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 a s an index of ChE activity in tissues targeted by ChE-inhibiting pesti cides, including the muscle end-plate region and the central nervous s ystem (CNS). While opinions vary regarding the utility of blood ChE ac tivity in predicting ChE activity in the target tissues, there appear to be no comprehensive studies designed to assess this possible correl ation in a time- and dose-dependent manner. We undertook this type of study by administering a single dose of an organophosphate, chlorpyrif os (0, 30, 60 or 125 mg/kg in corn oil, s.c.) to rats and then sacrifi cing animals at 1, 4, 7, 21 or 35 days after dosing. Whole blood, plas ma, erythrocytes, frontal cortex, hippocampus, striatum, hypothalamus and diaphragm tissue were collected and assayed for ChE activity. Coll apsed across dosages, optimal correlations of blood ChE activity with brain or muscle activity occurred 7-21 days after dosing (when ChE inh ibition was maximal and most stable). At all times after dosing, there was a high correlation among ChE activity in the hippocampus, striatu m and frontal cortex. Generally, ChE activity in whole blood and eryth rocytes correlated better with the activity in brain and muscle than d id activity in the plasma (whole blood greater than or equal to erythr ocytes >> 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 activi ty in the blood may accurately reflect activity in other tissues, but that this correlation is tissue- and time-specific.