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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

Development of a Caenorhabditis elegans model for the assessment of toxicity and its application in testing novel anthelmintics

Oluwadare, Eyitayo Olufemi January 2017 (has links)
The nematode Caenorhabditis elegans is an alternative model used in biomedical research for the investigation of descriptive and mechanistic toxicity assessment of chemicals. There are considerable differences in published data, especially in terms of reproducibility and validation of toxicity endpoints, and the techniques used in the investigation of these endpoints. This thesis describes the evaluation of toxicological endpoints following the exposure of C. elegans to chemicals which include; zinc oxide nanoparticles (ZnONP), Diethylstilbestrol (DES) and derivatized target-specific anthelmintics. The results suggest that ZnONP prepared in anionic and cationic dispersants (AZNP and CZNP respectively) were the most toxic against the nematode resulting in the ‘bag of worms' (BOW) phenotype which can be exploited as a marker for reproductive toxicity. Also, worms treated with ZnONP prepared in 0.1% FBS (FZNP), molecular grade water (WZNP) or E. coli OP50 supernatant (SZNP) presented three-fold embryo elongation showing fully differentiated tissues encapsulated within the eggshell and still within the hermaphrodite gravid adult. The phenotype has been named accelerated embryonic development (AED) and could be used as a developmental toxicity endpoint. The results suggest that the AED endpoint is the most sensitive while lethality endpoint appears to be the least sensitive despite its extensive use in the literature. Also, microRNA microarray expression appears to be the most sensitive molecular endpoint while behavioural endpoints such as speed should be interpreted with caution, especially when performed manually. Importantly, good C. elegans culture practice (GCeCP) is required for reproducible chemical toxicity assessment and different endpoints may be required for different types of toxicity assessment. Additionally, the thesis describes a second but related study which explores a potential for enhanced anthelmintic targeting. Novel fluorophore-based asparagine-containing oligopeptide substrate probes were used to target the helminth protease, legumain. These probes were selectively cleaved by legumain in C. elegans, Haemonchus contortus and Teladorsagia circumcincta. The protease-specific probes could potentially be exploited to achieve protease-mediated prodrug activation and drug delivery.
2

The importance of scaling in data mining for toxicity prediction.

Mazzatorta, P., Benfenati, E., Neagu, Daniel, Gini, G. January 2002 (has links)
No / While mining a data set of 554 chemicals in order to extract information on their toxicity value, we faced the problem of scaling all the data. There are numerous different approaches to this procedure, and in most cases the choice greatly influences the results. The aim of this paper is 2-fold. First, we propose a universal scaling procedure for acute toxicity in fish according to the Directive 92/32/EEC. Second, we look at how expert preprocessing of the data effects the performance of qualitative structure-activity relationship (QSAR) approach to toxicity prediction.
3

Distribuição do endosulfan em alguns elementos do ecossistema após aplicação na cultura do algodão / Distribution of endosulfan in some ecosystem elements after application in crop of cotton

Bertochi, Helena Romilda 10 February 2006 (has links)
Este estudo foi realizado na safra 2002/2003 quando foi avaliado os níveis de endosulfan e seus principais produtos de transformação numa área agrícola localizada na cabeceira de uma microbacia do município de Aguaí-SP. Os objetivos específicos foram: (i) avaliar a movimentação do endosulfan e seus principais transformação no solo sob a cultura do algodão (áreas submetidas à aplicação), (ii) avaliar sua transferência de compartimento (transporte para o solo sob milho e braquiária, adjacentes às áreas aplicadas, e para os corpos aquosos - nascente, lago, córrego jusante e poço), (iii) avaliar os resíduos de endosulfan e seus produtos de transformação nos peixes do açude e (iv) predizer, através de modelagem matemática, a concentração de endosulfan passível de atingir o corpo d\'água e a largura mínima da faixa de contenção (mata ciliar) para impedir a chegada dos produtos no lago. Para tanto, foram realizadas amostragens de solo, sedimento, água dos corpos hídricos e da enxurrada e de peixes, durante sete meses, nas quais foram realizadas análises de α- e β-endosulfan, endosulfan sulfato e endosulfan diol. As análises foram efetuadas por cromatografia gasosa com detecção por espectrometria de massa. Para prever a concentração do produto passível de atingir o açude, tanto associada ao sedimento como na forma livre, foi realizada uma modelagem matemática com base nas propriedades físico-químicas do produto e nas condições edafoclimáticas e de manejo da área estudada. Pôde-se concluir que: (i) o endosulfan e seu produto de transformação endosulfan sulfato não apresentam potencial de lixiviação no solo nas condições estudadas; (ii) a persistência do endosulfan no campo é menor em relação aos estudos de laboratório, sendo que o isômero alfa é o que apresenta a mais rápida degradação e o principal produto de transformação do endosulfan no solo é o endosulfan sulfato; (iii) a principal via de transporte do endosulfan e do endosulfan sulfato no ambiente é o escoamento superficial; (iv) o endosulfan e seus produtos de transformação são transportados associados as micropartículas de solo (\"resíduo-ligado\"); (v) quando a aplicação segue as recomendações estabelecidas pelo fabricante, o produto somente apresenta potencial para atingir áreas adjacentes se houver caminhamento da enxurrada para estas áreas; (vii) o endosulfan e seus produtos de degradação, em sua fase de \"resíduo-ligado\", não apresentam efeito agudo e bioacumulação para as espécies de lambari (Astyanax sp.) e tilápia (Oreochroms sp.) da área nas concentrações observadas neste estudo e (viii) pela modelagem matemática, dentro das condições estudadas, 40 metros de faixa de contenção seria suficiente para impedir a chegada do endosulfan e do endosulfan sulfato nos corpos d\'água, desde que não houvesse fluxo preferencial de enxurrada. / The study was carried out during 2002/2003, and its objective was to evaluate the levels of endosulfan and its main transformation products in a fanning area located at the head of a small valley close to the town of Águaí, SP, Brazil. The specific objectives were: (i) to evaluate the dynamics of endosulfan and its main transformation products in the soil beneath a crop of cotton (areas treated with endosulfan), (ii) to evaluate the transfer of endosulfan among various locations [transport from the applied areas into the adjacent areas cultivated with maize (Zea mays) and brachiaria (Brachiaria spp.), and into various bodies of water - a spring, a lake (pond), a small flowing stream and a well], (iii) to evaluate the presence of the residues of endosulfan and its transformation products on fish in the lake and (iv) to predict, using mathematical modeling, the endosulfan concentration able to reach the lake and the minimum width buffer zone (containment strip or riparian vegetation) needed to avoid the arrival of the pesticide in the lake. In order to achieve this, representative samples of the following types were collected - soil, sediment, fish, water from the spring, the pond, the stream and the well, as well as from the runoff. Samples were collected during a period of seven months, and were analyzed for α- and β-endosulfan, endosulfan sulfate and endosulfan diol. The analyses were performed by gas chromatography, with mass spectrometric detection. Mathematical approach was employed to predict the concentration of endosulfan that could reach the lake, and in which form it would be present (free or sorbed to soil microparticles). Input data for the model were the physical-chemical properties of endosulfan, the local soil and climatic conditions, and the management of the study area. It was possible to conclude that: (i) endosulfan and its transformation products endosulfan sulfate do not present potential leaching in the soil profile; (ii) the persistence of endosulfan in the field is shorter than has been found in laboratory studies, α-endosulfan is degrades more rapidly than β-endosulfan and endosulfan sulfate is the main transformation product; (iii) runoff is the principal transport mechanism for endosulfan and endosulfan sulfate in the environment; (iv) the transformation products are transported by attachment to microparticles of soil (\"bound residues\"); (v) when the application of endosulfan follows the recommendations of the manufacturer, the compound is only likely to reach adjacent areas if there is a runoff into these areas; (vii) the products, in the \"bound residue\" form, do not produce acute effects and bioaccumulation in the species of fish lambari (Astyanax sp.) and tilapia (Oreochroms sp.) from the area, and (viii) the modeling has established that, within the conditions of the study, a 40 m wide containment strip is sufficient to prevent the appearance of endosulfan and endosulfan sulfate in bodies of water, considering that there is no prefential flow of runoff water.
4

Distribuição do endosulfan em alguns elementos do ecossistema após aplicação na cultura do algodão / Distribution of endosulfan in some ecosystem elements after application in crop of cotton

Helena Romilda Bertochi 10 February 2006 (has links)
Este estudo foi realizado na safra 2002/2003 quando foi avaliado os níveis de endosulfan e seus principais produtos de transformação numa área agrícola localizada na cabeceira de uma microbacia do município de Aguaí-SP. Os objetivos específicos foram: (i) avaliar a movimentação do endosulfan e seus principais transformação no solo sob a cultura do algodão (áreas submetidas à aplicação), (ii) avaliar sua transferência de compartimento (transporte para o solo sob milho e braquiária, adjacentes às áreas aplicadas, e para os corpos aquosos - nascente, lago, córrego jusante e poço), (iii) avaliar os resíduos de endosulfan e seus produtos de transformação nos peixes do açude e (iv) predizer, através de modelagem matemática, a concentração de endosulfan passível de atingir o corpo d\'água e a largura mínima da faixa de contenção (mata ciliar) para impedir a chegada dos produtos no lago. Para tanto, foram realizadas amostragens de solo, sedimento, água dos corpos hídricos e da enxurrada e de peixes, durante sete meses, nas quais foram realizadas análises de α- e β-endosulfan, endosulfan sulfato e endosulfan diol. As análises foram efetuadas por cromatografia gasosa com detecção por espectrometria de massa. Para prever a concentração do produto passível de atingir o açude, tanto associada ao sedimento como na forma livre, foi realizada uma modelagem matemática com base nas propriedades físico-químicas do produto e nas condições edafoclimáticas e de manejo da área estudada. Pôde-se concluir que: (i) o endosulfan e seu produto de transformação endosulfan sulfato não apresentam potencial de lixiviação no solo nas condições estudadas; (ii) a persistência do endosulfan no campo é menor em relação aos estudos de laboratório, sendo que o isômero alfa é o que apresenta a mais rápida degradação e o principal produto de transformação do endosulfan no solo é o endosulfan sulfato; (iii) a principal via de transporte do endosulfan e do endosulfan sulfato no ambiente é o escoamento superficial; (iv) o endosulfan e seus produtos de transformação são transportados associados as micropartículas de solo (\"resíduo-ligado\"); (v) quando a aplicação segue as recomendações estabelecidas pelo fabricante, o produto somente apresenta potencial para atingir áreas adjacentes se houver caminhamento da enxurrada para estas áreas; (vii) o endosulfan e seus produtos de degradação, em sua fase de \"resíduo-ligado\", não apresentam efeito agudo e bioacumulação para as espécies de lambari (Astyanax sp.) e tilápia (Oreochroms sp.) da área nas concentrações observadas neste estudo e (viii) pela modelagem matemática, dentro das condições estudadas, 40 metros de faixa de contenção seria suficiente para impedir a chegada do endosulfan e do endosulfan sulfato nos corpos d\'água, desde que não houvesse fluxo preferencial de enxurrada. / The study was carried out during 2002/2003, and its objective was to evaluate the levels of endosulfan and its main transformation products in a fanning area located at the head of a small valley close to the town of Águaí, SP, Brazil. The specific objectives were: (i) to evaluate the dynamics of endosulfan and its main transformation products in the soil beneath a crop of cotton (areas treated with endosulfan), (ii) to evaluate the transfer of endosulfan among various locations [transport from the applied areas into the adjacent areas cultivated with maize (Zea mays) and brachiaria (Brachiaria spp.), and into various bodies of water - a spring, a lake (pond), a small flowing stream and a well], (iii) to evaluate the presence of the residues of endosulfan and its transformation products on fish in the lake and (iv) to predict, using mathematical modeling, the endosulfan concentration able to reach the lake and the minimum width buffer zone (containment strip or riparian vegetation) needed to avoid the arrival of the pesticide in the lake. In order to achieve this, representative samples of the following types were collected - soil, sediment, fish, water from the spring, the pond, the stream and the well, as well as from the runoff. Samples were collected during a period of seven months, and were analyzed for α- and β-endosulfan, endosulfan sulfate and endosulfan diol. The analyses were performed by gas chromatography, with mass spectrometric detection. Mathematical approach was employed to predict the concentration of endosulfan that could reach the lake, and in which form it would be present (free or sorbed to soil microparticles). Input data for the model were the physical-chemical properties of endosulfan, the local soil and climatic conditions, and the management of the study area. It was possible to conclude that: (i) endosulfan and its transformation products endosulfan sulfate do not present potential leaching in the soil profile; (ii) the persistence of endosulfan in the field is shorter than has been found in laboratory studies, α-endosulfan is degrades more rapidly than β-endosulfan and endosulfan sulfate is the main transformation product; (iii) runoff is the principal transport mechanism for endosulfan and endosulfan sulfate in the environment; (iv) the transformation products are transported by attachment to microparticles of soil (\"bound residues\"); (v) when the application of endosulfan follows the recommendations of the manufacturer, the compound is only likely to reach adjacent areas if there is a runoff into these areas; (vii) the products, in the \"bound residue\" form, do not produce acute effects and bioaccumulation in the species of fish lambari (Astyanax sp.) and tilapia (Oreochroms sp.) from the area, and (viii) the modeling has established that, within the conditions of the study, a 40 m wide containment strip is sufficient to prevent the appearance of endosulfan and endosulfan sulfate in bodies of water, considering that there is no prefential flow of runoff water.

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