Category | Effects | Occurrence, dosage, and frequency (Cases/Total number) |
---|---|---|
Hepatotoxicity | Increase in centrolobular hypertrophy, eosinophilic granuloma, and vacuolization of liver cells | (a) Male rats, 2 mg/kg of feed (b) Male and female rats, 5 or 20 mg/kg of feed |
Electron microscopic results | Mild to moderate hyperplasia of the smooth endoplasmic reticulum, minimal to mild hypertrophy of liver cells, and no peroxisome proliferation | In a proportion of the animals that received 20 mg/kg of feed |
Neoplastic effects | Significant increase in the incidence of (a) adenomas of the liver, (b) follicular adenomas of the thyroid, (c) hepatocellular adenomas, carcinomas, (d) follicular adenomas and carcinomas of the thyroid, (e) fibrocystic breast adenomas/adenomas, and (f) fibrocystic breast adenomas/adenomas/carcinomas | (a) Male rats, 20 mg/kg of feed (7/60), control (0/60) (b) Comparison group (9/39), control (3/60), group with highest dosage (4/59) (c) Female rats, 20 mg/kg of feed (d) Female rats, 5 mg/kg of feed (3/50), control (0/60) (e) Female rats with the exception of the group with the highest dosage (f) Female rats, 0.5 mg/kg of feed (36/50), 2 mg/kg (31/48), but not for the group with 5 and 20 mg/kg of feed (29/50 and 24/60), control (29/60) |