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

玉米油与胰腺外分泌增生性病变有关 对大鼠 因此，灌胃研究的替代溶剂为 正在调查 正在研究α-环糊精作为替代品 玉米油，因为它能够与有机分子“复合”， 提高它们的水溶性和/或悬浮性。 本研究旨在描述与以下药物相关的毒性（CTFT）： 14天重复暴露于4-氯-α，α，α-三氟甲苯 F344大鼠和B6 C3 F1小鼠通过灌胃给予玉米油， α-环糊精作为灌胃媒介物。 的生物利用度和 发现CTFT的生物半衰期在两种载体中相似： 尽管用α-环糊精从肠道吸收更快。 的 CTFT的主要毒性作用是引起α-2u球蛋白蓄积 在雄性大鼠的肾脏中，导致“透明小滴肾病”。 给药的雄性和雌性大鼠也出现肝细胞肥大和细胞质 肾上腺皮质空泡化。 肝细胞肥大和 临床病理学结果与轻度肝损伤一致， 小鼠 CTFT的毒性不受不同载体的影响， 这些研究。 这项研究已经完成。

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.