Role of detoxication pathways in acute toxicity levels of phosphorothionate insecticides in the rat.
Phosphorothionate insecticides and their active oxon metabolites can be detoxified by a variety of hepatic mechanisms. Cytochrome P450-mediated dearylation activity was higher in males than in females. While dearylation was induced by phenobarbital in both sexes, it was induced by beta-naphthoflavone in females only. Detoxication of oxons in the presence of EDTA was inducible by phenobarbital, was higher in males than in females, and paralleled aliesterase activity. In vitro Ca(++)-dependent A-esterase-mediated hydrolysis of chlorpyrifos-oxon but not of paraoxon occurred at biologically relevant nM concentrations. This hydrolysis was also inducible by phenobarbital. Glutathione-mediated conjugation did not appear to be relevant to the disposition of the phosphorothionates studied here. Hepatic detoxication via dearylation, aliesterase phosphorylation and A-esterase-mediated hydrolysis (for some organophosphates) all appear to be relevant reactions in the attenuation of acute toxicity.
Chambers
J E
JE
Department of Biological Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State 39762-9825.
Ma
T
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Boone
J S
JS
Chambers
H W
HW
D000110:Acetylcholinesterase / Q000378:metabolism*; D000818:Animals; D001571:Benzoflavones / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D043182:Carboxylesterase; D002265:Carboxylic Ester Hydrolases / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology; D004390:Chlorpyrifos / Q000378:metabolism* / Q000633:toxicity*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004492:Edetic Acid / Q000494:pharmacology; D005260:Female; D005978:Glutathione / Q000378:metabolism; D008658:Inactivation, Metabolic; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects / Q000201:enzymology; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D010261:Paraoxon / Q000378:metabolism / Q000633:toxicity; D010278:Parathion / Q000378:metabolism* / Q000633:toxicity*; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012737:Sex Factors; D019324:beta-Naphthoflavone
D001571:Benzoflavones; D019324:beta-Naphthoflavone; D010278:Parathion; D003577:Cytochrome P-450 Enzyme System; D004492:Edetic Acid; C019724:arginine esterase; D002265:Carboxylic Ester Hydrolases; D043182:Carboxylesterase; D000110:Acetylcholinesterase; D005978:Glutathione; D004390:Chlorpyrifos; D010261:Paraoxon; D002118:Calcium; D010634:Phenobarbital