• 대한약침학회지
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• 제17권4호
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• pp.27-35
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• 2014

Objectives: Mountain ginseng pharmacopuncture (MGP) is a pharmacopuncture made by distilling extract from mountain cultivated ginseng or mountain wild ginseng. This pharmacopuncture is injected intravenously, which is a quick, lossless way of strongly tonifying Qi function. The present study was undertaken to evaluate a 4-week, repeated, intravenous injection, toxicity test of MGP in Sprague-Dawley (SD) rats. Methods: Twenty male and female 6-week-old SD rats were used as subjects. We divided the SD rats into 4 groups: the high-dosage (10 mL/kg), medium-dosage (5 mL/kg), low-dosage (2.5 mL/kg) and control (normal saline) groups. MGP or normal saline was injected intravenously into the caudal vein of the rats once daily for 4 weeks. Clinical signs, body weights, and food consumption were monitored during the observation period, and hematology, serum biochemistry, organ weight, necropsy, and histological examinations were conducted once the observations had been completed. Results: No mortality was observed in any of the groups during the observation period. No changes due to MGP were observed in the experimental groups regarding clinical signs, body weights, food consumption, hematology, serum biochemistry, organ weight and necropsy. No histological changes due to MGP were observed in any of the male or female rats in the high-dosage group. Conclusion: During this 4-week, repeated, intravenous injection, toxicity test of MGP in SD rats, no toxic changes due to MGP were observed in any of the male or female rats in the high-dosage group. Thus, we suggest that the high and the low doses in a 13-week, repeated test should be 10 mL/kg and 2.5 mL/kg, respectively.

• 대한한방내과학회지
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• 제35권3호
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• pp.223-243
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• 2014

Objectives: To provide information on the safety of GST (GamiSasangja-tang; CnidiiFructus, Sophora Root, Angelica Gigas Root, Clematidis Radix, Stemonae Radix, Spirodelae Herba), we carried out a 13-week repeated oral dose toxicity and a 4-week recovery test of GST in Sprague-Dawley rats. Methods: Female and male rats were treated with GST at oral doses of 1,250, 2,500, and 5000 mg/kg. The GST was administered for 13 weeks. Mortality, clinical signs, body weight changes, food consumption, ophthalmologic findings, urinalysis, hematological and biochemical parameters, gross findings, organ weights and histological markers were monitored during the study period. The rats were then monitored for 4 extra weeks to determine recovery time after the study period. Results: We found no mortality or abnormalities among clinical signs, body weight, food consumption, ophthalmologic findings, urinalysis, hematological and biochemical parameters, gross findings, organ weights or histological markers in any of the rats tested. Conclusions: The no-observed adverse effects level (NOAEL) is considered as over 5000 mg/kg for male and female rats.

• 동의신경정신과학회지
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• 제23권3호
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• pp.143-160
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• 2012

Objectives : To provide information on the safety of ACM, we carried out a 13-week repeated oral dose toxicity and a 4-week recovery test of ACM in Sprague-Dawley rats. Methods : Female and male rats were treated with ACM with oral doses of 800, 2000, and 5000 mg/kg. The ACM was administered for 13 weeks. Mortality, clinical signs, body weight changes, food consumption, ophthalmologic findings, urinalysis, hematological and biochemical parameters, gross findings, organ weights and histological markers were monitored during the study period. Moreover, the rats were monitored for 4 extra weeks to determine recovery time after the study period. Results : We found no mortality and no abnormalities in clinical signs, body weight, food consumption, ophthalmologic findings, urinalysis, hematological and biochemical parameters, gross findings, organ weights and histological markers in any of the rats tested. Conclusions : The no-observed adverse effects level (NOAEL) was considered as over 5000 mg/kg for male and female rats.

• 대한한의학회지
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• 제24권1호
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• pp.41-53
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• 2003

The effect of Banhasasim-tang extracts on the hepatic, splenic and cardiac toxicity induced by doxorubicin administration (three injection protocol) were monitored using male ICR mice. Changes of body weight, clinical signs, necropsy findings and organ weights of liver, spleen and heart were observed with blood GOT and GPT levels. The results were as follows: 1. Decrease of body weight after doxorubicin treatment was dose-dependently inhibited by Banhasasim-tang extracts. 2. The degrees of anorexia, ataxia and dehydration that were observed in doxombicin treatment groups were dose-dependently inhibited by Banhasasim-rang extracts. 3. Increase of absolute and relative liver weight observed in the doxorubicin treatment group were dose-dependently inhibited by Banhasasim-tang extracts. In addition, the degrees of liver congestion and necrotic spot were significantly and dose-dependently decreased in the Banhasasim-rang extracts dosing group compared to that of the doxorubicin-only treatment group. It is also demonstrated that elevated serum GOT and GPT levels in the doxorubicin treatment group were significantly decreased in the Banhasasim-rang extracts dosing group. 4. Decrease of absolute and relative spleen weight observed in doxorubicin treatment groups were dose-dependently inhibited by Banhasasim-rang extracts. In addition, the degrees of splenic atrophy were significantly and dose-dependently decreased in the Banhasasim-rang extracts dosing group compared to that of doxorubicin-only treatment group. 5. Increase of absolute and relative heart weight observed in doxorubicin treatment groups were dose-dependently inhibited by Banhasasim-rang extracts. In addition, the degrees of heart congestion and enlargement were significantly and dose-dependently decreased in the Banhasasim-rang extracts dosing group compared to that of the doxorubicin-only treatment group. In conclusion, the toxicity of doxorubicin treatment (decrease of body weight, clinical signs such as anorexia, ataxia and dehydration, changes of organ weights of liver, spleen and heart, elevation of serum GOT and GPT levels) was inhibited and/or prevented by Banhasasim-rang extracts. According to these results, it is considered that Banhasasim-rang has some preventive effect against the toxicity induced by doxorubicin.

• 대한한방내과학회지
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• 제31권3호
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• pp.539-553
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• 2010

Objectives : The object of this study was to obtain accurate information (single oral dose toxicity) of Lonicerae Flos (LF; Dried flower bud parts of Lonicera japonica Thunb (Caprifoliaceae)), which has traditionally been used in Korean medicine for treating various inflammatory diseases. Methods : In order to observe the 50% lethal dose (LD 50), approximate lethal dosage (ALD) and target organs, test articles were once orally administered to female and male ICR mice at dose levels of 2,000, 1,000, 500 and 0 (control) mg/kg (body weight.). The mortality and changes on body weight, clinical signs and gross observation were monitored for 14 days after single oral treatment of LF aqueous extracts with organ weights and histopathological observations of 12 types of principle organs. Results : 1. After single oral treatment of LF aqueous extracts, we could not find any mortality and toxicological evidences up to 2,000 mg/kg treated group, the limited dosages in rodents at body and organ weights, clinical signs, gross and histopathological observations. 2. Slight diarrhea was detected in most mice treated with 2,000 mg/kg of LF aqueous extracts and male mice of LF aqueous extracts 1,000 mg/kg within 2 days after end of treatment, respectively. Conclusion : The results obtained in this study suggest that the LD 50 and ALD of LF aqueous extracts in both female and male mice after single oral treatment were considered as over 2,000 mg/kg because no mortalities were detected up to 2000 mg/kg, the highest dose recommended by KFDA and OECD. However, we also observed the possibility of digestive disorders like diarrhea when over 1,000 mg/kg of LF aqueous extracts were administered in the present study.

• 동의신경정신과학회지
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• 제24권1호
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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.

• 혜화의학회지
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• 제22권1호
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• pp.171-184
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• 2013

Single-and repeated-dose toxicities of Compound K (CK) were evaluated according to Toxicity Test Guidelines of Korea Food and Drug Administration using Sprague-Dawley rats. For single-dose toxicity study, CK was dissolved in drinking water, orally administered and examined for 14 days. As results, CK up to a dose of 5,000 mg/kg, the limited dose, neither induced death, clinical signs and necropsy findings, nor affected body weight gain and organ weights, in which 10% lethal dose could not be estimated. Based on the results of single-dose toxicity test, CK was administered at doses of 500, 1,000 or 2,000 mg/kg for 28 days for the evaluation of repeated-dose toxicity. All doses including the limited dose (2,000 mg/kg) of CK did not cause any abnormalities of rats, including mortality, clinical signs, body weight gain, feed/water consumption, necropsy findings, organ weights, hematology, blood biochemistry. Rather, high doses (1,000 - 2,000 mg/kg) of CK reduced the serum levels of alanine transaminase (ALT), aspartate transaminase (AST), creatinine phosphokinase (CPK), lactate dehydrogenase (LDH) and triglycerides, in addition to an increase in glucose, indicative of protective effects on hepatic and muscular injuries. Thus, both maximum tolerable dose (MTD) and no observed adverse effect level (NOAEL) were not determined. The results indicate that long-term intake of high-dose CK might not induce general adverse effects.

• 대한한의학방제학회지
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• 제21권1호
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• pp.186-199
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• 2013

Objectives : The objectives of this study was to obtain acute information (single oral dose toxicity) of Red-Koji (Monascus purpureus 12002) Fermented Scutellariae Radix Aqueous Extracts (fSR), has been traditionally used in Korean medicine for treating various diseases including inflammatory diseases. Methods : In order to observe the 50% lethal dose (LD50), approximate lethal dosage (ALD) and target organs, fSR powders were once orally administered to female and male ICR mice at dose levels of 2,000, 1,000, 500 and 0 (control) mg/kg (body weight.). The mortality and changes on body weight, clinical signs and gross observation were monitored during 14days after single oral treatment of fSR with organ weights and histopathological observations of 12 types of principle organs. Results : After single oral treatment of fSR, we could not find any mortality and toxicological evidences up to 2,000 mg/kg treated group, the limited dosages in rodents, on the body and organ weights, clinical signs, gross and histopathological observations, except for some accidental findings. Conclusions : The results obtained in this study suggest that the LD50 and ALD of fSR in both female and male mice after single oral treatment were considered as over 2,000 mg/kg because no mortalities were detected up to 2,000 mg/kg and can be safety used in clinics.

• 동의생리병리학회지
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• 제23권5호
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• pp.993-1002
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• 2009

The object of this study was to evaluate the single dose toxicity of Taeumjowui-tang(TUJWT), a polyherbal formula have been traditionally used as prevention or treatment agent for obesity, in male and female mice. Aqueous extracts of TUJWT (Yield = 10.5%) 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 diarrhea restricted in TUJWT 2000 mg/kg treated one male mouse at 1 day after administration, and increases of popliteal lymph node weights in all TUJWT administered groups. In addition, no TUJWT-treatment related abnormal gross findings and changes in histopathology of principle organs were detected except for increases of the frequency of hypertrophy and hyperplasia of lymphoid cells in the popliteal lymph nodes in all TUJWT treatment groups with some sporadic accidental findings. These increases of popliteal lymph node weights with hypertrophy and hyperplasia of lymphoid cells were considered that related to the immune modulate effect of TUJWT not toxicological signs. The results obtained in this study suggest that the TUJWT does not cause any toxicological signs. The 50% lethal dose and approximate lethal dose of TUJWT aqueous extracts in both female and male mice were considered as over 2000 mg/kg.

• 동의생리병리학회지
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• 제23권5호
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• pp.1145-1153
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• 2009

The object of this study was to obtain acute information single oral dose toxicity of Mahwangbujaseshin-tang extracts, with mouse bone marrow cell micronucleus test for detecting possible genotoxicity. In order to observe the 50% lethal dose, approximate lethal dosage, maximum tolerance dosage and target organs, test articles were once orally administered to ICR mice at dose levels of 2000, 1000, 50 mg/kg according to the recommendation of KFDA Guidelines. The mortality and changes on body weight, clinical signs and gross observation were monitored during 14 days after dosing according to KFDA Guidelines with organ weights of 12 types of principle organs. In addition, after twice oral treatment of Mahwangbujaseshin-tang extracts 2000, 1000 and 500 mg/kg, we checked the changes on the number of MNPCE. We could not find any mortality, clinical signs, changes in the body weight and gross findings upto 2000 mg/kg treated group. The limited dosages in rodents except for increases of lymphoid organ weights and hypertrophy encounted as results from pharmacological effects of Mahwangbujaseshin-tang extracts, immune modulator effects with some sporadic accidental findings not toxicological signs. No evidence of increases of MNPCE numbers were also detected in all three different dosages of Mahwangbujaseshin-tang extracts treated mice. The results obtained in this study suggest that the LD50 and ALD of Mahwangbujaseshin-tang extracts in mice were considered as over 2000 mg/kg because no mortalities were detected upto 2000 mg/kg that was the highest dose recommended by KFDA and OECD. And the results of mouse bone marrow micronucleus test of Mahwangbujaseshin-tang extracts is negative results.