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O b j e c t i v e s: Arsenic (As) is ubiquitously distributed in the environment and is known as a human carcinogen. In this study, acute As toxicity at lethal dosage in rats and mice was evaluated, and As-induced hepatotoxicity was characterized. M e t h o d s: Male Sprague-Dawley rats, male ICR mice and trivalent inorganic As, sodium arsenite, were used in this experiment. LD50 and LD 100 were calculated from 24-hour lethality after the single subcutaneous administration of As into rats and mice. Serum and liver were collected from the surviving animals. The activities of ALT, AST and γ-GT in serum were determined, and the concentrations of MDA, GSH and CYP450 in liver were analyzed. Results: The LD50 and LD100 of sodium arsenite were calculated as 12 mg/kg and 13 mg/kg for rats, and 16.5 mg/kg and 19 mg/kg for mice, respectively. Thus, the rat was more susceptible than the mouse to the acute lethal toxicity of As. The histopathological changes induced by As were similar between rats and mice. AST was increased in high-dose As-treated rats and mice, whereas ALT was increased in high-dose As-treated mice but not in rats. γ-GT was not significantly changed between the two animal groups. As increased lipid peroxidation, but decreased GSH and CYP450 in the liver of both rats and mice, in dose-dependent patterns. These results indicate that oxidative stress might be one of the mechanisms in As-induced hepatotoxicity. Conclusion: Rats were more susceptive than mice to acute As toxicity, and oxidative stress might play a part in liver injury induced by As.

Objectives: The purpose of this study was to evaluate the trichloroethylene (TCE) metabolism, acute toxicity, and the effects of diethyldithiocarbamate (DDTC) on the acute toxicity in TCE-intoxicated rats. Methods: TCE was administered orally at doses of 600, 1,200 and 2,400 mg/kg of body weight following pretreatment with either saline or 500 mg/kg of DDTC. 12 hours after administration of TCE, the concentrations of TCE, trichloroacetic acid (TCA) and trichloroethanol (TCEOH) in the blood and solid organs, and the histopathological changes in each organ were examined. Results: The level of CYP2E1 markedly decreased in the DDTC-pretreated groups. The CYP2E1 content in the TCE-treated rats increased in a dose-dependent manner. The concentrations of TCE and TCEOH were highest in the liver, and the level of TCA was highest in the blood. The DDTC-pretreated rats had a markedly increased level of TCE and decreased levels of TCA and TCEOH, than the rats pretreated with saline. These findings indicated that CYP2E1 was important in the metabolism of TCE. From the histopathological findings, centrilobular necrosis was observed in the livers of the TCE-treated rats, but no significant change was found in those rats pretreated with DDTC. Conclusions: DDTC is considered to be effective in protecting TCE-induced hepatic damage because it inhibits the TCE metabolism.