Effect of single and repeated-dose oral administration of carbon tetrachloride on liver in zebrafish

Acute toxicity and 14-day repeated-dose toxicity studies were performed via oral gavage to elucidate the effects of oral exposure to carbon tetrachloride (CCl₄) on the liver of zebrafish. In the acute toxicity studies, the lethal dose 50% (LD₅₀) 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 LD₅₀ 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 CCl₄-treated group, while it was 10% on Day 7 in the 300 μL/kg CCl₄-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 CCl₄-treated groups. Therefore, the present study demonstrates that the acute lethal dose of CCl₄ administered via oral gavage in zebrafish is nearly equivalent to that observed in rodents. However, zebrafish exhibit markedly low sensitivity to CCl₄-induced liver injury in a species-specific manner.