Acute Intravenous Injection Toxicity Study of Escherichia coli-Derived Recombinant Human Bone Morphogenetic Protein-2 in Rat.
METHODS
Prospective in vivo toxicity study.


OBJECTIVE
To evaluate the conducted acute toxicity study of Escherichia coli (E. coli)-derived recombinant human bone morphogenetic protein-2 (rhBMP-2) with 6-weeks old Sprague-Dawley rats.


BACKGROUND
rhBMP-2 has well-known osteoinductivity and it is used as a bone graft substitute. E. coli-derived rhBMP-2 can be mass-produced with relatively low costs. E. coli-derived rhBMP-2 facilitates osteoblastic differentiation and bone formation in vitro and in vivo. However, studies regarding side effects or toxicity of E. coli-derived rhBMP-2 have not been published. Thus, we conducted the acute toxicity study of E. coli-derived rhBMP-2 on 6-weeks old Sprague-Dawley rats.


METHODS
One mg of BMP-2 was diluted in 0.285 mL of glycine buffer to prepare high BMP-2 concentrations (3.5 mg/mL). Intermediate (0.9 mg/mL) or low (0.35 mg/mL) concentrations of BMP-2 solution was prepared by serial dilutions. The compound was administrated at a dose of 0, 0.7, 1.8, 7 mg/kg by single intravenous injection to five of male and female rats. After the injection, the gross general observations including changes of body weight and histopathological analysis was performed for 14 days.


RESULTS
No animal was found dead during the experiment and the body weight changes were both statistically insignificant in the control and experimental groups. No abnormal sign was shown in general observations and autopsy examinations.


CONCLUSIONS
Thus, the lethal dose of E. coli-derived rhBMP-2 should be higher than 7 mg/kg with a single intravenous injection.
Department of Orthopedic Surgery, SMG-SNU Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea. ; Institute of Medical and Biological Engineering, Medical Research Center, Seoul National University, Seoul, Korea.
Jae Hyup
JH
Lee
The Research and Development Institute, Daewoong Pharmaceutical Corporation, Yongin, Korea.
Eui-Nam
EN
Lee
Department of Orthopedic Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.
Bong-Soon
BS
Chang
Department of Orthopedic Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.
Choon-Ki
CK
Lee
Acute toxicity test; Intravenous injection; Mortality; Recombinant human-bone morphogenetic protein-2