The antibacterial compound
alpha-(1,4-dioxido-3-methylquinoxalin-2-yl)-N-methylnitrone (
DMNM), which was administered for a maximum period of 90 days, was given orally at 0, 7.5, 15.0 or 22.5 mg/kg/day for dogs; 0, 15, 50 or 100 mg/kg/day for rats; and 35 mg/kg/day for monkeys. Reduced food consumption and
weight gain, depression,
debility, and deaths occurred starting at doses (mg/kg/day) of 15 in dogs, 35 in monkeys and 50 in rats. Frequent
emesis and occasional black, tarry feces were also observed in most treated dogs. Necropsy examinations revealed small, pale adrenal glands in rats given a dose of 50 mg/kg/day and
gastrointestinal hemorrhage in dogs administered 15.0 or 22.5 mg/kg/day of
DMNM. Microscopically, vacuolar degeneration of the canine, monkey and rat adrenal cortex was seen at all dosages and appeared to progress from the zona reticularis to the zona glomerulosa. In rats treated with 50 mg/kg/day of the
drug chronic lesions of adrenal cortical
fibrosis,
atrophy, and nodular
hyperplasia were also detected. The only other significant microscopic lesions consisted of mild testicular
atrophy and occasional gastric erosions in dogs treated with 7.5 mg/kg/day of
DMNM.