• 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.

• Toxicological Research
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• v.12 no.2
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• pp.143-154
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• 1996

This paper reviews the toxicological role of median lethal dose ($LD_50$) based on animal and human data. Animal oral $LD_50$ values of eighty seven chemicals were collected and comparatively evaluated with human minimum toxic dose ($TD_50$). In general, animal $LD_50$ values were much higher than human $TD_50$. The ratios between $LD_50$ and TDlo were ranged from 0.01 and over 1000, suggesting safety factor of up to 1000 between humans and animals in the case of acute toxicity data. However, about 40% of chemicals investigated were within the ratio of 10. Although the cases (N=20) were small, $LD_50$ values of guinea pig were closer to human TDlo than those of other animal species. In interanimal species (rat, mouse, rabbit, dog), the ratios of $LD_50$ values were between 0.1 and 5 (up to 50-fold difference). When the data are analyzed by chemical strut-ares, human $TD_50$ values were very close to rat oral $LD_50$ values. These data suggest that rat oral $LD_50$ value might be a useful parameter predicting human TDlo and one animal species could be sufficient for acute toxicity test.

• Toxicological Research
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• v.13 no.4
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• pp.435-447
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• 1997

l-Muscone is synthesized for use as substitutive material of musk which is the active ingredient of woohwangchungsimwon. The objective of this investigation was to evaluate the acute and subacute toxicity of l-muscone in rats. In oral acute toxicity test, SPF Sprague-Dawley male and female rats were gayaged with l-muscone of two doses(0, 5.0 g/kg). No dead animal and abnormal autopsy findings were found in control and treated group. Body weights were slightly decreased in both sexes of rats treated with 5.0 g/kg. Therefore, oral $LD_{50}$ of l-muscone was consider to be higher than 5.0 g/kg in male and female rats. In intraperitoneal acute toxicity test, rats were injected intraperitoneally with dosages of 0, 1,000, 1,316, 1,732, 2,279 and 3.000 mg/kg. Decreased body weights and motor activities were observed at high dose group. Intraperitoneal $LD_{50}$ of l-muscone were 1,920 mg/kg in male and female rats. In the subacute study, l-muscone was administrated orally to both sexes of rats for 4 weeks as several doses(0, 10, 100 and 1,000 mg/kg). There were neither dead animals nor significant changes of body weights during the experimental period. In addition, no differences were found between control and treated groups in clinical signs, urinalysis, hematology, serum biochemical analysist and other findings. Above data suggest that no observed adverse effect level of l-muscone in rats might be over 1,000 mg/kg/day in this study.

• The Journal of Korean Medicine
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• v.44 no.3
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• pp.29-38
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• 2023

Objectives: This study aimed to investigate the acute oral toxicity of 77 herbal formulas and performed in male and female Sprague-Dawley (SD) rats as per the guidelines mentioned in Ministry of Food and Drug Safety. Methods: Each sex of SD rat were administered a single dose (2000 or 5000 mg/kg) of 77 herbal formulas via oral gavage; the control group received vehicle only. After administration, the mortality, clinical signs, gross findings, and body weight were followed up for 15 days. Results: After administration of 77 herbal formulas, mortality, clinical signs, body weight changes, and gross findings related to the test substances were not observed in both male and female groups. Conclusion: Our results demonstrate the single-dose oral administration of 77 herbal formulas produced no mortality indicating the approximate lethal dose is greater than 2000 or 5000 mg/kg body weight.

• The Korea Journal of Herbology
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• v.34 no.3
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• pp.31-36
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• 2019

Objectives : In this animal study, we performed the single oral dose toxicity test of Standardized Cornus officinalis Sieb. et Zucc. and Psoralea corylifolia L. 30% ethanol extract (SCP) in Sprague-Dawley (SD) rats owing to aims for verifying approximate lethal dose (ALD). Methods : According to OECD guidelines for the testing of chemicals section 4 health effects test No. 420 acute oral toxicity study - fixed dose procedure (17 December 2001), single oral dose toxicity test was performed. Animals were divided into two groups: Group 1, vehicle-treated rats (Control); Group 2, SCP 5000 mg/kg treated rats. SCP is composed of two medicinal herbs: Cornus officinalis Sieb. et Zucc. (650 g) and Psoralea corylifolia L. (350 g) in 30% ethanol. SCP was once orally administered to female and male SD rats at dose levels of 5000 mg/kg. Animals were monitored on the mortality, clinical signs, body weight changes and necropsy findings for 14 days. Results : After single oral treatment of SCP, we could not find any mortality up to 5000 mg/kg. Compared with the control group, there were also no significant differences in clinical sign, weight change, weight gain and gross abnormalities in SCP 5000 mg/kg-treated group. Conclusions : Taken together, these results suggest that the ALD of SCP in both female and male SD rats were considered as over 5000 mg/kg. Results from this study provide scientific evidence for the safety of SCP.

• Biomolecules & Therapeutics
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• v.2 no.3
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• pp.213-222
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• 1994

The acute tonicity of DWP305 (Ursodeoxycholic acid : Silymarin : Fursulthiamine : Riboflavin tetrabutyrate=1: 1 : 0.1 : 0.05) was evaluated in both sexes of Sprague-Dawley rats, 6weeks old by the oral route of administration. DWP305 was not considered to induce any toxic effect on the rats in mortalities, clinical findings, body weights and gross findings. It is suggested that LD$_{50}$ value in rats would be above 5 g/kg in the oral administration. Subacute toxicity of DWP305 was examined in Sprague-Dawley rats. Four groups of rats were administered orally at doses of 0, 0.32, 0.8, and 2.0 g/kg/day of DWP305 for one month. Any significant toxic clinical symptom was not observed in the treated rats during the experimental period. Macroscopic examination on the organs of tested animals showed no abnormal findings. On autopsy, no significant changes were found in organs examined. Maximum tolerated dose of DWP305 for the rat was estimated to be above 2 g/kg in this study.y.

• Journal of the Korean Society of Food Science and Nutrition
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• v.44 no.1
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• pp.29-34
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• 2015

The objective of this study was to obtain data on the safety-in-use of nano calcium as a dietary supplement by assessing its acute and subacute oral toxicities in female and male Sprague-Dawley rats. A single oral dose of 5,000 mg/kg of nano calcium did not result in mortality or significant changes in the general behavior and gross appearance of the internal organs of rats. For subacute toxicity study, nano calcium was administered orally at a dose of 1,000 mg/kg daily for 14 days. There were no significant differences in organ weights between control and treated groups of both sexes. Hematological analysis and blood chemistry revealed no toxic effects of nano calcium. Pathologically, neither gross abnormalities nor histopathological changes were observed. These results show that nano calcium possesses very low toxicity as indicated in a rat model.

• Toxicological Research
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• v.19 no.3
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• pp.211-215
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• 2003

This study was carried out to investigate the acute oral toxicity of a crude extract derived from fruiting body of Phellinus gilvus (PGE) using male and female SD rats. Groups consisted of five male and female rats were treated with a single dose of the test substance intragastrically at 0, 500, 1,000, 2,000, and 5,000 mg/kgaj, respectively. Clinical signs, body weight change, and food and water consumption change were observed for 14 days after administration. No mortality or abnormal clinical signs in animals were shown during the observation period at the dose used in this study. Also there was no difference in net body weight gain, water and food consumption or gross pathological findings at terminal sacrifice among the groups of rat treated with different doses of the test substance. The results suggested that acute oral toxicity of PGE in rats is very low at the conditions employed in this study and $LD_{50}$ of PGE was estimated to be over 5,000 mg/$\textrm{m}{\ell}$ in both sexes of rats.

• The Journal of Korean Obstetrics and Gynecology
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• v.26 no.4
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• pp.1-13
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• 2013

Objectives: In this study, it was carried out to evaluate the acute oral toxicity of Root of Polygala teunifolia Willd. in Sprague-Dawley (SD) rats. Methods: Male and female rats were administered orally with Root of Polygala teunifolia Willd. water extract of 1,000 mg/kg (low dosage group), 2,000 mg/kg (middle dosage group) and 4,000 mg/kg (high dosage group). We daily observed number of deaths, clinical signs and gross findings for 7 days. After 7 days, we measured body and organs weight. Also we analyzed hematological changes. Results: No dead SD rats and no clinical signs were found during the experiment period. Also other specific changes were not found between control and treated groups in hematology and serum biochemistry. But we found out histopathological changes in liver fat tissues of female. In addition, there were no significant changes of gross body and individual organs weight. Conclusions: These results suggest that water soluble extract of Root of Polygala teunifolia Willd. has not acute oral toxicity and oral $LD_{50}$ value was over 4,000 mg/kg in SD rats.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.26 no.4
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• pp.15-25
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• 2013

Objectives : This study was carried out to evaluate the acute oral toxicity of Alismatis Rhizoma in Sprague-Dawley(SD) rats. Methods : male and female rats were administered orally with Alismatis Rhizoma water extract of 1,000 mg/kg (low dosage group), 2,000 mg/kg(middle dosage group) and 4,000 mg/kg(high dosage group). We daily observed number of deaths, clinical signs and gross findings for 7 days. After 7 days, we measured body and organs weight. Also we analyzed hematological changes. Results : No dead SD rats and no clinical signs were found during the experiment period. Also other specific changes were not found between control and treated groups in hematology and serum biochemistry. In addition no significant changes of gross body and individual organs weight. Conclusions : These results suggest that water soluble extract of Alismatis Rhizoma has not acute oral toxicity and oral $LD_{50}$ value was over 4,000 mg/kg in SD rats.