Embryotoxicity 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. 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%.