The oral toxicity of α-cyclodextrin (α-CD) was examined in a 13-week feeding study in which groups of Beagle dogs received α-CD in the diet at concentrations of 0 (control), 5, 10, or 20% (4dogs/sex/group). No treatment-related changes were noted in behavior or appearance of the dogs and no mortalities occurred. Diarrhea occurred in all α-CD groups. The incidence and severity of diarrhea increased with increasing dietary levels of α-CD and was more pronounced in males than females. Nonetheless, all dogs remained in good health and gained weight. Food intake was slightly increased and food efficiency was slightly decreased in the 20% α-CD group. However, these changes did not reach statistical significance. No treatment-related differences were observed with respect to ophthalmoscopic examinations, hematological parameters, clinicochemical analyses of the plasma, and semiquantitative urine analyses. Only the urinary pH was slightly below control levels in males (p>0.05) and females (p<0.05) of the 20% α-CD group. No abnormalities were seen at necropsy that could be attributed to the treatment. The organ weight data revealed cecal enlargement in the 10 and 20% α-CD groups (significant only in males). The relative weight of the colon was also slightly increased in the 10 and 20% α-CD groups (significant only in females of the 10% α-CD group). On microscopic examination, no treatment-related alterations were observed in any of the various organs and tissues. In conclusion, transient diarrhoea, enlargement of the cecum and colon and a slightly increased acidity of the urine were the only treatment-related effects. These changes are well-known physiological responses to the presence of high amounts of not digested, fermentable carbohydrates in the lower gut. They are known to be reversible on cessation of the treatment and are not associated with histological alterations of the intestinal tissues. It is concluded, therefore, that the high dose level, at which the male and female dogs consumed about 9.8 and 10.4g α-CD/kgbw/d, respectively, is the NOAEL of this 13-week toxicity study. © 2004 Elsevier Inc. All rights reserved.