Acetyl-cholinesterase, pesticide inhibition

Organophosphate and carbamate pesticides are potent inhibitors of the enzyme cholinesterase. The inhibition of cholinesterase activity by the pesticide leads to the formation of stable covalent intermediates such as phosphoryl-enzyme complexes, which makes the hydrolysis of the substrate very slow. Both organophosphorus and carbamate pesticides can react with AChE in the same manner because the acetylation of the serine residue at the catalytic center is analogous to phosphorylation and carbamylation. Carbamated enzyme can restore its catalytic activity more rapidly than phosphorylated enzyme [17,42], Kok and Hasirci [43] reported that the total anti-cholinesterase activity of binary pesticide mixtures was lower than the sum of the individual inhibition values. 

The UK Pesticide Safety Directorate (PSD) has decided to use the TEF approach for assessment of combined risk from exposure to mixtures of acetyl cholinesterase inhibitors (organophosphate (OP) compounds and carbamates) (PSD 1999). Despite clear differences in the action of carbamates and OP compounds, the index compounds selected for all acetyl cholinesterase inhibitors were either aldicarb (carbamate) or chlorpyrifos (OP). The POD for determining relative potency was predetermined as the dose level that produced 20% inhibition of red blood cell cholinesterase in a 90-day dietary study in rats. 

With an excessive, single exposure, the result will be either a systemic pesticide poisoning or a topical lesion frequently observed on the skin or in the eyes. Since most acute intoxications are from the carbamate and organoposphate insecticides, the systemic manifestations are cholinergic and are due to the inhibition of acetyl cholinesterase and the resultant accumulation of the neurotransmitter acetylcholine, at the synapse. Topical effects, in contrast, either are the result of the irritant properties of the chemicals in the formulation or have an allergenic basis for their occurrence (3). However, topical effects are not necessarily exclusively the result of exposure to the active ingredient in the formulation but may result from a reaction to one or more inerts as well. 

---