All three jewelweeds species (Impatiens. L.)contain series of secondary metabolites from category of phenolic substances, e.g. naphthoquinones. This substances belong to allelochemicals, they can to affect germinability and growth of other plants. The extracts from jewelweeds (leaves, roots) and their fractions can to affect negatively germinability and growth of the chosen weed's seeds. Knowledges of allelopathic effects in jewelweeds species on other plants might be of important impact on ecological farming in the implementing of alternative herbicides.

Orientadores: Nelci Fenalti Hoerhr, Roberto Rittner Neto / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-06T21:30:04Z (GMT). No. of bitstreams: 1 Sega_EstelaMunhoz_M.pdf: 1403353 bytes, checksum: 0aec5b888298032d359cc1b3cf0905b6 (MD5) Previous issue date: 2006 / Resumo: Esse estudo analisou as propriedades toxicológicas de novos compostos organofosforados. Foram realizados experimentos para avaliar a atividade anticolinesterásica desses organofosforados, in vitro, no sangue total através do método de Ellman modificado. Para determinar a sua citotoxicidade foram utilizadas células PC 12, com as quais avaliamos a viabilidade celular após contato com os organofosforados e determinamos a IC 50, encontrando valores muito diferentes para os diversos organofosforados estudados. Estudos de toxicidade aguda in vivo foram realizados com camundongos, através da metodologia recomendada pela OECD nos quais determinamos a DL50 para três dos organofosforados estudados, sendo que um apresentou toxidade moderada. Foram analisados os efeitos dos solventes nas constantes de acoplamento JHH, JHH, JNC e 2Jnc em espectros de RMN de LH e 13C do cloreto de acetilcolina. Os valores das constantes de acoplamento em solventes de diferentes constantes dielétricas (s) não sofreram variações, indicando uma ausência de efeitos de solvente no equilíbrio conformacional do cloreto de acetilcolina (ACh). As constantes de acoplamento mostram que o sistema OCH2CH2N+ tem uma conformação gaúche (sinclinal). O Jnh e Jkc são observados na maioria dos solventes, mas não em solventes clorados e não são dependentes da viscosidade do solvente, esse comportamento foi explicado usando dados de medidas de Ti. Os valores dos coeficientes de difusão de RMN mostraram que a ACh tem uma grande tendência de se agregar quando dissolvida em solventes clorados, fato que pode explicar as diferenças observadas em valores de T1 para o 14N / Abstract: This study analyzed the properties of the news organophosphorus. Experiments had been carried through to evaluate the inhibition of acetylcholinesterase of these organophosphorus, in vitro, through the modified EUman's method. In order to determine its cytotoxicity cells PC 12 had been used, with which we evaluate the cellular viability after contact with the organophosphorus and determined the IC50, different values were found for the diverse organophosphorus. Studies of acute toxicity had been carried through with mice, following the methodology recommended by the OECD in which determine the DL50 for three of the organophosphorus studied, being that one presented moderate toxicity. Coupling constants values ( Jhh and Jnc) obtained from the 'H and 13 C NMR spectra of acetylcholine chloride (ACh) in several solvents with a wide range of dielectric constants (e) are remarkably invariant, indicating an absence of solvent effects in the conformational equilibrium of this compound. Those values show that the OCH2CH2N+ system occurs in a synclinal conformation. The Jnh and Jnc are observable in most solvents, but not in chlorine-containing solvents and are not dependent on solvent viscosity. This behavior was explained using data from Ti measurements. The measurement of NMR diffusion coefficients show that ACh has a greater tendency to aggregate when dissolved in chlorinated solvents, a fact that could explain the observed differences in 14N T1 / Mestrado / Patologia Clinica / Mestre em Ciências Médicas

Persistent organic pollutants (POPs) cause significant effects on organisms due to their resistance to environmental degradation and specific toxic responses. Although POPs toxicities were linked to oxidative stress in the previous studies, there are few POPs studies that link them with oxidative stress in zebrafish during development. Aim of this study is to investigate effect of selected POPs on expression of genes involved in oxidative stress response and biotransformation of xenobiotics in zebrafish. Zebrafish embryos in 96 hours’ post-fertilization were exposed to selected POPs and their mixture. To explore the developmental toxicity in zebrafish early stage, we exposed 3,3',4,4',5-pentachlorobiphenyl (PCB), perfluorooctanesulfonic acid (PFOS) and perfluorohexanoic acid (PFHxA) at concentrations of 7.5 μg/L, 50 μM, 50 μM until 96 hours’ post-fertilization. The effects were measured by gene expression quantification technique - quantitative real-time PCR (qPCR). Significant up-regulation in gene expression was detected in embryos treated with mixture of PCB with PFHxA and PCB with PFOS only for cytochrome P450(cyp1a). The results also showed the treatment with selected compound caused significant higher upregulation of cyp1a when we compare the treatment in the individual compounds to the mixture compounds. However, treatments did not cause changes in expression of genes involved in oxidative stress response (glutathione peroxidase 1a(gpx1a), tumor protein p53(tp53), aryl hydrocarbon receptor 2 (ahr2)). The result also suggests that exposure to selected POPs in mixtures or alone is not causing oxidative stress in early stage of embryonal development of zebrafish but activating biotransformation function of the organism. Effect of activation of biotransformation capacity by means of cyp1a upregulation is also higher when POPs are in mixtures over when used as individual substance.

Philosophiae Doctor - PhD / Pesticides are designed to control or eliminate pests such as insects, rodents, weeds, bacteria, and fungi. They are used at a global scale for agricultural produce. Although pesticides play a significant role in increasing food production and eliminating diseases, exposure to pesticides may be harmful to non-target organisms. As a result concern over safety and esistance to pesticides has increased and there is pressure to reduce use and search for more environmentally and toxicologically safe and efficacious pesticides. Most pesticides currently in use are synthetic; therefore an alternative to synthetic pesticides is the use of naturally occurring products/ botanicals with pesticidal properties. Two plants indigenous to South African with pesticidal properties were chosen for this study. Dicerothamnus rhinocerotis (D. rhinocerotis) and Galenia africana (G. africana) have potential antifungal properties thus, may have potential use on agricultural produce as fungicides. Galenia africana and D. rhinocerotis extracts inhibit growth of B. cinerea (a fungal pathogen) at concentrations greater than 31.25 mg/ml and 125mg/ml respectively. A major consideration in approving pesticides for use is whether they pose an unreasonable risk to humans and to the environment. Toxicity studies are required to determine the safety of the plant extracts. The purpose of this study was to evaluate potential toxicity of ethanol extracts of D. rhinocerotis and G. africana, which is important when designing practices to reduce or eliminate excess exposure to them. Natural plant products with pesticidal properties could provide an alternative to synthetic pesticides and may thus effectively reduce resistance levels. This first objective of this study was to assess the cytotoxicity of D. rhinocerotis and G. africana on human cell cultures. Human whole blood and the human breast adenocarcinoma cell line (MCF-7) were treated with varying concentrations of the plant extracts and cytotoxicity determined. Cytotoxicity was measured using several biomarkers. Inhibiotory concentration for a 50% effect (IC50) and no observable effect level (NOEL) values were obtained for D. rhinocerotis and G. africana. The results showed that extracts of D. rhinocerotis and G. africana had cytotoxic effects on the cell cultures. The second objective of this study was to determine the ecotoxicity of D. rhinocerotis and G. africana. A series of acute toxicity tests, with effective concentration for a 50% effect (EC50) and lethal concentration for a 50% effect (LC50) as biomarkers, were conducted to estimate the potential environmental effect of the two plants. The tests were carried out using Vibrio fischeri, Selenastrum capricornutum, Daphnia pulex, and Poecilia reticulata as bioindicators. Results obtained showed that G. africana had higher toxicity units than D. rhinocerotis, thus showing that G. africana is more toxic to the aquatic species used as compared to D. rhinocerotis. The third objective of this study was to investigate the immunomodulatory effects of the two plant extracts. This was achieved by using mouse spleen cell cultures. Exposure of pesticides to the immune system may result in alteration of the normal immune functions. The cytokines IFN-γ and IL-4 were used as biomarkers to determine the T-cell activity of the immune system when exposed to the two botanical products. The results obtained showed that both D. rhinocerotis and G. africana decrease of the cytokines interferongamma (IFN-γ) and interleukin-4 (IL-4), thus may have immunotoxic effects. The fourth objective was to investigate the hepatotoxicity of the two plant extracts. Injury to the liver was investigated using a range of clinical biochemical tests that monitor liver enzyme activity and metabolic activity. Primary liver cell cultures were exposed to the plant products in question, after which the biochemical tests were carried out. The enzymes that were monitored were alanine aminotrasferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH). The results obtained showed that both of D. rhinocerotis and G. africana may have effects on the liver, as shown by the increased levels of enzymes released from cells upon exposure to plant extracts. The final objective of this study was to investigate the effect of the two plants on the male reproductive system. Injury to the male reproductive system was investigated using testicular cell cultures. Primary cell cultures were stimulated with luteinizing-hormone (LH) and exposed to the plant extracts. LH results in the production of testosterone, thus testosterone was used as a biomarker for assessing reproductive toxicity. The results obtained showed that both of D. rhinocerotis and G. africana have effects on the male reproductive system, as shown by the decreased testosterone secretion. Botanicals provide a simple, inexpensive and environmentally friendly (non-pollution and lesser toxicological concerns) alternative for pest control. However, motivation for the commercial use of botanicals as pesticides requires validating the efficacy of the plant as a pesticide, and also assessing its effects on human health and the environment. An important component of this evaluation involves toxicity studies, which enables cautions of dangerous practices and toxic effects of the plants to be issued. / South Africa

Concern over sediment toxicity has increased the need for toxicity test information with organisms that inhabit sediments. Oligochaetes are exposed to toxicants through feeding and direct body contact with aquatic sediments. Chronic testing with oligochaetes has historically focused on tubificids with test lengths of one year or more to encompass several generations. Most naidid oligochaetes have generation times of three to seven days and could provide chronic information in a matter of weeks. The cosmopolitan distributed naidid, Pristina leidyi, was evaluated for use as a toxicity test organism. Results of research conducted includes culture methods, effects of temperature on reproduction, growth rates in a reference sediment, acute toxicity tests, and chronic toxicity tests.

付記する学位プログラム名: 充実した健康長寿社会を築く総合医療開発リーダー育成プログラム / 京都大学 / 新制・課程博士 / 博士(医学) / 甲第23092号 / 医博第4719号 / 新制||医||1050(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 黒田 知宏, 教授 上杉 志成, 教授 藤渕 航 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Určení vlivu volby zkušebního organismu na výsledek stanovení toxických účinků. Porovnání výsledků stanovení akutní toxicity mikrometodou při použití 5 různých druhů sladkovodních řas (podle TNV 75 7741), vyhodnocení rozdílů v citlivosti použitých druhů, optimalizace metodických postupů.

Philosophiae Doctor - PhD / Pesticides are designed to control or eliminate pests such as insects, rodents, weeds, bacteria, and fungi. They are used at a global scale for agricultural produce. Although pesticides playa significant role in increasing food production and eliminating diseases, exposure to pesticides may be harmful to non-target organisms. As a result concern over safety and resistance to pesticides has increased and there is pressure to reduce use and search for more environmentally and toxicologically safe and efficacious pesticides. Most pesticides currently in use are synthetic; therefore an alternative to synthetic pesticides is the use of naturally occurring products! botanicals with pesticidal properties. Two plants indigenous to South African with pesticidal properties were chosen for this study. Dicerothamnus rhinocerotis (D. rhinocerotis) and Galenia africana (G. africana) have potential antifungal properties thus, may have potential use on agricultural produce as fungicides. Galenia africana and D. rhinocerotis extracts inhibit growth of B. cinerea (a fungal pathogen) at concentrations greater than 31.25 mg/ml and 125mg/ml respectively. A major consideration in approving pesticides for use is whether they pose an unreasonable risk to humans and to the environment. Toxicity studies are required to determine the safety of the plant extracts. The purpose of this study was to evaluate potential toxicity of ethanol extracts of D. rhinocerotis and G. africana, which is important when designing practices to reduce or eliminate excess exposure to them. Natural plant products with pesticidal properties could provide an alternative to synthetic pesticides and may thus effectively reduce resistance levels. This first objective of this study was to assess the cytotoxicity of D. rhinocerotis and G. africana on human cell cultures. Human whole blood and the human breast adenocarcinoma cell line (MCF-7) were treated with varying concentrations of the plant extracts and cytotoxicity determined. Cytotoxicity was measured using several biomarkers. Inhibiotory concentration for a 50% effect (ICso) and no observable effect level (NOEL) values were obtained for D. rhinocerotis and G. africana. The results showed that extracts of D. rhinocerotis and G. africana had cytotoxic effects on the cell cultures. The second objective of this study was to determine the ecotoxicity of D. rhinocerotis and G. africana. A series of acute toxicity tests, with effective concentration for a 50% effect (ECso) and lethal concentration for a 50% effect (LCso) as biomarkers, were conducted to estimate the potential environmental effect of the two plants. The tests were carried out using Vibrio fischeri, Selenastrum capricornutum, Daphnia pulex, and Poecilia reticulata as bioindicators. Results obtained showed that G. africana had higher toxicity units than D. rhinocerotis, thus showing that G. africana is more toxic to the aquatic species used as compared to D. rhinocerotis. The third objective of this study was to investigate the immunomodulatory effects of the two plant extracts. This was achieved by using mouse spleen cell cultures. Exposure of pesticides to the immune system may result in alteration of the normal immune functions. The cytokines IFN-y and IL-4 were used as biomarkers to determine the T-cell activity of the immune system when exposed to the two botanical products. The results obtained showed that both D. rhinocerotis and G. africana decrease of the cytokines interferon gamma (IFN-y) and interleukin-4 (IL-4), thus may have immunotoxic effects. The fourth objective was to investigate the hepatotoxicity of the two plant extracts. Injury to the liver was investigated using a range of clinical biochemical tests that monitor liver enzyme activity and metabolic activity. Primary liver cell cultures were exposed to the plant products in question, after which the biochemical tests were carried out. The enzymes that were monitored were alanine aminotrasferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH). The results obtained showed that both of D. rhinocerotis and G. africana may have effects on the liver, as shown by the increased levels of enzymes released from cells upon exposure to plant extracts. The final objective of this study was to investigate the effect of the two plants on the male reproductive system. Injury to the male reproductive system was investigated using testicular cell cultures. Primary cell cultures were stimulated with luteinizing-hormone (LH) and exposed to the plant extracts. LH results in the production of testosterone, thus testosterone was used as a biomarker for assessing reproductive toxicity. The results obtained showed that both of D. rhinocerotis and G. africana have effects on the male reproductive system, as shown by the decreased testosterone secretion. Botanicals provide a simple, inexpensive and environmentally friendly (non-pollution and lesser toxicological concerns) alternative for pest control. However, motivation for the commercial use of botanicals as pesticides requires validating the efficacy of the plant as a pesticide, and also assessing its effects on human health and the environment. An important component of this evaluation involves toxicity studies, which enables cautions of dangerous practices and toxic effects of the plants to be issued.

In this project we review the developments of several variations of the up-and-down design utilized in Phase I clinical trials to estimate the maximum tolerated dose (MTD) of a drug which corresponds to a fixed probability of response or the pre-specified toxicity rate in the target population. In these designs selection of dose levels is restricted to one level higher, one level lower or the same. Several methods of estimation of the MTD are investigated. Some comparison of the designs by Monte Carlo simulation are carried out by the quality of the estimator of the target dose using the isotonic estimator. The designs are investigated under the generalized logistic (for different values of the power) and the gamma distributions. The NR is found to perform best on the basis of the quality of estimator under these distributions. The BCD is found to perform best on the basis of the average proportion of toxicity for a pre-specified toxicity rate of 0.2 whereas the KROW performs best for a toxicity rate of 0.3. / Thesis / Master of Science (MS)

PCBs are synthetic organic compounds known for their toxicity to many organisms and are notorious for having large discrepancies between measured and nominal concentrations. Historically thought to be less toxic, non-dioxin-like (NDL) PCBs represent the majority of congeners and are capable of eliciting neurotoxic effects. NDL-PCBs remain understudied, including their effects on aquatic organisms. In the first study, I collected extensive chemistry data and data on neurobehavioral and cardiac endpoints to test the acute effects of exposure to an NDL-PCB mixture on early life stage zebrafish. Neurobehavioral effects observed in the first study indicated a potential for longer term behavioral effects in these fish. In the second study, I collected data on feeding, social, and memory behavior of zebrafish at time points beyond the acute exposure from the first study. Acute and longer-term behavioral endpoints in the first and second studies demonstrated effects from PCB exposure but did not indicate mechanisms. In the third study, I collected untargeted and targeted metabolomic data on amino acid, sugar, anionic compound, and neurotransmitter profiles to determine the specific pathways affected by exposure to an NDL-PCB mixture. These combined data from these studies provide a unique insight into the chemical profile of an NDL-PCB mixture in biological applications and synthesize acute, longer-term, and mechanistic effects on developing zebrafish. These data fully illustrate an adverse outcome pathway from toxicokinetic to population level effects.