SUBCHRONIC (13-WEEK) ORAL TOXICITY STUDY OF GAMMA-CYCLODEXTRIN IN DOGS

The oral toxicity of gamma-cyclodextrin (gamma-CD) was examined in a 1 3-week feeding study in which four groups of four male and four female Beagle dogs received gamma-CD in the diet at concentrations of 0 (con trol), 5, 10, or 20%. No treatment-related changes were noted in behav ior or appearance of the dogs and no mortalities occurred. Transient d iarrhea occurred in some dogs of the 5 and 10% dose groups and in all dogs of the 20% dose group. However, all dogs remained in good health and gained weight. During the last 6 weeks of the study, the males of the 20% dose group gained less weight, but body weights were not signi ficantly reduced in comparison to controls. Food intakes and food effi ciencies were comparable among all groups. No treatment-related differ ences were observed with respect to ophthalmoscopic examinations, hema tological parameters, clinicochemical analyses of the plasma, and semi quantitative urine analyses. Only the urinary pH was slightly below co ntrol levels in males of the 20% dose group. No abnormalities were see n at necropsy that could be attributed to treatment. The organ weight data revealed some cecal enlargement in the 10 and 20% dose groups. Re lative ovary weights were significantly increased in the 10 and 20% gr oups but this was probably a result of an unusually low ovary weight i n the controls. An increase of relative liver weights in males of the 10 and 20% dose groups also was considered to lack toxicological relev ance because it was not associated with changes in plasma liver enzyme levels or histopathological changes. On microscopic examination, no t reatment-related effects were observed in any of the various organs an d tissues. In conclusion, transient diarrhea, cecal enlargement, and a slightly increased acidity of the urine were the only treatment-relat ed effects reported. These changes are well-known physiological respon ses to the presence of increased amounts of undigested, fermentable ca rbohydrates in the lower gut. At the high applied intakes an incomplet e digestion of gamma-CD and/or a partial inhibition of pancreatic amyl ase by gamma-CD could account for these effects. It is concluded that daily gamma-CD consumption of up to 20% in the diet (approximately 7.7 g/kg body wt in male and 8.3 g/kg body wt in female dogs) was tolerat ed without any toxic effects. (C) 1998 Academic Press.