TOXICOLOGICAL STUDIES ON PEPLEOMYCIN SULFATE (NK 631). VI: CHRONIC TOXICITY OF PEPLEOMYCIN IN DOGS

• Published in: Japanese journal of antibiotics 1979/03/25, Vol.32(3), pp.387-450
• Main Authors: ITO, KOHICHI, HANDA, JUN, IRIE, YUKIO, EZURA, HIKARU, KUMAGAI, MUTSUMI, IRIE, YAYOI, SUZUKI, ATSUKO, HAGIWARA, TAKAO, YAMANE, HIROYUKI, MIYAMOTO, KOHKICHI, YAMASHITA, TAKUMI, TSUBOSAKI, MASATOSHI, MATSUDA, AKIRA, KONOHA, NORIYASU
• Format: Article
• Language: Japanese
• Subjects: Animals; Bleomycin; Bleomycin - administration & dosage; Bleomycin - analogs & derivatives; Bleomycin - toxicity; Blood Chemical Analysis; Body Weight - drug effects; Chronic toxicity; Dogs; Eating - drug effects; Female; Hematologic Tests; Kidney - pathology; Liver - pathology; Lung - pathology; Male; Mouth - pathology; Nails - pathology; Pepleomycin; Recovery test (beagle dogs); Sex Factors; Skin Ulcer - chemically induced; Time Factors; Urine - analysis
• ISSN: 0368-2781; 2186-5477
• DOI: 10.11553/antibiotics1968b.32.387

Chronic toxicity and its recovery of pepleomycin sulfhte was studied in both sexes of beagle dogs. At dose levels of 0.3, 0.15 and 0.075mg/kg, pepleomycin was administered intramuscularly to dogs for 180 successive days.Twod ogs of the 0.15mg/kg dose group were used for recovery test for 35 days. As generalfindings, the decrease of food intake, the loss of body weight, ulceration of foot pad, nail root necrosis and onychoptosis, ulcer of tongue and labia, and alopecia, dermatitis and necrosis at friction sites were observed more severely in the 0.3mg/kg dose group of both sexes, especially in male, than those in bleomycin were. In the dose groups of 0.15 and 0.075mg/kg, their findings were observed as slightly as those in bleomycin were. The death occurred in the 0.3mg/kg dose group of both sexes. The lesions of liver and kidney were recognized in the 0.3mg/kg dose group of both sexes, severely in male, on histopathological findings. Additionally severe fibrosis of lung was observed in one of the 0.3mg/kg dose group of female. In general chronic toxicity of pepleomycin was revealed more severely in the 0.3mg/kg dose group than that of bleomycin was, but in the dose groups of 0.15 and 0.075mg/kg difference between their toxicities was not significant. In addition, chronic toxicity of pepleomycin in dogs showed more severely in male and its recovery was hardly recognized during its period. The maximum safety dose in this studies was estimated to be between 0.075 and 0.15mg/kg in dogs.