• The Journal of Dong Guk Oriental Medicine
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• v.11
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• pp.66-73
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• 2008

Objectives: The study was designed to evaluate the single dose toxicity of modified Bo-yang-Hwan-o-Tang (mBHT) in Sprague-Dawley (SD) rats. Methods: The mBHT was once administrated orally to both sexes of rats at dose 2,000 mg/kg body weight which are the recommended maximum limit dose for acute toxicity. We recorded clinical signs of toxicity, body weight, gross and histological changes in target organs for all rats. Results: Neither significant changes of body weight not death was observed during the observation period in mBHT-administrated rats. Neither significant toxic signs not histopathological changes were shown during the observation period. There were not observed significant gross abnormality between the control and mBHT-administrated rats. Conclusions: These results indicated that the toxicity of mBHT is greater than 2,000 mg/kg body weight in SD rats.

• Biomolecules & Therapeutics
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• v.6 no.2
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• pp.182-190
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• 1998

DA-3585 is a recombinant human erythropoietin produced by Dong-A pharmaceutical Co. Ltd. using recombinant DNA technique. Recently, recombinant human erythropoietin (rHu-EPO) has been used to treat various types of anemia. In this study, we examined acute and subacute toxicity of DA-3585 in rats. DA-3585 was intravenously administered to rats at dose levels of 0, 6,250, 12,500 and 25,000 lU/kg for single dose toxicity study and at dose levels of 0,100,500 and 2,500IU/kg daily for 4 week-repeated dose toxicity study. In the single dose toxicity study, there were no death, clinical signs and changes in body weight gain related to the treatment. Necropsy revealed no evidence of toxicity related to DA-3585, In the repeated dose toxicity study, all the rats survived throughout the study. There were no treatment-related changes in clinical signs, food and water intake, and body weight. Hematological examination showed increases in the number of erythrocytes, hemoglobin concentration, hematocrit value and mean corpuscular volume, and decrease in the number of platelet in 500 and 2,500 lU/kg dosed groups. Extramedullary hematopoiesis in the spleen and erythroid hyperplasia in the bone marrow were noted as treatment-related histological changes. Toxicologically significant changes were not observed in blood biochemistry, urinalysis, organ weights and in any other examinations. The treatment-related changes observed in this study were hematological or histological changes associated with pharmacological effects of DA-3585. On the basis of the results of this study, LD5n value of DA-3585 was above 25,000 lU/kg and the no-observed-adverse-effect-level was estimated to be 100 lU/kg.

• The Journal of Internal Korean Medicine
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• v.32 no.4
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• pp.599-609
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• 2011

Objectives : The aim of this study was to evaluate the single oral dose toxicity and safety of Bojungikgi-tang (Buzhongyiqi-tang) and fermented Bojungikgi-tang (Buzhongyiqi-tang) extracts in male and female ICR mice. Methods : In the single oral dose toxicity study, non-fermented and fermented Bojungikgi-tang (Buzhongyiqi-tang) were administered to male and female ICR mice as an oral dose of 1250, 2500 and 5000 mg/kg. Changes of body weights, general behaviors, adverse effects and mortality were determined throughout the experimental period. Hematological parameters, serum chemistry, organ weights and necropsy findings were evaluated at the end of the experiment. Results : There was no mortality or sign of toxicity in the single oral dose toxicity study. There were also no significant differences in body weights, organ weights, and hematological parameters, serum chemistry values between treatment and control groups. Conclusions : The results obtained in this study suggest that the 50% lethal dose of fermented Bojungikgi-tang (Buzhongyiqi -tang) in both female and male mice can be considered as well over 5,000 mg/kg, so these medicines can be safe in clinics.

• Biomolecules & Therapeutics
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• v.16 no.1
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• pp.61-68
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• 2008

In order to develop an improved paclitaxel formulation vehicle, a micelle forming solubilizer, Aceporol 330 was synthesized. It was previously reported that Aceporol 330 provided the linearity of paclitaxel plasma pharmacokinetics. In this study, the single dose toxicity test and 2-week repeated dose toxicity test of Aceporol 330 was performed in beagle dogs after intravenous administration. Single dose and 2-week repeated dose toxicity test of Aceporol 330 showed fever/generalized erythema, severe vomiting, and diarrhea in beagle dogs. However, those toxicities were less severe than those of Cremophor EL. Blood chemistry analysis of 2-week repeatedly treated beagle dogs with Aceporol 330 showed significant elevation of total cholesterol (TCHO) and triglyceride (TG) compared to that of control group. Cremophor EL also significantly increased total cholesterol (TCHO) and triglyceride (TG) as much as Aceporol 330. Results from this study indicated that Aceporol 330 was less toxic than Cremophor EL. Based on the pharmacokinetic advantages and the low toxicity of Aceporol 330 in single dose and 2-week repeated dose toxicity test, Aceporol 330 has a potential for use as a safer solubilizer for paclitaxel than Cremophor EL.

• Toxicological Research
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• v.18 no.2
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• pp.195-203
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• 2002

This study was performed to evaluate single and repeated-dose toxicities oj a new cophalosporin antibiotic agent IDC-7l81 in Sprague-Dawley rats. IDC-7181 was injected intravenously to rats at dose levels of 0, 3.2, 16, 80, 400 and 2,000 mg/kg/day for single-dose toxicity study and at dose levels of 0, 10, 50 and 250 mg/kg/day for 4-week repeated-dose toxicity study. In both studies, there were no dose-related changes in mortality clinical signs, body weight changes, food and water consumption, opthalmoscopy, organ weights, urine analysis, biochemical examination, and hematological findings of all animals treated with IDC-7l8l. Gross and histopathological findings revealed no evidence of specific toxicity related to IDC-7181. These results suggest that the intravenous maximum tolerated dose value of IDC-7181 may be over 250 mg/kg and $LD_{50}$ value may be over 2,000 mg/kg in rats.

• Journal of Physiology & Pathology in Korean Medicine
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• v.25 no.2
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• pp.242-245
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• 2011

Socheongryong-tang has been used for the treatment of inflammatory allergic diseases such as allergic rhinitis and bronchial asthma in Asian countries. This study was conducted to investigate the safety of Socheongryong-tang in rats. The safety of this tang on acute toxicity was evaluated by single dose toxicity study. Rats were orally administrated in a single dose of 0 and 2000 mg/kg (limited dose) Socheongryong-tang. There were 7 rats in each groups. All animals were sacrificed after 14 days of treatment. After single administration, mortality, clinlcal signs, body weight changes and gross pathological findings were observed for 14 days. Three parameters were tested: organ weight measurement, clinical chemistry, and hematology. In this study with rats, Socheongryong-tang treatment did not show any acute toxicity. No mortality was noted for 14 days of treatment. There were no adverse effects on clinical signs, body weight, organ eight and gross pathological findings at all treatment groups. The clinical chemistry parameters attesting to liver and kidney functions as well as the hematological parameters were within the normal ranges. From single dose toxicity study with rats, it is considered that $LD_{50}$ of Socheongryong-tang is over 2000 mg/kg in oral administration. This finding of the safety on single dose toxicity study of Socheongryong-tang are expected to strengthen the position of Socheongryong-tang as nontoxic medicine.

• Journal of Acupuncture Research
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• v.38 no.1
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• pp.47-59
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• 2021

Background: This study aimed to assess the toxicity of Aconitum sinomontanum Nakai (ASN) pharmacopuncture. Methods: To investigate the toxicity of ASN pharmacopuncture, single and 4-week repeated dose toxicity experiments were conducted on BALB/c mice. In the single-dose toxicity experiment, mice were assigned 1 of 4 groups (5 males, 5 females per group). Then, 31.25, 62.5, and 125 mg/kg of ASN pharmacopuncture were administered to the mice in the experimental groups at acupoint ST36, while 0.2 mL of normal saline was administered to the control group at ST36. After a 4-week repeated dose regimen, the mice were assigned into 4 groups (5 males, 5 females per group). Then, 15.625, 31.25, and 62.5 mg/kg of ASN pharmacopuncture at ST36 were administered to the mice in the experimental groups, while 0.2 mL of normal saline was administered to the control group at ST36. Mortality, morbidity, general body and organ weight changes (after 4 weeks repeated dose), serum hematological and biochemical values, and histopathological changes in the liver and kidney were observed. Results: In both single and 4-week repeated dose toxicity experiments, no deaths or symptoms occurred in any of the groups. There were no significant differences between groups in terms of body and organ weights, serum hematological and biochemical values, and specific organ histopathological changes. Conclusion: ASN pharmacopuncture injection did not demonstrate significant toxicity in BALB/c mice compared with the control group, with a no-observed-adverse-effect level for a single dose of >125 mg/kg, and for 4 weeks repeated dose it was more than 62.5 mg/kg/day.

• 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.

• Proceedings of the Korean Society of Toxicology Conference
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• 2001.10a
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• pp.169-169
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• 2001

This study was designed to evaluate an acute and subacute intravenous dose toxicity of a new cephalosporin antibiotic agent, IDC-7181 in 7-week-old Sprague-Dawley rats. IDC-7181 was intravenously injected to rats at dose levels of 0, 3.2, 16, 80, 400 and 2, 000 mg/kg/day for single dose toxicity study and at dose levels of 0, 10, 50 and 250 mg/kg/day for 4 week-repeated dose toxicity study. All rats survived throughout the study periods.(omitted)

• Toxicological Research
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• v.20 no.3
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• pp.281-292
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• 2004

The purpose of this study was to assess the single and 5 week oral dose toxicity of calcitriol and alendronate combination (1 : 10,000) treatment for osteoporosis or Paget's disease in male and female rats. In single dose oral toxicity study, the values of $LD_{50}$ of calcitriol and alendronate mixture were 750.075 mg/kg in male rats and 775.0775 mg/kg in female rats, respectively. Body weight and food consumption were continuously increased after adminstration of calcitriol and alendronate mixtures, and there was no significant changes in body weight and food consumption in all groups. In five-week oral toxicity study of calcitriol and alendronate mixture at a dose of 0.2 $\mu\textrm{g}$ + 2 mg, 1 $\mu\textrm{g}$ + 10 mg, 5 $\mu\textrm{g}$ + 50 mg and 25 $\mu\textrm{g}$ + 250 mg, respectively, there was no mortality, abnormal behavior and appearance in all groups throughout the administration period (5 weeks) and recovery period (2 weeks). Dose-dependent changes in parameters of urinalysis and hematological analysis were not observed in male and female rats treated with calcitriol and alendronate mixtures. All the values of the parameters appeared to be in the normal range. These data indicate that both calcitriol and alendronate are drugs having low toxicity in rats. NOAEL of calcitriol and alendronate mixtures were 50.005 mg/kg in 5-week oral toxicity.