title: Study of a 13-weeks, Repeated, Intramuscular Dose, Toxicity Test of Sweet Bee Venom in Sprague-Dawley Rats.
abstract: OBJECTIVE
  This study was performed to analyze a 13-week repeated dose toxicity test of Sweet Bee Venom (SBV) extracted from bee venom and administered in Sprague-Dawley (SD) rats.
  
  
  METHODS
  Male and female 5-week-old SD rats were treated once daily with SBV (high-dosage group: 0.28 mg/kg; medium-dosage group: 0.14 mg/kg; or low-dosage group: 0.07 mg/kg) for 13 weeks. Normal saline was administered to the control group in a similar manner (0.2 mL/kg). We conducted clinical observations, body weight measurements, ophthalmic examinations, urinalyses, hematology and biochemistry tests, and histological observations using hematoxylin and eosin (H&E) staining to identify any abnormalities caused by the SBV treatment.
  
  
  RESULTS
  During this study, no mortality was observed in any of the experimental groups. Hyperemia and a movement disorder were observed around the area of in all groups that received SBV treatment, with a higher occurrence in rats treated with a higher dosage. Male rats receiving in the high-dosage group showed a significant decrease in weight during the treatment period. Compared to the control group, no significant changes in the ophthalmic parameters, the urine analyses, the complete blood cell count (CBC), and the biochemistry in the groups treated with SBV. Compared to the control group, some changes in organ weights were observed in the medium-and the high-dosage groups, but the low-dosage group showed no significant changes. Histological examination of thigh muscle indicated cell infiltration, inflammation, degeneration, and necrosis of muscle fiber, as well as fibrosis, in both the medium- and the high-dosage groups. Fatty liver change was observed in the periportal area of rats receiving medium and high dosages of SBV. No other organ abnormalities were observed.
  
  
  CONCLUSIONS
  Our findings suggest that the No Observed Adverse Effect Level (NOAEL) of SBV is approximately 0.07 mg/kg in male and female SD rats.
authors.affiliation: Department of Acupuncture & Moxibustion Medicine, Sangji University College of Oriental Medicine, Wonju, Korea.
authors.forename: Hyunmin
authors.initials: H
authors.lastname: Kang
authors.affiliation: Department of Acupuncture & Moxibustion Medicine, Sangji University College of Oriental Medicine, Wonju, Korea.
authors.forename: Chungsan
authors.initials: C
authors.lastname: Lim
authors.affiliation: Research Center of the Korean Pharmacopuncture Institute, Seoul, Korea.
authors.forename: Ki-Rok
authors.initials: KR
authors.lastname: Kwon
authors.affiliation: Department of Acupuncture & Moxibustion Medicine, Sangji University College of Oriental Medicine, Wonju, Korea.
authors.forename: Kwangho
authors.initials: K
authors.lastname: Lee
keywords: 13 weeks repeated dose toxicity; intramuscular; melittin; pharmacopuncture; rats; sweet bee venom