• Journal of Ginseng Research
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• v.44 no.5
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• pp.717-724
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• 2020

Background: Malignant arrhythmias require drug therapy. However, most of the currently available antiarrhythmic drugs have significant side effects. Ginsenoside Rg2 exhibits excellent cardioprotective effects and appears to be a promising candidate for cardiovascular drug development. So far, the oral toxicity and antiarrhythmic effects of Rg2 have not been evaluated. Methods: Acute oral toxicity of Rg2 was assessed by the Limit Test method in mice. Subchronic oral toxicity was determined by repeated dose 28-day toxicity study in rats. Antiarrhythmic activities of Rg2 were evaluated in calcium chloride-induced arrhythmic rats. Antiarrhythmic mechanism of Rg2 was investigated in arrhythmic rats and H9c2 cardiomyocytes. Results: The results of toxicity studies indicated that Rg2 exhibited no single-dose (10 g/kg) acute oral toxicity. And 28-day repeated dose treatment with Rg2 (1.75, 3.5 and 5 g/kg/d) demonstrated minimal, if any, subchronic toxicity. Serum biochemical examination showed that total cholesterol in the high-dose cohort was dramatically decreased, whereas prothrombin time was increased at Day 28, suggesting that Rg2 might regulate lipid metabolism and have a potential anticoagulant effect. Moreover, pretreatment with Rg2 showed antiarrhythmic effects on the rat model of calcium chloride induced arrhythmia, in terms of the reduced duration time, mortality, and incidence of malignant arrhythmias. The antiarrhythmic mechanism of Rg2 might be the inhibition of calcium influx through L-type calcium channels by suppressing the phosphorylation of Ca²⁺/calmodulin-dependent protein kinase II. Conclusion: Our findings support the development of Rg2 as a promising antiarrhythmic drug with fewer side effects for clinical use.

• 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.

• The Journal of Internal Korean Medicine
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• v.32 no.3
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• pp.334-344
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• 2011

Objectives : Sipjeondaebo-tang is a medicine traditionally prescribed as a restorative. The aim of this study was to investigate the single oral dose toxicity and safety of extract of fermented Sipjeondaebo-tang in ICR mice. Methods : In single oral dose toxicity study, non-fermented or fermented Sipjeondaebo-tang were administered by oral gavage to ICR mice (5 males, 5 females) at single doses of varying concentrations: 1250, 2500 and 5000 mg/kg. Changes of body weight, general behavior, adverse effects and mortality were determined throughout the experimental period. Hematological parameters, organ weights and necropsy findings were evaluated at the end of the experiment. Results : There were no mortality or signs of toxicity in single oral dose toxicity studies. There were also no significant differences in body weight, organ weight, or hematological parameters between the treatment and control groups. Conclusions : Fermented Sipjeondaebo-tang did not cause remarkable adverse effects in ICR mice. The oral lethal dose of fermented Sipjeondaebo-tang is more than 5000 mg/kg and no-observed-adverse-effect level (NOAEL) of the extract for both male and female mice is 5000 mg/kg.

• Toxicological Research
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• v.20 no.3
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• pp.281-292
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• 2004

The purpose of this study was to assess the single and 5 week oral dose toxicity of calcitriol and alendronate combination (1 : 10,000) treatment for osteoporosis or Paget's disease in male and female rats. In single dose oral toxicity study, the values of $LD_{50}$ of calcitriol and alendronate mixture were 750.075 mg/kg in male rats and 775.0775 mg/kg in female rats, respectively. Body weight and food consumption were continuously increased after adminstration of calcitriol and alendronate mixtures, and there was no significant changes in body weight and food consumption in all groups. In five-week oral toxicity study of calcitriol and alendronate mixture at a dose of 0.2 $\mu\textrm{g}$ + 2 mg, 1 $\mu\textrm{g}$ + 10 mg, 5 $\mu\textrm{g}$ + 50 mg and 25 $\mu\textrm{g}$ + 250 mg, respectively, there was no mortality, abnormal behavior and appearance in all groups throughout the administration period (5 weeks) and recovery period (2 weeks). Dose-dependent changes in parameters of urinalysis and hematological analysis were not observed in male and female rats treated with calcitriol and alendronate mixtures. All the values of the parameters appeared to be in the normal range. These data indicate that both calcitriol and alendronate are drugs having low toxicity in rats. NOAEL of calcitriol and alendronate mixtures were 50.005 mg/kg in 5-week oral toxicity.

• Biomolecules & Therapeutics
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• v.4 no.4
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• pp.310-313
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• 1996

Acute oral toxicity studies of KDRD-002 (Coriolus versicolor polysaccharide :DDB= 19.2:1) were carried out in Sprague-Dawley rats of both sexes. In this study, we daily examined number of deaths, clinical signs, body weights and pathological examinations for 7 days after single oral administration of KDRD-002 with different dose levels. KDRD-002 did not show any toxic effect in rats and oral LD$_{50}$ value was over 3.25 g/kg in rats.s.

• The Journal of Internal Korean Medicine
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• v.32 no.4
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• pp.599-609
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• 2011

Objectives : The aim of this study was to evaluate the single oral dose toxicity and safety of Bojungikgi-tang (Buzhongyiqi-tang) and fermented Bojungikgi-tang (Buzhongyiqi-tang) extracts in male and female ICR mice. Methods : In the single oral dose toxicity study, non-fermented and fermented Bojungikgi-tang (Buzhongyiqi-tang) were administered to male and female ICR mice as an oral dose of 1250, 2500 and 5000 mg/kg. Changes of body weights, general behaviors, adverse effects and mortality were determined throughout the experimental period. Hematological parameters, serum chemistry, organ weights and necropsy findings were evaluated at the end of the experiment. Results : There was no mortality or sign of toxicity in the single oral dose toxicity study. There were also no significant differences in body weights, organ weights, and hematological parameters, serum chemistry values between treatment and control groups. Conclusions : The results obtained in this study suggest that the 50% lethal dose of fermented Bojungikgi-tang (Buzhongyiqi -tang) in both female and male mice can be considered as well over 5,000 mg/kg, so these medicines can be safe in clinics.

• Toxicological Research
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• v.32 no.2
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• pp.159-173
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• 2016

Crickets have been attracting considerable interest in the field of nutrition and toxicology due to the global exhaustion of food resulting from a growing population. The cricket is normally eaten in several countries after roasting, similar to the grasshopper; however, safety evaluation data on cricket powder is limited. Here, we performed general toxicity studies of cricket powder including a single, 2-week repeated dose range evaluation test, a 13-week repeated oral dose toxicity test in Sprague-Dawley rats, a single oral dose toxicity test in Beagle dogs, and a skin sensitization test in guinea pigs following the Organization for Economic Cooperation and Development test guidelines 406 and 408 in addition to Good Laboratory Practice. To investigate the NOAEL and target organs of cricket powder, Sprague-Dawley rats were allocated to 4 groups: vehicle control, 1,250 mg/kg, 2,500 mg/kg, 5,000 mg/kg dose test groups and cricket powder was administered over 13 weeks after single dose and dose range finding studies in rats based on the results of the single oral administration toxicity study in rats and Beagle dogs. The results of the study showed that the NOAEL of cricket powder was over 5,000 mg/kg for both sexes of rats without adverse effects in a 13-week repeated oral toxicity study and there was no skin hypersensitivity reaction. Therefore, our results reveal that crickets can be widely used as a new substitute food or nutrient resource.

• YAKHAK HOEJI
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• v.43 no.2
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• pp.180-197
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• 1999

Acute and subacute oral toxicity of $HELIKIT^{TM}$ ($^{13}C-urea$) were carried out in Sprague-Dawley rats of both sex. The toxicity of $HELIKIT^{TM}$ was compared with urea($^{12}C-urea$ which is used for control). In acute toxicity studies, we daily examined number of deaths, clinical signs, body weights and pathological examination for 14 days after single oral administration of HELIKIT or urea($^{12}C-urea$) at a dose of 5000 mg/kg. The subacute oral toxicity was investigated in Sprague-Dawley rats treated with $HELIKIT^{TM}$ at a dose of 40, 200 and 1,000 mg/kg/day or $^{12}C-urea$ at a dose of 1,000 mg/kg/day for 4 weeks. In acute toxicity studies, $HELIKIT^{TM}$ and urea did not show any toxic effect in rats and oral LD50 value was over 5,000 mg/kg rats. In subacute toxicity studies, no death occured and no drug-related changes were found in clinical observations; body weight, food consumption, opthalmoscopy. auditory test, urinalysis, hematology, blood chemistry, gross pathological examination or organ weight between $HELIKIT^{TM}$, urea and control groups. In histopathological examinations, the slight thickening of mucosa of the limiting ridge in the stomach was noted in the animals treated with $HELIKIT^{TM}$ at a dose of 1,000 mg/kg/day and also the changes in urea group at a dose of 1,000 mg/kg/day was found, but all of these changes in the changes in ures group at a dose of 1,000 mg/kg/days was found, but all of these changes in the stomach regressed after withdrawal of the test article for 2 weeks and reversibility of the effect was revealed. These results indicate that the non toxic dose level of $HELIKIT^{TM}$ was 1,000 mg/kg/day in the 4 weeks-repeated dose study, suggesting that the substitution of $^{13}C$ for carbon in urea molecule has no effect on the toxicity of urea and changes in stomach are reversible.

• The Journal of Korean Medicine
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• v.21 no.3
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• pp.199-208
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• 2000

Objectives : In order to investigate the toxicity of rats after oral administration of Eumcheonyijin-tang extract. Methods : The experimental animals were subdivided into control, short term administration group, and long term administration group. With changes of gross appearance, the histological changes of liver and kidney were observed. Blood chemical indexes used in this study were AST, ALT, total bilirubin, albumin, BUN and creatinine in serum. Results : In the long term administration group, histological changes were detected in the liver as centrolobular disposition of fatty tissue(adipose cell), and in serum test, AST, ALT increased at 21 days after administration group, serum total bilirubin were increased 21, 28 and 35 days after administration group. So it seems to induce toxicity. Kidneys of the long term administration group revealed histological changes : increasing of connective tissue and pyknosis of glomerulus cell were observed at 28 days after administration group, and in serum test, significant changes of albumin, BUN, and creatinine were admitted. So it seems to induce toxicity. Conclusions : In long term administration of Eumcheonyijin-tang toxicity was induced.

• 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.