• Journal of Korean Medicine Rehabilitation
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• v.25 no.3
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• pp.1-9
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• 2015

Objectives To evaluate Shinbaro Pharmacopuncture safety through analysis of potential single-dose intramuscular toxicity of Sinbaro Pharmacopucture in SD rats and Beagle dogs. Methods Single-dose intramuscular toxicity of Shinbaro Pharmacopuncture was assessed in accordance with Korea Food and Drug Administration Guidelines for toxicity testing of Medicinal Products. The SD rats were treated intramuscularly with Shinbaro Pharmacopuncture at doses of 0, 4.6, 9.2, and 18.5 mg/kg, respectively. The Beagle dogs were treated intramuscularly with Shinbaro Pharmacopuncture at doses of 2.3, and 4.6 mg/kg, respectively, and after 3 days, the procedure was repeated a second time at doses of 0.6, and 1.2 mg/kg, respectively, for toxicity testing. Mortality, change in body weight, and necropsy findings were examined for the study period. Results There were no mortalities, general symptoms, or body weight changes in the SD rats. While pyelectasis of the left kidney was observed in a male rat in the 4.6 mg/kg administration group, natural occurrence is common, and does not appear to be related with the test substance. No mortalities were observed in the Beagle dogs. In assessment of general symptoms, a female dog in the 9.2 mg/kg group displayed body weight decrease due to leftover food, but the change in body weight was within the normal range seen at 6~7 months, and the necropsy findings were not significant. The toxicity of the test substance appears to be minimal. Conclusions The results suggest that the lethal dose 50 ($LD_{50}$) and approximate lethaldose (ALD) value in single intramuscular administration of Shinbaro Pharmacopuncture in SD rats and Beagle dogs are higher than 18.5 mg/kg.

• Journal of Pharmacopuncture
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• v.13 no.4
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• pp.43-61
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• 2010

Objectives : This study was performed to analyse single dose toxicity of Sweet Bee Venom(Sweet BV) extracted from the bee venom in Beagle dogs. Methods : All experiments were conducted under the regulations of Good Laboratory Practice (GLP) at Biotoxtech Company, a non-clinical study authorized institution. Male and female Beagle dogs of 5-6 months old were chosen for the pilot study of single dose toxicity of Sweet BV which was administered at the level of 9.0 mg/kg body weight which is 1300 times higher than the clinical application dosage as the high dosage, followed by 3.0 and 1.0 mg/kg as midium and low dosage, respectively. Equal amount of excipient(normal saline) to the Sweet BV experiment groups was administered as the control group. Results : 1. No mortality was witnessed in all of the experiment groups. 2. Hyperemia and movement disorder were observed around the area of administration in all the experiment groups, and higher occurrence in the higher dosage treatment. 3. For weight measurement, Neither male nor female groups showed significant changes. 4. To verify abnormalities of organs and tissues, thigh muscle which treated with Sweet BV, brain, liver, lung, kidney, and spinal cords were removed and histologocal observation using H-E staining was conducted. In the histologocal observation of thigh muscle, cell infiltration, inflammation, degeneration, necrosis of muscle fiber, and fibrosis were found in both thigh tissue. And the changes depend on the dose of Sweet BV. But the other organs did not showed in any abnormality. 5. The maximum dose of Sweet BV in Beagle dogs were over 9 mg/kg in this study. Conclusions : The above findings of this study suggest that Sweet BV is a relatively safe treatment medium. Further studies on the toxicity of Sweet BV should be conducted to yield more concrete evidences.

• Journal of Pharmacopuncture
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• v.18 no.2
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• pp.42-50
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• 2015

Objectives: The aims of the study were to test the single- dose intravenous toxicity of Daebohwalryeok pharmacopuncture (DHRP) in Sprague-Dawley (SD) rats and to estimate the crude lethal dose. Methods: The experiments were conducted at Biotoxtech Co., a Good Laboratory Practice (GLP) laboratory, according to the GLP regulation and were approved by the Institutional Animal Care and Use Committee of Biotoxtech Co. (Approval no: 110156). The rats were divided into three groups: DHRP was injected into the rats in the two test groups at doses of 10 mL/kg and 20 mL/kg, respectively, and normal saline solution was injected into the rats in the control group. Single doses of DHRP were injected intravenously into 6 week old SD rats (5 male and 5 female rats per group). General symptoms were observed and weights were measured during the 14 day observation period after the injection. After the observation period, necropsies were done. Then, histopathological tests were performed. Weight data were analyzed with a one-way analysis of variance (ANOVA) by using statistical analysis system (SAS, version 9.2). Results: No deaths and no statistical significant weight changes were observed for either male or female SD rats in either the control or the test groups during the observation period. In addition, no treatment related general symptoms or necropsy abnormalities were observed. Histopathological results showed no DHRP related effects in the 20 mL/kg DHRP group for either male or female rats. Conclusion: Under the conditions of this study, the results from single-dose intravenous injections of DHRP showed that estimated lethal doses for both male and female rats were above 20 mL/kg.

• Korean Chemical Engineering Research
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• v.54 no.6
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• pp.762-766
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• 2016

In this study, natural extract including Phellodendro namurense, Eucommia ulmides Oliv and Prunus padus were tested for antimicrobial activity and safety. Antimicrobial activity was measured by using opportunistic microbes such as Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli and Candida albicans. As safety test, cell viability test, single dose oral toxicity test, single dose inhalation toxicity test, repeat dose inhalation toxicity test and eye irritation test were done. From antimicrobial test, natural extract showed execellent antimicrobial activity against Staphylococcus aureus, Pseudomonas aeruginosa, Candida albicans, Escherichia coli. From 5 kinds of safety tests, toxicity was not observed. From experimental results, natural extract including Phellodendro namurense, Eucommia ulmides Oliv and Prunus padus showed superb safety and antimicrobial effect.

• Biomolecules & Therapeutics
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• v.15 no.4
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• pp.245-251
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• 2007

The object of this study was to evaluate the single dose toxicity of Kong-Jin-Dan (KJD), a polyherbal formula in male and female mice. KJD was administered to female and male ICR mice as an oral dose of 2000, 1000 and 500 mg/kg (body wt.) according to the recommendation of 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 changes in the body and organ weight except for increases of lymphoid organ weights in KJD-dosing groups. These increases of lymphoid organ weights considered that related to the immune modulate effect of KJD not toxicological signs. In addition, no KJD-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 KJD does not cause any toxicological signs. The $LD_{50}$ and approximate LD of KJD extracts in both female and male mice were considered as over 2000 mg/kg.

• Journal of Korean Medicine Rehabilitation
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• v.31 no.1
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• pp.95-108
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• 2021

Objectives This study was conducted to investigate the beta-glucan, ginsenoside content, antioxidant activity and safety of modified Kyungohkgo added to Sparassis crispa and Hericium erinaceum. Methods The marker compounds contents, antioxidant activity and safety of modified Kyungohkgo were tested. The contents of beta-glucan and ginsenoside Rb1, Rg1, and Rg3 marker compounds were measured, the antioxidant activity was measured using 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging activity, and a safety test was conducted via single dose toxicity assessment. Results Analyzing the contents of marker compounds showed 351.75 mg/g of beta-glucan, 0.0327 mg/g of ginsenoside Rb1 and 0.0802 mg/g of ginsenosai Rg3. In the DPPH free radical scavenging activity, the inhibition concentration 50% of modified Kyungohkgo was 0.2880%. The scavenging activity of modified Kyungohkgo was 5.49% activity at 0.05% concentration, 89.66% activity at 0.5% concentration, 94.68% activity at 1% concentration, and 96.06% activity at 5% concentration. In the single dose toxicity test of modified Kyungohkgo, a dose of 2,000 mg/kg B.W. was set at its highest capacity and observed after oral administration to female and male rats. No toxicological findings were recognized. It was observed that the resulting lethal dose can be set to 2,000 mg/kg B.W. or higher for both females and males. Conclusions The results of the experiment on modified Kyungohkgo showed that the marker compounds contents were beta-glucan and ginsenoside Rb1 and Rg3, that antioxidant activity was observed through the DPPH free radical scavenging activity, and safety was confirmed through the single dose toxicity assessment.

• Journal of the Korean Society of Food Science and Nutrition
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• v.45 no.10
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• pp.1406-1413
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• 2016

This study was carried out to evaluate the toxicity of ethanolic extracts of Morus alba L. branch (ME). In the reverse mutation test, Salmonella Typhimurium TA98, TA100, TA1535, TA1357, and Escherichia coli WP2uvrA were used to estimate the mutagenic potential of ME. Sprague-Dawley rats were orally administered ME at levels of 1,250, 2,500, and 5,000 mg/kg for the single-dose toxicity test and 500, 1,000, and 2,000 mg/kg/d for the repeated-dose toxicity test for 28 consecutive days. As expected, reverse mutation was not detected at any concentration of ME, regardless of application of the metabolic activation system with or without S9 mix. In the single-dose toxicity test, ME caused neither significant visible signs of toxicity nor mortality in rats, and $LD_{50}$ was estimated to be over 5,000 mg/kg. In the repeated-dose toxicity test, ME administration at 500, 1,000, and 2,000 mg/kg for 28 days to male or female rats did not result in mortality. Similarly, no toxicologically significant treatment-related changes in body weight, food intake, or organ weights were noted. Several hematological and biochemical parameters in both genders showed significant differences, but these were within normal ranges. These results support the safe use of ME.

• The Journal of Internal Korean Medicine
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• v.27 no.1
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• pp.102-113
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• 2006

Objectives & Methods : To obtain the 50% lethal dose(LD50), approximated lethal dose(ALD) and approximated target organs of 'Mahwangyounpae-tang' for further study into such things as repeated dose toxicity, genotoxicity and reproductive toxicity, single dose toxicity was tested in male SD rats according to KFDA Guideline 1999-61[KFDA, 1999] at dosage levels of 2,000, 1,000, 500, 250 and 125 mg/kg/$10m{\ell}$. In this study, mortalities, clinical signs, body weight changes and body weight gains, gross findings and weight of principal organs were detected during and/or after 14 days of single dosing. Results & Conclusions : After 2 or 3 days of dosing, 1 or 2 animals in 2,000 mg/kg-dosing groups died. Excitation and leaping response were observed as test article-treatment related clinical signs. These abnormal signs were restricted to 2,000 and 1,000 mg/kg-dosing groups and survivors recovered to normal within 3 or 4 days after dosing. Significant decrease in body weight were observed in some periods of observation in 2,000 and 1,000 mg/kg-dosing group, from 1 days after dosing compared to those of vehicle control group. Significantly diminished body weight gains were observed in observation periods in 2,000 and 1,000 mg/kg-dosing group compared to those of vehicle control group. Hypertrophy and hemorrhage of heart and decoloration of kidney were observed as test article-treatment related gross findings. These abnormal findings were restricted to 2,000 and 1,000 mg/kg-dosing groups. A significant increase of absolute and relative heart and kidney weight were demonstrated in 2,000 mg/kg-dosing groups. The value for LD50 found in this study was 2,218.57 mg/kg. ALD in this study was 2,000 mg/kg, and the target organs are considered to be the heart and the kidney.

• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.2
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• pp.442-448
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• 2006

To obtain the 50% lethal dose (LD50), approximated lethal dose (ALD) and approximated target organs of 'Mahwangyounpae-tang' for further study like repeat dose toxicity, genotoxicity and reproductive toxicity, single dose toxicity was tested in male ICR mouse according to KFDA Guideline 1999-61 [KFDA, 1999] at a dosage level of 2,000, 1,000, 500, 250 and $125\;mg/kg/10m{\ell}$. In this study, mortalities, clinical signs, body weight changes and body weight gains, gross findings and weight of principal organs were detected during and/or after 14 days of single dosing. After 2 or 3 days of dosing, 1 or 2 animals in 2,000 and 1,000 mg/kg-dosing groups were died. Excitation and leaping response were observed as test article-treatment related clinical signs. These abnormal signs were restricted to 2,000 and 1,000 mg/kg-dosing groups and they were recovered to normal within 4 days after dosing in case of survivors. A significant decrease of body weight were observed in some periods of observation in 2,000 and 1,000 mg/kg-dosing group from 1 days after dosing compared to those of vehicle control group. A significant decrease of body weight gains were observed in observation periods in 2,000 and 1,000 mg/kg-dosing group compared to those of vehicle control group. Hypertrophy of heart and decoloration of kidney were observed as test article-treatment related gross findings. These abnormal findings were restricted to 2,000 and 1,000 mg/kg-dosing groups. A significant increase of absolute and relative heart and kidney weight were demonstrated in 2,000 mg/kg-dosing groups. LD50 in this study was detected as 2,242.42 mg/kg. ALD in this study was detected as 1,000 mg/kg and the target organ was considered as the heart and kidney.

• Journal of Acupuncture Research
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• v.40 no.4
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• pp.344-350
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• 2023

Background: 4-carvomenthenol[4-methyl-1-(1-methylethyl)-3-cyclohexen-1-ol] is a main component of Origanum vulgare L., Zanthoxylum piperitum (L.) DC., and other plants. It has been reported to exhibit anti-inflammatory, antibacterial, and anti-tumor effects. Furthermore, it is necessary to conduct a toxicity test on 4-carvomenthenol to ensure its safety. Methods: This study included 5-week-old Institute of Cancer Research mice that were categorized into 3 treatment groups (12, 25, and 50 mg/kg 4-carvomenthenol dose levels) and a control group (10% dimethyl sulfoxide, 40% polyethylene glycol 300, 5% Tween 80, and 45% normal saline injection of the final volume), with 5 male mice and 5 female mice per group. All groups were observed for clinical symptoms and body weight in a period of 14 days and were subjected to gross necropsy after euthanasia. Results: No deaths were recorded. No test substance-related clinical signs in the female mice of the 12 mg/kg dose group were observed. Abnormal gait was observed in 1 male from day 1 to day 3 in the 12 mg/kg dose group; 1-3 males from day 1 to day 7 and 1-5 females from day 1 to day 15 in the 25 mg/kg dose group; and 2-5 males and 2-5 females from day 1 to day 15 in the 50 mg/kg dose group. No test substance-related effect on the body weight and necropsy findings was observed. Conclusion: The results of this study suggested that the lethal dose of 4-carvomenthenol could be greater than 50 mg/kg. However, further research is needed, especially repeated-dose toxicity studies, to confirm the efficacy and safety of 4-carvomenthenol.