Interspecies variation in toxicity of cholinesterase inhibitors

Stephanie J. Garcia, Michael Aschner, Tore Syversen

Research output: Chapter in Book/Report/Conference proceedingChapter

3 Scopus citations

Abstract

The chapter discusses how various species differ in response to anticholinesterases (anti-ChEs), and proposes potential causes, focusing on pharmacokinetics and pharmacodynamics (i.e., how the body handles the compound and the mechanism of action of the compound). Cholinesterase (ChE) inhibition by organophosphorus compounds (OPs), and to a lesser extent carbamates (Cms), has been studied extensively as the primary mechanism of toxicity for these broad-spectrum insecticides. Although several factors must be considered in toxicology testing of anti-ChEs, including the specific compound in question, species, and age, as well as level and duration of exposure, the chapter focuses on interspecies variability. Various species respond differently to anti-ChEs. Response, recovery, and reversal depend on both the species affected and the compound. Abundant studies exist on various species, from the intended target group (insects) to animals vulnerable to unsolicited effects, including fish, amphibians, birds, and mammals. These interspecies comparisons seek to improve species selectivity, and to extrapolate toxicity testing between unrelated species for regulatory purposes. First, to improve selectivity for target species, it would be helpful to exploit the differences between species. Second, similarities among unrelated species provide insight into conserved mechanisms of action and toxicity. The extrapolation of toxic effects from animal testing to humans may impact human health and safety by providing a basis for setting reference dose levels. At present, uncertainty factors are applied to account for interspecies variability from experimental animals to humans, as well as intraspecies variability to account for the sensitive individuals within a species.

Original languageEnglish (US)
Title of host publicationToxicology of Organophosphate & Carbamate Compounds
PublisherElsevier Inc.
Pages145-158
Number of pages14
ISBN (Print)9780120885237
DOIs
Publication statusPublished - Dec 1 2006
Externally publishedYes

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Garcia, S. J., Aschner, M., & Syversen, T. (2006). Interspecies variation in toxicity of cholinesterase inhibitors. In Toxicology of Organophosphate & Carbamate Compounds (pp. 145-158). Elsevier Inc.. https://doi.org/10.1016/B978-012088523-7/50012-0