Objectives: This study was performed to analyse a 13-week repeated dose toxicity and 4-week recovery test of Sweet Bee Venom (SBV) extracted from bee venom in Sprague-Dawley (SD) rats.

Methods: Male and female 5-week-old SD rats treated once daily with SBV (high dosage, 0.28 ㎎/㎏; medium dosage, 0.14 ㎎/㎏; or low dosage, 0.07 ㎎/㎏) for 13 weeks followed by a 4-week recovery period. Normal saline was administered to the control group in a similar manner. We conducted clinical observations, body weight measurement, ophthalmic examination, urinalysis, hematology, biochemistry, histological observations using H-E staining to identify any abnormalities from SBV treatment.

Results:
1. No mortality was observed in any of the experimental groups.
2. Hyperemia and a movement disorder were observed around the area of administration in all experiment groups, with a higher occurrence in rats treated with the higher dosage, during the treatment period compared to the control group. These symptoms were not observed during the recovery period.
3. Male rats receiving the high dosage treatment showed a significant decrease in weight during weeks of the treatment period.
4. No significant changes in the experimental groups compared to controls were observed with respect to ophthalmic parameters, urine analysis, CBC, and biochemistry.
5. Some changes in organ weights were observed in the experimental groups, but these changes were not observed during the recovery period.
6. Histological examination of thigh muscle indicated cell infiltration, inflammation, degeneration, necrosis of muscle fiber, and fibrosis in both the medium and high dosage groups. These changes were not observed during the recovery period. Fatty liver change was observed in the periportal area of rats receiving medium and high dosage SBV treatment. These changes were not observed during the recovery period. No other organ abnormalities were observed.