Abstract
Acute toxicity and 14-day repeated-dose toxicity studies were performed via oral gavage to elucidate the effects of oral exposure to carbon tetrachloride (CCl(4)) on the liver of zebrafish. In the acute toxicity studies, the lethal dose 50% (LD(50)) was 386 μL/kg (614 mg/kg, based on density conversion) for both males and females when using a 1% Tween aqueous solution vehicle, and 5,045 μL/kg (8,036 mg/kg) for males and 6,419 μL/kg (10,206 mg/kg) for females when using a corn oil vehicle (cf., rats: 10,054 mg/kg; mice: 13,000 mg/kg, according to known LD(50) values). The doses in the repeated toxicity study were set at 0, 200, and 300 μL/kg using a 1% Tween aqueous solution as the vehicle. The survival rate was 87% on Day 7 and 50% on Day 14 in the 200 μL/kg CCl(4)-treated group, while it was 10% on Day 7 in the 300 μL/kg CCl(4)-treated group. Histopathological findings, including focal bile duct proliferation, focal macrophage aggregation, and focal fibrosis, were detected in both acute and repeated-dose toxicity studies. However, no significant differences were observed in the incidence of these lesions between the control and CCl(4)-treated groups. Therefore, the present study demonstrates that the acute lethal dose of CCl(4) administered via oral gavage in zebrafish is nearly equivalent to that observed in rodents. However, zebrafish exhibit markedly low sensitivity to CCl(4)-induced liver injury in a species-specific manner.