Application of Molecular Encapsulation for Toxicology Studies: Comparative Toxicity of p-Chloro-{alpha},{alpha},{alpha}-trifluorotoluene in {alpha}-Cyclodextrin Vehicle versus Corn Oil Vehicle in Male and Female Fischer 344 Rats and B6C3F1 Mice

The application of -cyclodextrin (-CD) as an alternative vehiclefor water insoluble and volatile chemicals was investigatedin toxicity studies of p-chloro-,,-trifluorotoluene (CTFT).Groups of F344 rats and B6C3F1 mice of each sex were administeredCTFT (97% pure) by gavage in either corn oil or -CD aqueousformulations daily for 14 consecutive days. The dose levelsused were 10 (mice only), 50, 400, and 1000 mg/kg for corn oilvehicle and 10, 50, and 400 mg/kg (maximum achievable dose atgavage volume of 5 ml/kg) for -CD vehicle. With both vehiclesCTFT and a_2u-globulin were found to accumulate in the male ratkidney after 14 days of exposure and a dose-related toxic nephropathywas observed at dose of 50 mg/kg or higher. The hepatocellularhypertrophy and cytoplasmic vacuolation of the adrenal cortexwhich appeared in dosed male and female rats were also foundto be independent of vehicle. Clinical pathology findings suggesteda mild anemia and cholestasis in rats. With both vehicles notissue bioaccumulation of CTFT was found in male or female mice.Vehicle-independent hepatocellular hypertrophy and cholestasiswere also observed in mice at doses of 400 and 1000 mg/kg. Inconclusion, the -CD vehicle does not affect the toxic responsesof CTFT in both sexes of both species. The results of the studiessuggest that -CD may be an appropriate alternative vehicle fortoxicity studies.