Date of this Version
Emerging Topics in Ecotoxicology 5
The concentration of a compound at the site of action is a determinant of its toxicity. This principle is affected by a variety of factors including the chemical properties of the compound (pKa, lipophilicity, molecular size), receptor binding affinity, route of exposure, and physiological properties of the organism. Many compounds have to undergo chemical changes, biotransformation, into more toxic or less toxic forms. Because of all of these variables, predicting toxic effects and performing risk assessments of compounds based solely on dose are less accurate than those that include data on absorption, distribution, metabolism (biotransformation), and excretion of the compound. These factors are commonly referred to as ADME. The quantitative study of these properties is called pharmacokinetics and often encompasses the determination of compound concentrations in tissues of interest including blood and the time course of absorption, metabolism, and excretion. A goal of pharmacokinetics is an understanding of the relationship between dose and the concentration of the active compound at the target site. Toxicokinetics is a “unique expansion of pharmacokinetics”, with doses being much greater than those in pharmacokinetic studies (Welling 1995). This is a complicated task, especially for anticoagulant rodenticides (ARs), as exposure (dose) frequently occurs over multiple days and can result from consumption of poisoned animals containing varying concentration of ARs and their metabolites, not simply a toxic bait.