Studies on the correlation between blood cholinesterase inhibition and 'target tissue' inhibition in pesticide-treated rats.
Inhibition of cholinesterase activity in the blood has been proposed as an index of ChE activity in tissues targeted by ChE-inhibiting pesticides, including the muscle end-plate region and the central nervous system (CNS). While opinions vary regarding the utility of blood ChE activity in predicting ChE activity in the target tissues, there appear to be no comprehensive studies designed to assess this possible correlation in a time- and dose-dependent manner. We undertook this type of study by administering a single dose of an organophosphate, chlorpyrifos (0, 30, 60 or 125 mg/kg in corn oil, s.c.) to rats and then sacrificing animals at 1, 4, 7, 21 or 35 days after dosing. Whole blood, plasma, erythrocytes, frontal cortex, hippocampus, striatum, hypothalamus and diaphragm tissue were collected and assayed for ChE activity. Collapsed across dosages, optimal correlations of blood ChE activity with brain or muscle activity occurred 7-21 days after dosing (when ChE inhibition was maximal and most stable). At all times after dosing, there was a high correlation among ChE activity in the hippocampus, striatum and frontal cortex. Generally, ChE activity in whole blood and erythrocytes correlated better with the activity in brain and muscle than did activity in the plasma (whole blood > or = erythrocytes >> plasma). Similar relationships were also observed in a more abbreviated study using a direct acting organophosphate, paraoxon. ChE activity was determined in blood components, brain and muscle at the time of maximal inhibition (4 h after injection) and during recovery (24 hrs after injection) using two dosage levels (0.17 or 0.34 mg/kg, s.c.). Taken together, these data indicate that the level of ChE activity in the blood may accurately reflect activity in other tissues, but that this correlation is tissue- and time-specific.
Padilla
S
S
Cellular and Molecular Toxicology Branch, United States Environmental Protection Agency, Research Triangle Park, NC 27711.
Wilson
V Z
VZ
Bushnell
P J
PJ
D000818:Animals; D001711:Biotransformation; D001921:Brain / Q000201:enzymology; D004390:Chlorpyrifos / Q000633:toxicity; D002800:Cholinesterase Inhibitors / Q000633:toxicity*; D002802:Cholinesterases / Q000097:blood* / Q000378:metabolism*; D004912:Erythrocytes / Q000201:enzymology; D007306:Insecticides / Q000493:pharmacokinetics* / Q000633:toxicity*; D008099:Liver / Q000378:metabolism; D008297:Male; D009132:Muscles / Q000201:enzymology; D009928:Organ Specificity; D010261:Paraoxon / Q000633:toxicity; D051381:Rats
D002800:Cholinesterase Inhibitors; D007306:Insecticides; D002802:Cholinesterases; D004390:Chlorpyrifos; D010261:Paraoxon