Subchronic Toxicity of Orally Administered Beta-Cyclodextrin in Rats

Olivier, Philippe; Verwaerde, Francoise; Hedges, Allan R.

doi:10.3109/10915819109078639

Cited by 30 publications

(19 citation statements)

References 8 publications

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“…It is namely considered that the adverse hepatic and renal effects of b-CD result from an interaction of absorbed b-CD with the cholesterol of the cellular and lyosomal membranes. The absorption of unchanged b-CD has been estimated at 0.1-1.1% in rats (Frijlink et al, 1990;Kubota et al, 1996;Olivier et al, 1991). Experiments with human erythrocytes have indeed shown that incubation in the presence of a-CD (5 mM), b-CD (2 mM), and c-CD (15 mM) released 0, 19.9, and 2.0% cholesterol, respectively (Irie et al, 1982).…”

Section: Discussionmentioning

confidence: 96%

Subchronic oral toxicity studies with α-cyclodextrin in rats

Lina

Bär²

2004

Regulatory Toxicology and Pharmacology

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Section: Discussionmentioning

confidence: 96%

Subchronic oral toxicity studies with α-cyclodextrin in rats

Lina

Bär²

2004

Regulatory Toxicology and Pharmacology

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“…In a 90-day dietary study with Sprague-Dawley rats (6 groups/20 animals/sex per group) were fed diets supplemented with b-cyclodextrin at concentrations of 1.25, 2.5, 5 or 10% (equal to 668, 1,335, 2,676 or 5,439 mg/kg bw per day and to 738, 1,488, 3,045 or 6,074 mg/kg bw per day for males and females, respectively) (Olivier et al, 1991). One group received a diet with 10% lactose (mean 90-day intake 5,235 mg/kg bw per day for males and 5,875 mg/kg bw per day for females).…”

Section: Short-term and Subchronic Toxicitymentioning

confidence: 99%

Re‐evaluation of β‐cyclodextrin (E 459) as a food additive

Mortensen¹,

Aguilar²,

Crebelli³

et al. 2016

EFS2

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The EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS) provides a scientific opinion re‐evaluating the safety of β‐cyclodextrin (E 459) as a food additive. β‐Cyclodextrin is a non‐reducing cyclic oligosaccharide consisting of seven α‐1,4‐linked d‐glucopyranosyl units. The Scientific Committee on Food (SCF) allocated an acceptable daily intake (ADI) of 5 mg/kg body weight (bw) per day to β‐cyclodextrin (E 459) in 1996. β‐Cyclodextrin is poorly absorbed following oral administration in animals and humans. It is hydrolysed to maltose and glucose by the gut microflora and endogenous amylases in the colon; consequently, β‐cyclodextrin levels in tissues and serum are low (< 1%). β‐Cyclodextrin has a low acute oral toxicity. Short‐term and subchronic toxicity studies were available in rats and dogs. In rats, the main reported effect was an adaptive enlargement of the caecum, resulting from consumption of poorly digestible carbohydrates. From a 6‐month study in rats, a no observed adverse effect levels (NOAEL) of 600 mg/kg bw per day was identified and from a 52‐week dogs study, the NOAEL was 466 and 476 mg/kg bw per day in males and females, respectively. The Panel considered that there was no indication for genotoxicity of β‐cyclodextrin. From a chronic toxicity studies in rats, a NOAEL of 654 and 864 mg/kg bw per day in males and females, respectively, was identified. Carcinogenicity studies in mice and rats were available and no evidence for carcinogenicity was found. The Panel concluded that, based on the available toxicological database, there is no reason to revise the current ADI of 5 mg/kg bw per day for β‐cyclodextrin. Based on the available reported use and use levels, the Panel also concluded that the ADI was exceeded in the refined brand‐loyal scenario (considered the most relevant scenario) in all population groups except for infants at the mean and in all population groups at the 95th percentile.

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“…48 The only consistent treatment-related effect noted was an increase in filled cecal weight, which was considered to be a generic response to poorly digestible carbohydrates. Mortality is not observed even in animals receiving the highest possible oral doses of the parent CDs.…”

Section: Safety Profilesmentioning

confidence: 99%

Pharmaceutical Applications of Cyclodextrins. III. Toxicological Issues and Safety Evaluation

Irie

Uekama

1997

Journal of Pharmaceutical Sciences

843

520

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The objective of this review is to summarize recent findings on the safety profiles of three natural cyclodextrins (alpha-, beta- and gamma-CDs) and several chemically modified CDs. To demonstrate the potential of CDs in pharmaceutical formulations, their stability against non-enzymatic and enzymatic degradations in various body fluids and tissue homogenates and their pharmacokinetics via parenteral, oral, transmucosal, and dermal routes of administration are outlined. Furthermore, the bioadaptabilities of CDs, including in vitro cellular interactions and in vivo safety profiles, via a variety of administration routes are addressed. Finally, the therapeutic potentials of CDs are discussed on the basis of their ability to interact with various endogenous and exogenous lipophiles or, especially for sulfated CDs, their effects on cellular processes mediated by heparin binding growth factors.

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Subchronic Toxicity of Orally Administered Beta-Cyclodextrin in Rats

Cited by 30 publications

References 8 publications

Subchronic oral toxicity studies with α-cyclodextrin in rats

Subchronic oral toxicity studies with α-cyclodextrin in rats

Re‐evaluation of β‐cyclodextrin (E 459) as a food additive

Pharmaceutical Applications of Cyclodextrins. III. Toxicological Issues and Safety Evaluation

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