Ninety-Day Subchronic Oral Toxicity Study of Nitroguanidine in Rats

The 90-day subchronic oral toxicity of nitroguanidine was evaluated in male and female Sprague-Dawley rats. Nitroguanidine was administered in the diet at dose levels of 0, 100, 316, and 1000 mg/kg/day for 90 days. The addition of nitroguanidine to the diet consistently reduced food consumption and caused significant (p or = 0.05) increases in water consumption. Significantly (p or = 0.05) reduced weight gains were observed in the female high-dose group for 5 of the 13 weeks of the study period. No other clinical signs attributable to the test compound were observed during the study. Blood samples taken at necropsy for hematological and serum chemistry analyses exhibited no significant (p or = 0.05) abnormalities that could be attributed to nitroguanidine dosing. Microscopic examination of tissues from the control and 1000 mg/kg/day dose group animals revealed no lesions attributable to the administration of nitroguanidine. These findings indicate that nitroguanidine is nontoxic in rats when administered at doses as high as 1000 mg/kg/day for 90 days. The findings of increased water consumption suggest that nitroguanidine, which is excreted unchanged in the rat's urine, may be acting as an osmotic diuretic.