Call number: LD2668 .T4 1958 E32 / Master of Science

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Thesis (Ph. D.)--University of Texas at Austin, 2005. / Supervisor: Lee A. Fuiman. Vita. Includes bibliographical references.

Thesis (M.S.)--University of Wisconsin--Madison, 1968. / eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

Thesis (M.S.)--University of Wisconsin--Madison, 1967. / eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

The mechanism of toxic action for organophosphates (OPs), originally developed as insecticides, is the persistent inhibition of acetylcholinesterase (AChE) resulting in accumulation of acetylcholine and subsequent hyperstimulation of the nervous system. Many OPs require bioactivation via cytochromes P450 to oxon metabolites which are anticholinesterases. Organophosphates display a wide range of acute toxicities. Differences in the OPs’ chemistries results in differences in the compounds' metabolism and toxicity. Acute toxicities of OPs appear to be principally dependent on compound specific efficiencies of detoxication, and less dependent upon efficiencies of bioactivation and sensitivity of AChE. Esterases, such as carboxylesterase (CaE) and butyrylcholinesterase (BChE), play a prominent role in OP detoxication. Organophosphates can stoichiometrically inhibit these enzymes, removing OPs from circulation thus providing protection for the target enzyme, AChE. This in vitro study investigated: 1) age-related sensitivity of AChE, BChE and CaE to structurally different OPs in rat tissues; 2) interspecies and intraspecies differences in bioactivation and detoxication of the OP insecticide malathion in rat and human hepatic microsomes; and 3) interspecies and intraspecies differences in sensitivity of AChE from erythrocyte ghost preparations to malaoxon. Sensitivities of esterases to 12 OPs was assessed by IC50s. The OPs displayed a wide range of AChE IC50s (low nM-µM) with no differences among ages; however, the CaE IC50s generally increased with age (up to 100old) reflecting greater protection in adults. Kinetic analysis of the bioactivation of malathion to the anticholinesterase metabolite, malaoxon, was measured in hepatic microsomes from rats (adult) and humans (various ages) of both sexes. No statistical interspecies (rat and human) or intraspecies (among humans) differences were found. The CaE degradation of malathion and malaoxon was determined in the microsomal samples using indirect measurements. No interspecies or intraspecies differences were found; however, CaE activity in rat microsomes was significantly higher than in humans. Inhibition of AChE by malaoxon was analyzed kinetically in erythrocyte ghost preparations from rats (adults) and humans (three age groups) of both sexes. No statistical interspecies or intraspecies differences were found. These results suggest the age-related differences in acute toxicities of OPs in mammals is primarily a result of their detoxication capacity.

A biota nos ecossistemas aquáticos é geralmente exposta a diversas condições de estresse, como variações ambientais naturais e distúrbios antropológicos, incluindo as descargas de poluentes nos recursos hídricos. Sendo assim importante a realização de estudos que avaliem os efeitos desses poluentes sobre os ecossistemas. O malathion é um exemplo de poluente, pois, é um inseticida comumente utilizado como defensivo agrícola em culturas ao redor do mundo e, embora apresente baixa toxicidade para espécies de mamíferos, espécies aquáticas podem ser sensíveis mesmo a pequenas concentrações. Dentre os diversos organismos aquáticos os crustáceos tem se destacado como organismos sensíveis para avaliar a poluição do ecossistema aquático. Nesse sentido, o objetivo do presente trabalho foi avaliar os efeitos do malathion sobre camarões Macrobrachium amazonicum através da obtenção da DL50 e da análise morfológica de suas brânquias. Para isso, camarões nativos do rio Grande foram capturados e aclimatados ao ambiente laboratorial para a realização de bioensaios. Os camarões foram divididos em grupos de dez animais cada e expostos a concentrações crescentes do inseticida por 48 horas. Nossos achados mostraram que a DL50 foi atingida a 0,73 mg/L de malathion, e que alterações relevantes na arquitetura das brânquias podem ser observadas em camarões expostos a concentrações de 1,25 a 1,5 mg/L do inseticida. Este é o primeiro estudo demonstrando que mesmo em curto prazo, o malathion interfere na estrutura microscópica das brânquias de camarões do gênero Macrobrachium, e vem contribuir para uma melhor compreensão dos efeitos promovidos por determinados defensivos agrícolas sobre organismos aquáticos que, comumente ficam expostos a estes. / Biota in aquatic ecosystems is usually exposed to various stress conditions, like natural environmental variations and anthropological disturbs including pollutant discharges into water resources. Malathion is an insecticide commonly used as an agricultural pesticide in crops around the world, and although it presents low toxicity to mammalian species, aquatic species may be sensitive even at small concentrations. Among the various aquatic organisms, crustaceans have distinguished themselves as sensitive organisms to evaluate the pollution of the aquatic ecosystem. In this sense, the objective of the present work was to evaluate the effects of malathion on Macrobrachium amazonicum shrimps by obtaining LD50 and morphological analysis of the gills. For this, native prawns of the Rio Grande were captured and acclimated to the laboratory environment for the realization of bioassays. The shrimp were divided into groups of ten animals each and exposed to increasing concentrations of the malathion for 48 hours. Our findings showed that the LD50 was reached at 0.73 mg/L malathion, and that relevant changes in the architecture of the gills can be observed in shrimps exposed to concentrations of 1.25 and 1.5 mg/L of the insecticide. This is the first report demonstrating that even in the short term, malathion interferes in the microscopic structure of Macrobrachium shrimp gills, and contributes to a better understanding of the effects promoted by certain pesticides on aquatic organisms that are commonly exposed to these.

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