Chapter 77 - Toxicology and Mode of Action of Pyrethroid Insecticides

Abstract

This chapter provides a review of the toxicological properties of pyrethroid insecticides in mammals, with emphasis on the neurotoxic properties that are characteristic of pyrethroids as a class. Pyrethrum is arguably the most effective natural insecticide, but its use is limited by its instability in light and air, which limits its effectiveness in crop protection and other insect control contexts in which residual activity is essential. The development of pyrethroids involved an iterative process of structural modification and biological evaluation in an effort to identify compounds with increased photostability that retained the potent and rapid insecticidal activity and relatively low acute mammalian toxicity of pyrethrum. The insecticidal properties of pyrethroids derive from their ability to alter the function of voltage-gated sodium channels in insect neuronal membranes, thereby disrupting electrical signaling in the nervous system. Although the discovery and development process for pyrethroids involved the optimization of insecticidal activity using whole insects, optimization for high intrinsic activity on insect sodium channels was implicit throughout this process. The structure, function, and pharmacology of voltage-gated sodium channels are highly conserved between insects and mammals. It is therefore not surprising that pyrethroids also alter the function of mammalian sodium channels. There is broad agreement that voltage-gated sodium channels are the primary target sites for the neurotoxic actions of pyrethroids, they may not be the only targets involved in pyrethroid intoxication in mammals. Pyrethroids also are known to affect a variety of voltage- and ligand-gated ion channels.