Date of Award

1978

Degree Type

Dissertation

Degree Name

Doctor of Pharmacy (PharmD)

First Advisor

George C. Fuller

Abstract

Parathion is an organophosphate pesticide used in great quantities in the United States and around the world. The mechanism of toxicity for parathion in mammals has been attributed to its enzymatic desulfuration to its oxygen analog paraoxon which subsequently fonns a covalent bond with acetylcholinesterase (AChE), inhibiting the activity of that enzyme and precipitating cholinergic toxicity. The mechanism by which parathion produces its toxic effects in insects has not been completely determined, but it is believed to be due to the same mechanism. The effect parathion exposure has on fresh water invertebrates has not been investigated to any great extent, and a goal of this project was to determine the effects of parathion exposure and the relationship of this toxicity to the metabolism of parathion by the fresh water snail Viviparus malleatus and the crayfish Orconectes rusticus. The determination of the toxicity of parathion in Orconectes and Viviparus was made by exposing the organisms to different concentrations of parathion or by the direct injection of parathion. The possibility that any toxicity exhibited by parathion was produced by paraoxon was determined by observing the effect the oxygen analog of parathion would have when exposed to the species, and determining the metabolism of parathion by the two species. The metabolism of parathion was determined in vitro and in vivo. The efficient and specific separation and identification of parathion and its metabolites were accomplished through the use of thin layer chromatography. Parathion has been shown to be metabolized by different species by a multitude of pathways. Three of the important pathways produce p-nitrophenol as an end product. A spectrophotometric assay was used to measure the in vitro production of p-nitrophenol from homogenates of crayfish and snail tissues incubated with parathion. The excretion of parathion metabolites by Orconectes and Viviparus was determined by identifying the compounds extracted from water samples that had contained crayfish or snails exposed to parathion. The accumulation of parathion or metabolites in the species was determined by extracting the parathion exposed tissues of crayffsh or snails and identifying and quantifying the parathion and metabolites present. The excretation and accumulation experiments were accomplished with the use of 14c labeled parathion which was labeled either in the ring or ethyl position. The possible metabolism of parathion was also investigated by the direct determination of the formation of paraoxon, p-nitrophenol, diethyl phosphate and diethyl phosphorothionate by the homogenates of crayfish or snail tissues incubated with parathion and appropriate cofactors. This determination was also aided by the use of labeled parathion. The snail Viviparus malleatus did not metabolize parathion or paraoxon and did not accumulate parathion in its tissues. The snail did not exhibit any toxic reaction to parathion or paraoxon by exposure or direct injection. Concentrations of parathion that equaled the compound's solubility in water produced no effect in exposure experiments while injections of 250 mg/kg parathion had no untoward effect.

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