INVESTIGATION OF SUBCHRONIC ORAL TOXICITY OF 4-CHLORO-A,A,A-TRIFLUOROTOLUENE

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Corn oil has been associated with proliferative exocrine pancreatic lesions in rats. Because of this, alternative vehicles for gavage studies are being investigated. Alpha-Cyclodextrin is being studied as an alternative to corn oil because of its ability to "complex" with organic molecules and enhance their water solubility and/or suspendability. This study was designed to characterize the toxicity (CTFT) associated with a 14-day repeated exposure of 4-chloro-alpha, alpha, alpha-trifluorotcluene to F344 rats and B6C3F1 mice via gavage using corn oil and alpha-cyclodextrin as the gavage vehicles. The bioavailability and biological half life of CTFT was found to be similar in both vehicles: although absorption from the gut was faster with alpha-cyclodextrin. The major toxic effects of CTFT was to cause accumulation of alpha-2u globulin in the kidney of the male rat, leading to "hyaline droplet nephropathy". Dosed male and female rats also had hepatocyte hypertrophy and cytoplasmic vacuolization of the adrenal cortex. Hepatocellular hypertrophy and clinical pathology findings consistent with mild liver injury were noted in mice. The toxicity of CTFT was not affected by the different vehicles in these studies. This study has been completed.