ABSTRACT
In vivo animal studies are generally designed to classify toxic effects into those developing after a single dose (acute exposure) or multiple (repeated) exposures; studies with multiple exposures are of varied duration and include short-term repeat dosing (<5% of the animal’s normal life span), subchronic (5 to 20% of the life span), and chronic (the greater proportion or entire expected life span, e.g., 2 years). The possible routes of compound administration include oral, intravenous, intramuscular, subcutaneous, inhalation, intraperitoneal, and by suppository. The formulations of the test compound are mainly selected based on the route of administration and the physical, chemical, and stability properties of the compound. The dose levels are chosen generally after preliminary studies where the doses are higher than the proposed use or expected exposure; studies of drugs may include several ascending dosages that are above the proposed human therapeutic dose (Timbrell, 1999; Derelanko and Hollinger, 2001; Hayes, 2007). Evidence may be sought to show that any test-related compound effects observed during the dosing period are reversible during a subsequent period when dosing has ceased (the reversibility or recovery study phase).
