|
KMID : 0379520020180010087
|
|
한국독성학회지
2002 Volume.18 No. 1 p.87 ~ p.98
|
|
|
Safety Evaluation of Recombinant Human Factor VIII(GC-{gamma} AHF))
|
|
Kim Min-Young
Son Jang-Won
Shin Min-Ki
Bae Mi-Ok
Kim Hyun-Woo
Choi J.-h.
Kim J.-S.
Moon Seo-Hyun
Kim Jung-Hyon
|
|
|
Abstract
|
|
|
|
This study was conducted to evaluate the safety of a recombinant human Factor VIII(GC-gamma AHF) manufactured by Korea Green Cross Company with different technology according to the Regulation of Korean Food and Drug Administration (l 998. 12. 3). In acute toxicity test, both genders of Sprague-Dawley rats and Beagle dogs were administered intravenously with GC-gamma AHF of three doses (3,125, 625 and 125 IU/kg), and single dose of 3,125 IU/kg, respectively. No dead animal and abnormal autopsy findings were found in Control and GC-gamma AHF treated group. Therefore, the 50% lethal dose (LD_{50}) of GC-gamma AHF was conidered to be higher than 3,125 IU/kg in rats and dogs. In the four weeks repeated intravenous toxicity study, GC-gamma AHF was administrated intravenosly to both genders of rats and dogs with 3 doses (500, 150, 50 IU/kg). There were neither dead animals nor significant changes of body weights during the experimental Period. In addition, no significant GC-gamma AHF related changes were found in clinical sign, urinalysis and other finding. Statistically changes were observed in hematological, biochemical and organ weight parameters of treated groups: however these changes were not dose dependent. No histopathological lesion were observed in both control and treated animals. Above data suggest that no observed adverse effect level of test materials in rats and dogs might be over 500 IU/kg/day in this study. In ocular irritation test, any injury on iris, conjunctiva and cornea in rabbits were not observed. The acute ocular irritation index (A.O.I.), mean ocular irritation index (M.O.I.) and Day-7 individual ocular irritation Index (I.O.I.) of GC-gamma AHF were 0. In the primary skin Irritation test, the primary irritation index (P.I.I.) oj GC-gamma AHF were 0. Therefore, the GC-gamma AHF is considered not to have the primary skin and eye toxicity in rabbits. In active systemic anaphylaxis (ASA) test, GC-gamma AHF and GC-gamma AHF emulsified with Freund’s complete adjuvant (FCA) did not induce any symptom of anaphylactic shock in guinea pigs. In passive cutaneous anaphylxis (PCA) test, after sensitization with antisera of GC-gamma AHF sensitized mice, blue spots were observed on the hypodermis of back of rats, but diameter of each spot was smaller than 5 mm in each test groups except the positive control group. Based on the results of this study, GC-gamma AHF is not conidered to have any antigenic potential. In conclusion, at levels of up to 500 IU/kg, GC-gamma AHF did not produce treatment-related toxicity under the conditions of these acute-, four week repeated-toxicity, primary skin and eye toxicity, and antigenicity test.
|
|
|
KEYWORD
|
|
|
GC-gammaAHF, Recombinant human factor VIII, Acute and repeated toxicity, Ocular Irritation, Primary skin irritation, Active systemic anaphylaxis, passive cutaneous anaphylaxis
|
|
|
FullTexts / Linksout information
|
|
|
|
|
Listed journal information
|
|
 
|
|