• Journal of Physiology & Pathology in Korean Medicine
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• v.25 no.1
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• pp.122-131
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• 2011

The object of this study was to evaluate the single dose toxicity of Yukmijihwangtanggamibang (YMJHTGMB), a polyherbal formula have been traditionally used as prevention or treatment agent for various lung diseases including chronic obstructive pulmonary disease (COPD), in male and female mice. Aqueous extracts of YMJHTGMB (Yield = 16.33%) wasadministered to female and male ICR mice as an oral dose of 2,000, 1,000 and 500 mg/kg (body weight) according to the recommendation of Korea Food and Drug Administration (KFDA) Guidelines. Animals were monitored for the mortality and changes in body weight, clinical signs and gross observation during 14 days after dosing, upon necropsy; organ weight and histopathology of 12 principle organs were examined. As results, we could not find any mortality, clinical signs, and changesin the body and organ weight except for soft feces restricted to YMJHTGMB 2,000 mg/kg treated two male mice (2/5; 40%) at 1 day after administration. In addition, no YMJHTGMB-treatment related abnormal gross findings and changes in histopathology of principle organs were detected except for some sporadic accidental findings. The results obtained in this study suggest that the 50% lethal dose and approximate lethal dose of YMJHTGMB aqueous extracts in both female and male mice were considered as over 2,000 mg/kg, the limited highest dosage recommended by KFDA Guidelines.

• Journal of Physiology & Pathology in Korean Medicine
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• v.24 no.6
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• pp.1019-1026
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• 2010

The object of this study was to evaluate the single dose toxicity of Iijintanggami-bang (IJTGMB), a polyherbal formula have been traditionally used as prevention or treatment agent for various digestive disorders including reflux esophagitis, in male and female mice. Aqueous extracts of IJTGMB (Yield = 8.45%) was administered to female and male ICR mice as an oral dose of 2,000, 1,000 and 500 mg/kg (body weight) according to the recommendation of Korea Food and Drug Administration (KFDA) Guidelines. Animals were monitored for the mortality and changes in body weight, clinical signs and gross observation during 14 days after dosing, upon necropsy; organ weight and histopathology of 12 principal organs were examined. As results, we could not find any mortality, clinical signs, and changesin the body and organ weight except for soft feces restricted to IJTGMB 2,000 mg/kg treated two male mice (2/5; 40%) at 1 day after administration. In addition, no IJTGMB-treatment related abnormal gross findings and changes in histopathology of principle organs were detected except for some sporadic accidental findings. The results obtained in this study suggest that the 50% lethal dose and approximate lethal dose of IJTGMB aqueous extracts in both female and male mice were considered as over 2,000 mg/kg, the limited highest dosage recommended by KFDA Guidelines.

• The Journal of Korean Obstetrics and Gynecology
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• v.27 no.1
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• pp.28-40
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• 2014

Objectives: This study was to evaluate the single dose toxicity of Sobokchuko-tang (SBC) in male and female mice. Methods: Aqueous extract of SBC (yield=6.60%) was administered to female and male mice as an oral dose of 2,000, 1,000 and 500 mg/kg (body weight) according to the recommendation of Korea Food and Drug Administration (KFDA) Guidelines. Animals were monitored for the mortality and changes in body weight, clinical signs and gross observation during 14 days after dosing, upon necropsy; organ weight and histopathology of 14 principle organs were also examined. Results: we could not find any SBC treatment related mortality and clinical signs, changes in the body and organ weights, gross findings and changes in histopathology of principle organs, except for pharmacological immunomodulatory effects related findings including significant increases of submandibular lymph node weights, hypertrophy and hyperplasia of lymphoid cells in the submandibular lymph nodes restrictly detected in 2,000 mg/kg treated female and male mice with some sporadic accidental findings. Conclusions: The results obtained in this study suggest that the 50% lethal dose and approximate lethal dose of SBC aqueous extracts in both female and male mice were considered as over 2,000 mg/kg, the limited highest dosage recommended by KFDA Guidelines, and can be safety used in clinics.

• Journal of Korean Medicine Rehabilitation
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• v.25 no.2
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• pp.73-80
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• 2015

Objectives To assess the safety of Shinbaro3 Pharmacopuncture by analyzing the potential single-dose intramuscular toxicity of Shinbaro3 Pharmacopuncture at various dose levels in SD (Spraque-Dawley) rats and Beagle dogs. Methods For evaluation of single-dose intramuscular toxicity of Shinbaro3 Pharmacopuncture, 40 SD rats (20 male and 20 famale) and 4 Beagle dogs (2 male and 2 female) were used. The rats were divided in four groups of 10 each, and treated intramuscularly with Shinbaro3 Pharmacopuncture at doses of 0.3, 0.6 and 1.2 mg/kg in distilled water, and distilled water as a vehicle control group, respectively. The Beagle dogs were divided into two groups of 2 each, and treated intramuscularly with Shinbaro3 Pharmacopuncture at doses of 0.15, and 0.3 mg/kg in distilled water, respectively, and signs of toxicity were observed. After a wash-out period of 3 days, the procedure was repeated with Shinbaro3 Pharmacopuncture at doses of 0.6, and 1.2 mg/kg in distilled water, respectively. Mortality, body weight changes, and necropsy findings were examined during the study period. Results There were no mortalities in either the SD rats or Beagle dogs. There were also no significant differences in adverse effects, body weight, or necropsy findings between the Shinbaro3 Pharmacopuncture and control groups. Conclusions There results suggest that the lethal dose 50 ($LD_{50}$) and approximate lethal dose (ALD) value of the test substance Shinbaro3 Pharmacopuncture are higher than 1.2 mg/kg in SD rats and Beagle dogs.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2021.04a
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• pp.59-59
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• 2021

Stachys sieboldii Miq. (SSM) and Acorus gramineus Soland. (AGS) have been used as traditional medicines for thousands of years in parts of Asia, including Korea, China, and Japan. Recent researches on SSM and AGS have documented a wide spectrum of therapeutic properties, including anti-inflammatory, anti-oxidative, neurodegenerative disease effects. However, the toxicity and safety of SSM and AGS, and their mixture (medicinal herber mixture, MHMIX) were not confirmed. Therefore, this study was performed to evaluate the acute toxicity and safety of SSM, AGS and MHMIX. SSM, AGS and MHMIX were orally administered at a dose of 5,000 mg/kg in ICR mice. Animals were monitored for the mortality and changes in the body weight, clinical signs and gross observation during the 14 days after dosing, upon necropsy. We also measured parameters of organ weight, clinical chemistry, and hematology. No dead and no clinical signs were found during the experiment period after administration of a single oral dose of SSM, AGS and MHMIX. There were no adverse effects on clinical signs, body weight, or organ weight and no gross pathological findings in any treatment group. Therefore, LD50 value of SSM, AGS and MHMIX may be over 5,000 mg/kg and it may have no side toxic effect to ICR mice. The results on the single-dose toxicity of SSM, AGS and MHMIX indicate that it is not possible to reach oral dose levels related to death or dose levels with any harmful side effects.

• The Journal of Korean Medicine
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• v.32 no.1
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• pp.67-83
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• 2011

Objectives: The purpose of this study was to examine the single dose toxicity with oral administration and genotoxicities of Ssanghwa-tang fermented with Lactobacillus acidophyllus. Materials and Methods: Clinical signs, weight changes, lethal doses$(LD_{50})$, and postmortem evaluation were determined by Globally Harmonized Classification System(GHCS) in a single-dose oral toxicity study. In vitro mammalian chromosomal aberration test was conducted with Ames test by cell proliferation suppression assessment using the cultivated CHO-K1(Chinese hamster ovary fibroblast) origins. Bacterial reversion assay was performed using Salmonella typhimurium (TA98, TA100, TA1535, and TA1537) and Escherichia coli (WP2uvrA). In vivo micronucleus test was performed using ICR mouse bone marrow. Results: No clinical sign was observed and none of the groups with doses up to 2000 mg/kg showed significant acute oral toxicity in the single dose oral administration. None of the sample doses taken during the 6 to 18 hour groups showed significant aberrant metaphases comparing to the negative control group in the in vitro mammalian chromosomal aberration test. No evidence of mutagenicity was seen for Escherichia coli (WP2uvrA) or Salmonella typhimurium (TA98, TA100, TA1535, and TA1537). No significant increase in the frequency of micronuclei was seen in the micronucleus test. Conclusion: These results indicate that the $LD_{50}$ value of Ssanghwa-Tang fermented with Lactobacillus acidophyllus may be over 2000 mg/kg and it have no acute oral toxicity and genotoxicity.

• Biomolecules & Therapeutics
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• v.9 no.1
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• pp.46-50
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• 2001

The current study was performed to determine the acute oral toxicity of a crude extract of sanghwang mushroom (Phellinus linteus), in SD rats. 5 rats of each sex were orally treated with a single dose of extract of sanghwang mushroom at doses of 0, 500, 1,000, 2,000 mg/kg, respectively. After the treatment, clinical signs and body weight change, the food and water consumption were observed for 14 days. All animals survived during the study and did not show any clinical signs. Body weight gain showed no significant difference between the control and treated rats. However, body weight gain delayed in high dose group (2,000 mg/kg) on day 1~3 after administration. Another 5 rats of each sex were orally treated with a single dose of extract of sanghwang mushroom at dosages 4,000, 5,000 mg/kg respectively, but all animals survived during the study and did not show any clinical signs. It is suggested that LD$_{50}$ of extract of sanghwang mushroom by oral administration was estimated to be over 5,000 mg/kg in both sexes of rats.s.

• Biomolecules & Therapeutics
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• v.8 no.2
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• pp.167-170
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• 2000

The present study was conducted to investigate the acute toxicity of plant sterol ester by a single oral dose in Sprague-Dawley rats. Ten males and 10 females aged 5 weeks were randomly assigned to two groups of 5 rats each and were administered by gavage at dose level of 0 or 20 ml/kg body weight. Parameters measured during the 14-day observation period were mortality, clinical signs, body weight changes, and gross findings. No mortality was observed in the present study. Treatment-related clinical signs, such as pasty stool and diarrhea, were observed on the day of treatment and these signs resulted in soiled fur on day 1 after the treatment. However, no clinical signs were observed on days 2-14 after the treatment. There was no significant difference in body weight changes between the control and treatment groups. At necropsy on day 14 after the treatment, no treatment-related gross findings were observed in the treatment group. Based on these results, it was concluded that a single oral dose of plant sterol ester induced pasty stool and diarrhea in Sprague-Dawley rats at dose level of 20 ml/kg and that the lethal doses were considered to be over 20 ml/kg for both sexes.

• Toxicological Research
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• v.12 no.2
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• pp.309-318
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• 1996

This study was conducted to investigate the subacute intravenous toxicity of rHu-EPO in Sprague-Dawley rats. rHu-EPO was daily administered to male and female rats for 30 days with different dose levels(100, 500, 2,500 unit/ kg). After the administration period of 30 days, 5 males and 5females rats per each dose group were assigned for recovery period of additional 30 days. There were no clinical signs compared with control group but slight decrease in spontaneous motor activities and locomotions were observed at high dose groups of males and females. In males, feed consumption was reduced at 500 unit/kg and body weight gain was retarded. In the administration sites of tail, focal congestion was observed in a few animals treated with rHu-EPO. No deaths were occurred during the course of study. In hematological examination. a significant increase of hemoglobin and hematocrit was observed in the males and females rats receiving high dose of rHu-EPO. rHu-EPO administration for 30 days showed a marked decrease in glucose concentration. At the highest dose groups, there was a significant incerase in the weights of spleens in both sexes. but this was considered to be related to its pharmacological activity. These results indicate that rHu-EPO does not induce any significant toxic effect on Sprague-Dawley rats for 30 days.

• Journal of Pharmacopuncture
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• v.17 no.2
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• pp.46-56
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• 2014

Objectives: This study was performed to examine the single-dose toxicity of Samgihwalryeok pharmacopuncture. Methods: Forty six-week-old Sprague-Dawley (SD) rats were divided into four groups of 10 rats each; each group was then sub-divided into two smaller groups, one of five males and the other of five females. Group 1 (G1, control) received 1.0 mL of normal saline solution, while group 2 (G2, low-dose group), group 3 (G3, mid-does group, and group 4 (G4, high-dose group) received 0.1, 0.5, and 1.0 mL of Samgihwalryeok pharmacopuncture, respectively. Results: No mortalities or clinical signs were observed in the four groups. Also, no significant changes in body weights were observed among the group, and no significant differences in hematology/biochemistry, necropsy, or histopathology results were noted. Conclusion: The above findings suggest that treatment with Samgihwalryeok pharmacopuncture is relatively safe. Further studies on this subject are needed.