Regulatory toxicology and pharmacology : RTP
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Regul. Toxicol. Pharmacol. · Apr 1998
Subchronic (13-week) oral toxicity study of gamma-cyclodextrin in dogs.
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. ⋯ 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.
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Regul. Toxicol. Pharmacol. · Apr 1998
Comparative StudyDisposition of [14C]gamma-cyclodextrin in germ-free and conventional rats.
The absorption, disposition, metabolism, and excretion of 14C-labeled gamma-cyclodextrin ([14C]gamma-CD) was examined in four separate experiments with Wistar rats. In experiment 1, [14C]gamma-CD (25 microCi, 600 mg/kg body wt) was administered intravenously to four male and four female conventional rats. In experiment 2, [14C]gamma-CD (25 microCi, 1000 mg/kg body wt) was given by gavage to four male and four female germ-free rats. ⋯ It is concluded from the data that ingested [14C]gamma-CD is rapidly and essentially completely digested in the small intestine to absorbable [14C]glucose. The absorption of intact [14C]gamma-CD by passive diffusion is very low (<0.02%). Therefore, the metabolism of gamma-CD resembles closely that of starch or linear dextrins.
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Regul. Toxicol. Pharmacol. · Apr 1998
Comparative StudySubchronic intravenous toxicity studies with gamma-cyclodextrin in rats.
The toxicity of gamma-cyclodextrin (gamma-CD), a cyclic polymer of 8 alpha-1,4-linked glucopyranosyl units with potential applications in food and pharmaceutical preparations, was examined in two toxicity studies in rats with intravenous administration of gamma-CD for 1 and 3 months, respectively. Each study comprised four groups of 15 rats/sex each. In the 1-month study, gamma-CD was administered to the four groups at daily doses of 0 (controls), 200, 630, or 2000 mg/kg body wt, respectively. ⋯ However, degenerative changes (fibrosis) were not seen, and at the end of the recovery period only some small residual changes were noted in the lungs of a few animals. In conclusion, daily intravenous gamma-CD doses of 120-200 mg/kg body wt were tolerated without adverse effects. The changes observed at higher dose levels (>/=600-630 mg/kg body wt) were reversible on cessation of the treatment and are considered to be biochemical responses, without toxicological relevance, to the presence of transiently high concentrations of gamma-CD in the circulating blood.
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Regul. Toxicol. Pharmacol. · Apr 1998
Comparative StudyEmbryotoxicity and teratogenicity study with gamma-cyclodextrin in rabbits.
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. ⋯ 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%.
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Regul. Toxicol. Pharmacol. · Apr 1998
Comparative StudySubchronic 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. ⋯ 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.