ACUTE AND CHRONIC TOXICITY OF BUTAZOLIDIN

¹ Hazleton Laboratories, Falls Church, Virginia

1. The acute intravenous LD₅₀' s in mice of Butazolidin, aminopyrine, and Irgapyrin were determined to be 123, 170, and 155 mgm./kgm., respectively. There was no significant difference in these values. Following intraperitoneal administration to rats, Butazolidin (LD₅₀ 215 mgm./kgm.) and aminopyrine (LD₅₀ 248 mgm./kgm.) were significantly more toxic than Irgapyrin (LD₅₀ 290 mgm./kgm.). The acute toxicological signs resulting from injection of each drug were those generally associated with antipyrine derivatives.

2. Ninety-day feeding studies at different levels in rats indicated reduced food intake and significant growth retardation in males and females receiving 0.5 per cent Butazolidin. Rats at 0.05 and 0.1 per cent did not differ from the controls. There was no mortality at any level; hematological values appeared normal, and tissues on gross inspection at sacrifice appeared within normal limits.

3. Oral administration of Butazolidin to dogs at dosages of 10 and 100 mgm./kgm./day for ninety days produced no evidence of drug toxicity. Hematological values were within normal limits; histological examination of the tissues at sacrifice revealed no evidence of changes associated with administration of Butazolidin. Two daily doses of 250 mgm./kgm. of Butazolidin to one dog caused toxicity. Reduction of dosage to 200 mgm./kgm./day for eleven weeks produced gradual loss of body weight and anorexia. This animal died during the twelfth week. Hematological values showed consistently low red blood cell counts and hemoglobin values. Gross inspection of tissues at autopsy showed only an area of gangrenous bowel; microscopic examination of tissues revealed no abnormalities which could be associated with the drug.