• Journal of Ginseng Research
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• 제44권5호
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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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• 제26권1호
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• pp.53-59
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• 2010

This study was conducted to obtain acute information of the oral dose toxicity of DHU001, a polyherbal formula in male and female mice. In order to calculated 50% lethal dose ($LD_{50}$) and approximate lethal dose (LD), test material was once orally administered to male and female ICR mice at dose levels of 2000, 1000, 500, 250 and 0 (vehicle control) ml/kg (body weight). The mortality and changes on body weight, clinical signs, gross observation, organ weight and histopathology of principle organs were monitored 14 days after treatment with DHU001. We could not find any mortalities, DHU001 treatment-related clinical signs, changes on the body and organ weights, gross and histopathological findings. The results obtained in this study suggest that $LD_{50}$ and approximate LD in mice after single oral dose of DHU001 were considered over 2000 mg/kg in both female and male mice.

• Toxicological Research
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• 제32권2호
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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.

• Toxicological Research
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• 제17권2호
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• pp.107-114
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• 2001

This study was designed to evaluate a repeated oral dose toxicity of a new hepatotherapeutic agent GODEX in Sprague-Dawley rats. Male and female rats were orally administered with dosages of 500, 100, 20, and 0 /kg/day of GODEX daily for 4 weeks, respectively. There were no dose-related changes in clinical signs, body weight changes, food and water consumption, opthalmoscopy, organ weights, urine analysis, biochemical examination, and hematological findings of all animals treated with GODEX. Gross and histopathological findings revealed no evidence of specific toxicity related to GODEX. These indicate that GODEX may have no side effects and its oral maximum tolerated dose value may be over 500 mg/kg in rats.

• 한국산업보건학회지
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• 제25권3호
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• pp.322-327
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• 2015

Objectives: The major objective of this study is the oral dose toxicity test and skin irritation test of eco-friendly plasticizer using crude glycerol derived from the biodiesel process. Methods: Glyceroldiacetate laurate(GDL) was synthesized from glycerol monolaurat(GML) and acetic acid. The synthesis of the GDL plasticizer was measured with nuclear magnetic resonance spectroscop(NMR) and FT-IR(Fourier Transform Infrared Spectrometer). To provide information on the safety of GDL, we carried out an oral dose toxicity test for GDL in Sprague-Dawley rats. Also, we carried out a skin irritation test for GDL in New Zealand White rabbits. Results: The oral dose toxicity test in Sprague-Dawley rats showed that GDL is a non-toxic material. The result of the skin irritation test on New Zealand White rabbits showed that GDL is non-irritating. Conclusions: From the results of oral dose toxicity test and skin irritation test, we concluded that the developed plasticizer showed excellent eco-friendly property. Based on our results, we confirmed the development of an eco-friendly non-phthalate plasticizer. Applicability for PVC toys and food and drug packaging materials was found.

• Journal of Applied Biological Chemistry
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• 제59권3호
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• pp.227-231
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• 2016

Deep sea water (DSW) is located 100 to 500 m below the sea surface. DSW is widely used in various fields, and is an important source of minerals that can be used to treat mineral deficiency. In the present study, the oral toxicity of DSW-mineral extracts was determined using single-dose and 14-day repeated dose oral toxicity tests in ICR mice. For the single-dose oral toxicity tests, mineral extracts of magnesium (Mg) and calcium (Ca) at doses of 0, 6, 270, 810, and 1,350 mg/kg, respectively, were orally administered to mice once at the beginning of the experiment, and the mice were observed for 14 days. For the 14-day repeated dose oral toxicity tests, Mg and Ca mineral extracts at doses of 0, 3, 135, 405, 675 mg/kg, respectively, were orally administered to mice daily, and the mice were observed for 14 days. Various tests were performed including visual observation; analysis of relative organ weight, food intake, and organ weight; biochemical analysis, and histopathology. The results indicated that mortality and changes in appearance were not observed among differentially administered groups of male and female ICR mice during the experimental period. Differences in body weight gain, food intake, organ weight, and histopathology parameters were not significant between the control and mineral-administered groups. Some results of the biochemical analyses were significantly different, but showed no specific tendencies. Overall, no evidence of toxicity was observed from the oral administration of DSW extracts of Ca and Mg in ICR mice.

• Toxicological Research
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• 제18권3호
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• pp.285-292
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• 2002

The repeated toxicity of Gleditschia-saponin produced and provided by S.S. Bio-Tech Bench Co. was evaluated in Sprague-Dawley rats. Gleditschia-saponin was administered to rats by oral route at dose levels of high (180 mg/kg/day), medium (90 mg/kg/day) and low (45 mg/kg/day) once a day for 14 days. Saline was administered to another group of rats as control. Each group was consisted of 5 male and female rats. There were no dose-related changes in clinical findings, food and water consumption, organ weights, urine analysis, biochemical examination and hematological findings in all groups of animals treated with Gleditschia.- saponin, except body weights. Body weighs in male and female rats were increased significantly (p < 0.05) from day 4 to 14 in low, middle and high dose groups than control group. Body weight in high dose group was increased higher than control or low, middle dose groups on day 14. Gross and histopathological findings revealed no evidence of specific toxicity to Gleditschia.-saponin. Therefore, it was concluded that Gleditschia-saponin had no toxic or side effects in Sprague-Dawley rats in an repeated oral toxicity tests.

• Toxicological Research
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• 제18권2호
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• pp.149-157
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• 2002

Though the bamboo salt, called as "JUKYUM" has been widely used in Korea as panacea, it's toxicity was not screened completely. To investigate the toxicity of bamboo salt, we compared with the toxicity of crude salt and reagent-grade NaCl by performing repeated dose (3 month's) oral toxicity test in SD rats. Crude salt, natural sun-dried salt (crude salt) production, was purchased from the western seashore of Korean peninsular and reagent-grade NaCl was purchased from Sigma company. Results of repeated dose oral toxicity tests for 3 months (bamboo salt; 750, 1500, 3000 mg/kg/day, crude salt : 3000 mg/kg/day, reagent-grade NaCl; 3000 mg/kg/day) suggested that the bamboo salt treated group show no significant toxicological findings with body weights and organ weighs changes, and hematological, serum bio-chemical and histopathological findings compared with other groups.er groups.

• 동의생리병리학회지
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• 제28권2호
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• pp.186-194
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• 2014

The object of this study was to obtain acute toxicity information (single-dose oral toxicity) of Woohwangchungshim-won (WHCSW), a pill type herbal medicine used in Korean Medicine (KM) for treating stroke. In order to obtain the 50% lethal dose (LD50), approximate lethal dosage (ALD) and target organs, WHCSW 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.) according to the recommendation of Korea Food and Drug Administration (KFDA) Guidelines (Notification No. 2009-116). The mortality and changes in the body weight, clinical signs and gross observation were monitored for 14 days after single-dose oral administration of WHCSW according to KFDA Guidelines with organ weights and histopathological changes were observed in 12 principle organs. After single-dose oral administration of WHCSW, we could not find any mortality and toxicological evidences up to 2,000 mg/kg-administered group, except for some accidental findings and dose-independent increases of body weight gains in female 1,000 and 500 mg/kg-administered female mice. The results obtained in this study suggest that the LD50 and ALD of WHCSW in both female and male mice after single-dose oral administration were considered as over 2,000 mg/kg because no mortalities were detected up to 2,000 mg/kg that was the highest dose recommended by KFDA and Organization for Economic Co-Operation and Development (OECD), and can be safely used in clinics.

• 대한본초학회지
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• 제33권4호
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• pp.53-58
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• 2018

Objectives : Kaempferia parviflora Rhizome is black ginger indigenous to Laos and Thailand. It has been used as a folk medicine to improve blood flow and promote vitality and longevity with good health and well being. For these reasons, Kaempferia parviflora Rhizome has been focused on developing it as a food or food supplement. In addition, Kaempferia parviflora Rhizome could be under consideration of new prescription based on its characteristic compounds, polymethoxyflavonoids. However, it needs to be certified as safe before it can be used. Here, a single-oral toxicity test and safety classification was carried out to identity acute information of the toxicity of Kaempferia parviflora Rhizome powder and to make sure of its safety in clinical applications. Methods : Test substance was orally administered to male and female SD-rat at dose levels of 5000 mg/kg to estimate approximate lethal dose(ALD). Based on the acute information of the toxicity, the safety classification was estimated using the HED(human equivalent dose)-based MOS(margin of safety). Results : At 14 days after treatment with test substance. there were no of test substance related with mortalities and clinical signs. In addition, no changes in the body or organ weights and no gross or histopathological findings were observed. Thus, the ALD of Kaempferia parviflora Rhizome powder was considered over 5,000 mg/kg in both female and male mice. Conclusions : Based on the single oral toxicity test using the highest and limit dose, 5,000 mg/kg and the decision guideline for safety classification based on HED-based MOS, it was estimated that Kaempferia parviflora Rhizome powder is classified as "Specified class B" indicating that clinical dose is not limited to patients as safe as food.