Single dosing toxicity study of SY5555 in mice, rats and dogs

• Published in: CHEMOTHERAPY Vol. 42; no. Supplement1; pp. 101 - 114
• Main Authors: Sugiyama, Kazushi, Yamamoto, Keiji, Yamamoto, Shinichi, Ochiai, Taehito, Otaka, Tadahiko
• Format: Journal Article
• Language: Japanese
• Published: Japanese Society of Chemotherapy 1994
• ISSN: 0009-3165; 1884-5894
• DOI: 10.11250/chemotherapy1953.42.Supplement1_101

Single dosing toxicity studies of SY5555 in mice, rats and dogs, and single dosing toxicity studies of major metabolites (M-1 and M-2) in mice were performed, and the following results were obtained. 1) No deaths were observed in mice and rats treated orally with 5, 000 mg/kg of SY5555. The intravenous LD50 values of SY5555 were 3, 300 mg/kg for males and 3, 668 mg/kg for females in mice, and between 1, 000 and 2, 000 mg/kg for males and more than 2, 000 mg/kg for females in rats. No deaths were observed in dogs treated orally at 3, 000 mg/kg and intravenously at 1, 000 mg/kg. 2) No abnormal signs were observed in mice and rats treated orally. Decreased activity, prone position, dyspnea, convulsion and disapperance of righting reflex were observed in mice and rats treated intravenously. In dogs, vomiting was observed after oral and intravenous treatment, and soft stool or diarrhea was also observed after oral treatment. 3) Blood urea nitrogen and creatinine were transiently increased in dogs treated orally at 2, 000 mg/kg or more, and intravenously at 250 mg/kg or more. Regeneration of renal proximal tubules was observed in dogs treated orally at 2, 000 mg/kg or more. 4) The intravenous LD50 values of two major metabolites, M-1 (2Na) and M-2 (2Na), in mice treated intravenously were approximately 2, 500 mg/kg. Convulsion, prone position, staggering gait, bradypnea and gasping respiration were observed as general signs.