Cholinesterase target species

The onset of symptoms depends on the particular organophosphorus compound, but is usually relatively rapid, occurring within a few minutes to a few hours and the symptoms may last for several days. This depends on the metabolism and distribution of the particular compound and factors such as lipophilicity. Some of the organophosphorus insecticides such as malathion for example (figure 5,10). are metabolized in mammals mainly by hydrolysis to polar metabolites which are readily excreted, whereas in the insect oxidative metabolism occurs which produces the cholinesterase inhibitor. Metabolic differences between the target and non-target species are exploited to maximize the selective toxicity. Consequently, malathion has a low toxicity to mammals such as the rat in which the LD50 is about 10 g/... 

Pharmacokinetic studies provide important data on the amount of toxicant delivered to a target site as well as species-, age-, and gender-specific and dose-dependent differences in biological response. The objective of this chapter is to further illustrate the utility of pharmacokinetics to address health concerns associated with cholinesterase inhibiting insecticides and, more specifically, to focus on the development, validation, and potential application of PBPK/PD models. The.se PBPK and PBPK/PD models can be used as a quantitative tool for integrating our understanding of dosimetry and biological response for these important classes of chemical insecticides. 

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