Registration Dossier

Toxicological information


Currently viewing:

Administrative data

Description of key information

The substance did not show any evidence of carcinogenic effects when administered orally in feed at concentrations of up to 675 mg/kg bw to rats and mice. 

Key value for chemical safety assessment

Carcinogenicity: via oral route

Endpoint conclusion
Dose descriptor:
675 mg/kg bw/day

Additional information

The carcinogenic potential of beta-cyclodextrin (86.6 and 87.0 % pure) was investigated in a life-time feeding study according to OECD Guidelines 451. Four groups of CD-1 mice were fed diet containing beta-cyclodextrin continuously to provide dosages of 25, 15, 225 and 675 mg/kg/day for a maximum of 106 weeks in females and 93 weeks in males. A control group fed basal diet, was treated concurrently. Treatment at all doses was well tolerated with no clinical signs of reaction to treatment. There were no palpable masses attributed to treatment. Survival rate was similar in all groups. Body weight, food intake and water consumption were similar in all groups throughout the entire study period. Slight changes sporadically observed in the haematology parameters examined are not considered as treatment-related but the result of normal biological variances. At terminal sacrifice no difference was apparent in any of the organs weighed at necropsy.Findings related to treatment with beta-cyclodextrin were noted in the large intestine; a reduction of abdominal fat pads in decedent mice, mainly of the highest dosage group was also observed. The main changes in the highest dosage group observed in the large intestine included: abnormal contents, distended lumen and oedematous mucosa. All other macroscopic changes were considered unrelated to treatment with beta-cyclodextrin.None of the observed neoplastic lesions was associated with the life-span treatment with beta-cyclodextrin. The only treatment-related changes associated with this compound were of the non-neoplastic type and were observed particularly in decedent mice mainly of the highest dosage group (7 male and 6 female mice of the highest dosage group, one male mouse of the high intermediate and two male mice of the low intermediate dosage group). Such changes were limited to various segments of the large intestine, mostly the caecum, and atrophy of abdominal fat pads. The latter achieved statistical significance (p<0.05) with an increase of dose in males and in data combined by sex. The lesions observed in the large intestine included: evidence of active desquamation of surface epithelium and mucosa covered by mucous secretion containing exfoliated cells. Changes noted solely in the caecum were: acute catarrhal inflammation, mucosal flattening and atrophy of intestinal glands. The last two lesions achieved significant values for males and females (p < 0.01, p < 0.01) respectively. Colonic mucosa covered by mucous secretion achieved a highly significant value (p < 0.01) in females and in data combined by sex. No non-neoplastic treatment-related lesion was observed in terminally killed mice, except for one male mouse of the highest dosage group showing caecal lesions. Under the conditions of this study beta-cyclodextrin is assessed as showing no evidence of carcinogenicity in the mouse.

beta-cyclodextrin (86.6 and 87.0 % pure) was examined in an oncogenicity study in F344 rats according to OECD Guideline 451 found to have no effect on survival,or potential to cause carcinogenic effects in this species. 50 animals of each sex were administered with 0, 25, 75, 225 and 675 mg/kg/day for 122 weeks (males) and 130 weeks (females) respectively. In addition, neither toxic clinical signs nor effects on body weight, food and water consumption were detected throughout the study period. The highest dosage tested in this study was 675 mg/kg per day. Regarding the observed increased incidence of several tumors in the study, none of the tumors exceed the background data. Uterine adenocarcinomas, although occurring at a slightly higher incidence in the highest dosage group, but not statistically significant, are regarded as a spontaneous, incidental finding, and of no biological significance. In fact, the incidence of this neoplasm showed a dramatic increase when the incidence of the testing facility background data accumulated for 24 month studies, was compared to the concurrent controls (range of 3.3-8.3% in 24 month studies, compared to 24% incidence in the current control). Therefore it can be concluded that the slight increase of uterine adenocarcinoma in the current study in the highest dosage group occurred by chance and has no bearing on the treatment with beta-cyclodextrin. Regarding the parathyroid adenoma and subcutaneous fibroma, the incidence in all groups was comparable with the background data. In relation to the significant trend for the Leydig cell tumour, this effect was not considered related to treatment but due to the naturally high incidence of this tumor in this strain, and due to the fact that the incidence of the tumor did not exceed the literature data on this tumor in Fischer 344 rats, which is generally considered to be about 100%. In conclusion, chronic feeding of beta-cyclodextrin to Fischer 344 rats mice did not cause any treatment related carcinogenic effects.

Another examination of the carcinogenicity of .beta.-cyclodextrin was carried out in Fischer 344 (F344) rats.Groups of 50 males and 50 females were given the compound in their diet at concentrations of 0 (control), 2.5 or 5% for 104 wk. Surviving rats were then given a basal diet for a further 5 wk and killed at 109 wk. The dose levels were selected from the results of a 13-wk subchronic toxicity study. Dose dependent inhibitory effects of .beta.-cyclodextrin on growth were observed in both sexes of the treated groups. The survival rates, mean survival times and range, however, demonstrated no significant differences between the control and treated groups.A variety of tumours developed in all groups, including the control group, but all the neoplastic lesions were histologically similar to those known to occur spontaneously in this strain of rat. and no statistically significant increase in the incidence of any tumour was found for either sex of the treated groups. Thus it is concluded that under the present experimental conditions the high dose, about 340-400 times higher than the current daily human intake from ingestion as a food additive and from pharmaceutical usedoes not have any carcinogenic potential in F344 rats.


Justification for classification or non-classification