Dose-related inhibition of brain and plasma cholinesterase in neonatal and adult rats following sublethal organophosphate exposures.
Developing mammals are markedly more sensitive to acute toxicity from exposure to a variety of organophosphorus (OP) pesticides. The present study examined dose-related inhibition of both brain and plasma cholinesterase activity in neonatal and adult rats exposed to sublethal doses of one of three common OP pesticides, methyl parathion, parathion and chlorpyrifos. Effective dose 50 (i.e., ED50 or dose which would inhibit 50% of the cholinesterase activity) values were determined and then correlated with an indicator of acute toxicity, the maximal tolerated dose (MTD). It was found that ED50 estimates for both brain and plasma cholinesterase correlated highly (r = 0.932-0.992) with previously derived MTD values. In no case was there a significant difference between in vivo brain and plasma cholinesterase inhibition across doses in neonatal rats was high (r = 0.962-0.975) but lower in adults (r = 0.700-0.943). The results suggest that in vivo inhibitory potency of the three OPs towards either brain or plasma ChE activity is highly correlated with sensitivity to acute toxicity in both neonatal and adult rats. Additionally, under defined experimental conditions, plasma ChE inhibition may be a useful quantitative index for the degree of brain cholinesterase inhibition following OP exposures.
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Division of Pharmacology and Toxicology, School of Pharmacy, Northeast Louisiana University, Monroe 71209-0470.
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D000375:Aging / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000201:enzymology*; D004390:Chlorpyrifos / Q000633:toxicity; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000633:toxicity*; D002802:Cholinesterases / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005260:Female; D007306:Insecticides / Q000008:administration & dosage / Q000633:toxicity*; D008297:Male; D008743:Methyl Parathion / Q000633:toxicity; D010278:Parathion / Q000633:toxicity; D051381:Rats; D011919:Rats, Inbred Strains
D002800:Cholinesterase Inhibitors; D007306:Insecticides; D008743:Methyl Parathion; D010278:Parathion; D002802:Cholinesterases; D004390:Chlorpyrifos