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dc.contributor.authorMcCracken, Nigel William-
dc.descriptionPhD Thesisen_US
dc.description.abstractOccupational exposure of pesticides occurs via inhalation through the lungs or by absorption through the skin. The assessment of the possible importance of these extrahepatic tissues in the hydrolysis of pesticides is important. Although the liver has been shown to be the most metabolically active tissue, both the skin and lung have the ability to metabolise pesticides. Therefore, the possibility exists that pesticides which are absorbed through the lung and skin may undergo first pass metabolism in these tissues. In the study, the esterase enzymes responsible for the hydrolysis and subsequent detoxification of a number of pesticide substrates were identified and quantified. Esterases which hydrolysed the pesticides fluazifop-butyl and carbaryl and phenylacetate, a marker substrate for esterase activity, were found to be distributed in the microsomal fraction of the liver and lung and in the blood. In vitro studies in the rat show that lung, skin and plasma have an important role to play in the first pass metabolism of the pesticides fluazifop-butyl and carbaryl. In paraoxon hydrolysis, the plasma plays an important role in first pass metabolism, whereas the lung and skin have little effect. With the use of inhibitors and inducers these esterase enzymes were characterised as `A' or `B' esterases. Fluazifop-butyl and carbaryl were hydrolysed by carboxylesterase, a `B' esterase, whereas paraoxon was hydrolysed by paraoxonase, an `A' esterase. Phenylacetate was found to be hydrolysed by both `A' and `B' esterases. Parallel studies were carried out in human liver and blood to establish whether the rat was an appropriate model for study of the detoxification of pesticides by esterases. Studies have shown that there is considerable similarity in the nature of human and rat esterase enzymes, although there are significant differences in absolute activities.en_US
dc.publisherNewcastle Universityen_US
dc.titleRole of esterases in the detoxification of pesticidesen_US
Appears in Collections:Institute of Cellular Medicine

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