Gordon_1993_Neurotoxicol.Teratol_15_21

Risk assessment of the neurotoxicology of organophosphate (OP) pesticides calls for a thorough understanding of the relationship between tissue cholinesterase (ChE) activity and changes in behavioral and autonomic responses to OP treatment. To address this issue, motor activity, core and skin temperature, and serum ChE activity were measured 2 h after rats of the Long-Evans strain were treated with the OP, diisopropyl fluorophosphate (DFP) at a dose of 0, 0.1, 0.25, 0.5, 0.75, 1.0, 1.25, and 1.5 mg/kg (SC). DFP doses > or = 0.25 mg/kg led to significant decreases in serum ChE activity, whereas doses of > or = 0.5 mg/kg caused reductions in motor activity and body temperature. The highest dose of DFP caused an increase in tail skin temperature, indicating an elevation in skin blood flow. A hockey stick regression analysis was used to determine threshold inhibition in ChE activity associated with depressions in motor activity and colonic temperature. The threshold serum ChE activity, relative to controls for inhibition of motor activity and reduction in body temperature was 46%. A wide range in individual motor activity and colonic temperature responses was noted when the inhibition in ChE activity exceeded threshold levels. This may be indicative of marked genetic variability to ChE inhibition. That is, rats appear to be either responsive or unresponsive when subjected to extreme inhibition in ChE activity. This pattern has been reported in other rodents and may represent a fundamental aspect of ChE toxicity.