Pre-clinical toxicology evaluation.

a- The number of animals used for analysis: CD-1 (n = 10), BALB/c, Wistar rats and Hartley guinea pigs (n = 5) and Beagles (n = 1) per group.
b- Histological lesions were evaluated on a scale from 0 to 10 with +1 single microscopic focus, +2 at least 2 microscopic foci, +3 more than 3 foci or multiple locally extensive areas of pathology, +4 to +6 were associated increasing severity and more extensive distribution (these lesions could be associated with morbidity), +7 and above had increasing degrees of inflammation (+10 associated with mortality).
c- Other tissues evaluated include heart, liver, kidneys, spleen, esophagus, trachea, stomach, intestines, pancreas, and adrenals.
d- Metabolic analysis evaluated by standard biochemical serum profile analysis on a IDEXX Vet Test Analyzer™ and performed at the Animal Diagnostic Laboratory through the Unit for Laboratory Animal Medicine at the University of Michigan. Normal indicates all analytes fell within normal expected distributions per species.
e- Administered every 2 weeks.
f- Administered every 15 minutes.
g- Administered every 4 hours.
h- Administered every 4 weeks.