Toxicokinetic and toxicodynamic aspects of organophosphorus (OP) insecticide poisoning.

As the majority of OP insecticides are lipophilic and not ionised they are absorbed rapidly following inhalation or ingestion; dermal absorption is slower but severe poisoning may still ensue if exposure is prolonged. Following absorption, OP compounds accumulate in fat, liver, kidneys and salivary glands. Phosphates (P=O) are biologically active as AChE inhibitors, whereas phosphorothioates (P=S) need bioactivation to their phosphate anologues (oxons) to become biologically active. Oxons inhibit AChE by phosphorylation of the serine hydroxyl group in the substrate-binding domain of the enzyme. The rate of spontaneous reactivation of alkyl phosphorylated AChE depends on the chemical structure of the OP compound. Spontaneous reactivation of dimethyl phosphorylated AChE proceeds quite rapidly. However, unless oximes are employed, there is no such expectation of rapid recovery for patients intoxicated with diethyl phosphoryl insecticides.