Chinese Medical Sciences Journal ›› 2011, Vol. 26 ›› Issue (1): 20-27.doi: 10.1016/S1001-9294(11)60015-1

• Original Article • Previous Articles     Next Articles

Chronic Toxicity of a Novel Recombinant Human Granulocyte Colony-stimulating Factor in Rats

Fei Xia1, Qing-yu Zhang1, and Yong-ping Jiang1, 2   

  1. 1Biopharmaceutical R&D Center , Chinese Academy of Medical Sciences & Peking Union Medical College , Suzhou 215126, China 2Biopharmagen Corporation, Suzhou 215126,China
  • Received:2011-01-05 Revised:2011-04-18 Online:2011-04-18 Published:2011-04-18
  • Contact: Yong-ping Jiang
  • About author:Tel: 86-512-62831269

Abstract: Objective To assess the severity and reversibility of the chronic toxicity of a novel recombinant human granulocyte colony-stimulating factor (rhG-CSFa) in rats and the dose-effect relationship. 
Methods A total of 100 Sprague-Dawley rats (equal numbers of male and female) were randomly divided into five groups (20 rats in each group): four groups were treated with rhG-CSFa at 500, 100, 10, 1 µg/kg, respectively, and one group was treated with vehicle only to serve as the control. The rats were received subcutaneous injections of rhG-CSFa or vehicle daily for 13 weeks. During the course of the chronic toxicity study, the physical status, body weight, and food consumption were monitored. Half of the rats in each group (n=10) were sacrificed after the last rhG-CSFa administration, and the other half were sacrificed at five weeks after the last rhG-CSFa administration. Urinalyses, blood biochemistry, hematological analysis, histopathological examination, and immunological tests were performed for each of the rats. 
Results The hematological analyses revealed that the mean white blood cells count, neutrophils count, and neutrophils percentage were increased in male rats at the dose of 10 µg/kg or higher, and these were related with the biological activity of rhG-CSFa. Some small abnormalities were observed in the spleen of a few rats when used highest dose (500 µg/kg, a dosage of 200 folds higher than the normal clinical dosage), but these abnormalities were recovered within 5-week recovery period. No other rhG-CSFa-related abnormalities were observed in this chronic toxicity study. 
Conclusion No significant toxicity and immunogenicity are observed with rhG-CSFa administration to rats in the chronic toxicity studies.

Key words: chronic toxicity, Sprague-Dawleyrat, novel recombinant human granulocyte colony-stimulating factor


State Scientific Key Projects for New Drug Research and Development(2009ZX09102-250) and High-tech Research Project for Medicine and Pharmacology of Jiangsu Province (BG20070605).

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