Studies on the Toxicity of Nicotinamide Following Daily Oral Administration to Beagle Dogs

摘要

Nicotinamide when administered orally to beagle dogs was toxic at dose levels of 1,000 mg/kg/day x 3 and 6, and 500 mg/kg/day x 6 and 8. The tolerable dose was 100 mg/kg/day x 14. Overt toxic symptoms noted at 1,000 and 500 mg/kg/day consisted of emesis, diarrhea, anorexia, weight loss, sedation, hypothermia, but the eyes of the animals were effected to the greatest extent. The changes noted in the eyes consisted of conjunctivitis, chemosis, bluish gray discoloration and in some of the animals, blindness. At these dose levels the drug produced a leukocytosis, hyperglycemia, BSP retention and increase in alkaline phosphatase (1/2 animals on 500 mg/kg/day), and increases in SGOT and SGPT (1/2 animals on 500 mg/kg/day). At the dose level of 100 mg/kg/day the animals remained in good condition except for a mild injection of the sclera in one of the two animals. At this dose level the animals also showed increases in WBC and alterations in SGOT and SGPT. These changes in blood chemistry and hematology were reversible in the one animal studied during an observation period. Histopathology: Liver pathology was noted consisting of a mild reactive hepatitis at all dose levels, but apparently was reversible at the 100 mg/kg/day dose level since the one animal which was allowed to recover from the effects of the drug showed a normal liver. (Author)