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.
Fundam Appl Toxicol
; 18(3): 460-70, 1992 Apr.
Article
in En
| MEDLINE
| ID: mdl-1375921
ABSTRACT
The application of alpha-cyclodextrin (alpha-CD) as an alternative vehicle for water insoluble and volatile chemicals was investigated in toxicity studies of p-chloro-alpha, alpha, alpha-trifluorotoluene (CTFT). Groups of F344 rats and B6C3F1 mice of each sex were administered CTFT (97% pure) by gavage in either corn oil or alpha-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 alpha-CD vehicle. With both vehicles CTFT and alpha 2u-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 alpha-CD vehicle does not affect the toxic responses of CTFT in both sexes of both species. The results of the studies suggest that alpha-CD may be an appropriate alternative vehicle for toxicity studies.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Toluene
/
Alpha-Cyclodextrins
Limits:
Animals
/
Female
/
Humans
/
Male
/
Newborn
Language:
En
Journal:
Fundam Appl Toxicol
Year:
1992
Document type:
Article