• Toxicological Research
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• v.19 no.1
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• pp.51-66
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• 2003

This study was performed to evaluate single and repeated-dose toxicities of Bee Venom Extracts (F1, F3) in Spraque-Dawley. F1 was injected subcutaneously to rat at dose levels of 0, 0.0002, 0.002, 0.02 mg/kg/day for single-dose toxicity study and repeated-dose toxicity study. F3 was injected subcutaneously to rat at dose level of 0, 0.003, 0.03, 0.3 mg/kg/day for single-dose toxicity study and repeated-dose toxicity study. In both studies, there were no dose related changes in mortality, clinical sign, body weight change, food and water consumption, opthalmoscopy, organ weights, urine analysis, biochemical examination, and hematological findings of all animals treated with Bee Venom (F1, F3). Gross and histopathological findings revealed no evidence of specific toxicity related to Bee Venom (F1, F3). These results suggest that the subcutaneous NOEL (No Observed Effect Level) of Bee Venom (F1, F3) may be over F1 -0.02 mg/kg, F3-0.3 mg/kg.

• Toxicological Research
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• v.19 no.3
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• pp.173-180
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• 2003

The present study was conducted to investigate the single and 2-week repeated dose toxicity of red ginseng acidic polysaccharide (RGAP) in Sprague-Dawley rats. The test article was administered orally to rats at dose levels of 0, and 2000 mg/kg/day for single dose toxicity study and at dose levels of 0, 250, 500, and 1000 mg/kg/day for repeated dose toxicity study. In both studies, there were no treatment-related effects on mortality, clinical signs, food and water consumption, ophthalmoscopy, urinalysis, hematology, serum biochemistry, necropsy findings and organ weights of all animals treated RGAP. Based on these results, it was concluded that the 2-week repeated oral dose of RGAP may have no toxic effect in rats at a dose level of 1000 mg/kg/day. In the condition of this study, the no-observed-adverse-effect level (NOAEL) was considered to be 1000 mg/kg/day for both sexes.

• Toxicological Research
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• v.20 no.2
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• pp.123-129
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• 2004

The present study was conducted to investigate the single and 2-week repeated dose toxicity of DHP2, a hydrophobic drug delivery vehicle, in ICR mice. The test article was administered orally to mice at the dose levels of 2.5, 12.5 and 37.5 g/kg for single dose toxicity study and at the dose levels of 0, 2.5, 5, and 10 g/kg for repeated dose toxicity study. In both studies, there were no treatment-related effects on mortality, clinical signs, food and water consumption, ophthalmoscopy, urinalysis, hematology, serum biochemistry, necropsy findings and organ weights of all animals treated DHP2. Based on these results, it was concluded that the 2-week repeated oral dose of DHP2 may have no toxic effect in mice at a dose level of 10 g/kg. In the condition of this study, the no-observed-adverse-effect level (NOAEL) was considered to be 10 g/kg/day for both sexes.

• Proceedings of the Korean Society of Toxicology Conference
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• 2003.10b
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• pp.150-150
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• 2003

Botulinum toxin type A was intramuscularly administered to Sprague-Dawley rats in both single and 28-day repeated dose toxicity studies. In the single dose toxicity study performed at 25, 50, 100, and 200 ng/kg, LD50 was estimated to be 70.71 ng/kg for males and 97.63 ng/kg for females.(omitted)

• Journal of Pharmacopuncture
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• v.19 no.3
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• pp.253-258
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• 2016

Objectives: The goals of this research were to evaluate acute (single-dose) and sub-acute (repeated-dose) toxicity profiles of methanolic extract of Pistacia integerrima J. L. Stewart ex Brandis (PI) for Wistar rats and to assess the safety profile of PI by observing physiological changes, mortality, changes in body weight, the histopathology of body organs, the hematology and the biochemistry of the animals. Methods: The toxicity profile of PI was evaluated using Wistar rats of both sexes. Animals were divided into four groups: Group 1; control group (normal saline), Group 2; PI-1 (250 mg/kg), Group 3; PI-2 (500 mg/kg), Group 4; PL-3 (1,000 mg/kg). An acute-toxicity study in which animals received a single dose of PI extract (2,000 mg/kg) and were then observed for 14 days for changes in skin, fur, eye color, mucous membrane secretions and excretions, gait, posture, and tonic or clonic movements was performed according to guideline 425 of the Organization of Economic and Corporation Development (OECD). In the repeated-dose toxicity study (OECD - 407) animals received a daily dose of PI extract for 28 days (4 weeks). The parameters observed in this study include body weight, hematology and biochemistry of the animals. Results: In the acute toxicity study, no mortalities or changes in behavior were noted in the animals. The repeated-dose toxicity study was also devoid of any toxicity in the animals during the 28 days of testing with PI extract. The extract did not alter- the body weight, hematology or biochemistry of the animals. The methanolic extract of PI was to be found safe to the no-observed-adverse-effect-level (NOAEL) for the single-dose and repeated-dose toxicity tests in rats. Conclusion: The methanolic extract of PI was devoid of toxicity; hence, it can be used for various ayurvedic preparations and treatments of diseases.

• 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.

• Biomolecules & Therapeutics
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• v.10 no.1
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• pp.59-69
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• 2002

Recently, recombinant human erythropoietin (rHu-EPO) has been used to treat various types of anemia. YHB216 is a new rHu-EPO developed by Yuhan Research Institute. In this study, we investigated the single dose and 4-week repeated dose toxicity of YHB216 in Beagle dogs. In the single dose toxicity study, YHB216 was administered intravenously at single dose levels of 0 and 25,000 IU/kg to dogs (2 dogs/sex/group). There were no treament-related changes in survivals, clinical signs, body weight gain, hematological values, blood chemical values, and necropsy finding during experimental period. In the repeated dose toxicity study, YHB216 was administered intravenously to dogs for 4 weeks at the dose levels of 0, 100, 500, and 2,500IU／kg (3 dogs/sex／group). There were no toxicologically significant changes in clinical signs, body weights, food and water consumptions, ophthalmoscopy, urinalysis and blood chemistry. There were increased values of red blood cell, hemoglobin, and hematocrit at all treated groups. Spleen revealed increased weight and extramedullary hematopoiesis at 500 IU/kg or more. These changes are all considered to be Pharmacology-related effects and were recovered after 4-week recovery period. From these results, it is concluded that LD50 value was above 25,000 IU/kg in the single dose toxicity study of YHB216 in dogs and the no observed adverse effect level (NOAEL) was 100 IU/kg day in the repeated dose toxicity study of YHB216 in dogs.

• Journal of Oriental Neuropsychiatry
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• v.24 no.1
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• pp.131-144
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• 2013

Objectives : To provide information on the safety of ACM, we carried out a single oral dose-increasing toxicity and 4-weeks repeated oral dose determining test of ACM in beagle dogs. Methods : In a single oral dose-increasing toxicity test, beagles were treated with ACM orally increasing dose level (1,000, 2,000, 5,000 mg/㎏) at interval of 3 days. After administration, signs of toxicity were observed for two weeks. In 4-weeks repeated oral dose determinating test, beagles were treated with ACM with oral dose 500, 1,000, 2,000 mg/kg for 4 weeks. Mortality, clinical signs, body weight changes, food consumption, urinalysis, hematological and biochemical parameters, organ weights, necropsy findings, and histological findings were monitored during the study period. Results : In a single oral dose-increasing toxicity test, we found no mortality, abnormalities in clinical signs, body weight, and necropsy findings during the study period. In 4-weeks repeated oral dose determinating test, we found no mortality, abnormalities in clinical signs, body weight, food consumption, urinalysis, hematological and biological parameters, gross findings, organ weights, necropsy findings, and histopathological findings in any of the beagles tested. Conclusions : The results obtained in these studies suggest that maximum tolerated dose (MTD) of ACM in male and female beagle dogs was supposed to be over 5,000 mg/kg. For the future studies of toxicity, it is advisable that high dose and low dose are set at 2000 mg/kg and 500 mg/kg, respectively.

• Toxicological Research
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• v.19 no.4
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• pp.259-266
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• 2003

Although 'Cinnamon' has been widely used for the food and biophamacy in the world, it's toxicity was not screened completely. Major component of 'cinnamon' is CB-OH and CB-PH. CB-PH has been reported to have antimutagenic effect. To investigate the toxicity of 2-o-Benzoylcinnama-Idehyde (CB-PH), repeated dose (4 weeks) oral toxicity test performed in SD rats. Results of repeated dose oral toxicity tests for 4 weeks (CB-PH; 500, 1000, 2000 mg/kg/day) suggested that the CB-PH treated group showed no significant toxicological findings with body weights, organ weights, hematological and histopathological findings. Therefore, these data indicated that the maximum tolerated dose of CB-PH was 2000 mg above/kg/day in the rats.

• Biomolecules & Therapeutics
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• v.2 no.2
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• pp.161-172
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• 1994

This study was conducted to examine DA-3002, a biosynthetic human growth hormone, for its acute and subacute toxicities in mice and rats. The drug was administered subcutaneously and orally at a dose level of 1.0, 3.0, 8.9, 26.7 or 80.0 lU/kg once for single dose toxicity and given subcutaneously at a dose level of 0.34, 1.7 or 8.4 lU/kg daily for 13 weeks to investigate repeated dose toxicity. In the acute toxicity study, doses up to 80 lU/kg had no adverse effect on the behavior or body weight gain. Pathological examinations revealed no abnormal changes which could be attributed to toxic effect of DA-3002. In the subacute toxicity study, the growth hormone was tolerated well in broth mice and rats. No drug related deaths occurred and all animals appeared to be normal throughout the dosing period. Increases in body weight gain, food utilisation and absolute organ weights were observed in the rats in the high dose group. Mild changes in the blood chemical parameters were also seen in the treated groups. Histopathologically, however, no abnormal changes were observed in any organ. The changes noted during the treatment periods presumably represent exaggerated pharmacological effects of the growth hormone, and no observed adverse effect level (NOAEL) was considered to be more than 8.4 lu/kg/day.