• The Korean Journal of Community Living Science
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• v.27 no.3
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• pp.437-449
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• 2016

To provide information on the safety of crude antifungal compounds produced by Bacillus subtilus SN7 isolated from Meju, we carried out an acute (single) oral dose toxicity test and 4 week repeated oral dose determination test on crude antifungal compounds in male and female Sprague Dawley rats. In the acute toxicity test, rats were treated with crude antifungal compounds produced by Bacillus subtilus SN7 orally at increasing dose levels (500, 1,000, and 2,000 mg/kg) and observed for 2 weeks. In the repeated-dose 28-day oral dose determination study, rats were orally administered doses of 500, 1,000, and 2,000 mg/kg daily for 4 weeks. There were no test article-related deaths or abnormal clinical signs in the two studies. In the 4 week repeated oral dose determination test, there were also no significant differences in clinical signs, body and organ weight changes, or any other hematological and biochemical parameters between the control and treated groups. The results suggest that the crude antifungal compounds produced by Bacillus subtilus SN7 up to a dosage level of 2,000 mg/kg are not toxic in male and female rats.

• 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.

• The Journal of Internal Korean Medicine
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• v.34 no.2
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• pp.155-164
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• 2013

Objectives : This study aimed to evaluate the single oral dose toxicity of Jaeumganghwa-tang (Ziyinjianghuo-tang) and Jaeumganghwa-tang (Ziyinjianghuo-tang) fermented with Lactobacillus acidophyllus in male and female ICR mice. Methods : In this single oral toxicity study, non-fermented and fermented Jaeumganghwa-tang (Ziyinjianghuo-tang) were administered to male and female ICR mice as an oral dose of 500, 1000 and 2000 mg/kg. After single administration, body weight changes, general behavior, adverse effects and mortality were determined for 14 days. Serum chemistry, organ weights and necropsy findings were evaluated at the end of the experiment. Results : There were no mortality or signs of toxicity for 14 days. There were also no significant differences in body weights, organ weights, or serum chemistry values between treatment and control groups. Conclusions : These results indicate that the 50% lethal dose of Jaeumganghwa-tang (Ziyinjianghuo-tang) fermented with Lactobacillus acipophullus may be over 2000 mg/kg. This finding can be expected to provide scientific evidence for the safety of Jaeumganghwa-tang (Ziyinjianghuo-tang) fermented with Lactobacillus acidophyllus.

• Toxicological Research
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• v.28 no.4
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• pp.263-268
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• 2012

The aim of this study was to investigate the acute oral toxicity of fermented Scutellariae Radix (JKTMHGu-100) in rats and dogs. JKTM-HGu-100 was orally administered at a dose of 2,000 mg/kg in Sprague-Dawley rats. An escalating single-dose oral toxicity test in beagle dogs was performed at doses of 500, 1000, and 2000 mg/kg with 4-day intervals. Clinical signs, changes in body weight, mortality, and necropsy findings were examined for 2 weeks following oral administration. No toxicological changes related to the test substance nor mortality was observed after administration of a single oral dose of JKTM-HGu-100 in rats or dogs. Therefore, the approximate lethal dose (LD) for oral administration of JKTMHGu-100 in rats was considered to be over 2,000 mg/kg, and the maximum tolerance doses (MTDs) in rats and dogs were also estimated to be over 2,000 mg/kg. These results indicate that JKTM-HGu-100 shows no toxicity in rodents or non-rodents at doses of 2,000 mg/kg or less.

• The Journal of Internal Korean Medicine
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• v.34 no.4
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• pp.349-361
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• 2013

Objectives : This study aimed to evaluate the single oral dose toxicity and four weeks repeated dose determination of Gamisasangja-tang (GST) in male and female Sprague-Dawley rats. Methods : In the single oral toxicity study, rats were orally administered a single dose of 0 and 5,000 mg/kg GST. There were 5 rats in each group. After single administration, mortality, clinical signs, body weight changes and gross pathological finding were observed for 14 days. In the 4-weeks repeated oral dose determination study, rats were orally administered a single dose of 0, 1,250, 2,500 or 5,000 mg/kg GST. There were 5 rats in each group. Mortality, clinical signs, body weight changes, food consumption and gross pathological finding were observed for 28 days. Organ weight, clinical chemistry and hematology were tested after 28 days. Results : There was no mortality in either of the two studies. There were also no significant differences in clinical sign, body weight, organ weights, hematological or serum chemical parameters between the GST and control groups. Conclusions : The results obtained in this study suggest that the 50% lethal dose of GST is over 5,000 mg/kg, so this finding would be expected to provide scientific evidence for the safety of GST.

• The Journal of Korean Medicine
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• v.32 no.1
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• pp.67-83
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• 2011

Objectives: The purpose of this study was to examine the single dose toxicity with oral administration and genotoxicities of Ssanghwa-tang fermented with Lactobacillus acidophyllus. Materials and Methods: Clinical signs, weight changes, lethal doses$(LD_{50})$, and postmortem evaluation were determined by Globally Harmonized Classification System(GHCS) in a single-dose oral toxicity study. In vitro mammalian chromosomal aberration test was conducted with Ames test by cell proliferation suppression assessment using the cultivated CHO-K1(Chinese hamster ovary fibroblast) origins. Bacterial reversion assay was performed using Salmonella typhimurium (TA98, TA100, TA1535, and TA1537) and Escherichia coli (WP2uvrA). In vivo micronucleus test was performed using ICR mouse bone marrow. Results: No clinical sign was observed and none of the groups with doses up to 2000 mg/kg showed significant acute oral toxicity in the single dose oral administration. None of the sample doses taken during the 6 to 18 hour groups showed significant aberrant metaphases comparing to the negative control group in the in vitro mammalian chromosomal aberration test. No evidence of mutagenicity was seen for Escherichia coli (WP2uvrA) or Salmonella typhimurium (TA98, TA100, TA1535, and TA1537). No significant increase in the frequency of micronuclei was seen in the micronucleus test. Conclusion: These results indicate that the $LD_{50}$ value of Ssanghwa-Tang fermented with Lactobacillus acidophyllus may be over 2000 mg/kg and it have no acute oral toxicity and genotoxicity.

• Toxicological Research
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• v.25 no.3
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• pp.147-157
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• 2009

This study was conducted to obtain acute information of the oral dose toxicity of lyophilized water extract of Pinelliae Rhizoma, a dried tuber of Pinellia ternata (PR) in male and female mice. In order to calculated 50% lethal dose (LD$_{50}$) and approximate lethal dose (ALD), test material was once orally administered to male and female ICR mice at dose levels of 2000, 1000, 500, 250, 125 and 0 (vehicle control) ml/kg (body weight). The mortality and changes in body weight, clinical signs, gross observation, organ weight and histopathology of principle organs were monitored 14 days after treatment with PR extract. We could not find any mortalities, clinical signs, changes in the body and organ weights, gross and histopathological findings except for dose-dependent increases in the hepatic fatty change frequencies detected in PR extract 2000 and 1000mg/kg treated in both male and female mice. The results obtained in this study suggest that LD$_{50}$ and approximate LD in mice after single oral dose of PR extracts were considered over 2000 mg/kg in both and female male mice, but more than 1000mg/kg of PR extracts treatment could induce slight hepatotoxicity the fatty changes in mice.

• 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 Korean Journal of Community Living Science
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• v.26 no.3
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• pp.511-522
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• 2015

This study investigates the acute and repeated-dose oral toxicity of crude antifungal compounds produced by Lactobacillus plantarum AF1 (Lb. plantarum AF1) and Lactobacillus plantarum HD1 (Lb. plantarum HD1) in male and female Sprague Dawley rats. In the acute toxicity study, crude antifungal compounds (500, 1,000, and 2,000 mg/kg) did not reduce mortality or produce significant changes in general behaviors or the gross appearance of external and internal organs. In the repeated-dose toxicity study, crude antifungal compounds were administered orally to rats at doses of 500, 1,000, and 2,000 mg/kg daily for 28 days. There were no test-article-related deaths, abnormal clinical signs, or body weight changes. In addition, there were no significant differences between groups treated with crude antifungal compounds and the control group in their organ weight, hematological and serum biochemical parameters, or any other factors. These results suggest that the acute or repeated-dose oral administration of crude antifungal compounds produced by Lb. plantarum AF1 plus Lb. plantarum HD1 is not toxic in male and female rats.

• Toxicological Research
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• v.20 no.2
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• pp.123-129
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• 2004

The present study was conducted to investigate the single and 2-week repeated dose toxicity of DHP2, a hydrophobic drug delivery vehicle, in ICR mice. The test article was administered orally to mice at the dose levels of 2.5, 12.5 and 37.5 g/kg for single dose toxicity study and at the dose levels of 0, 2.5, 5, and 10 g/kg 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 DHP2. Based on these results, it was concluded that the 2-week repeated oral dose of DHP2 may have no toxic effect in mice at a dose level of 10 g/kg. In the condition of this study, the no-observed-adverse-effect level (NOAEL) was considered to be 10 g/kg/day for both sexes.