© 1992 Oxford University Press
research-article |
Application of Molecular Encapsulation for Toxicology Studies: Comparative Toxicity of p-Chloro-
,,-trifluorotoluene in -Cyclodextrin Vehicle versus Corn Oil Vehicle in Male and Female Fischer 344 Rats and B6C3F1 Mice
National Institutes of Health, National Institute of Environmental Health Sciences P.O. Box 12233, Research Triangle Park, North Carolina 27709
Received April 18, 1991; accepted October 9, 1991
The application of 
-cyclodextrin (-CD) as an alternative vehicle for water insoluble and volatile chemicals was investigated in toxicity studies of p-chloro-,,-trifluorotoluene (CTFT). Groups of F344 rats and B6C3F1 mice of each sex were administered CTFT (97% pure) by gavage in either corn oil or -CD aqueous formulations daily for 14 consecutive days. The dose levels used were 10 (mice only), 50, 400, and 1000 mg/kg for corn oil vehicle and 10, 50, and 400 mg/kg (maximum achievable dose at gavage volume of 5 ml/kg) for -CD vehicle. With both vehicles CTFT and a2u-globulin were found to accumulate in the male rat kidney after 14 days of exposure and a dose-related toxic nephropathy was observed at dose of 50 mg/kg or higher. The hepatocellular hypertrophy and cytoplasmic vacuolation of the adrenal cortex which appeared in dosed male and female rats were also found to be independent of vehicle. Clinical pathology findings suggested a mild anemia and cholestasis in rats. With both vehicles no tissue bioaccumulation of CTFT was found in male or female mice. Vehicle-independent hepatocellular hypertrophy and cholestasis were also observed in mice at doses of 400 and 1000 mg/kg. In conclusion, the -CD vehicle does not affect the toxic responses of CTFT in both sexes of both species. The results of the studies suggest that -CD may be an appropriate alternative vehicle for toxicity studies.