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, it 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 Swiss Albino mice 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 17. On gd 17, the dams were terminated and the fetuses removed from the uterus and examined for evidence of developmental toxicity.
In the dams, 20% CDEX increased maternal relative food consumption at the end of (gd 12 to 16) and after (gd 16 to 17) the dosing period, with an increase in maternal weight gain after the dosing period (gd 16 to 17). No CDEX-related effects on maternal food intake were noted for the lower doses of the compound. Based on the average relative food consumption during the dosing period, the 5, 10, and 20% CDEX groups ingested approximately 13.7, 23.1, and 49.3 g/kg/day CDEX. Maternal relative water consumption was unaffected by CDEX administration. Maternal liver (absolute and relative) and gravid uterine weights in the CDEX-treated animals were also comparable to control values.
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/litter, 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 CDEX administered to pregnant mice at levels as high as 20% in feed had no adverse effect on embryo/fetal development. Thus the no observed adverse effect level for developmental toxicity was approximately 49.3 g/kg/day. The lowest observed adverse effect level maternal toxicity of CDEX was 49.3 g/kg/day based on altered maternal weight gain late in gestation and the NOAEL for maternal toxicity was 23.1 g/kg/day.