Regulatory and research issues related to cholinesterase inhibition

Assessing the neurotoxic potential of organophosphate and carbamate pesticides should be greatly facilitated by the knowledge that the mechanism of action of these insecticides is presumed to be the inhibition of cholinesterase, the enzyme which controls the levels of neurotransmitter, acetycholine. Although the inhibition of cholinesterase activity is the recognized mechanism of action, many questions remain regarding the use of cholinesterase inhibition data as a critical effect for establishing risk of cholinesterase-inhibiting pesticides. Specifically, questions have arisen regarding whether blood cholinesterase inhibition correlates with inhibition in target tissues (e.g. brain or muscle) and whether cholinesterase inhibition in any tissue correlates with the adverse clinical and behavioral effects produced by exposure to cholinesterase-inhibiting pesticides. Studies in our laboratory indicate that blood cholinesterase inhibition in both acute and subchronic dosing regimens correlates with inhibition in other tissues, if measurements are taken at the appropriate times. Moreover, there is evidence in the literature and from our laboratory that cholinesterase inhibition correlates with the emergence and severity of clinical signs of poisoning by cholinesterase-inhibiting pesticides.