gamma-cyclodextrin and Diarrhea

The oral toxicity of gamma-cyclodextrin (gamma-CD) was examined in a 13-week feeding study in which four groups of four male and four female Beagle dogs received gamma-CD in the diet at concentrations of 0 (control), 5, 10, or 20%. No treatment-related changes were noted in behavior or appearance of the dogs and no mortalities occurred. Transient diarrhea occurred in some dogs of the 5 and 10% dose groups and in all dogs of the 20% dose group. However, all dogs remained in good health and gained weight. During the last 6 weeks of the study, the males of the 20% dose group gained less weight, but body weights were not significantly reduced in comparison to controls. Food intakes and food efficiencies were comparable among all groups. No treatment-related differences were observed with respect to ophthalmoscopic examinations, hematological parameters, clinicochemical analyses of the plasma, and semiquantitative urine analyses. Only the urinary pH was slightly below control levels in males of the 20% dose group. No abnormalities were seen at necropsy that could be attributed to treatment. The organ weight data revealed some cecal enlargement in the 10 and 20% dose groups. Relative ovary weights were significantly increased in the 10 and 20% groups but this was probably a result of an unusually low ovary weight in the controls. An increase of relative liver weights in males of the 10 and 20% dose groups also was considered to lack toxicological relevance because it was not associated with changes in plasma liver enzyme levels or histopathological changes. On microscopic examination, no treatment-related effects were observed in any of the various organs and tissues. In conclusion, transient diarrhea, cecal enlargement, and a slightly increased acidity of the urine were the only treatment-related effects reported. These changes are well-known physiological responses to the presence of increased amounts of undigested, fermentable carbohydrates in the lower gut. At the high applied intakes an incomplete digestion of gamma-CD and/or a partial inhibition of pancreatic amylase by gamma-CD could account for these effects. It is concluded that daily gamma-CD consumption of up to 20% in the diet (approximately 7.7 g/kg body wt in male and 8.3 g/kg body wt in female dogs) was tolerated without any toxic effects.

Topics: Administration, Oral; Amylases; Animal Feed; Animals; Cecum; Cyclodextrins; Diarrhea; Dogs; Female; gamma-Cyclodextrins; Lactose; Liver; Male; Organ Size; Ovary; Pancreas; Weight Gain

In a standard embryotoxicity/teratogenicity study, gamma-cyclodextrin (gamma-CD) was administered to groups of 16, artificially inseminated New Zealand White rabbits at dietary concentrations of 0, 5, 10, or 20%. A comparison group received a diet containing 20% lactose. Treatment started on day 0 of gestation and ended on day 29 when the animals were killed. Except for the occurrence of transient diarrhea in 2 and 3 rabbits of the 10 and 20% gamma-CD groups, respectively, in the first few days, the treatment was well tolerated. A reduced food intake in the 20% gamma-CD group during the first week of treatment resulted in a reduced weight gain during this period. However, after week 1 there were no differences in weight gains between the groups, and at termination of the study body weights were similar in all groups. Even at the highest dose level, which corresponds to an intake of 5-7 g/kg body wt/day, no signs of maternal toxicity were observed. Reproductive performance was not affected by the treatment. Uterine weight, placental weight, fetal weight, number of fetuses, sex ratio, number of implantation sites, resorptions, and corpora lutea did not differ among the groups. Visceral and skeletal examinations of the fetuses did not reveal any malformations, anomalies, or variations that could be attributed to treatment. It was concluded that dietary gamma-CD is well tolerated by pregnant rabbits, has no adverse effect on reproductive performance, and is not embryotoxic, fetotoxic, or teratogenic at dietary concentrations of up to 20%.

Topics: Animal Feed; Animals; Body Weight; Cyclodextrins; Diarrhea; Dose-Response Relationship, Drug; Eating; Female; Fetus; gamma-Cyclodextrins; Gestational Age; Lactose; Litter Size; Male; Organ Size; Placenta; Pregnancy; Rabbits; Teratogens; Uterus; Weight Gain

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) wa

Topics: Administration, Oral; Animal Feed; Animals; Body Weight; Cecum; Cyclodextrins; Diarrhea; Drinking; Eating; Feces; Female; gamma-Cyclodextrins; Hematologic Tests; Kidney; Lactose; Liver; Male; Organ Size; Rats; Rats, Wistar