Modelling the interactions of mixtures of organophosphorus insecticides with cholinesterase

The organophosphorus (OP) insecticides are one of the most widely used and important insecticide classes. These insecticides exert toxicity through inhibition of the critical nervous system enzyme cholinesterase (ChE) which functions to rapidly destroy the ubiquitous neurotransmitter acetylcholine. When ChE is inhibited, the acetylcholine accumulates, causing hyperactivity within the cholinergic pathways. Considerable effort has gone into assessing the risks of various OP insecticides. Unfortunately, people are often exposed to different OP insecticides in different dosages at different or overlapping times. The usual statistical methods seem inadequate to the task of assessing the effect of OP mixtures. This paper will discuss a simple model using systems of ordinary differential equations. Using this model, we have had success in predicting the effect of cumulative in vitro OP compound exposure in terms of ChE inhibition using data from experiments measuring ChE inhibition by a single OP compound. We will describe our model and compare our simulations to in vitro experiments where binary mixtures have been used