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. 2008 Dec 1;24(4):315–320. doi: 10.5487/TR.2008.24.4.315

Subcutaneous Four-Week Repeated Dose Toxicity Studies of Rice Cell-Derived Recombinant Human Granulocyte-Macrophage Colony Stimulating Factor in Rats

Jung Eun Ji 110, Jung Min Lee 110, Jong Min Choi 110, Young Hwa Choi 110, Eun Kyung Kim 110, So Jung Chu 110, Seok Kyun Kim 110, Kyong Hoon Ahn 110, Dong Hoon Lee 110, Ha Hyung Kim 110, Kyuboem Han 210, Dae Kyong Kim 110,✉
PMCID: PMC7006265  PMID: 32038810

Abstract

Recombinant human granulocyte-macrophage colony stimulating factor (hGM-CSF) is a glycoprotein and hematopoietic growth factors that regulates the proliferation of myeloid precursor cells and activates mature granulocytes and macrophages. In a previous study, we reported that hGM-CSF could be produced in transgenic rice cell suspension culture, termed rhGM-CSF. In the present study, we examined the repeated dose toxicity of rhGM-CSF in SD rats. The repeated dose toxicity study was performed at each dose of 50 and 200 µg/kg subcutaneous administration of rhGM-CSF everyday for 28-days period. The results did not show any changes in food and water intake. There were also no significant changes in both body and organ weights between the control and the tested groups. The hematological and blood biochemical parameters were statistically not different in all groups. These results suggest that rhGM-CSF may show no repeated dose toxicity in SD rats under the conditions.

Keywords: Recombinant hGM-CSF, Rice cells, Repeated dose toxicity, SD rats

Abbreviations

hGM-CSF

Recombinant human granulocyte-macrophage colony stimulating factor

LD50

50% lethal dose

E. coli

Escherichia coli

CHO

Chinese hamster ovary

rhGM-CSF

rice cells-derived hGM-CSF

PBS

phosphate buffered saline

EDTA

ethylenediaminetetraacetic acid

RBC

red blood cell

WBC

white blood cell

NEU

neutrophil

LYM

lymphocyte

MONO

monocyte

EOS

eosinophil

BASO

basophil

PLT

platelet

HCT

hematocrit

MCV

mean corpuscular volume

HGB

hemoglobin

MCH

mean corpuscular hemoglobin

MCHC

mean corpuscular hemoglobin concentration

AST

aspartate aminotransferase

ALT

alanine aminotransferase

ALP

alkaline phosphatase

BUN

blood urea nitrogen

CRE

creatinine

GLU

glucose

CHO

total cholesterol

PRO

total protein

CPK

creatine phosphokinase

ALB

albumin

BIL

total bilirubin

yhGM-CSF

yeast-derived hGMCSF

s.c.

subcutaneous

b.wt.

body weight

SD

standard deviation

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