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The In Vitro Degradation of [^14 C]-Malathion and [^14 C]-Malaoxon in Resistant and Susceptible Strains of Drosophila Melanogaster / Malathion Resistance in Drosophila MelanogasterHolwerda, Barry 06 1900 (has links)
Malathion-resistance in Drosophila Melanogster was studied in susceptible laboratory strains (CS and OR), a heterogeneous intermediate-resistant strain (C1-39), and a more resistant, artificially selected (with malathion). strain (MH19) by comparing the in vitro metabolism of [¹⁴c]-malathion and [¹⁴c]-malaoxon in crude enzyme preparations made from adult flies.
Extracts from all strains were found to contain two enzymatic activities that metabolized malathion and/or malaoxon. One activity degraded malathion to its α- and β-monocarboxylic acids and was designated as malathion-carboxylesterase activity (ME-activity). ME-activity was progressively lost in CS-extracts during reaction with [¹⁴c]-malathion due to inhibition of the enzyme(s) by a tightly bound [¹⁴c]-labeled molecule (not identified) that could not be removed by chromatography on Sephadex G-25. ME-activity, based on initial (0-1 min) rates with or without metyrapone present was similar in all strains and furthermore, the carboxylesterase inhibitors TPP and DEF did not synergize malathion toxicity in either resistant or susceptible strains. It was concluded that carboxylesterase-mediated degradation of malathion was not a factor in the resistance of the C1-39 and MH19 strains. A second enzyme system, microsomal mixed-function oxidases (MFO), converted malathion to malaoxon (activation) and degraded malaoxon to at least two products that were tentatively identified (malaoxon α-and β-monoacids and demethyl-malaoxon). The rate of conversion of malathion to malaoxon was highest in crude extracts of the most resistant MH19 flies, intermediate in C1-39 and could not be detected in the susceptible CS flies while the rate of malaoxon degradation was similar between MH19 and C1-39, but higher than that in the susceptible OR flies. Furthermore, malaoxon (but not malathion) toxicity was most strongly synergized by the MFO-inhibitor MTP in the more resistant strains (MH19 and C1-39) . These results were used along with a previous result that MH19 strain possesses a less sensitive form of the target enzyme, acetylcholinesterase (R.A. Morton, personal communication), to propose a biochemical mechanism that accounts for the increased malathion-resistance of the C1-39 and MH19 strains. / Thesis / Master of Science (MS)
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Neurotoxic effects of malathion and lead acetate on the blood-brain barrier: Disruptive effects caused by different mechanisms examined with an in vitro blood-brain barrier systemBalbuena, Pergentino 23 July 2010 (has links)
Organophosphates (OP) such as malathion are organic derivatives of phosphoric acid with broad use in everyday life throughout the world, especially as insecticides. Lead particles can accumulate in soil and from there leach into our water supplies.
Interaction with the environment offers opportunities for multiple exposures to combinations of different toxicants (such as lead and malathion). Thus, it is important to assess effects that these compounds exert not only on the nervous system, but also on the blood-brain barrier (BBB). The BBB consists of specialized endothelial cells that form the vasculature of the brain; it regulates passage of nutrients, while preventing potentially damaging substances from entering the brain. The main feature of the BBB is the presence of tight junctions between cells, which provide the BBB with its low permeability.
The work presented in this dissertation tests the hypothesis that lead and malathion disrupt BBB integrity by affecting tight junctions of the BBB. The hypothesis suggests that disruptions involve changes in protein levels and gene expression as well as activation of transient receptor potential canonical channels (TRPC) that in turn increase intracellular calcium levels affecting tight junction structure. The hypothesis was tested by assessing lead-malathion interactions in an in vitro BBB model. This model was constructed with rat astrocytes and rat brain endothelial cells (RBE4).
Assessments of cell toxicity in response to different concentrations of the neurotoxicants tested showed that concentrations between 10-5 µM and 10-6 µM were ideal to assess combinations of neurotoxicants. In general, protein levels of occludin, claudin 5, ZO1, and ZO2 decreased at all times, however, qPCR analysis of gene expression for all the proteins did not correlate with the assessments on protein levels. TRPC channel protein levels increased in response to neurotoxicant insult, which correlated with results for gene expression.
This study suggests that at least one of the mechanisms that neurotoxicants lead and malathion utilize to disrupt permeability of the BBB is by affecting tight junction structure. This effect could be regulated by increases in gene expression of TRPC1 and TRPC4 that are associated with increases in the number of TRPC channels on the membrane of endothelial cells of the cerebral microvasculature. / Ph. D.
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Dermal absorption of a dilute aqueous solution of malathion [electronic resource] / by John E Scharf.Scharf, John E. January 2003 (has links)
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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Dermal Absorption Of A Dilute Aqueous Solution Of MalathionScharf, John E, MD 11 July 2003 (has links)
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.
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