doctor of Public Health in Environmental and Occupational Health. The main goal this dissertation was to develop and assess quantitative relationships for predicting doses associated with chronic non-cancer toxicity levels in situations where there is an absence of chronic toxicity data, and to consider the applications of these findings to chemical substitution decisions. Data from National Toxicology Program (NTP) Technical Reports (TRs) (and where applicable Toxicity Reports), which detail the results of both short-term and chronic rodent toxicity tests, have been extracted and modeled using the Environmental Protection Agency’s (EPA’s) Benchmark Dose Software (BMDS). Best-fit minimum benchmark doses (BMDs) and benchmark dose lower limits (BMDL) were determined. Endpoints of interest included non-neoplastic lesions, final mean body weights and mean organ weights. All endpoints were identified by NTP Pathologists in the abstract of the TRs as either statistically or biologically significant. A total of 41 chemicals tested between 2000 and 2012 were included with over 1700 endpoints for short-term (13 week) and chronic (2 year) exposures.
Non-cancer endpoints were the focus of this research. Chronic rodent bioassays have been used by many methodologies in predicting the carcinogenic potential of chemicals in humans (1). However, there appears to be less emphasis on non-cancer endpoints. Further, it has been shown in the literature that there is little concordance in cancerous endpoints between humans and rodents (2). The first study, Quantitative Relationship of Non-Cancer Benchmark Doses in Short-Term and Chronic Rodent Bioassays (Chapter 2), investigated quantitative relationships between non-cancer chronic and short-term toxicity levels using best-fit modeling results and orthogonal regression techniques. The findings indicate that short-term toxicity studies reasonably provide a quantitative estimate of minimum (and median) chronic non-cancer BMDs and BMDLs.
The next study, Assessing Implicit Assumptions in Toxicity Testing Guidelines (Chapter 3) assessed the most sensitive species and species-sex combinations associated with the best-fit minimum BMDL10 for the 41 chemicals. The findings indicate that species and species-sex sensitivity for this group of chemicals is not uniform and that rats are significantly more sensitive than mice for non-cancerous outcomes. There are also indications that male rats may be more than the other species sex groups in certain instances.
The third and final study, Comparing Human Health Toxicity of Alternative Chemicals (Chapter 4), considered two pairs of target and alternative chemicals. A target is the chemical of concern and the alternative is the suggested substitution. The alternative chemical lacked chronic toxicity data, whereas the target had well studied non-cancer health effects. Using the quantitative relationships established in Chapter 2, Quantitative Relationship of Non-Cancer Benchmark Doses in Short-Term and Chronic Rodent Bioassays, chronic health effect levels were predicted for the alternative chemicals and compared to known points of departure (PODs) for the targets. The findings indicate some alternatives can lead to chemical exposures potentially more toxic than the target chemical.
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Lampi, Mark. "Environmental Photoinduced Toxicity of Polycyclic Aromatic Hydrocarbons: Occurrence and Toxicity of Photomodified PAHs and Predictive Modeling of Photoinduced Toxicity." Thesis, University of Waterloo, 2005. http://hdl.handle.net/10012/1248.
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Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental contaminants known for their photoinduced toxicity. There are two mechanisms through which this may occur: photosensitization and photomodification. Photosensitization generally leads to the production of singlet oxygen, a reactive oxygen species (ROS), which is highly damaging to biological molecules. Photomodification of PAHs, usually via oxygenation, results in the formation of new compounds (oxyPAHs), and can occur under environmentally relevant levels of actinic radiation. PAHs and oxyPAHs readily adsorb to the organic phase of particulate matter in the environment such as sediments. It is logical to conclude that sediment transport will also facilitate the transport of these contaminants, and it has been shown that in the course of transport, degradative processes evoke a change in the profile of the PAHs present. Sediment samples taken along a transect from Hamilton Harbour were fractionated, and analyzed using a 2D HPLC method. All sediments contained intact and modified PAHs, although a marked change was noted in the profile of compounds present in the samples, which differ in distance from shore. Fractions of sediment extract were tested for toxicity using a bacterial respiration assay. Toxicity was observed in fractions containing modified PAHs, and was similar to that of intact PAH-containing fractions.
Subsequently, the toxicities of 16 intact PAHs were assessed to Daphnia magna under two ultraviolet radiation (UV) conditions. The toxicity of intact PAHs generally increased in the presence of full spectrum simulated solar radiation (SSR), relative to visible light plus UVA only. To expand the existing data on the effects of PAH photoproducts to animals, fourteen oxyPAHs were also assayed with D. magna, most of which were highly toxic without further photomodification. The data presented highlight the effects of UV radiation on mediating PAH toxicity. The importance of the role of photomodification is also stressed, as several oxyPAHs were highly toxic to D. magna, a key bioindicator species in aquatic ecosystems.
A QSAR model previously developed for Lemna gibba showed that a photosensitization factor (PSF) and a photomodification factor (PMF) could be combined to describe toxicity. To determine whether it was predictive for D. magna, toxicity was assessed as both EC50 and ET50. As with L. gibba and Vibrio fischeri, neither the PSF nor the PMF alone correlated to D. magna toxicity. However, a PSF modified for D. magna did in fact exhibit correlation with toxicity, which was further improved when summed with a modified PMF. The greatest correlation was observed with EC50 toxicity data. This research provides further evidence that models that include factors for photosensitization and photomodification will likely be applicable across a broad range of species. To gain further knowledge of the roles that the variables contributing to the photosensitization and photomodification, a structural equation model was constructed based on the D. magna QSAR. This model accounted for a high amount of variance in six sets of toxicity data, as well as insight into the mechanisms of phototoxicity affecting different aquatic organisms.
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Mazzatorta, Paolo. "Evaluation of pesticide toxicity : a hierarchical QSAR approach to model the acute aquatic toxicity and avian oral toxicity of pesticides." Thesis, Open University, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.424819.
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The thesis aimed to extract information relevant to the hazard and risk assessment of pesticides. In particular, quantitative structure-activity relationship (QSAR) approaches have been used to build up a mathematical model able to predict the aquatic acute toxicity, Leso, and the avian oral toxicity, LDso, for pesticides. Ecotoxicological values were collected from several databases, and screened according to quality criteria. A hierarchical QSAR approach was applied for the prediction of acute aquatic toxicity. Chemical structures were encoded into molecular descriptors by an automated, seamless procedure available within the OpenMolGRID system. Different linear and non-linear regression techniques were used to obtain reliable and thoroughly validated QSARs. The final model was developed by a counter-propagation neural network coupled with genetic algorithms for variable selection. The proposed QSAR is consistent with McFarland's principle for biological activity and makes use of seven molecular descriptors. The model was assessed thoroughly in test (R2 = 0.8) and validation sets (R2 = 0.72), the y-scrambling test and a sensitivity/stability test. The second endpoint considered in this thesis was avian oral toxicity. As previously, the chemical description of chemicals was generated automatically by the OpenMolGRID system. The best classification model was chosen on the basis of the performances on a validation set of 19 data points, and was obtained from a support vector machine using 94 data points and nine variables selected by genetic algorithms (Error Ratetraining = 0.021, Error Ratevaiidalion = 0.158). The model allowed for a mechanistic estimation of the toxicological action. In fact, several descriptors selected for the final classification model encode for the interaction of the pesticides with other molecules. The presence of hetero-atoms, e.g. sulphur atoms, is correlated with the toxicity, and the pool of descriptor selected is generally dependent from the 3D conformation of the structures. These suggest that, in the case of avian oral toxicity, pesticides probably exert their toxic action through the interaction with some macromolecule and/or protein of the biological system.
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Travers, Sarah. "Toxicity of Lake Sediments." Thesis, Ulster University, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.487669.
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The profundal sediment of many lakes is contaminated by heavy metals and persistent organic pollutants (POPs) deposited from the atmosphere, yet there has been little assessment of the biological effects of these toxicants. A Tier I sediment ecological risk assessment of profundal lake sediment that covers the range of contamination in the UK and Ireland was completed. Three laboratory sediment bioassays were used, Daphnia magna 7-day survival and reproduction, Gammarus pulex 14-day survival and growth and Chironomus riparius 10-day survival and growth/reproduction, and the concentrations of seven heavy metals and four groups of POPs (polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls, organochlorine pesticides and polybrominated diphenyl ethers) were determined.
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Al-Mustafa, Z. H. "Methotrexate pharmacokinetics and toxicity." Thesis, University of Newcastle Upon Tyne, 1988. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.383988.
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Aljebab, Fahad. "Corticosteroid toxicity in children." Thesis, University of Nottingham, 2017. http://eprints.nottingham.ac.uk/43388/.
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Corticosteroid medicines have anti-inflammatory and immunosuppressant effects. Corticosteroids are prescribed for a wide range of conditions in children. The duration of treatment ranges from a few days (short course) to long term. They are usually given orally in the different dosage form of tablets, syrup or soluble tablets. There are a wide range of adverse drug reactions (ADRs) associated with corticosteroids. This thesis initially evaluates the incidence of each individual ADR in children using systematic reviews. Prospective studies of palatability and pharmacoepidemiology using different methods are also used to evaluate aspects of using corticosteroids in children in Saudi Arabia and the UK. A systematic review of the toxicity of short-course oral corticosteroids in children was conducted. Six electronic databases were searched for articles that evaluated the toxicity of oral corticosteroids in children for up to and including 14 days of treatment. Thirty eight articles including 22 randomised controlled trials (RCTs). The review found that the three most frequent ADRs were vomiting, behavioural changes and sleep disturbance, with incidence rates of 4.3 – 5.4% of patients. Infection was one of the most serious ADRs. A systematic review of the toxicity of long-course oral corticosteroids in children was conducted. One hundred studies including 33 prospective cohort studies and 21 RCTs met the inclusion criteria. The review found that the three most frequent ADRs were weight gain, growth retardation and Cushingoid features, with incidence rates of 18.1 – 21.1% of patients. Infection was one of the most serious ADRs, with twenty one deaths. Hypothalamic-pituitary-adrenal (HPA) axis suppression was detected in 249 of 429 patients in whom it was measured. Based on the findings that were highlighted from the systematic review, a prospective observational/interview study was performed. This study evaluated the tolerability and palatability of oral prednisolone and dexamethasone in children in Saudi Arabia and the UK. Palatability was evaluated by asking patient/parent’s opinions of the taste and acceptability of the medication. Tolerability in particular nausea, vomiting and abdominal pain was evaluated by direct questioning of the patient/parents after each administration. Dexamethasone sodium phosphate solution was the most palatable preparation. Prednisolone base tablets were rated the least palatable and were also the least well tolerated. Palatability scores seemed to improve with second doses. A prospective pharmacoepidemiological study of corticosteroids use in Saudi Arabian children was conducted. This study aimed to evaluate the prescribing pattern of corticosteroids for children in the Emergency, outpatient clinics and paediatric wards in the Gurayat General Hospital (GGH) in Saudi Arabia. A total of 1000 patients were approached for the study. Most of whom were asthmatic, eczema, bronchiolitis, and croup patients. A total of 1209 prescriptions were prescribed from different departments. The three most frequently prescribed corticosteroids medications were hydrocortisone ampoules (24.4%), prednisolone tablets (16.4%) and mometasone furoate ointment (9%). This research has contributed to the field of corticosteroids in children by providing more information about the most common and serious ADRs and determining their relative risk levels.
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Jacox, Laura (Laura A. ). "Molecular toxicity of lead." Thesis, Massachusetts Institute of Technology, 2008. http://hdl.handle.net/1721.1/114343.
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Thesis: S.B., Massachusetts Institute of Technology, Department of Earth, Atmospheric, and Planetary Sciences, 2008.Cataloged from PDF version of thesis.
Includes bibliographical references (pages 23-28).
Introduction - Lead is a heavy metal that has been in use for over 8000 years (White, 2007). It was first smelted it 4000BC as a byproduct of silver processing. Since then, Pb has played a dynamic role in history, possibly contributing to the fall of the Roman Empire (Nraigu, 1983). Pb is a highly malleable and ductile Group IVa metal. It has been utilized in a variety of products including makeup, water pipes, cooking vessels, wine bottle seals, glass, batteries, solder, electronic components, paint, and antiknock fuel additives (White, 2007). Its prevalent, long-term use has distributed anthropogenic Pb across the planet in soil, air-borne dust, and water (White, 2007). As a result, human exposure can occur via inhaled air, dust, food, and drinking water. Pb has no known biological functions, yet it has numerous detrimental effects on the body, several of which have been recognized for millennia.
by Laura Jacox.
S.B.
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SOO, CAROL. "MECHANISMS OF OZONE TOXICITY." University of Cincinnati / OhioLINK, 2002. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1020710528.
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Jagtap, Smita [Verfasser]. "Developmental toxicity and embryo toxicity modelling using human embryonic stem cells / Smita Jagtap." Köln : Deutsche Zentralbibliothek für Medizin, 2012. http://d-nb.info/1031095519/34.
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Benlashehr, Imad. "Fumonisin toxicity in ducks and turkeys." Thesis, Toulouse, INPT, 2013. http://www.theses.fr/2013INPT0070/document.
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Les fumonisines (FBs) sont les principales mycotoxines produites par Fusarium verticillioides et Fusarium proliferatum, qui se retrouvent partout dans le monde dans le maïs et ses produits dérivés. Les doses toxiques et les signes cliniques de toxicité provoqués par les FBs varient dune espèce à lautre. La toxicité des FBs est généralement liée à leur capacité à bloquer le métabolisme des sphingolipides chez les espèces animales, y compris chez les espèces aviaires. De précédentes études ont démontré que les canards présentent une plus grande sensibilité à la toxicité des FBs que les dindes, alors que laccumulation de sphinganine (Sa) dans les tissues est plus importante chez les dindes que chez les canards. Lobjectif de nos travaux était de comprendre les différences de toxicité entre les dindes et les canards los dune exposition aux FBs. Les trois hypothèses suivantes ont été explorées : i) La toxicocinétique de la fumonisine B2 chez les dindes et les canards. ii) La capacité des cellules aviaires à se protéger de limportante accumulation de sphingolipides libres en augmentant leur catabolisme (phosphorylation). iii) Des mécanismes de toxicité des FBs autre que leur altération via le métabolisme des sphingolipides (stress oxydatif et les réponses inflammatoires). Lanalyse des paramètres de toxicocinétique de la fumonisine B2 na pas mis en évidence de différence significative entre les dindes et les canards. Les mesures de la toxicité simultanée de plusieurs FBs chez les dindes et les canards ont confirmé la forte sensibilité des canards. Laccumulation de shingasine-1-phosphate (Sa1P) dans le foie a également été corrélée avec la quantité de Sa mais pas avec les paramètres hépatiques de toxicité. De plus cette étude a mis en évidence que la quantité de Sa dans le foie était fortement dépendante de la teneur en FBs. Cependant les FBs nont eu aucun effet sur les paramètres de stress oxydatif pour les deux espèces. De manière intéressante, les FBs ont eu une légère réponse inflammatoire chez les canards mais pas chez les dindes. Des investigations plus poussées sur les effets des FBs sur le métabolisme des céramides et sur les processus inflammatoires seraient nécessaires pour comprendre les différences de toxicité entre les dindes et les canards exposés aux FBsFumonisins (FBs) are the major mycotoxins produced by Fusarium verticillioides and Fusarium proliferatum, which are found worldwide in maize and maize products. FBs toxic dose and clinical signs of toxicity vary from one species to another. FBs toxicity is commonly linked to their ability on blocking sphingolipids metabolism in all animal species, including avian species. Previous studies have demonstrated that ducks exhibit higher sensitivity to FBs toxicity than turkeys, whereas, the accumulation of sphinganine (Sa) in tissues is more pronounced in turkeys than in ducks. The objectives of our works were to investigate the causes which lead to different toxicity between ducks and turkeys to FBs exposure. The following three hypotheses were investigated: i) Toxicokinetics of fumonisin B2 in ducks and turkeys. ii) Ability of bird cells to protect themselves against high accumulation of free sphingolipids by increasing their catabolism (phosphorylation). iii) Other toxicity mechanisms of FBs rather than their alteration of sphingolipids metabolism (oxidative stress damage and inflammatory responses). The analysis of toxicokinetic parameters of fumonisin B2 did not provide a significant difference between ducks and turkeys. The measurement of simultaneous toxicity of FBs in ducks and turkeys confirmed higher sensibility of ducks. Also the accumulation of Sphingasine-1-Phosphate (Sa1P) in the liver correlated with the amount of Sa but not parameters of hepatic toxicity. Moreover, this study revealed that the amount of Sa in the liver was strongly dependent on the amount of FBs. On the other hand, FBs had no effect on oxidative damages parameters in both species. Interestingly, FBs had mild inflammatory response effect in ducks but not in turkeys. Further investigation on the effects of FBs on ceramide metabolism and inflammatory processes would be necessary to understand the different toxicity between ducks and turkeys to FBs exposure
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Clay, Robert. "Developmental toxicity of aluminium and silver to Drosophila melanogaster." Thesis, University of Manchester, 2014. https://www.research.manchester.ac.uk/portal/en/theses/developmental-toxicity-of-aluminium-and-silver-to-drosophila-melanogaster(f9d8e295-8ce2-4627-bb38-1dae0998b57f).html.
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Aluminium (Al) and silver (Ag), through human activities, are present in the environment at concentrations sufficient to cause toxicity. The aim of this study was to administer Al and Ag to the short lived model organism Drosophila melanogaster, so that developmental toxicity and potential ameliorative interventions could be examined over a compressed timescale relative to mammalian models. Aluminium was administered to Drosophila in food as either the chloride salt or citrate complex at concentrations of 1, 10 and 100 mM and various developmental parameters were assessed. The lowest concentration to delay pupation relative to the control was 10 mM but this depended upon the food in which it was administered. Higher whole body tissue levels of Al were seen following Al citrate administration compared to AlCl3, but Al citrate was less toxic as this did not did not impair larval viability at 100 mM; 100 mM AlCl3 resulted in 100% mortality. Eclosion success was significantly impaired with either form of Al at 10 mM, but no difference was seen between the forms of Al. When Drosophila were fed AlCl3 over their entire lifespan, a small but significant reduction in the lifespan of male flies was seen. No behavioural toxicity could be demonstrated. Existing studies have demonstrated significant tissue Al concentrations and toxicity whereas these have been minimal in this study. It is suggested that these differences may have a genetic component, with food composition exerting an influence also. Silver, either as AgNO3 or Ag nanoparticles (AgNPs) was administered in concentrations up to 500 micromolar and 10 mM, respectively. Either form of Ag, at 50 micromolar was sufficient to significantly retard pupation rate, although pupation or eclosion success was not impaired until 100 micromolar. The concentration-response relationship for AgNO3 was steep with pupation success dropping to nearly zero by 300 micromolar; Drosophila in this study were far more sensitive to AgNO3 than those in other reports. Animals exposed to AgNPs were still able to pupate at 500 micromolar, but these pupae were almost all non-viable when exposed to 400 micromolar AgNPs. At 1 mM and above, AgNPs, however, showed reduced toxicity compared to lower concentrations. The reasons for this are unclear. Both forms of Ag caused de-pigmentation in adults after larval exposure that may be explainable by inhibition of polyphenol oxidase enzymes by Ag (I) ions. The de-pigmentation was preventable by pre-loading larvae with Cu. Ascorbate prevented the de-pigmentation caused by AgNPs but not AgNO3 suggesting that AgNP toxicity is due to Ag (I) ion release. Oxidation of AgNPs was found to be greatly accelerated by Fe (III) and Cu (II) ions in the presence of Cl- ions. Although some of the results here conflict with the literature, developmental toxicity has been observed here, for both Al and Ag, and the variability across studies may provide an opportunity for dissecting the mechanisms behind Al and Ag toxicity through identification of the traits that confer sensitivity or resistance.
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Niwa, Toshimitsu. "Uremic Toxicity of Indoxyl Sulfate." Nagoya University School of Medicine, 2010. http://hdl.handle.net/2237/12904.
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Ramaekers, Johannes Gerardus. "Behavioral toxicity of medicinal drugs." Maastricht : Maastricht : Neuropsych Publishers ; University Library, Maastricht University [Host], 1998. http://arno.unimaas.nl/show.cgi?fid=8527.
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Sundstøl, Eriksen Gunnar. "Metabolism and toxicity of trichothecenes /." Uppsala : Dept. of Animal Nutrition and Management, Swedish Univ. of Agricultural Sciences, 2003. http://epsilon.slu.se/a400.pdf.
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Schick, Brian Adam. "Statin-induced muscle mitochondrial toxicity." Thesis, University of British Columbia, 2008. http://hdl.handle.net/2429/908.
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Statins are the mainstay of cholesterol-lowering therapy and are taken by millions of people worldwide. These drugs are generally well-tolerated but can cause myopathy ranging from mild muscle pain to fatal rhabdomyolysis. The mechanism of statin-induced myopathy (SIM) is not fully understood and there is currently no convenient and reliable marker of SIM, but mitochondrial dysfunction has been implicated.
We sought to investigate the effect of statins on mitochondrial DNA (mtDNA) levels in order to gain information on the mechanism of SIM and to explore the possibility of utilizing changing mtDNA levels as a marker of SIM.
Several approaches were used. First, mtDNA levels were quantified in skeletal muscle biopsies collected from a previously published 8-week clinical trial of high-dose simvastatin or atorvastatin versus placebo. Forty-eight hypercholesterolemic subjects were randomly assigned to receive placebo (N=16), high dose atorvastatin 40mg/day (N=16), or high dose simvastatin 80mg/day (N=16) for 8 weeks. Muscle mtDNA content was assessed by real-time PCR atbaseline and after 8-weeks on statin treatment and found to be significantly reduced in the groupreceiving simvastatin (P=0.005) but not the other two. In addition, a significant positive correlation was observed between mtDNA and muscle ubiquinone in all groups (R=0.63, P<0.01), with the strongest association found in the simvastatin-treated subjects (R=0.75, P=0.002). Next, in an attempt to determine whether statin-induced muscle pain may be associated with muscle mtDNA depletion, archived muscle biopsies collected from statin users with muscle complaints were sought through a review of a muscle biopsy database and possible study samples were identified; however, this was put on hold as too much information was missing from the pathology reports. Third, a series of cell culture experiments were carried out in which human skeletal muscle myotubes were exposed to various concentrations of simvastatin or atorvastatin, in order to determine an appropriate dose range for subsequent mitochondrial toxicity experiments. Lastly, mtDNA content and expression was quantified in skeletal muscle biopsies collected from 10 patients with statin-induced rhabdomyolysis (SIR) and compared to 8 healthy controls to investigate whether muscle mtDNA is altered in rhabdomyolysis. No differences in mtDNA content or expression were observed between the two study groups, but this may have been be due to the SIR subjects' marked heterogeneity.
Statin therapy can be associated with considerable alterations in mtDNA content, which may play a role in the aetiology of SIM. MtDNA levels alterations with statin exposure should be investigated further to explore the involvement of mitochondrial alterations in the mechanism of SIM, and determine whether these may represent a useful clinical tool for assessing statin-induced muscle toxicity.
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Balharry, Dominique. "Gene profiling of lung toxicity." Thesis, Cardiff University, 2005. http://orca.cf.ac.uk/55980/.
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Bleomycin is a potent anti-tumour compound used in the treatment of squamous cell carcinomas. An unfortunate side effect of this drug is pulmonary toxicity. The onset of this damage manifests as mild oedema and inflammation which eventually develops into pulmonary fibrosis. The ability to correctly identify patients showing early signs of lung injury could significantly reduce the morbidity associated with bleomycin treatment. As such, this study was undertaken to identify genetic markers of early oedema and inflammation. A model of mild pulmonary injury was induced by bleomycin. Conventional quantitative analysis of broncho-alveolar lavage was used to indicate the severity of the oedematous response, whilst morphological changes were identified by histology and electron microscopy. Macroarrays were used to measure the expression of multiple genes during mild, progressive and severe oedema. Following normalisation and statistical analysis, gene expression patterns were compared from saline- and bleomycin-treated rats. A variety of genes were differentially expressed during each model, with the number increasing with the severity of the oedema. A cluster and two individual genes were consistently expressed across two of the models of oedema. The magnitude of the changes in gene expression were quantified and confirmed by quantitative PCR. In summary, complete toxicological and histological characterisation of the bleomycin-induced model of pulmonary injury successfully identified specific endpoints of injury. This model proved to be ideal for studying differential gene expression in response to drug-induced pulmonary oedema. A cluster of ion channels and trafficking genes has the potential to act as a biomarker. Two specific genetic markers (Na+/CI- betaine/GABA transporter, glucocorticoid receptor), and a protein marker (cocoacrisp) have been identified for the oedema. In addition to these genes and protein being potential biomarkers of injury, they are also prospective targets for clinical treatment.
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Craff, Melody Nikki. "The pathogenesis of fructose toxicity." Thesis, University of Cambridge, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.620036.
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江卓庭 and Cheuk-ting Kong. "Chloramphenicol-induced toxicity on haemopoiesis." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 1998. http://hub.hku.hk/bib/B3122099X.
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Stec, Anna Agnieszka. "Fire toxicity and its measurement." Thesis, University of Bolton, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.440710.
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The steady state tube furnace (Purser furnace, BS 7990 and ISO TS 19700) has been used in conjunction with FTIR gas analysis to investigate the toxic product yields of fire effluents. The repeatability and interlaboratory reproducibility of the apparatus is shown to be satisfactory, based on results from 6 operators at 4 laboratories. The set-up and calibration of FTIR for gases and volatiles is described, together with a discussion on reliability and interpretation of spectra. A novel recirculation system for calibration of volatile components (including organoirritants) has been validated by quantification in triplicate. Seven materials (LDPE, Nylon 6.6, Polystyrene, PVC, Medium density fibreboard with and without flame retardant and glass reinforced polyester) were investigated under different fire conditions, and the results presented in terms of toxic product yields and predicted fire gas toxicity as a function of equivalence ratio. This showed that in the case of PVC and nylon 6.6 the most toxicologically significant species were HCl and HCN respectively, in other materials, such as LDPE and polystyrene, CO was the major toxicant, and for the polyester, very high yields of CO were observed. Data from the Purser furnace and the NF X 70-100 toxicity test are compared for the seven materials, showing generally good agreement for all products except hydrocarbons. The clearer definition of fire condition from the Purser furnace allows better estimation of the fire condition of the NF X test. The yields of CO and hydrocarbons show good agreement with predictions based on data from the fire propagation apparatus (ASTM E2058), both methods using equivalence ratio to define the fire condition. Similar comparisons have been made with large scale test data from the ISO 9705 room again showing good agreement, and highlighting the ability of the tube furnace to identify the fire condition occurring in the large scale test.
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Reid, Vanessa Claire. "Macrophage toxicity of lipid oxidation." Thesis, University of Cambridge, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.308384.
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Pu, Yubing. "Toxicity assessment of engineered nanoparticles." Thesis, Troyes, 2017. http://www.theses.fr/2017TROY0001/document.
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L'objectif de cette thèse est d'améliorer la compréhension de la toxicité de diverses nanoparticules de synthèse (ENPs) pour l'homme et l'écosystème. Les travaux réalisés s’appuient sur la combinaison de données toxicologiques et d’un modèle environnemental - le modèle USEtox. En tant qu'élément important de l'évaluation de l'impact du cycle de vie, le facteur de caractérisation (CF) a été utilisé, dans ce travail, comme indicateur de toxicité pour l'homme et l'écosystème. Pour avoir accès aux courbes dose-réponse et à différentes données toxicologiques, des expériences in vitro ont été réalisées en exposant des neutrophiles porcins fraîchement isolés à trois types de nanoparticules de synthèse. Les modifications morphologiques, les taux de mortalité et la chimioluminescence des neutrophiles ont été évaluées. De plus, pour estimer le temps de persistance des nanoparticules de synthèse dans l'écosystème eau douce, un modèle basé sur la science des colloïdes a été développé. Il prend en compte les comportements spécifiques des nanoparticules de synthèse et inclut des recommandations sur le choix des paramètres hydrologiques régionaux. Enfin, une enquête documentaire exhaustive a été réalisée pour recueillir les données écotoxicologiques de diverses nanoparticules de synthèse. Dans le cadre du modèle USEtox, le CF toxicologique non cancérogène pour cuivre NPs et les CF écotoxicologiques pour 14 ENPs sont recommandés. Ces valeurs des CF pourraient être utiles à l'avenir pour évaluer les impacts environnementaux des produits contenant des ENPsThe objective of this thesis is to improve understandings of toxicity of various engineered nanoparticles (ENPs) to human and ecosystem. It is realized via coordinating toxicological data and a scientific consensus environmental model -- the USEtox model. As an important element in life cycle impact assessment, the characterization factor (CF) is employed as a toxicity indicator for human and ecosystem in this work. To obtain the firsthand dose-response phenomena and human toxicological data, in vitro experiments have been conducted by exposing freshly isolated porcine neutrophils to three kinds of ENPs (i.e. copper, nickel and aluminum oxide nanoparticles). The morphologies, mortality rates, and chemiluminescence, of neutrophils are observed or monitored. Additionally, to estimate the persistence time of ENPs in freshwater ecosystem, a fate model on the basis of colloid science is developed. It takes nano-specific behaviors of ENPs into account and includes recommendations of regionalized hydrological parameters. Finally, a comprehensive literature survey is accomplished to collect the ecotoxicological data of various ENPs. Under the framework of USEtox model, the non-carcinogenic human toxicological CFs for Copper NPs and the ecotoxicological CFs for 14 ENPs are recommended. These CF values could be useful in the future when evaluating the environmental impacts of products containing ENPs
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Cook, Rosemary Elisabeth Dalzell. "Iron toxicity to wetland plants." Thesis, University of Sheffield, 1991. http://etheses.whiterose.ac.uk/14833/.
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Motsoeneng, Khothatso Patricia. "The toxicity of silver nanoparticles." University of the Western Cape, 2012. http://hdl.handle.net/11394/4700.
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>Magister Scientiae - MScUnavailability and contamination of available water resources are major factors contributing to adverse health conditions worldwide. AgNPs present a potential strategy for water purification; however, their ability to accumulate in organs such as the kidneys, lungs and spleen is a possible source of toxicity. This study investigates the toxicity of AgNPs to Saccharomyces cerevisiae (S. cerevisiae). S. cerevisiae is an excellent model organism for assessing toxic compounds that affect eukaryotic organisms due to their ease of cultivation. AgNPs were prepared by photo-reduction of silver nitrate with OSRAM Vitalux lamp (300 W and 230 V) in the presence of stabilizing agents such as polyvinylpyrrolidone and citric acid, yielding AgNPs. The effects of varying the concentration of the stabilizing agent, time of exposure to the light source, and pH were investigated. The formation of AgNPs was analysed by ultra-violet spectroscopy (UV-Vis) and transmission electron microscope techniques. The results showed that the AgNPs absorbed ultra-violet radiation between 400 and 500 nm and TEM images showed the particles to be both spherical and needle-like in shape. The shapes of the AgNPs were largely dependent on the synthesis method applied. The toxicity of AgNPs was assessed using metabolic activity of yeast cells as biomarker andmonitored with of the chromogenic assay, XTT. S. cerevisiae was introduced into different concentrations of AgNPs and incubated at 37oC for 72 h. After the incubation, XTT assay was performed to assess the cell viability. The XTT results showed that high concentration of AgNPs (100 µg/mL) inhibited the growth of S. cerevisiae. The synthesis of AgNPs and theassessment of their toxicity on S. cerevisiae was thus undertaken and established in this work.
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Ng, Jasmine Christina. "Toxicity of cadmium in hepatocytes." Thesis, University of Surrey, 1986. http://epubs.surrey.ac.uk/844145/.
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Freshly isolated hepatocytes from fed and starved rats were used as a model in the investigation of the mechanisms by which cadmium chloride exerts its toxic effects at the cellular level. Exposure to cadmium chloride resulted in a slight decrease in viability, more pronounced in hepatocytes from starved rats. Morphological changes preceded the increase in membrane permeability. Hepatocytes exhibited a rapid initial uptake of cadmium chloride, followed by a second slower phase. The accumulation of more metal in hepatocytes from starved rats may contribute to their enhanced susceptibility to cadmium chloride. Adverse metabolic effects of cadmium chloride included an increase in the lactate:pyruvate ratio in hepatocytes from fed rats, with a concomitant decrease in the 3-hydroxybutyrate:acetoacetate ratio in hepatocytes from fed and starved rats. Incubation with cadmium chloride resulted in increased glycogenolysis and glycolysis. Decreased rates of gluconeogenesis from lactate and pyruvate reflected the decreased uptake of gluconeogenic precursors. Studies of intracellular lactate concentrations could not resolve whether the decrease in gluconeogenesis was due to an inhibition of lactate transport into the hepatocyte or due to a decrease in its metabolism. Cadmium chloride caused a slight decrease in the basal and pyruvate-stimulated rates of cellular respiration, a marked dose-related decrease with lactate, and no significant effects with succinate. Carbonyl- cyanide-m-chlorophenylhydrazone was less effective in stimulating respiration in hepatocytes incubated with cadmium chloride, this effect being more pronounced with lactate and pyruvate than with succinate. Cadmium chloride had little effect on the uncoupled rates of FADH2 oxidation with succinate suggesting that electron transport from succinate dehydrogenase to cytochrome a/a3 was not impaired. The results from these studies suggest a primary effect of cadmium chloride on mitochondrial function and cellular energy production, resulting in secondary metabolic changes in an attempt to overcome the declining levels of ATP within the cell.
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Anneken, John H. "Glutamate and MDMA Neurobehavioral Toxicity." University of Cincinnati / OhioLINK, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1353342344.
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Peebles, Brian Christopher. "Pulmonary Toxicity of Manufactured Nanoparticles." The Ohio State University, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=osu1274902471.
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Hsieh, Heidi. "Zinc Toxicity in Odora Cells." University of Cincinnati / OhioLINK, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1313756131.
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Vieira, Pedro Emanuel Ferreira dos Reis. "Amino acid toxicity in Zebrafish." Master's thesis, Universidade de Aveiro, 2011. http://hdl.handle.net/10773/8229.
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Mestrado em Biologia Aplicada - Biologia Molecular e CelularProteins are synthetized through the mechanism of translation and are constituted by amino acids. Besides being the basic units of proteins, amino acids also play other important roles in the cell such as signaling or regulation of cell growth. However, in excess, amino acids can be toxic, although the mechanism of toxicity is still not clear. In this study we used zebrafish as a vertebrate model to assess the toxicity induced by different amino acids as a result of nutritional imbalance. Moreover, we evaluated the changes induced by amino acid toxicity during zebrafish development in order to understand if this toxicity could be related with wrong incorporation of mischarged amino acids during translation. The results show that some of the canonical amino acids cause high toxicity in zebrafish, namely L-tryptophan, L-glutamine, Lphenylalanine and L-arginine. To understand if this toxicity could be caused by the production of aberrant proteins, due to tRNA mischarging, result of an unbalanced amino acid pool, we analyzed the activation of protein degradation pathways. For this we did western blot analysis of the poliubiquitination state of the proteome. No differences were observed between different amino acid concentrations and the control indicating that the ubiquitin-proteasome pathway is not directly correlated with the amino acid toxicity observed.
As proteínas são sintetizadas através do mecanismo de tradução e são constituídas por aminoácidos. Além de serem as unidades básicas das proteínas, os aminoácidos também desempenham outras funções importantes na célula, tais como sinalização ou regulação do crescimento celular. No entanto, em excesso, os aminoácidos podem ser tóxicos, embora o mecanismo de toxicidade não esteja claro. Neste estudo, usámos o peixezebra como modelo vertebrado para avaliar a toxicidade induzida por diferentes aminoácidos como resultado do desiquílibrio nutricional. Para tal, avaliámos as alterações induzidas pela toxicidade de aminoácidos durante o desenvolvimento do peixe-zebra, para compreender se esta toxicidade podia estar relacionada com a incorporação errada de aminoácidos durante a tradução. Os resultados mostram que alguns dos aminoácidos causam toxicidade em peixe-zebra, nomeadamente, L-triptofano, L-glutamina, Lfenilalanina e L-arginina. Para entender se esta toxicidade pode ser causada pela produção de proteínas aberrantes, devido ao carregamento errado de aminoácidos no tRNA, resultante de um excesso de aminoácidos, analisámos a activação de vias de degradação de proteínas. Para isso realizámos análises por western blot do estado de poliubiquitinação do proteoma. Não foram observadas diferenças entre as diferentes concentrações de aminoácidos e do controlo, indicando que a via da ubiquitina-proteossoma não está directamente relacionada com a toxicidade de aminoácidos observada.
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Promtong, Pawika. "Determinants of silver nanoparticle toxicity." Thesis, University of Manchester, 2015. https://www.research.manchester.ac.uk/portal/en/theses/determinants-of-silver-nanoparticle-toxicity(5b09211a-35b6-4f8c-8677-a76f652494b3).html.
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Silver nanoparticles (AgNPs) containing consumer products have increasingly emerged in the market because of their potential antibacterial property, which might result in increased human exposure and environmental contamination. AgNPs are toxic to mammalian and other cells but the determinants of this toxicity remain to be fully characterised and the potential impact of DNA repair systems has been poorly explored. This study, therefore, examined to what extent the size and shape of synthesised AgNPs determined AgNP toxicity in DNA repair proficient and deficient (8-oxoguanine DNAglycosylase; WT and OGG1-/-, respectively) mouse embryonic fibroblasts (MEFs) as well as a well-known human cell line used in the toxicity testing, HepG2 cells. Citrate-stabilised spherical- and triangular-shaped AgNPs (S-AgNPs andT-AgNPs, respectively) were synthesised chemically from AgNO3 using combinations of NaBH4 and sodium citrate as a reducing and stabilising agent, respectively, and purified by dialysis. Three different sized S-AgNPs were prepared with diameters of 7.6 ± 1.2, 14.3 ± 4.2, and 52.5 ± 17.9 nm as measured using transmission electron microscope (TEM), and their zeta potentials were -36.1±2.7, -39.5±2.7 and -36.7±4.1 mV, respectively. T-AgNPs had an edge length and thickness of 71.4 ± 11.1 nm and 5.7 ± 0.8 nm, respectively. The size and zeta potential of the purified AgNPs were constant in distilled water for at least 6 months. The uptake of both S- and T-AgNPs by cells resulted in a time and dose-dependent increase in the number of cellular AgNPs and the amount of Ag+ released intracellularly. These increases were associated with a decrease in cell viability (as measured using the MTT assay) and cell survival (the clonogenic assay), and an induction in ROS generation (the DCF assay) and DNA damage(the alkaline Comet assay) for all three cell lines. AgNPs were observed in cells using TEM, suggesting the uptake of AgNPs via an endocytosis pathway. Results suggested that an increase in cellular AgNP level and intracellular released Ag+ content were associated with a time and dose-dependent toxicity. Interestingly, cellular AgNP level and intracellular released Ag+ content might play an important role in size-dependent AgNP toxicity, in which exposure to the smaller S-AgNP sizes (7nm and 14nm) resulted in higher levels of both cellular AgNPs and Ag+ released intracellularly, and then to increased toxicity when compared with the larger S-AgNP size (50nm). Moreover, different shaped AgNPs might induce toxicity by different mechanisms: ROS-mediated toxicity might be induced by both 70nm T-AgNPs and 50nm S-AgNPs and 70nm T-AgNPs might also induce cell membrane damage. AgNP-induced toxicity was different in different cell lines with HepG2 cells being more sensitive to AgNPs particularly using the clonogenic assay, and this toxicity was associated with higher DNA damage observed in HepG2 cells after 24 h. OGG1-/- MEFs were more sensitive to intracellular released Ag+, leading to higher ROS formation and DNA damage in OGG1-/- MEFs than that observed in WT MEFs. In summary, this study strongly suggests that AgNPs induce toxicity via a Trojan-horse type mechanism, and not only Ag+ released intracellularly but also cellular AgNPs take part in this toxicity, and will eventually result in the biological responses of the cells.
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Sheridan, Peter Oliver. "Amalgam restorations and mercury toxicity." Connect to full text, 1991. http://hdl.handle.net/2123/4412.
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Thesis (M.D.S.)--University of Sydney, 1992.Title from title screen (viewed Apr. 23, 2009) Submitted in fulfilment of the requirements for the degree of Master of Dental Surgery to the Faculty of Dentistry. Degree awarded 1992; thesis submitted 1991. Includes bibliography. Also available in print form.
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Stewart, Christine Catherine. "Toxicity of mutant membrane proteins /." Thesis, Connect to this title online; UW restricted, 1996. http://hdl.handle.net/1773/10259.
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Kong, Cheuk-ting. "Chloramphenicol-induced toxicity on haemopoiesis /." Hong Kong : University of Hong Kong, 1998. http://sunzi.lib.hku.hk/hkuto/record.jsp?B20604531.
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Quay, Brigitte de. "Drug toxicity in human lymphocytes /." Bern, 1990. http://www.ub.unibe.ch/content/bibliotheken_sammlungen/sondersammlungen/dissen_bestellformular/index_ger.html.
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VanEngelen, Michael Robert. "Molecular aspects of uranium toxicity." Thesis, Montana State University, 2009. http://etd.lib.montana.edu/etd/2009/vanengelen/VanEngelenM1209.pdf.
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Sheridan, Peter. "Amalgam restorations and mercury toxicity." Thesis, The University of Sydney, 1991. http://hdl.handle.net/2123/4412.
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The safety of amalgam restorations has been challenged, claims having been made that health risks are associated with the constituent mercury. There are assertions that mercury released from amalgam produces mercury poisoning, and is thus responsible for diverse symptoms of impaired health as well as disease states such as Multiple Sclerosis. This study examines the various forms of mercury and their effects and attempts particularly to delineate the significance of dental amalgam as a factor in hypersensitivity reactions and in the human body burden of mercury. Dental personnel are evaluated as a potentially high-risk group for mercury exposure. Dental amalgam and alternative restorative materials are considered, the removal of amalgam being evaluated as a therapeutic modality. The “anti-amalgam” perspective is scrutinised and the validity of the claims assessed. A review of the scientific literature, and the statements of national and international dental and scientific literature, and the statements of national and international dental and scientific organisations reflect the general support for the safety of dental amalgam. There is no evidence that health risks are associated with the use of dental amalgam other than rare local allergic reactions and oral lichenoid lesions. Notwithstanding the usefulness and safety of dental amalgam certain recommendations and conclusions are made in respect of future approaches to the utilisation of this material and for mercury in general. Further objective scientific research is necessary to determine the effects on human health of chronic exposure to low levels of mercury. There is the need for accurate general population threshold levels to be established for mercury vapour with special consideration for the vulnerable members of the community. The health professions have a significant role to play in providing informed opinion and advice for their patients and the public, in countering the more eccentric claims of the anti-amalgamists and assuaging the anxiety and confusion which accompanies this subject.
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Sheridan, Peter. "Amalgam restorations and mercury toxicity." University of Sydney, 1991. http://hdl.handle.net/2123/4412.
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Master of Dental SurgeryThe safety of amalgam restorations has been challenged, claims having been made that health risks are associated with the constituent mercury. There are assertions that mercury released from amalgam produces mercury poisoning, and is thus responsible for diverse symptoms of impaired health as well as disease states such as Multiple Sclerosis. This study examines the various forms of mercury and their effects and attempts particularly to delineate the significance of dental amalgam as a factor in hypersensitivity reactions and in the human body burden of mercury. Dental personnel are evaluated as a potentially high-risk group for mercury exposure. Dental amalgam and alternative restorative materials are considered, the removal of amalgam being evaluated as a therapeutic modality. The “anti-amalgam” perspective is scrutinised and the validity of the claims assessed. A review of the scientific literature, and the statements of national and international dental and scientific literature, and the statements of national and international dental and scientific organisations reflect the general support for the safety of dental amalgam. There is no evidence that health risks are associated with the use of dental amalgam other than rare local allergic reactions and oral lichenoid lesions. Notwithstanding the usefulness and safety of dental amalgam certain recommendations and conclusions are made in respect of future approaches to the utilisation of this material and for mercury in general. Further objective scientific research is necessary to determine the effects on human health of chronic exposure to low levels of mercury. There is the need for accurate general population threshold levels to be established for mercury vapour with special consideration for the vulnerable members of the community. The health professions have a significant role to play in providing informed opinion and advice for their patients and the public, in countering the more eccentric claims of the anti-amalgamists and assuaging the anxiety and confusion which accompanies this subject.
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Shubat, Pamela Jane. "Monocrotaline toxicity and pulmonary arteries." Diss., The University of Arizona, 1988. http://hdl.handle.net/10150/184533.
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Monocrotaline is a pyrrolizidine alkaloid found in plants implicated in livestock and human poisoning. Laboratory rats given monocrotaline develop pulmonary hypertension and right heart hypertrophy in the weeks following administration of the chemical. Lung weight increases and right heart hypertrophy correlate with increased pulmonary artery pressure. Rats which consumed monocrotaline drinking water (20 mg/l) for only 4 days developed significant increases in lung and heart weights 14 days after exposure began. This exposure was equivalent to a dose of 15 mg/kg. Other treatment combinations of time (0-10 days exposure) and monocrotaline concentration (5-60 mg/l in drinking water) were tested. The accumulative dose calculated for each of the treatment combinations which produced toxicity was in the range of 15 to 20 mg/kg. Monocrotaline injury appears to be cumulative, but organ weight increases reverse once exposure is stopped. As pulmonary hypertension develops and pulmonary arteries hypertrophy, the force with which isolated pulmonary artery segments contract decreases. This is a loss of efficacy rather than potency to the contracting agents KCl, norepinephrine, and 5-hydroxytryptamine. Relaxation of arteries under conditions of potassium-return (a measure of Na⁺/K⁺ ATPase activity) was also altered by monocrotaline treatment. In vivo monocrotaline treatment had little effect on the force of K⁺-return relaxation. However, the rate at which arteries relaxed was significantly decreased following 4 days ingestion of monocrotaline drinking water (20 mg/l). In vitro ouabain treatment and endothelial injury also decreased the rate of K⁺-return relaxation. Another Na⁺/K⁺ ATPase activity, ⁸⁶Rb⁺ uptake, was decreased following monocrotaline treatment only when 5-hydroxytryptamine was present and only uptake associated with the endothelium was affected. These studies utilized a very low exposure to monocrotaline (4 days ingestion of 20 mg/l monocrotaline drinking water or 15 mg/kg) to produce toxicity in rats. Monocrotaline-induced toxicity measured 20 days after treatment included right heart and lung hypertrophy and decreased contractions of isolated pulmonary arteries. Monocrotaline treatment decreased the rate of Na⁺/K⁺ ATPase-dependent relaxation of isolated pulmonary arteries 4 days after treatment began.
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Spanarkel, Robert. "Carbon Dioxide Toxicity in Wheat." DigitalCommons@USU, 1990. https://digitalcommons.usu.edu/etd/6766.
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This research was conducted to quantify short- and long-term effects of atmospheric carbon dioxide on wheat. Growth, development, and yield of the spring wheat cultivar Veery-10 were measured in response to CO2 concentrations of 340 (ambient), 1200, and 2500 μmol moI-1 of CO2 air. These 3 CO2 levels were chosen to provide a control group, a predicted optimal CO2 environment, and a potentially toxic CO2 environment, respectively. A recirculating hydroponic system provided a near-optimal root-zone environment that was identical for all CO2 treatment levels. Environmental factors, other than CO2, were controlled at near optimal levels, although photosynthetic photon flux was actually suboptimal and higher levels would increase growth. Standard growth analysis procedures were used to measure growth rates and carbon partitioning to leaves, stems, and roots. Yield components were measured on mature plants. Because elevated CO2 levels may increase growth by increasing radiation absorption or by increasing photosynthetic efficiency, measurements of absorbed photosynthetic photon flux were calculated from measurements of incident, reflected, and transmitted photosynthetic photon flux. Growth and yield were increased by the 1200 μmol moI-1 of CO2 in air treatment in all trials. Growth and yield were reduced by the 2500 μmol moI-1 treatment in both long-term trials, but growth was not reduced by this treatment in two short-term trials. These data indicate that CO2 is toxic to wheat at 2500 μmol moI-1 (0.25%), but the effects are not expressed until the last half of the life cycle.
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Vignaud, Hélène. "Étude de la toxicité du peptide amyloïde beta Aß42 dans la levure Saccharomyces cerevisiae." Thesis, Bordeaux 2, 2013. http://www.theses.fr/2013BOR22068/document.
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La maladie d’Alzheimer est la maladie neurodégénérative la plus fréquente chez l’Homme et constitue un enjeu économique et de santé publique majeur. Les cerveaux de patients atteints présentent une atrophie corticale associée à deux types de lésions : les dégénérescences neurofibrillaires, constituées de protéines Tau agrégées, et les plaques amyloïdes, composées majoritairement de peptides amyloïde beta Aß agrégés. Les peptides Aß et leur agrégation seraient à l’origine de la pathogenèse. Afin d’éclaircir les mécanismes moléculaires à la base de la toxicité d’Aß, nous avons construit un modèle de toxicité d’Aß dans la levure Saccharomyces cerevisiae. Ce modèle a permis d’établir que la toxicité d’Aß dans la levure est intimement liée à sa sécrétion et au trafic vésiculaire. Ce modèle nous a également permis de réaliser une étude structure-toxicité du peptide et de mettre en évidence des éléments en cis importants pour la toxicité d’Aß. Une nouvelle voie d’agrégation des peptides toxiques en structure riche en feuillet ß anti-parallèle a pu ainsi être mise en évidence. Le modèle de toxicité d’Aß et l’existence de variants très toxiques d’Aß dans la levure nous a permis de réaliser des cribles génétiques afin de rechercher les éléments modulant la toxicité d’Aß in vivo. Le trafic vésiculaire, en particulier l’endocytose via le remodelage du cytosquelette d’actine, un complexe responsable de la formation de vésicules intraluminales appelé ESCRT, forment autant de pistes à étudier pour améliorer notre compréhension de la toxicité d’AßAlzheimer’s disease is the most common neurodegenerative disease. This pathology is caused by aggregation of Aß peptides. The exact mechanism of neuronal cell dysfunction in Alzheimer’s disease is poorly understood and numerous models have been used to decipher the mechanisms leading to cellular death. In order to clarify the molecular mechanisms underlying the toxicity of Aß, we generated a new model to study Aß toxicity in yeast Saccharomyces cerevisiae. In our model, Aß toxicity is closely related to its secretion and its intracellular traffic. Indeed, when Aß is targeted to the secretory pathway, it is able to produce toxic species. Interestingly, we demonstrated also that even if Aß is addressed to the secretory pathway, it is still able to form cytoplasmic aggregates. Moreover, with this model, we generated new highly toxic mutants of Aß by random mutagenesis. In order to correlate structural conformation ‘signature’ to Aß toxicity, we performed a structure-toxicity study of these new variants. In vitro, we demonstrated that a new anti-parallel aggregation pathway is associated with highly toxic mutants of Aß. Then, using our Aß yeast model and also these harmful variants, we performed genetic screens in order to identify candidate genes able to modulate Aß toxicity in vivo. Given these different screens, we found that vesicular trafficking, endocytosis via actin cytoskeleton remodeling, and ESCRT-III (Endosomal Sorting Complex Required for Tansport) open new avenues to improve our understanding of Aß toxicity
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Billat, Pierre-André. "Relations exposition-effets et pharmacogénétique du ganciclovir chez le patient transplanté." Thesis, Limoges, 2015. http://www.theses.fr/2015LIMO0050/document.
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Les infections par cytomégalovirus sont un problème majeur en transplantation rénale du fait de l’augmentation du risque de perte de greffon et de l’augmentation de la morbi-mortalité des patients. Toutefois la mise en place d’un traitement prophylactique par ganciclovir a significativement fait diminuer l’incidence de ces infections. Cette efficacité est toutefois limitée par une importante hématotoxicité notamment des neutropénies. La survenue de cet évènement indésirable conduit à une réduction des doses voire à un arrêt du traitement, favorisant ainsi l’émergence de résistances virales. Ces résistances sont un problème grandissant chez les personnes transplantées du fait du manque de protocole de prise en charge de celles-ci. Dans ce contexte notre objectif était de mieux comprendre la survenue et le mécanisme de cette toxicité. Dans un premier temps nous avons étudié le métabolisme intracellulaire du ganciclovir chez des patients. Nous avons remarqué qu’il y a une forte corrélation entre l’exposition à la forme active du ganciclovir et la diminution du nombre de neutrophiles au 3ème mois de traitement. Nous avons par la suite étudié l’impact de variations génétiques sur des transporteurs. Nous avons remarqué qu’un polymorphisme était fortement associé à une diminution du nombre de neutrophiles et qu’il entrainait également une augmentation de la concentration intracellulaire de ganciclovir à l’aide d’un modèle in vitro. Cette thèse fournit de nouveaux outils d’exploration du métabolisme et de l’accumulation intracellulaire du ganciclovir qui pourraient être utiles pour la prévention de la survenue de neutropénies sous ganciclovirCytomegalovirus infection is a major issue in transplant patients as it affects the graft survival and contributes to patients’ morbi-mortality. The implementation of ganciclovir prophylaxis has significantly decreased its incidence, however GCV frequently induces neutropenia. This adverse effect leads to a decrease in the ganciclovir dose or to a discontinuation of the therapy, thereby favoring viral resistance. Resistance to ganciclovir is a growing problem in solid organ transplantion because of the lack of proper data to support treatment decisions when it is encountered. In this context we aim at better understanding the factors involved in this toxicity. First we explored the intracellular metabolism of ganciclovir in patients’ white blood cells. We found that the active form of ganciclovir is associated with neutrophil toxicity at month 3 of treatment. Then we explored the effect of targeted polymorphisms among transporter genes in two cohorts of renal transplant patients. We found that a single nucleotide polymorphism is strongly associated with a decrease in the neutrophil count and in ganciclovir intracellular accumulation. This thesis provides relevant tools for a deeper exploration of ganciclovir intracellular metabolism and accumulation which might be useful for the prevention of ganciclovir induced neutropenia
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Gillespie, Annika Margaret. "Environmental toxicity of complex chemical mixtures." [College Station, Tex. : Texas A&M University, 2006. http://hdl.handle.net/1969.1/ETD-TAMU-1017.
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Reimers, Mark J. "Ethanol-dependent developmental toxicity in zebrafish /." Connect to full text via ProQuest. IP filtered, 2005.
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Finnilä, M. A. (Mikko A. J. ). "Bone toxicity of persistent organic pollutants." Doctoral thesis, Oulun yliopisto, 2014. http://urn.fi/urn:isbn:9789526205090.
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Abstract Persistent organic pollutants (POPs), especially dioxin-like chemicals, have been shown to have adverse effects on skeleton and these effects are likely to be mediated via the aryl hydrocarbon receptor (AHR). In spite of the extensive research, the characteristics of developmental effects of POPs are poorly known and the role of AHR in POP bone toxicity and skeletal development in general. In this project changes in bone morphology and strength as well as tissue matrix mechanics are studied by applying state of the art biomedical engineering methods. This allows understanding of the effects of dioxins exposure and AHR activity on the development and maturation of extracellular matrix in musculoskeletal tissues from a completely new perspective, and thereby improving the health risk assessment of POPs. In the present study skeletal properties of rats exposed maternally to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), Northern Contaminant Mixture (NCM) and Aroclor1254 (A1254) were studied for cross-sectional morphometric and biomechanical properties, and data were analysed with benchmark dose modelling. In addition, extracellular matrix properties were analysed using nanoindentation. Similar measurements were performed for adult wild-type and AHR-null mice after TCDD exposure. The same animals were also analysed for microstructural changes using micro-computed tomography and their bone cell activity was estimated from serum markers and gene expression. Analyses show decreased bone length and cross-sectional properties with consequently decreased bone strength. On the other hand, an increased trabecular BMD in response to NCM and A1254 was observed. In addition, bone matrix properties indicated delayed maturation or early senescence after maternal or adult exposure, respectively. The AHR is mainly responsible for bone toxicity of dioxin-like compounds and plays a role in bone development. This is likely due to disturbed bone remodeling as indicated by altered serum markers and gene expression. Overall these results indicate that POPs decrease bone strength, but the interpretation is difficult as there is more trabecular bone within cortical bone with compromised quality and increased porosityTiivistelmä Altistumisen pysyville orgaanisille ympäristökemikaaleille on todettu heikentävän luustoa. Dioksiinien ja dioksiininkaltaisten yhdisteiden vaikutusten on havaittu välittyvän aryylihiilivetyreseptorin (AHR) välityksellä. Huolimatta pitkään kestäneestä tutkimuksesta POP-yhdisteiden sikiönkehityksen aikaisen altistuksen vaikutukset ja etenkin niiden mekanismit ovat edelleen huonosti tunnettuja, samoin kuin AHR:n osuus POP-yhdisteiden luutoksisuudessa ja luuston kehityksessä ylipäätään. Tässä työssä tutkittiin luuston rakenteellisia ja mekaanisia ominaisuuksia niin perinteisillä kuin uusimmilla biolääketieteen tekniikan menetelmillä. Tutkimuksen tavoitteena on saada uutta tietoa POP-altistuksen ja AHR-aktiivisuuden vaikutuksista luuston kehitykseen ja luukudoksen ikääntymisprosesseihin, mikä edesauttaa kyseisten yhdisteiden riskinarviointia. Tutkimuksissa altistettiin kantavia rottaemoja 2,3,7,8-tetraklooridibenzo-p-dioksiinille (TCDD), pohjoiselle saasteseokselle ja kaupalliselle Arokloori 1254 PCB-seokselle. Sikiönkehityksen aikana altistuneiden jälkeläisten luuston poikkileikkausen morfologia ja biomekaaniset ominaisuudet mitattiin ja tulokset mallinnettiin vertailuannoksen määrittämiseksi. Lisäksi TCDD-altistettujen rottien luustomatriisin ominaisuuksia selvitettiin nanoindentaatiomenetelmällä. Samaa menetelmää käytettiin myös aikuisiässä TCDD:lle altistettujen villityypin hiirten ja AHR-poistogeenisiten hiirten tutkimiseen. Näiden hiirten luuston hienorakennetta mitattiin myös korkean resoluution mikro-tietokonetomografialla ja niiden luusolujen aktiivisuutta tutkittiin seerumin biomarkkerien ja luun muodostumiseen osallistuvien geenien ekspressiotasojen avulla. Sikiönkehityksen aikainen altistuminen pohjoiselle saasteseokselle ja Arokloori 1254:lle hidasti luiden pituuskasvua. Lisäksi luiden poikkileikkauspinta-alat olivat pienentyneet ja mekaaniset ominaisuudet heikentyneet. Toisaalta hohkaluun määrä oli lisääntynyt altistumisen seurauksena. Myös sikiönkehityksen aikainen altistuminen TCDD:lle hidasti luukudoksen kypsymistä ja johti aikuisiällä luukudoksen ennenaikaiseen vanhenemiseen. AHR:llä oli päärooli ainakin aikuisiän vaikutusten ilmenemiselle ja reseptorilla vaikutti olevan rooli luuston kehityksessä ylipäätään. Seerumin biomarkkereiden ja geeniekspression muutosten perusteella nämä vaikutukset johtuvat todennäköisesti luuston uusiutumisen häiriöistä. Yhteenvetona voidaan todeta, että POP-yhdisteet heikentävät luustoa, mutta tämän ilmiön diagnosoiminen on hankalaa, koska huonolaatuisen kuoriluun sisällä hohkaluun määrä on lisääntynyt
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Soliman, Gamal. "A study of acetaminophen analogues' toxicity." Thesis, University of Ottawa (Canada), 1985. http://hdl.handle.net/10393/4926.
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Leo, Bey Fen. "Stability and toxicity of silver nanomaterials." Thesis, Imperial College London, 2015. http://hdl.handle.net/10044/1/40887.
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Understanding the electrochemical stability or corrosion behaviour of metallic nanoparticles in aqueous environments is of central importance in the fields of catalysis, sensing and nano-electronics. The electrochemical stability of silver nanoparticles (AgNPs) was investigated as a function of applied potential, pH and particle size. The direct voltammetric measurements of the Ag oxidation potential indicate that the electrochemical stability of nanoparticles (NPs) is different from their bulk metal, suggesting that theoretically derived energy diagrams for a bulk material might not always be accurate for NPs. In order to understand interactions of nanomaterials (NMs) with biological systems, the cellular environment can be considered as an electrochemical cell, since metal ion release is a major pathway underlying their potential toxicity. NPs inhaled from the air into the deep lung first contact with the lung lining fluid where they have the potential to translocate into other organs like the brain, liver, spleen and heart via blood circulation. Here, this thesis specifically focuses on the impact of AgNMs on two major organs, the lung and brain. AgNMs as potential occupational and environmental hazards may raise health and safety concerns. For this reason, there is a need to assess the interaction of NMs with biological systems for early prediction of their cytotoxicity. The stability of AgNPs in dipalmitoylphosphatidylcholine (DPPC), the major component of lung surfactant, was investigated as a function of pH. TEM images revealed that the AgNPs were coated with a DPPC layer serving as a semi-permeable layer, improving their dispersion and delaying ions release in the lung. Furthermore, these studies suggested that size, stability and chemical composition of NP have to be taken into account in the evaluation of NP cytotoxicity. These observations have important implications for predicting the potential reactivity of AgNPs in the lung and the environment. In response to potential neurotoxicity, studies have shown that AgNPs can cross the blood brain barrier (BBB) via the systemic blood supply and then localise inside the brain, causing neurodegeneration, but much less is known about the distribution of AgNMs and their interaction with protein complexes inside the brain cells. Interaction of microglia with AgNMs, as well as their uptake, cytotoxicity and processing inside cells were investigated. The findings demonstrate that Ag2S formation acts as an ion trap for free Ag+, significantly limiting short term toxicity effects with important consequences for the neuro safety of AgNMs. In order to manipulate particular NPs features with favourable bio-availability and bio-distribution, not only NP uptake into cells, but also a fundamental understanding of the NPs-protein complex is necessary.
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Bain, Peter A., and n/a. "Gene Expression Profiling of Cylindrospermopsin Toxicity." Griffith University. School of Biomolecular and Physical Sciences, 2007. http://www4.gu.edu.au:8080/adt-root/public/adt-QGU20080404.145834.
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Cylindrospermopsin (CYN) is a toxic alkaloid produced by several freshwater cyanobacterial species, the most prevalent in Australian waters being Cylindrospermopsis raciborskii. The occurrence of CYN-producing cyanobacteria in drinking water sources worldwide poses a potential human health risk, with one well-documented case of human poisoning attributed to the toxin. While extensive characterisation of CYN-induced toxicity has been conducted in rodents both in vivo and in primary cell cultures, little is known about mechanisms of toxicity in human cell types. This thesis describes studies undertaken to further define the molecular mechanisms of CYN toxicity in human cells. Concentration-response relationships were determined in various cultured human cell types using standard toxicity assays. As expected, CYN caused dose-dependent decreases in the growth of three cell lines, HepG2, Caco-2 and HeLa, and one primary cell type, human dermal fibroblasts, according to tetrazolium reduction assays. CYN treatment did not disrupt cellular membranes according to the lactate dehydrogenase release assay in HepG2 or Caco-2 cells after 24, 48 or 72 h exposure, but did cause membrane disruption in fibroblasts after 72 h exposure to relatively high concentrations of the toxin. Apoptosis occurred more readily in HeLa cells than HepG2 cells or fibroblasts, with 72 h exposure to 1 &mug/mL required before statistically significant rates of apoptosis occurred in the latter cell types. CYN did not appear to directly affect the structure of actin filaments or microtubules under the conditions used in the present study. The major portion of the work presented in this thesis comprises a large-scale interrogation of changes in gene expression induced by the toxin in cultured cells. To assess the effects of CYN on global gene expression, relative messenger RNA (mRNA) levels in human dermal fibroblasts and HepG2 cells after 6 h and 24 h exposure to 1 &mug/mL CYN were determined using oligonucleotide microarrays representing approximately 19 000 genes. Overall, the number of transcripts significantly altered in abundance was greater in fibroblasts than in HepG2 cells. In both cell types, mRNA levels for genes related to amino acid biosynthesis, carbohydrate metabolism, and protein folding and transport were reduced after CYN treatment, while transcripts representing genes for apoptosis, RNA biosynthesis and RNA processing increased in abundance. More detailed data analyses revealed the modulation of a number of stress response pathways—genes regulated by NF-&kappaB were induced, DNA damage response pathways were up-regulated, and a large number of genes involved in endoplasmic reticulum stress were strongly down-regulated. Genes for the synthesis and processing of mRNA, tRNA and rRNA were strongly up-regulated, indicating that CYN treatment may increase the turnover of all forms of cellular RNA. A small group of genes were differentially expressed in HepG2 cells and fibroblasts, revealing cell-specific responses to the toxin. Selected changes in transcript level were validated using real-time quantitative reverse transcriptase PCR (qRT-PCR). The modulation of stress response pathways by CYN, indicated by microarray analysis, was further investigated using other methods. The role of tumour suppressor protein p53 in CYN-mediated gene expression was confirmed by measuring the expression of known p53-regulated genes following CYN treatment of HepG2 cells and human dermal fibroblasts using qRT-PCR. Western blotting of protein extracts from CYNtreated cells showed that p53 protein accumulation occurred in HepG2 cells, providing additional evidence of the activation of the p53 pathway by CYN in this cell line. The immediate-early genes JUN and FOS were found to be induced by CYN in a concentration-dependent manner, and MYC was induced to a lesser extent. The mitogen-activated protein kinase c-Jun NH2-terminal kinase, implicated in the ribotoxic stress response initiated by damage to ribosomal RNA, appeared to become phosphorylated in HeLa cells after CYN exposure, suggesting that ribotoxic stress may occur in response to CYN in at least some cell types. The expression of a reporter gene under the control of a response element specific for NF-&kappaB was induced at the mRNA level but inhibited at the protein level. This shows that while transcription factors such as p53 and NF-&kappaB are apparently activated in response to the toxin, transactivation of target genes may not necessarily manifest a corresponding increase at the protein level. The current work contributes significantly to the current understanding of cylindrospermopsin toxicity in human-derived cell types, and provides further insight into putative modes of action.
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LeBlanc, Gregory Andrew. "The nigrostriatal toxicity of beta-carbolines." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1998. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp01/MQ31222.pdf.
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