This project is designed to perform repeated dose acute toxicity studies with AMT in (a) rabbits and (b) mice that comply with the FDA animal toxicology data requirements for approval of AMT as an IND. LCS does not have the facilities to perform these laboratory tests. Three groups of each animal (mice and rabbits) with 20 animals per group (10 males and 10 females) will receive placebo, 50x usual dose, and I00x recommended dose of AMT respectively. The dose levels will be l.) no dose (control); 2.) 5.125 mcg/kg (50x recommended dose group); and 3.) 10.250 mcg/kg (1 00x recommended dose group). Dose administration will be intravenous (mouse: tail vein; rabbit ear vein), once per day, for a duration of 14 days. Animals will be weighed on days o and 7 prior to dosing and animals will be observed daily for changes in physical and behavioral signs. Records of potential signs of toxicity will be made as they occur, and include time of onset, degree, and duration. Blood samples will be drawn from rabbits at the beginning and end of the study; blood samples will be drawn from mice at the end of the study only. At the end of the dosing period animals will be sacrificed and evaluated for signs of toxicity by necropsy and histopathology. Animals will be necropsied as close as possible to time of death or at scheduled sacrifice. The dosing and analysis methods are outlined by the United States Food and Drug.
