Pharmacologic challenges for establishing interspecies extrapolation models in neurotoxicology.

Pharmacologic challenges and dose/response studies are discussed as tools for aiding in the extrapolation of nonhuman animal models to human neurotoxicology. Specific experiments conducted using humans, baboons, rhesus monkeys, and dogs are cited as examples of the use of pharmacologic methods for neurotoxicology applications. Respiratory sinus arrhythmias are quantified following atropine sulfate administration and the resulting vagolytic blockade is used as a pharmacologic challenge technique. Dose/response studies in humans and rhesus monkeys are cited as an example for interspecies comparisons using ED50 calculations for a 30% decrease in the respiratory sinus arrhythmias following atropine. Pharmacologic challenges with drugs of relevant mechanisms of action are useful for demonstrating relative physiologic responses for interspecies extrapolations.