Subchronic oral toxicity studies with gamma-cyclodextrin in rats.

The toxicity of gamma-cyclodextrin (gamma-CD), a cyclic polymer of eight alpha-1,4-linked glucopyranosyl units with potential applications as a food ingredient, was examined in a 2-week pilot study followed by a 13-week oral toxicity study in Wistar rats. In the 2-week study, the test substance was administered to groups of 5 male rats at dietary levels of 0, 5, 10, 15, and 20%. In the 13-week study, groups of 20 rats/sex received diets with 0, 1.5, 5, or 20% gamma-CD. In each study, a comparison group receiving a diet with 20% lactose also was included. The 13-week study also included satellite groups of 10 rats/sex for the control and 20% gamma-CD groups. These satellite groups were kept on a standard, cereal-based rodent diet for a 4-week recovery period after termination of the treatment period. Parameters measured during the two studies were clinical signs, body weights, food and water intake, clinicochemical parameters, organ weights, and gross observation at necropsy. In the 13-week study, ophthalmoscopic and hematological examinations, urine and feces analyses, and histopathological examination of standard organs and tissues were conducted. There were no treatment-related mortalities in either study. Soft stools and, in the 13-week study, infrequent occurrences of diarrhea were noted in the lactose group at the beginning of treatment. Among the gamma-CD groups, soft stools occurred in only a few animals of the high-dose groups (>/=10% gamma-CD) during the first few days of treatment. Mean body weights tended to be slightly reduced in males of the 20% gamma-CD and 20% lactose groups. However, food efficiency was not affected by treatment except in the 13-week study in males of the 20% gamma-CD group during the first week of treatment. The hematological examinations and the semiquantitative urinalyses (conducted in the 13-week study) and the clinicochemical investigations (both studies) did not reveal any changes that could be attributed to gamma-CD treatment. Except for a slight cecal enlargement, which is commonly observed in rodents upon ingestion of incompletely absorbed carbohydrates, organ weights did not exhibit relevant changes as a result of gamma-CD treatment. On histopathological examination (13-week study), no treatment-related abnormalities were found. In conclusion, the ingestion of gamma-CD for 13 weeks at dietary levels of up to 20% (corresponding to intakes of 11.4 and 12.7 g/kg body wt/day for male and female rats, respectively) was well tolerated and did not produce any signs of toxicity.