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Title: The In Vivo Quantitation of Diazinon, Chlorpyrifos and their Major Metabolites in Rat Blood for the Refinement of a Physiologically-based Pharmacokinetic/pharmacodynamic Models.

Abstract

Chlorpyrifos (CPF) and diazinon (DZN) are inhibitors of acetylcholinesterase due to the effects of their active oxon metabolites. The inhibition of acetylcholinesterase results in a buildup of acetylcholine within the nerve synapses leading to a variety of neurotoxic effects (Mileson et al., 1998). These effects are most clearly seen following acute high dose exposures but they can also be observed in lower dose chronic cases as well. Chlorpyrifos is the active ingredient in commonly used organophosphorous (OP) insecticides like DURSBAN and LORSBAN (Timchalk et. al, 2002). Chlorpyrifos and diazinon are used to eliminate pests in agricultural applications like cotton and fruit crops. Every year globally there are approximately 3 million cases of organophosphate poisoning reported resulting in 200,000 deaths (Haywood et al., 2000). The public is exposed to these chemicals on a regular basis at chronic low levels from food and water contamination, dermal contact and inhalation. The United States National Health and Nutrition Examination Survey indicated that of approximately 3,600 persons from all 64 NHANES III locations, 70% tested positive for TCP in urine, suggesting exposure to chlorpyrifos (NHANES III, 1994). The chemical structures of chlorpyrifos, diazinon, and their major metabolites trichlorpyridinol (TCP), and isopropyl-methyl-hydroxypyrimidine (IMHP) are shown inmore » Figure 1. The parent compounds, CPF and DZN, are metabolized to their potent inhibiting oxon forms via a desulfuration reaction initiated by cytochrome P450 (CYP)(Poet et al., 2003; Amitai et al., 1998). Competing with the formation of oxon is the detoxification metabolism of CPF to TCP and DZN to IMHP via a dearylation reaction utilizing the same enzymes. A-esterase (PON1) and other B-esterases also contribute to the production of TCP and IMHP through the metabolism of CPF-oxon and DZN-oxon, respectively (Poet et al., 2003; Ma et al., 1994). The ratio between the toxification/detoxification reactions determines the degree of enzyme inhibition and can be used to evaluate metabolism processes (Timchalk et al., 2002).« less

Authors:
; ;
Publication Date:
Research Org.:
Pacific Northwest National Lab., Richland, WA (US)
Sponsoring Org.:
US Department of Energy (US)
OSTI Identifier:
15015210
Report Number(s):
PNWD-SA-6247
TRN: US200509%%347
DOE Contract Number:  
AC05-76RL01830
Resource Type:
Journal Article
Journal Name:
Journal of Undergraduate Research
Additional Journal Information:
Journal Volume: 4; Other Information: PBD: 1 Dec 2004
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES; ACETYLCHOLINE; BLOOD; BUILDUP; CONTAMINATION; CYTOCHROMES; DETOXIFICATION; ENZYMES; IN VIVO; INHALATION; INSECTICIDES; METABOLISM; METABOLITES; NERVES; NUTRITION; POISONING

Citation Formats

Busby, Andrea L, Kousba, Ahmed A, and Timchalk, Chuck. The In Vivo Quantitation of Diazinon, Chlorpyrifos and their Major Metabolites in Rat Blood for the Refinement of a Physiologically-based Pharmacokinetic/pharmacodynamic Models.. United States: N. p., 2004. Web.
Busby, Andrea L, Kousba, Ahmed A, & Timchalk, Chuck. The In Vivo Quantitation of Diazinon, Chlorpyrifos and their Major Metabolites in Rat Blood for the Refinement of a Physiologically-based Pharmacokinetic/pharmacodynamic Models.. United States.
Busby, Andrea L, Kousba, Ahmed A, and Timchalk, Chuck. 2004. "The In Vivo Quantitation of Diazinon, Chlorpyrifos and their Major Metabolites in Rat Blood for the Refinement of a Physiologically-based Pharmacokinetic/pharmacodynamic Models.". United States.
@article{osti_15015210,
title = {The In Vivo Quantitation of Diazinon, Chlorpyrifos and their Major Metabolites in Rat Blood for the Refinement of a Physiologically-based Pharmacokinetic/pharmacodynamic Models.},
author = {Busby, Andrea L and Kousba, Ahmed A and Timchalk, Chuck},
abstractNote = {Chlorpyrifos (CPF) and diazinon (DZN) are inhibitors of acetylcholinesterase due to the effects of their active oxon metabolites. The inhibition of acetylcholinesterase results in a buildup of acetylcholine within the nerve synapses leading to a variety of neurotoxic effects (Mileson et al., 1998). These effects are most clearly seen following acute high dose exposures but they can also be observed in lower dose chronic cases as well. Chlorpyrifos is the active ingredient in commonly used organophosphorous (OP) insecticides like DURSBAN and LORSBAN (Timchalk et. al, 2002). Chlorpyrifos and diazinon are used to eliminate pests in agricultural applications like cotton and fruit crops. Every year globally there are approximately 3 million cases of organophosphate poisoning reported resulting in 200,000 deaths (Haywood et al., 2000). The public is exposed to these chemicals on a regular basis at chronic low levels from food and water contamination, dermal contact and inhalation. The United States National Health and Nutrition Examination Survey indicated that of approximately 3,600 persons from all 64 NHANES III locations, 70% tested positive for TCP in urine, suggesting exposure to chlorpyrifos (NHANES III, 1994). The chemical structures of chlorpyrifos, diazinon, and their major metabolites trichlorpyridinol (TCP), and isopropyl-methyl-hydroxypyrimidine (IMHP) are shown in Figure 1. The parent compounds, CPF and DZN, are metabolized to their potent inhibiting oxon forms via a desulfuration reaction initiated by cytochrome P450 (CYP)(Poet et al., 2003; Amitai et al., 1998). Competing with the formation of oxon is the detoxification metabolism of CPF to TCP and DZN to IMHP via a dearylation reaction utilizing the same enzymes. A-esterase (PON1) and other B-esterases also contribute to the production of TCP and IMHP through the metabolism of CPF-oxon and DZN-oxon, respectively (Poet et al., 2003; Ma et al., 1994). The ratio between the toxification/detoxification reactions determines the degree of enzyme inhibition and can be used to evaluate metabolism processes (Timchalk et al., 2002).},
doi = {},
url = {https://www.osti.gov/biblio/15015210}, journal = {Journal of Undergraduate Research},
number = ,
volume = 4,
place = {United States},
year = {Wed Dec 01 00:00:00 EST 2004},
month = {Wed Dec 01 00:00:00 EST 2004}
}