Embryotoxicity and teratogenicity study with α-cyclodextrin in rabbits

Abstract

In a standard embryotoxicity/teratogenicity study, alpha-cyclodextrin (alpha-CD) was administered to groups of sixteen, artificially inseminated New Zealand White rabbits at dietary concentrations of 0, 5, 10, or 20%. An additional 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 diarrhoea in one rabbit of the 20% alpha-CD group for a few days, the treatment was well tolerated. A reduced food intake in the 20% alpha-CD group during the first week of treatment resulted in a reduced weight gain from day 0 to 12 of the study. However, the difference to the controls was not significant 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 5.9-7.5 g/kg bw/day, no signs of maternal toxicity were observed. Maternal reproductive performance was not affected by the treatment. Uterine weight, placental weight, fetal weight, number of fetuses, sex ratio, number of implanation 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 alpha-CD is generally well tolerated by pregnant rabbits, has no adverse effect on maternal reproductive performance and is not embryotoxic, fetotoxic, or teratogenic at dietary concentrations of up to 20%, the highest dose level tested.

Safety assessment of γ-cyclodextrin

“…The decrease in the incidence of hemorrhagic fluid in the 5 and 20% dose groups was considered unlikely to be treatment-related. Under the conditions of the study, c-CD had no adverse effect on reproductive performance and was not embryotoxic, fetotoxic or teratogenic at dietary concentrations of up to 20% corresponding to an intake of 5-7 g/kg bw/day (Waalkens-Berendsen et al, 1998a).…”

Cyclodextrins as Food Additives and in Food Processing

“…administration, long-term toxicity on organs, carcinogenicity and reproductive toxicity are available. The likelihood that interaction of α-CD with lipophilic vitamins may impair their bioavailability has not been studied experimentally [32]. γ-CD does not cause significant irritation after i.m.…”

Pulmonary function and pathology in hydroxypropyl-beta-cyclodextin-treated and untreated Npc1−/− mice

“…They appear to be non-toxic: even massive orally administered doses to pregnant rabbits resulted in no teratogenic or embryotoxic effects [31]. Much of the early literature is reviewed by Thompson [32] (337 references) and a critical discussion of beta-cyclodextrin modifications is provided by Blanchard and Proniuck [33].…”