• Biomolecules & Therapeutics
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• v.2 no.1
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• pp.77-81
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• 1994

The acute toxicity of recombinant human epidermal growth factor, DWP-401 was evaluated in ICR mice of both sexes. Six groups of mice were administered orally or subcutaneously with 0, 0.125, 0.25, 0.5, 1 and 2 mg/kg of DWP-401. Abnormal clinical signs related to the compound were not observed, and no deaths occurred. Gross findings of necropsy revealed no evidence of specific toxicity related to DWP-401. LD$_{50}$ values for both male and female mice were evaluated to be over 2 mg/kg, which is approximately 2, 000 fold of presumed clinical dose.e.

• Biomolecules & Therapeutics
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• v.1 no.2
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• pp.270-274
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• 1993

The acute toxicity of a recombinant granulocyte-macrophage colony stimulating factor (code name: LBD-005) was evaluated in both sexes of ICR mice, 5~6 weeks old, by the oral, subcutaneous and intravenous routes of administration. Based on the results of the acute toxicity study, LBD-005 was not considered to induce any toxic effect on the mice in mortalities, clinical findings, body weights and gross findings. It is suggested that $LD_50$ values in mice would be >48 mg/kg in the oral route and >24 mg/kg in the subcutaneous or intravenous route.

• Toxicological Research
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• v.8 no.1
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• pp.41-48
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• 1992

The actue toxicity of a recombinant granulocyte macrophage colony-stimulating factor (code name: LBD-005) was evaluated in both sexes of Sprague-Dawley rats, 4 weeks old, by the oral, subcutaneous and intravenous routes of administration. LBD-005 in the acute toxicity study in the rats was not considerde to induce any toxicological effect on the rats in mortalities, clinical findings, body weights and gross findings. It is suggested that $LD_{50}$ values in rats would be >48 mg/kg in the oral route and >12 mg/kg in the subcutaneous or intravenous route.

• Journal of Food Hygiene and Safety
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• v.9 no.1
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• pp.31-36
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• 1994

The acute toxicity of recombinant human epidermal growth factor, DWP-401 was evaluated in SD rats. Male and female rats aging 6 weeks were administered orally or subcutaneously with 0, 0.125, 0.25, 0.5, 1 and 2 mg/kg of DWP-401. No deaths and no toxic symptoms related to the DWP-401 were observed. The body weights of treated animals were not significantly different from the controls. The results of necropsy revealed no abnormal gross findings of the organs in treated animals. LD50 values of DWP-401 for male and female rats were estimated to be over 2 mg/kg, which is approximately 2, 000 times of expected clinical dose.

• Biomolecules & Therapeutics
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• v.4 no.2
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• pp.138-147
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• 1996

DWP401, a recombinant human epidermal growth factor, was subcutaneously administered to ICR mice at the dose levels of 0, 0.04, 0.2 and 1.0 mg/kg/day (15rats/sex/group) in order to evaluate the subchronic toxicity. General observations, examinations for food and water consumption, ophthalmoscopy and urinalysis were carried out during the study. For the complete gross and microscopic examinations, 10 mice/ sex/group were sacrificed at the ends of the dosing period, and the remaining animals were sacrificed with a 5 week recovery period. Examinations for hematology and blood biochemistry were also carried out at the time of recovery period. Based on the results, it was thought that the target tissue or organs were mesothelial cell, injection site, spleen, adrenal gland, ovary and transitional epithelial cell of urinary tract, and no observed toxic level of DWP401 was 0.04 mg/kg while definite toxic dose level might be 0.2 mg/kg.

• Toxicological Research
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• v.29 no.3
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• pp.165-172
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• 2013

Acetaminophen (APAP) known as paracetamol is the main ingredient in Tylenol, which has analgesic and anti-pyretic properties. Inappropriate use of APAP causes major morbidity and mortality secondary to hepatic failure. Overdose of APAP depletes the hepatic glutathione (GSH) rapidly, and the metabolic intermediate leads to hepatocellular death. This article reviews the mechanisms of hepatotoxicity and provides an overview of current research studies. Pharmacokinetics including metabolism (activation and detoxification), subsequent transport (efflux)-facilitating excretion, and some other aspects related to toxicity are discussed. Nuclear factor erythroid 2-related factor 2 (Nrf2)-regulated gene battery plays a critical role in the multiple steps associated with the mitigation of APAP toxicity. The role of Nrf2 as a protective target is described, and potential natural products inhibiting APAP toxicity are outlined. This review provides an update on the mechanism of APAP toxicity and highlights the beneficial role of Nrf2 and specific natural products in hepatoprotection.

• Biomolecules & Therapeutics
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• v.2 no.3
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• pp.256-259
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• 1994

This study was performed to evaluate the acute toxicity of DA-3030(granulocyte-colony stimulating factor, G-CSF) in mice and rats via intragastrical and intravenous routes. DA-3030(G-CSF) in the acute toxicity study did not induce any toxic signs in the mice and rats in mortalities, clinical findings, body weights and gross findings. It is suggested that LD$_{50}$ values in mice and rats would be >13, 800 $\mu\textrm{g}$/kg in the oral route and >6, 900 $\mu\textrm{g}$/kg in the intravenous route.e.

• Biomolecules & Therapeutics
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• v.23 no.1
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• pp.12-18
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• 2015

Skin is an emerging target tissue in pharmaceutical and cosmetic science. Safety assessment for dermal toxicity is a critical step for development of topically applicable pharmaceutical agents and ingredients in cosmetics. Urgent needs exist to set up toxicity testing methods for dermal safety, and identification of novel biomarkers for pathological cutaneous alteration is highly required. Here we will discuss if vascular endothelial growth factor (VEGF) has a potential as a biomarker for dermal impairment. Experimental and clinical evidences for induction of keratinocytic VEGF under pathological conditions will be reviewed.

• Toxicological Research
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• v.18 no.1
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• pp.87-98
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• 2002

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.

• Toxicological Research
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• v.23 no.4
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• pp.383-389
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• 2007

Recombinant human granulocyte-macrophage colony stimulating factor (hGM-CSF) regulates proliferation and differentiation of hematopoietic progenitor cells and modulates function of the mature hematopoietic cells. In the 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 single and repeated dose toxicity of rice cells-derived hGM-CSF in SD rats. During single dose toxicity study for 7 days, there were no any toxic effects at any dose of from 10 to $1000{\mu}g/kg$. The lethal dose ($LD_{50}$) was not found in this range. Moreover, repeated dose toxicity study of 14-days period and at the doses of 50 and $200{\mu}g/kg$ (i. v.) of rhGM-CSF 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 test groups. The hematological and blood biochemical parameters were statistically not different in all the groups. These results suggest that rhGM-CSF has no toxicity in SD rats.