[13-week oral toxicity study of lactitol (NS-4) in dogs followed by 4-week recovery test].

ABSTRACT

UNLABELLED 13-week repeated dose toxicity studies were conducted on lactitol, a hepatic encephalopathy drug. In the experiment I, male and female dogs were orally treated with lactitol at doses of 0, 1.0, 2.5 and 6.25 g/kg/day for 13 weeks, followed by 4 weeks recovery period. In the experiment II, male and female dogs were orally treated with lactitol at doses of 0, 0.25, 0.50 and 1.0 g/kg/day for 13 weeks in order to require the no-toxic dose. RESULTS: 1. Soft stool and diarrhea were observed at the 0.50 g/kg group and above, and vomiting was observed at the 1.0 g/kg group and above. Increased water consumption was observed at the 6.25 g/kg group. No deaths occurred at all groups. 2. In urinalysis, increased urine volume was observed at the 6.25 g/kg group. 3. Blood chemistry showed decreased BUN at the 6.25 g/kg group. 4. There were no drug-related changes in body weight, food consumption, ophthalmological examination, electrocardiography, hematology and pathology. 5. At the end of the recovery period, all these changes observed at the end of the administration period were disappeared. Based on these results, it was considered that the no-toxic dose of lactitol is 0.25 g/kg/day.