Safety assessment of gamma-cyclodextrin.

I C Munro, P M Newberne, V R Young, A Bär

Index: Regul Toxicol Pharmacol 39 Suppl 1 , S3-13, (2004)

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Abstract

Gamma-cyclodextrin (gamma-CD) is a cyclic alpha-(1,4)-linked oligosaccharide consisting of eight glucose molecules. Like other cyclodextrins, gamma-CD can form inclusion complexes with a variety of organic molecules because the inner side of the torus-like molecule is less polar than the outer side. In foods, gamma-CD may be used as a carrier for flavors, vitamins, polyunsaturated fatty acids, and other ingredients. It also has useful properties as a stabilizer in different food systems. The daily intake from all its intended uses in food at highest feasible concentrations has been estimated at 4.1g/person/day for consumers of gamma-CD containing foods. The present review summarizes the safety data of gamma-CD. The toxicity studies consist of standard genotoxicity tests, subchronic rat studies with oral and intravenous administration of gamma-CD for up to 3 months, a subchronic (3-month) toxicity study in dogs, a (1-year) oral toxicity study in rats, and embryotoxicity/teratogenicity studies in rats and rabbits. In the studies with oral administration, gamma-CD was given at dietary concentrations of up to 20%. All these studies demonstrated that gamma-CD is well tolerated and elicits no toxicological effects. Metabolic studies in rats showed that gamma-CD is rapidly and essentially completely digested by salivary and pancreatic amylase. Therefore, the metabolism of gamma-CD closely resembles that of starch and linear dextrins. A human study with ingestion of single doses of 8 g gamma-CD or 8 g maltodextrin did not reveal a difference in gastrointestinal tolerance of these two products. An interaction of ingested gamma-CD with the absorption of fat-soluble vitamins or other lipophilic nutrients is not to be expected because the formation of inclusion complexes is a reversible process, gamma-CD is readily digested in the small intestine, and studies with beta-CD, a non-digestible cyclodextrin, have shown that the bioavailability of vitamins (A, D, and E) is not impaired. On basis of these studies it is concluded that gamma-CD is generally recognized as safe (GRAS) for its intended uses in food.