• Toxicological Research
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• v.24 no.1
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• pp.79-86
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• 2008

This study was conducted to obtain information of the oral dose toxicity of low molecular fucoidan (LMF) in male and female mice. In order to calculate 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, 125 and 0 (vehicle control) mg/kg (body wt.). The mortality and the changes on body weight, clinical signs, gross observation and organ weight and histopathology of principle organs were monitored 14 days after LMF treatment. We could not find any mortalities, clinical signs, body weight changes and gross findings. In addition, significant changes in the organ weight and histopathology of principal organs were not observed except for some sporadic findings. The results obtained in this study suggest that LMF may not be toxic in mice and may be therefore safe for clinical use. The $LD_{50}$ and approximate LD in mice after single oral dose of LMF were considered over 2000 mg/kg in both female and male mice.

• Toxicological Research
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• v.34 no.1
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• pp.55-63
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• 2018

As a part of general toxicity studies of Enterococcus Faecalis 2001 (EF 2001) prepared using heat-treatment bacillus mort body EF 2001 in mice, this study examined the toxicity of EF 2001 in single and repeated administrations following the previous report in order to apply this product to preventive medicine. The safety of oral ingestion of EF 2001 was examined in 6-week-old male and female ICR mice with 1,000 mg/kg, 3,000 mg/kg and 5,000 mg/kg body weight/day administrated by gavage of the maximum acceptable dose of EF 2001. The study was conducted using distilled water as a control following the methods for general toxicity studies described in the "Guidelines for Non-clinical Studies of Pharmaceutical Products 2002". As a control, 1) observation of general conditions, 2) measurement of body weight, 3) determination of food consumption, 4) determination of water consumption, 5) blood test and urinalysis and 6) pathological examination were performed for the administration of EF 2001. Mice received EF 2001 for 13 weeks and results were compared with those of the control group that received distilled water. The results of the above examinations revealed no significant differences between control and EF 2001 groups for both males and females. Thus, no notable toxicity was confirmed with single and repeated oral administrations of EF 2001. Oral administration in the above doses did not result in abnormal symptoms or death during the observation period. No abnormalities in blood cell count or organ weights were seen. Without any evidence of toxicity to cells and organs, EF 2001 is speculated to not adversely affect living organisms. The 50% lethal dose of EF 2001 with oral administration in mice is estimated to be greater than 5,000 mg/kg body weight/day for both male and female mice. Therefore, $LD_{50}$ value for animals was 5,000 mg/kg or more.

• Herbal Formula Science
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• v.28 no.2
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• pp.169-177
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• 2020

Objectives : This experiment was designed to assess the single oral toxicity of Ethanol Extract Inulae Flos (IF) ethanol extracts. IF is one of the important herbs to remove phlegmy which is the viscous turbid pathological product that can accumulate in the body, causing a variety of diseases. Nevertheless, there has been a lack of research on the pharmacology toxicity of IF. Methods : In this study, IF was orally administered to 5 weeks ICR mice as an oral dose of 2,000 or 3,000 or 5,000 mg/kg. The condition of the mice was observed for 14 days and their weights were measured every two days. Results : None of the mice died for 14 days. The abnormal clinical symptoms and anatomical signs of toxicity were not found in any treatment groups. The gain of net body weight was observed. There was also no significant difference in the organ weight. The serum biochemistry and hematological analysis showed a decrease in BUN, red blood cells, white blood cells and platelets although within the normal ranges. Conclusions : These results suggest that the 50% lethal dose of IF is more than 5,000 mg/kg. This could be thought that IF is a safe drug without acute toxicity and side effects. However, IF showed some weight loss and change in blood test, so it will need to be careful when using it for high doses.

• Biomedical Science Letters
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• v.18 no.1
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• pp.10-15
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• 2012

A 12-week repeated-dose oral toxicity study of water-soluble Orostachys japonicus extract (WOJ) was performed in Sprague-Dawley (SD) rats of both genders. Each group of ten rats was orally administered in doses of either 0 or 250 mg/day over a 12-week period. As a result, no WOJ-related changes were observed in terms of survival rate, clinical signs, body weight, or food intake. In addition, no difference in organ weight between the control and treated groups was detected. Furthermore, serum biochemistry parameters revealed some changes within normal ranges although significant decreases in total-bilirubin in the females. In spite of some alterations in serum biochemistry, the clinical signs, body weight changes from food intake, and autoptical remarks indicated that WOJ was not toxic. This study suggests that repeated treatment of O. japonicus very low toxicity and the NOAEL (no observed adverse effect dose) of WOJ exceeds 250 mg/kg in the SD rats.

• The Journal of Internal Korean Medicine
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• v.26 no.2
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• pp.369-378
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• 2005

An herbal water extract of Bojungikkeehapdaechilkitang(BDT) was prepared to test it for single-dose and repeated-dose toxicity, genotoxicity and reproductive toxicity, and to obtain a 50% lethal dose$(LD_{50})$, approximated lethal dose(ALD), and approximated target organs for BDT. The extract was tested on female and male ICR mice according to KFDA Guideline 1999-61 at doasge level of 2000, 1000, 500, 250 and 125mg/kg/10mL In this study, clinical signs, mortalities and gross findings of principal organs were observed for 14 days of single dosing, and afterwards in some cases. The ALD and $LD_{50}$ of BDT extract obtained in this study was>2000mg/kg for both male and female ICR mice. Also, any possible digestive toxicity of BDT extract was found to be above 1000mg/kg in both male and female ICR mice. The results of this study strongly suggest that BDT extract has no toxic effect at dosage level below 500mg/kg.

• Toxicological Research
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• v.24 no.4
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• pp.315-320
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• 2008

Recombinant human granulocyte-macrophage colony stimulating factor (hGM-CSF) is a glycoprotein and hematopoietic growth factors that regulates the proliferation of myeloid precursor cells and activates mature granulocytes and macrophages. In a previous study, we reported that hGM-CSF could be produced in transgenic rice cell suspension culture, termed rhGM-CSF. In the present study, we examined the repeated dose toxicity of rhGM-CSF in SD rats. The repeated dose toxicity study was performed at each dose of 50 and 200 ${\mu}g/kg$ subcutaneous administration of rhGM-CSF everyday for 28-days period. The results did not show any changes in food and water intake. There were also no significant changes in both body and organ weights between the control and the tested groups. The hematological and blood biochemical parameters were statistically not different in all groups. These results suggest that rhGM-CSF may show no repeated dose toxicity in SD rats under the conditions.

• Korean Journal of Agricultural Science
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• v.48 no.4
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• pp.1003-1013
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• 2021

Thioredoxin (TRX) protein is an antioxidant responsible for reducing other proteins by exchanging cysteine thiol-disulfide and is also known for its anti-allergic and anti-aging properties. On the other hand, epidermal growth factor (EGF) is an important material used in the cosmetics industry and an essential protein necessary for dermal wound healing facilitated by the proliferation and migration of keratinocytes. EGF also assists in the formation of granulation tissues and stimulates the motility of fibroblasts. Hence, genetically modified soybeans were developed to overexpress these industrially important proteins for mass production. A single-dose oral-toxicity-based study was conducted to evaluate the potential toxic effects of TRX and EGF proteins, as safety assessments are necessary for the commercial use of seed-specific protein-expressing transgenic soybeans. To achieve this rationale, TRX and EGF proteins were mass purified from recombinant E. coli. The single-dose oral-toxicity tests of the TRX and EGF proteins were carried out in six-week old male and female Institute of Cancer Research (ICR) mice. The initial evaluation of the single-dose TRF and EGF treatments was based on monitoring the toxicity signatures and mortality rates among the mice, and the resultant mortality rates did not show any specific clinical symptoms related to the proteins. Furthermore, no significant differences were observed in the weights between the treatment and control groups of male and female ICR mice. After 14 days of treatment, no differences were observed in the autopsy reports between the various treatment and control groups. These results suggest that the minimum lethal dose of TRX and EGF proteins is higher than the allowed 2,000 mg·kg^-1 limit.

• Journal of Life Science
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• v.26 no.10
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• pp.1153-1162
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• 2016

Termitomyces albuminosus (Berk.) Heim is a well-known wild edible mushroom in the southern region of China. Novel cerebrosides, termed termitomycesphins, isolated from EtOH extract of T. albuminosus have shown significant neuritogenic activity. Neurotrophic factors have been targeted as potential therapeutic drugs for the treatment of neurodegenerative disorders. However, before expanding their applications to include food or therapeutic agents in Korea, a safety evaluation of T. albuminosus is needed. Herein, in a repeated-dose 90-day oral toxicity study, rats were exposed to a basal diet of powder ground from dried T. albuminosus at dose levels of 5%, 2.5%, 1.25%, and 0%. The following endpoints were evaluated: clinical observation, body weight, gross and microscopic pathology, clinical chemistry, and hematology. Significant dose-dependent increases in the weight of the left kidney were observed, possibly due to the test substance. Based on toxicity-decision criteria for minor compound-related changes (no observed adverse effect level [NOAEL] and no observed effect level [NOEL]), NOAEL was observed in male rats at a dose of 5% of dried T. albuminosus powder, and NOEl was observed in female rats at the same dose. The results point to the safety and potential use of T. albuminosus as a nontoxic neurotrophic factor.

• Journal of Physiology & Pathology in Korean Medicine
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• v.28 no.2
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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.

• 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.