[52-week oral toxicity study of lactitol (NS-4) in rats followed by 9-week recovery test].

ABSTRACT

Twenty five male and 25 female SlcSD rats were given orally lactitol, a hepatic encephalopathy drug, for 52 weeks at doses of 0, 0.4, 2 or 10 g/kg/day. A 9 week recovery test was conducted after the discontinuation of the drug treatment. Treatment related death, soft stool, diarrhea, decreased body weight gain and food intake and increased water consumption were observed in the 10 g/kg group. Urinalysis showed increased Ca excretion in the 2 and 10 g/kg groups. In the 10 g/kg group, there were increased Ca++ excretion and urine specific gravity and decreased K+ and Na+ excretion and urine volume. Hematologic examination showed decreased platelet count in the 10 g/kg group. Biochemical examination revealed higher A/G ratio in the 2 and 10 g/kg groups. In the 10 g/kg group, there were lowered level of total cholesterol, triglyceride, phospholipid, Na+, Cl- and total protein. Distention of the cecum with increased organ weight was seen pathologically in the 2 and 10 g/kg groups. In the 10 g/kg group, cecal mucosa was hyperplasic. The adrenal gland was hypertrophic in the zona glomerulosa in the 2 and 10 g/kg groups. In the 10 g/kg group, the adrenal weight was increased. Dilatation of renal tubules was also found in the 10 g/kg group. The above mentioned changes were satisfactorily reversible except for the increased cecum weight in the 10 g/kg group. Based on the results obtained, the NOAEL of this study was suggested to be 0.4 g/kg/day.