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[Three months oral repeated dose toxicity of T-3761 in rats].

Yoshimi Kawamura, Akio Nagai, Ken Yoshida, M Nagasawa, N Kitoh, Terutaka Kodama

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Abstract

A three months oral repeated dose toxicity study was carried out in rats at dosages of 1,500, 400, 100 and 25 mg/kg. The following results were obtained. 1. There was no dead rat caused by administration of T-3761. Soft feces were observed in male and female rats at 1,500 mg/kg. Body weight gain was slightly suppressed in male rats at 1,500 mg/kg. 2. Crystals which seemed to be test compound in the urinary sediment, were observed in male and female rats at 1,500 and 400 mg/kg. 3. There was no abnormality caused by administration of T-3761 in both hematological and ophthalmological examination. 4. Mild increase in total cholesterol (males and females in 1,500 mg/kg group, females at 400 mg/kg group), phospholipids (males at 1,500 mg/kg group) and A/G ratio (males and females in all treated groups) were observed. However, these biochemical changes were reversible in the recovery period. 5. Dilatation of the cecal lumen was observed in male and/or female rats at 1,500, 400, 100 mg/kg. However, no histological abnormalities were seen in the mucosa of cecum. 6. Blister and erosion were observed at articular cartilage of knee or hip joints in 2 of the 19 rats at 1,500 mg/kg, 1 of the 9 rats at 1,500 mg/kg of recovery study and 3 of the 10 rats at 400 mg/kg of recovery study. 7. No toxic dose level was regarded to be 100 mg/kg/day in this study.

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What this paper is about

A three months oral repeated dose toxicity study was carried out in rats at dosages of 1,500, 400, 100 and 25 mg/kg. The following results were obtained. 1. There was no dead rat caused by administration of T-3761. Soft feces were observed in male and female rats at 1,500 mg/kg. Body weight gain was slightly suppressed in male rats at 1,500 mg/kg. 2. Crystals which seemed to be test compound in the urinary sediment, were observed in male and female rats at 1,500 and 400 mg/kg. 3. There was no abnormality caused by administration of T-3761 in both hematological and ophthalmological examination. 4. Mild increase in total cholesterol (males and females in 1,500 mg/kg group, females at 400 mg/kg group), phospholipids (males at 1,500 mg/kg group) and A/G ratio (males and females in all treated groups) were observed. However, these biochemical changes were reversible in the recovery period. 5. Dilatation of the cecal lumen was observed in male and/or female rats at 1,500, 400, 100 mg/kg. However, no histological abnormalities were seen in the mucosa of cecum. 6. Blister and erosion were observed at articular cartilage of knee or hip joints in 2 of the 19 rats at 1,500 mg/kg, 1 of the 9 rats at 1,500 mg/kg of recovery study and 3 of the 10 rats at 400 mg/kg of recovery study. 7. No toxic dose level was regarded to be 100 mg/kg/day in this study.

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Available abstract

A three months oral repeated dose toxicity study was carried out in rats at dosages of 1,500, 400, 100 and 25 mg/kg. The following results were obtained. 1. There was no dead rat caused by administration of T-3761. Soft feces were observed in male and female rats at 1,500 mg/kg. Body weight gain was slightly suppressed in male rats at 1,500 mg/kg. 2. Crystals which seemed to be test compound in the urinary sediment, were observed in male and female rats at 1,500 and 400 mg/kg. 3. There was no abnormality caused by administration of T-3761 in both hematological and ophthalmological examination. 4. Mild increase in total cholesterol (males and females in 1,500 mg/kg group, females at 400 mg/kg group), phospholipids (males at 1,500 mg/kg group) and A/G ratio (males and females in all treated groups) were observed. However, these biochemical changes were reversible in the recovery period. 5. Dilatation of the cecal lumen was observed in male and/or female rats at 1,500, 400, 100 mg/kg. However, no histological abnormalities were seen in the mucosa of cecum. 6. Blister and erosion were observed at articular cartilage of knee or hip joints in 2 of the 19 rats at 1,500 mg/kg, 1 of the 9 rats at 1,500 mg/kg of recovery study and 3 of the 10 rats at 400 mg/kg of recovery study. 7. No toxic dose level was regarded to be 100 mg/kg/day in this study.

Key concepts: Toxicity, Dose, Cecum, Medicine, Oral administration, Feces, Lumen (anatomy), Internal medicine

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