Document formatted into pages; contains 78 pages. / Title from PDF of title page. / Thesis (M.S.P.H.)--University of South Florida, 2003. / Includes bibliographical references. / Text (Electronic thesis) in PDF format. / ABSTRACT: Malathion is a commonly used organophosphate pesticide on field crops, fruits, nut trees, vegetables, livestock, agricultural premises, and land. The approved uses also include mosquito and medfly control. These uses can result in human skin contact. The purpose of this study is to evaluate the human skin absorption of malathion for the purpose of assessing the risks associated with aqueous solution exposures following applications. Aerial applications can result in solubilized malathion in swimming pools and other waters that may be contacted. Human volunteers were selected and exposed to aqueous solutions of malathion at various concentrations. Participants submerged their arms and hands in twenty liters of dilute malathion solution in either a stagnant or stirred environment. The "disappearance method" was applied by measuring malathion concentrations in the water before and after human subject exposure to the water for various periods of time. Malathion was measured using Gas Chromatography. No measurable skin absorption was detected in 42% of the participants. Measurable skin absorption among the remaining 58% of participants resulted in doses that were more than an order of magnitude less than the minimal dose necessary to cause a measurable change in red blood cell acetylcholinesterase (RBC-AChE). Extrapolation of these results to a mathematical model for recreational swimmers and bathers exposed to contaminated swimming pools and surface waters typically detected after bait application again are an order of magnitude below the doses needed to cause a detectable change in RBC-AChE. These data indicate that exposure to aqueous malathion following usual aerial bait applications is not appreciably absorbed, and therefore, it is not a public health hazard. / System requirements: World Wide Web browser and PDF reader. / Mode of access: World Wide Web.

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Malathion is a commonly used organophosphate pesticide on field crops, fruits, nut trees, vegetables, livestock, agricultural premises, and land. The approved uses also include mosquito and medfly control. These uses can result in human skin contact. The purpose of this study is to evaluate the human skin absorption of malathion for the purpose of assessing the risks associated with aqueous solution exposures following applications. Aerial applications can result in solubilized malathion in swimming pools and other waters that may be contacted. Human volunteers were selected and exposed to aqueous solutions of malathion at various concentrations. Participants submerged their arms and hands in twenty liters of dilute malathion solution in either a stagnant or stirred environment. The "disappearance method" was applied by measuring malathion concentrations in the water before and after human subject exposure to the water for various periods of time. Malathion was measured using Gas Chromatography. No measurable skin absorption was detected in 42% of the participants. Measurable skin absorption among the remaining 58% of participants resulted in doses that were more than an order of magnitude less than the minimal dose necessary to cause a measurable change in red blood cell acetylcholinesterase (RBC-AChE). Extrapolation of these results to a mathematical model for recreational swimmers and bathers exposed to contaminated swimming pools and surface waters typically detected after bait application again are an order of magnitude below the doses needed to cause a detectable change in RBC-AChE. These data indicate that exposure to aqueous malathion following usual aerial bait applications is not appreciably absorbed, and therefore, it is not a public health hazard.

Paraoxonase-1 (PON1) is a high density lipoprotein (HDL)-associated enzyme displaying esterase and lactonase activity. PON1 hydrolyzes the oxons of several organophosphorous insecticides (e.g. paraoxon, diazoxon and chlorpyrifos-oxon) and metabolizes lipid peroxides of low density lipoproteins (LDL) and HDL. As such, PON1 plays a relevant role in determining susceptibility of organophosphate toxicity and cardiovascular disease. The objective of this study was to determine associations of PON1 status (i.e. genotype and activity levels) with atherosclerosis (ATH) in individuals from the Southeastern United States. An additional objective was to determine whether PON1 genotype and/or PON1 activity levels influence the capacity of PON1 to metabolize chlorpyrifos-oxon (CPO) at a relatively low concentration. Data indicated increasing PON1 activity assessed by hydrolysis of phenyl acetate is associated with decreased odds of ATH. Furthermore, neither PON1 genotype nor PON1 activity levels influence capacity of PON1 to metabolize CPO at a relatively low concentration.

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Organophosphates (OPs) are a major class of pesticides and nerve agents that elicit acute toxicity by inhibiting acetylcholinesterase (AChE), the enzyme responsible for the degradation of the neurotransmitter acetylcholine in the central and peripheral nervous systems. Acetylcholine accumulation following extensive AChE inhibition leads to an acute cholinergic syndrome characterized by autonomic dysfunction, involuntary movements, muscle fasciculations, respiratory distress, and seizures. Despite their classification as moderate to highly toxic, OP pesticides are the most widely used class of insecticides in the U.S., and are even more commonly used worldwide. Additionally, there is a growing concern that OP nerve agents could be used to cause mass civilian casualties. It is well known that the survivors of acute nerve gas poisoning and chronic OP pesticide exposure exhibit neurobehavioral deficits including mood changes, depression, and memory impairments. Despite this, there are very few treatments available for OP-intoxication survivors and this topic is under-researched. In this study we investigated whether animals surviving a single severe OP exposure exhibited long-term neurological impairments, using two OP agents: paraoxon (POX) and diisopropyl fluorophosphates (DFP), as well as a non-OP chemoconvulsant, pilocarpine (Pilo), which acts as a muscarinic agonist. Exposure to POX, DFP, or Pilo led to overt signs of cholinergic toxicity. POX and DFP rats were rescued with an optimized atropine, 2-PAM, and diazepam therapy per current OP-exposure treatment guidelines, while Pilo rats were given only diazepam. Saline was administered to control rats at all pharmacological timepoints. Surviving rats were studied using established behavioral assays for identifying symptoms of depression and memory impairment 3-6 months after exposure to toxic agents. In the forced swim test, POX, DFP, and Pilo animals exhibited increased immobility time indicative of a despair-like state. In the sucrose preference test, POX, DFP, and Pilo rats did not display a preference for sucrose water, indicating an anhedonia-like condition. POX, DFP, and Pilo rats also displayed increased anxiety as characterized by significantly lower performance in the open arm of the elevated plus maze. Furthermore, when tested with a novel object recognition paradigm, POX, DFP, and Pilo rats exhibited a significantly lower discrimination ratio, indicating impaired recognition memory. The results indicate that these models of survival from severe POX and DFP exposure can be employed to study chronic behavioral and cognitive comorbidities and to further investigate the molecular bases for these comorbidities, potentially leading to the development of pharmacological therapies.

<p>This study firstly reports the development, characterisation, and application of thick-film acetylcholinesterase (AChE) biosensors based on a gold electrode modified with a mercaptobenzothiazole (MBT) self-assembled monolayer and either poly(omethoxyaniline) (POMA) or poly(2,5-dimethoxyaniline) (PDMA) in the presence of polystyrene(4-sulphonic acid) (PSSA). The Au/MBT/POMA-PSSA/AChE and Au/MBT/PDMA-PSSA/AChE biosensors were then applied to successfully detect standard organophosphorous and carbamate pesticides in a 0.1 M phosphate buffer, 0.1 M KCl (pH 7.2) solution. Secondly, it reports the construction of the Au/MBT/PANI/AChE/PVAc thick-film biosensor for the determination of certain organophosphate and carbamate pesticide solutions in selected aqueous organic solvent solutions.</p>

The focus of this thesis was to investigate developmental neurotoxic effects of different persistent and non-persistent environmental pollutants, alone or in binary mixtures, when exposure occurs during a critical period of brain development, in mice. The compounds investigated included a perfluorinated compound, perfluorohexane sulphonate (PFHxS), and four different pesticides, endosulfan, cypermethrin, chlorpyrifos and carbaryl. Both persistent and non-persistent pollutants are detected in the environment and in humans, which shows that exposure to these compounds is occurring in real life. Humans can therefore be exposed to various pollutants during their whole lifetime, starting from the gestational period to adulthood. Furthermore, exposure to environmental pollutants is rarely exclusive to a single compound, but rather occurs through combinations of various pollutants present in the environment. Exposure to environmental pollutants during human brain development have been suggested to be a possible cause for neuropsychiatric disorders, such as autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD). Previous studies have shown that chemicals can induce irreversible disorders in brain function when exposure to these chemicals occurs during a critical defined period of the brain development known as the brain growth spurt (BGS). The BGS is characterized by a rapid growth and development of the immature brain. In humans, and mice, this period also overlaps the lactation period indicating that newborns and toddlers can be exposed via mothers’ milk as well. This thesis has shown that a single oral exposure to PFHxS, endosulfan, cypermethrin, chlorpyrifos or carbaryl can induce developmental neurotoxic effects in mice, when exposure occurs during a critical period of brain development. These effects are manifested as persistent altered adult spontaneous behavior in a novel home environment, modified habituation, altered susceptibility of the cholinergic system and changed levels of neuroproteins in the mouse brain. Furthermore, a single neonatal co-exposure to a binary mixture of carbaryl/chlorpyrifos or PFHxS/endosulfan can interact and exacerbate the adult behavioral effects. These effects were seen at dosages were the single compound did not elicit a response or induced a much weaker behavioral effect. This indicates that risk assessments conducted on single compounds might underestimate interaction effects of mixtures when co-exposed.

<p>This study firstly reports the development, characterisation, and application of thick-film acetylcholinesterase (AChE) biosensors based on a gold electrode modified with a mercaptobenzothiazole (MBT) self-assembled monolayer and either poly(omethoxyaniline) (POMA) or poly(2,5-dimethoxyaniline) (PDMA) in the presence of polystyrene(4-sulphonic acid) (PSSA). The Au/MBT/POMA-PSSA/AChE and Au/MBT/PDMA-PSSA/AChE biosensors were then applied to successfully detect standard organophosphorous and carbamate pesticides in a 0.1 M phosphate buffer, 0.1 M KCl (pH 7.2) solution. Secondly, it reports the construction of the Au/MBT/PANI/AChE/PVAc thick-film biosensor for the determination of certain organophosphate and carbamate pesticide solutions in selected aqueous organic solvent solutions.</p>