Regulatory toxicology and pharmacology : RTP
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Regul. Toxicol. Pharmacol. · Jun 2004
Disposition of 14C-alpha-cyclodextrin in germ-free and conventional rats.
The absorption, disposition, metabolism, and excretion of uniformly (14)C-labeled alpha-cyclodextrin ((14)C-alpha-CD) was examined in four separate experiments with Wistar rats. In Experiment 1, (14)C-alpha-CD (25 microCi, 50 mg/kg bw) was administered intravenously to four male and four female conventional rats. In Experiment 2, (14)C-alpha-CD (25 microCi, 200 mg/kg bw) was given by gavage to four male and four female germ-free rats. ⋯ No (14)C-alpha-CD was found in the feces. It is concluded from the data that ingested (14)C-alpha-CD is not digested in the small intestine of rats but is fermented completely by the intestinal microbiota to absorbable short-chain fatty acids. Therefore, the metabolism of alpha-CD resembles closely that of resistant starch or other fermentable dietary fibers.
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Regul. Toxicol. Pharmacol. · Jun 2004
Embryotoxicity and teratogenicity study with alpha-cyclodextrin in rats.
The embryotoxicity/teratogenicity of alpha-cyclodextrin (alpha-CD) was examined in Wistar Crl:(WI)WU BR rats. alpha-CD was fed at dietary concentrations of 0, 1.5, 5, 10, or 20% to groups of 25 pregnant female rats from day 0 to 21 of gestation. An additional group received a diet with 20% lactose. The additions to the diet of alpha-CD and lactose were made at the expense of pregelatinized potato starch. ⋯ Maternal reproductive performance was not affected by the alpha-CD treatment. Examination of the fetuses for external, visceral and skeletal changes did not reveal any fetotoxic, embryotoxic, or teratogenic effects of alpha-CD. In conclusion, no adverse effects were observed at alpha-CD intakes of up to 20% of the diet, the highest dose level tested at which the rats consumed about 13 g/kg bw/day.
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Regul. Toxicol. Pharmacol. · Jun 2004
Embryotoxicity and teratogenicity study with alpha-cyclodextrin in rabbits.
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. ⋯ 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.
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Regul. Toxicol. Pharmacol. · Jun 2004
Allometric principles for interspecies extrapolation in toxicological risk assessment--empirical investigations.
Four types of data (toxicokinetic data of pharmaceuticals from six species including humans, LD(50) values from eight animal species, long-term NOAEL values of pesticides from mice, rats, and dogs, and toxicity data on anti-neoplastic agents from six species including humans) were used for interspecies comparisons. Species differences with regard to kinetic parameters and toxicity were evaluated and the concordance with predictions by allometric scaling according to caloric demand (allometric exponent 0.75) or to body weight (allometric exponent 1) was checked. For LD(50) values, agreement was poor for both allometric concepts. ⋯ The other three datasets are clearly in agreement with the allometric scaling according to caloric demand. Caloric demand scaling is thus proposed as a generic interspecies extrapolation method in the absence of substance-specific data. Moreover, the evaluated data make it possible to describe uncertainty associated with the process of interspecies extrapolation by allometric rules.
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summary“Cyclodextrin is frequently used in foods and cosmetics because it can change the physical properties of various compounds by their encapsulation within the cyclic structure. The average person is thought to ingest about 4 g of gamma-cyclodextrin per day from food. ... even people who have never received sugammadex may be sensitised by food and cosmetics.” (Mertes 2019)