• The Korea Journal of Herbology
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• v.35 no.4
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• pp.45-50
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• 2020

Objective : This study was performed to evaluate the toxicity after a single oral administration of black raspberry extract to male and female Sprague-Dawley (SD) rats and to determine the approximate lethal dose (ALD). Methods : We previously showed that the black raspberry extract repressed the simvastatin-mediated expression of Proprotein convertase subtilisin/kexin type 9 (PCSK9) and improved Low-Density Lipoprotein cholesterol (LDL-C) uptake by hepatocytes through the induction of the Low-Density Lipoprotein Receptor expression in hepatocytes. The groups consisted of black raspberry extract groups, as an oral dose of 2,000 mg/kg and a control group. 5 weeks SD rats were randomly assigned to 4 groups of 5 rats. Each male and female SD rats were administered orally once. For 14 days after the administration, mortality, clinical signs, changes in body weight, and necropsy findings were observed according to the "Standard for Toxicity Study of Pharmaceuticals" of Korea Food and Drug Administration (KFDA) guideline and "Acute Oral Toxicity- Fixed Dose Procedure" of OECD Test Guideline. Results : There were no cases of mortality in the group administered with 2,000 mg/kg of male and female, and no abnormalities in body weight change and clinical signs. Also, no gross abnormalities were observed at the autopsy. Conclusions : As a result of a single oral administration of the black raspberry extract to SD rats, the ALD was determined to exceed 2,000 mg/kg for both male and female SD rats.

• The Journal of Internal Korean Medicine
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• v.39 no.4
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• pp.676-685
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• 2018

Objectives: The aim of this study was to estimate the single oral toxicity of Peucedani Radix (PR) ethanol extracts. PR is one of the important herbs for removal of phlegm, the viscous turbid pathological product that can accumulate in the body and cause a variety of diseases. However, research on the pharmacologic toxicity of PR is lacking. Methods: In this study, PR was orally administered to 5-week-old male ICR mice at an oral dose of 2,000, 3,000, or 5,000 mg/kg. After a single-dose administration, the mortality and behavioral changes were observed daily and body weights were measured every two days. After 14 days, the organ weight, organ index, macroscopy, hematological analysis, and serum biochemistry analysis were determined. Results: No mortality, body weight changes, abnormal behavioral changes, or anatomical signs of toxicity were found. The organ weight, organ index, hematological analysis, and serum biochemistry analysis were also within the normal ranges. Conclusions: These results suggest that the 50% lethal dose of PR is more than 5,000 mg/kg. This could indicate that PR is a safe drug without acute toxicity and side effects.

• Korean Journal of Acupuncture
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• v.24 no.4
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• pp.151-162
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• 2007

Objectives : The purpose of this study was to examine the anti-allergic effect in vivo, and to observe single toxicity in mice of Armeniacae Semen herbal acupuncture solution (ASHA). Methods : We investigated anti DNP IgE-mediated passive cutaneous anaphylaxis in rodents and compound 48/80-induced active systemic anaphylatic shock in mice after treatment at both BL13 with ASHA of 25 ${\mu}{\ell}$(mice) or 50 ${\mu}{\ell}$(rats) 3 times for 5 days. To ascertain safety and toxicity of ASHA, we examined single toxicity test. In single test, three groups were treated with different dosages of ASHA (ASHA250, ASHA500 and ASHA1000) according to on Korean Food and Drug Administration, respectively. We observed attentively motality, abnormal clinical sign, body weight change, and organ weight of mice after ASHA treatment. Results : ASHA inhibited passive cutaneous anaphylaxis and active systemic anaphylatic shock by oral administration. During toxicity experiment period, there was no difference in body weight change, and organ weight among different dose groups. Death were not found in single test i.p. group. (ASHA250, ASHA500 and ASHA1000). Several individuals of single test i.p. group were observed yellow brown discharge around anus in early period after administration. Conclusions : These results indicate that ASHA have inhibition effects on passive cutaneous anaphylaxis and active systemic anaphylatic shock, and suggest that has some toxicity in high dosage.

• 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.

• Journal of Acupuncture Research
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• v.31 no.1
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• pp.105-110
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• 2014

Objectives : The objective of this study is to analyze the single-dose toxicity of horse placenta hydrolysate extracts. Methods : Sprague-Dawley rats were chosen for the study. Doses of horse placenta hydrolysate extracts, 2,000 mg/kg, 1,000 mg/kg and 500 mg/kg, were administered to the experimental group, and the same doses of normal saline solution were administered to the control group. This study was conducted under the approval of the Institutional Animal Ethics Committee. Results : In all 4 groups, no deaths occurred, and the horse placenta hydrolysate extracts administered by oral was over 2,000 mg/kg. No significant changes in the weight between the control group and the experimental group were observed. To check for abnormalities in organs and tissues, we used microscopy to examine representative histological sections of each specified organ, the results showed no significant differences in any organs or tissues. Conclusions : The above findings suggest that treatment with horse placenta hydrolysate extracts is relatively safe. Further studies on this subject should be conducted to yield more concrete evidence.

• Toxicological Research
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• v.20 no.3
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• pp.263-272
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• 2004

This study was to investigate single and repeated-dose toxicities of DFA IV, a new candidate of nutraceutical which has preventive effect on anemia and osteoporosis. In single-dose oral toxicity study, the test article were administered once by gavage to rats at dose level of 0, 2,000 and 5,000 mg/kg. No dead animal, abnormal sign and abnormal necropsy finding was found in control and treated groups. Thus the approximate lethal dose of DFA IV was considered to be higher than 5,000 mg/kg in rats. In four week repeated dose oral toxicity study, the test article was administered once daily by gavage to rats at dose levels of 0, 500, 1,000 and 2,000 mg/kg. No abnormality was observed in mortality, clinical findings, body weight changes, food and water consumptions, opthalmoscopic findings, hematological findings, necropsy findings, organ weights and histopathological findings. In urinalysis, specific gravity was increased in 2,000 mg/kg groups of male rats. In serum biochemical analysis, creatine phosphokinase was increased in all treatment groups of male rats. These increases in urine specific gravity and serum creatine phosphokinase activity were not accompanied with related signs such as histopathological changes or clinical findings. In conclusion, four week repeated oral dose of DFA IV to rats did not cause apparent toxicological change at the dose of 500, 1,000 or 2000 mg/kg body weight. Thus it is suggested that no-observed-adverse-effect level (NOAEL) of DFA IV in rats would be 2,000 mg/kg/day body weight.

• The Journal of Internal Korean Medicine
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• v.31 no.3
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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.

• Toxicological Research
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• v.20 no.2
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• pp.143-151
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• 2004

This study was to investigate single and repeated-dose toxicities of CJ-11555, an anticirrhotic agent, in Sprague-Dawley (SO) rats. In single-dose oral toxicity study, the test article were administered once by gavage to males and females at dose levels of 0 and 2,000 mg/kg. No dead animals and abnormal necropsy findings were found in control and CJ-11555 treated group. Therefore, the approximate lethal dose of CJ-11555 was considered to be higher than 2,000 mg/kg in rats. In the 4-week repeated oral toxicity study, the test article was administered once daily by gavage to male and female rats at dose levels of 0, 10, 50 and 200 mg/kg/day for 4-weeks. In clinical signs, yellow-colored urine and yellow hair coat were observed in the 50 and 200 mg/kg male and female groups. In hematology, erythrocyte count and hemoglobin were significantly decreased in the 200mg/kg male and female groups. In serum biochemistry, total cholesterol was significantly increased and aspartate aminotransferase (AST) was significantly decreased in the 50 or 200 mg/kg male and female groups. In histopathological examinations, centrilobular hepatocellular hypertrophy in the liver, congestion and pigmentation in the spleen, hyaline droplets in the kidney were observed in the 50 and 200 mg/kg male and female groups. In toxicokinetic study, CJ-11555 was dose-dependent in systemic exposure and showed better absorption in female with minimum accumulation after multidosing. Based on these results, it was concluded that the 4-week repeated oral dose of CJ-11555 resulted in the suppression of AST activity and centrilobular hepatocellular hypertrophy in both sexes at a dose level of 50 or 200 mg/kg/day. The target organ was estimated to be liver, spleen and male's kidney. The no-observed-adverse-effect level (NOAEL) for CJ-11555 in rats following gavage for at least 4-week is 10 mg/kg/day.

• Korean Journal of Pharmacognosy
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• v.40 no.3
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• pp.251-256
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• 2009

Cordyceps bassiana is a parasitic fungus and used as a Chinese traditional medicine. It has been called as DongChungHaCho(summer-plant, winter-worm) in China. Acute oral toxicity was examined in male and female ICR mice. Butanol fraction from Cordyceps bassiana(BuCb) was administered orally at a dose of 2,500 mg/kg, 5,000 mg/kg, 10,000 mg/kg. No death and abnormal clinical signs were observed throughout the administration period. The acute toxicity test on mouse did not show any oversign in net body weight gain, food and water consumptions, organ weights, gross pathological findings by different doses of BuCb. Also, biochemical examination revealed no evidence of specific toxicity. These findings show that BuCb has wide margin of safety on acute toxicity with single exposure.

• Journal of Physiology & Pathology in Korean Medicine
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• v.23 no.5
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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.