The following abstract presents results of a study conducted by a contract laboratory for the National Toxicology Program. The findings may not have been peer reviewed and were not evaluated in accordance with the levels of evidence criteria established by NTP in March 2009. For more information, see the Explanation of Levels of Evidence for Developmental Toxicity. The findings and conclusions for this study should not be construed to represent the views of NTP or the U.S. Government.
a-Cyclodextrin is a cyclic oligosaccharide composed of six glucopyranose units in a C1 -chair conformation linked by a -1,4 glycosidic bonds. The torus structure of the cyclodextrin forms a cavity which can form inclusion complexes with hydrophobic compounds, greatly increasing their solubility. This property of CDEX has made it increasingly popular as a vehicle for the oral and topical administration of drugs and chemicals. Because of the potentially large population at risk to CDEX exposure and because of its possible use as a vehicle in toxicity testing, CDEX was evaluated for developmental toxicity. In the current study, we determined the effect of CDEX on maternal health and fetal growth, viability, and morphological development. Since the probable route for CDEX exposure would be oral administration, the dextrin was administered in ground feed (0, 5, 10, or 20%) to pregnant Sprague-Dawley rats during the major period of organogenesis (gd 6 to 16). Maternal clinical signs, body weight, and food and water consumption were monitored at regular intervals from gd 0 to 20. On gd 20, the dams were terminated and the fetuses removed from the uterus and examined for evidence of developmental toxicity.
In the dams, CDEX caused dose-dependent increases in maternal relative food consumption during the dosing period (gd 6 to 16). Relative food consumption remained elevated on gd 16 to 18 in the 10% and 20% CDEX groups, but returned to normal by gd 18 to 20. Based on the amount of food consumed during the dosing period, the dams in the control, 5, 10, or 20% CDEX groups ingested approximately 0, 4.2. 9.0, or 20 g/kg/day CDEX, respectively. Maternal water consumption during the dosing period showed no distinct dose-related effects; however, sporadic, individually significant increases in water consumption were observed in all CDEX dose groups. After the dosing period, relative maternal water consumption was elevated on gd 16 to 18 in the 10% and 20% CDEX groups. In spite of the treatment-related increases in maternal food consumption, average maternal body weight or average maternal body weight gain during or after the dosing period was not affected by CDEX administration. This probably resulted from the fact that CDEX is sweet, but has little or no nutritional value. Maternal liver (absolute and relative) and gravid uterine weights were also unaffected by CDEX treatment.
Examination of the uterine contents indicated that CDEX was not developmentally toxic. The percent resorptions/litter, average number of live fetuses/litter, average fetal body weight/Iitter, and sex ratio/litter were comparable to controls at all CDEX dose levels. The incidence of external, visceral, or skeletal malformations showed no treatment-related effects. The incidence of variations was similarly unaffected by CDEX administration.
These results indicate that the no observed adverse effect level for CDEX-induced developmental and maternal toxicity is equal to or greater than 20 g/kg/day, the lowest observed adverse effect level for either developmental or maternal toxicitv could not be determined at the doses tested.