• YAKHAK HOEJI
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• v.38 no.1
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• pp.46-56
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• 1994

Daily oral administration to Sprague Dawly rats for 4 weeks of DWP-301, at doses of 0, 500, 1000, 2000 mg/kg presented following results; 1) No animals died and there were no significant differences in general signs, body weight, food consumption, urinalysis haematological, biochemical, gross pathological and histopathological examination between control and treated rats. 2) Water consumption, pH-, protein- urobilinogen-, ketone-values in urine were significantly increased in the treated male and female rats. It is supposed that these differences in animals are a consistent feature of repeated overdosage with test suspensions. The results indicate that the non toxic dose of test compounds in rats is over 2000 mg/kg in this test system.

• The Journal of Korean Medicine
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• v.30 no.5
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• pp.102-114
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• 2009

Objectives: HMCO5 is an extract obtained from 8 different herbal mixtures. We undertook a safety evaluation of HMCO5 for a dose range finding (DRF) toxicity test in specific pathogen free (SPF) Sprague-Dawley (SD) male and female rats. Methods: The male and female rats were divided into 4 groups, respectively; G(0), treated with distilled water: G(1), treated with 222 mg/kg HMC05: G(2), treated with 667 mg/kg HMC05, and G(3), treated with 2,000 mg/kg HMC05; HMC05 was administered orally for 4 weeks. The safety evaluation examined clinical signs, mortality, body weight, food consumption, water consumption, ophthalmic findings, urinalysis, hematological values, absolute & relative organ weights, and necropsy findings during the tests. Results: There were no changes in clinical signs, mortality, body weight, food consumption, water consumption, and ophthalmic findings examined during the test periods. In serum biochemical values, triglyceride was increased in male group G(3) and Na$^+$ decreased significantly in male groups G(2), G(3) and G(4). In male group G(4), spleen weight decreased relatively and increases of absolute & relative left ovary weights were found. In addition, an adhesion of liver to diaphragm was found in male group G(2). However, we could not find any dose-interrelationships in these changes. Conclusions: These results indicate that HMC05 extract did not show any toxicity in the DRF toxicity study. Therefore, it suggests that establishment of 1,000, 333 and 111 mg/kg dosages are moderate in a repeated dose 26-week oral toxicity study of HMC05.

• Biomolecules & Therapeutics
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• v.11 no.1
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• pp.72-79
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• 2003

The present study was conducted to investigate the potential subacute toxicity of AS6, [(3$\beta$, 4$\alpha$)-3,23-dihydroxyurs-12-en-28-oic acid], by a 4-week repeated oral administration in Sprague-Dawley rats. To test the subacute toxicity, AS6 was administered once daily by gavage to rats at dose levels of 0, 250, 500, and 1000 mg/kg/day for 4 weeks. There were no treatment-related effects on mortality, clinical signs, body weight, food and water consumption, ophthalmoscopy, urinalysis, hematology, serum biochemistry, necropsy findings, organ weights, and histopathology in any treatment group. In the condition of this study, target organ was not observed and the no-observed-adverse-effect level (NOAEL) was considered to be 1000 mg/kg/day for both male and female rats.

• The Korea Journal of Herbology
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• v.28 no.1
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• pp.15-21
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• 2013

Objectives : To evaluate the safety of KOB, a polyherbal medicine for allergic rhinitis, we conducted a subchronic toxicology study. Methods : Dried extract of KOB(Lot. No. 11003, yield : 41.1%) was prepared from GLP company (Hanpoong Pharm & Food Co., Ltd). KOB was repeatedly administrated orally of male SD rats at daily dose levels of 500 (G2), 1250 (G3) and 5000 (G4) mg/kg/day for 13 weeks. We recorded the clinical signs of toxicity, body weight, food intake/consumption, optometry, urine analysis, organ weights, hematology, and conducted serum biochemical analysis, necropsy, gross and histological changes in target organs of Sprague-Dawley rats, and clinical chemistry analysis. Results : Neither death nor any toxicological signs were obserbed in KOB at all doses of 500, 1250 and 5000 mg/kg/day during the administration period for thirteen-week. Furthermore, there was no difference in body weight and food-take consumption, optometry, necropsy, organ weight, gross pathological findings, and urine analysis among the groups of rats treated with different doses of KOB, during at the observation period for thirteen-week. The hematological analysis and clinical blood chemistry data were revealed no toxic effects from repeated-dose administration of KOB in rats during the observation period. Conclusions : Based on these results, the no observable adverse effect level (NOAEL) of KOB was considered to be 5000 mg/kg/day for male rats under these study conditions.

• 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.

• Proceedings of the Korea Environmental Mutagen Society Conference
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• 2003.10a
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• pp.170-170
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• 2003

• Journal of Physiology & Pathology in Korean Medicine
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• v.24 no.6
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• pp.1034-1041
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• 2010

The oriental medicine Jangwonhwan, which is a boiled extract of 12 medicinal herbs/mushroom, has been prescribed for patients with cognitive dysfunction and it is originally from the Korean medical text, DonguiBogam(amnesia chapter). Recently, a modified recipe of Jangwonhwan (LMK02-Jangwonhwan) consisting of seven medicinal plants/mushroom, was shown to reduce ${\beta}$-amyloid deposition in the brain of Tg-APPswe/PS1dE9 mouse model of Alzheimer disease. The toxicity of LMK02 was investigated in SD rats by oral repeated adminstration for 4 weeks and we tried to determine test does for 13 weeks repeated study. Quality control of tablet form of LMK02 was established by estimating indicative components, Ginsenoside Rg3 of Red Ginseng and Decursin of Angelicagigas Nakai. The toxicity of LMK02 was investigated in 6 weeks old specific pathogen free (SPF) Sprageu-Dawley rats by oral administration. Each test group were consist of 5 male and 5 female and they received doses of 500, 1,000 and 2,000 mg/kg/day of test substance for 4 weeks. The clinical signs, death rate, body weight, food consumption, ophthalmic examination, urinalysis, hematological and serum biochemistry, organ weight and pathological changes were examined and compared with those of control group. Urinalysis : We observed increase of PRO(p<0.01), SG(p<0.01) in female rats of 1,000 mg/kg/day and 2,000 mg/kg/day(p<0.01). Also, we observed increase of pH and KET in female rats of 1,000 mg/kg/day(p<0.05) and of 2,000 mg/kg/day(p<0.01). WBC in female rats in 1,000 mg/kg/day and 2,000 mg/kg/day were on increase. Hematological test : We observed increase of MCV in male rats of 250 mg/kg/day. (p<0.05) Serum biochemistry test : We found increase of CHO in female rats of 2,000 mg/kg/day(p<0.05). During the experimental period, there were no animals dead or moribund. There were no treatment related changes of general symptom, food and water consumption, organ weight and autopsy According to the results of 4-week repeated dose range finding study, the highest dose was established as 1000 mg/kg for 13-week repeated dose toxicity study and we determined to put 2 more groups by common ratio two.

• Journal of Physiology & Pathology in Korean Medicine
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• v.26 no.2
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• pp.189-198
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• 2012

Our former study indicated efficacy of apoptotic cell death on animal study by using Egg white combined Chalcanthite (EC). Clinically, bamboo salt is using because of safety. Hence we investigated a toxicity study for determining safety by adding bamboo salt in former materiel. We had two studies: toxicity of EC and of Bamboo salt with egg white combined Chalcanthite (BC). Both were studied in 1-week single and 5-week repeated oral dose toxicity tests on male Imprinting Control Region mice. In EC, doses used in 1 week single oral dose toxicity tests were 0, 0.05, 0.5, 5 and 50 mg/kg/day and 0, 0.01, 0.05, 0.25 and 0.5 mg/kg/day. In BC, doses used by 0, 0.08, 8.3, 83.3 and 166.6 mg/kg/day in single oral dose toxicity and 0, 4.2, 8.3, 41.7 and 83.3 mg/kg/day in repeated oral dose toxicity tests. Their blood and urine were assayed and organ morphology were examined. Mann-Whitney U test and ANOVA tests were used by analysing methods. First, significant increased left renal weight in all groups of EC and BC. Second, increased ALT score was found in EC-S2 and increased relative liver weight was found in EC-S3. In addition, increased relative weight and urine bilirubin and urobilinogen were found in EC-R2 and EC-R3. There was no significant toxic change in BC. The Mixture of EC had a possibility of hepatotoxicity in the short and long term. Processed BC appears to be safe and non-toxic in these studies and a no-observed adverse effect level (NOAEL) was established at 83.3 mg/kg/day in mice. Relatively, The BC were safer than The EC.

• Biomolecules & Therapeutics
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• v.5 no.2
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• pp.133-149
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• 1997

4-week repeated dose toxicity of DA-5018, a new capsaicin analogue analgesic agent, was examined in 5D rats at dosage levels of 0,0.4,2, 10 and 50 mg/kg/day. DA-5018 was administered orally to 17 males and 17 females per group at doses of 0, 10 and 50 mg/kg and to 12 males and 12 females per group at doses of 0.4 and 2 mg/kg. After the administration period, 5 males and 5 females at the 0, 10 and 50 mg/kg were placed on withdrawal for 2 weeks. Treatment-related clinical signs were observed at 10 and 50 mg/kg. Clinical signs observed immediately after the administration of DA-5018 were grooming, sedation or depression, lacrimation, atacia, reddening of extremities and ears, ventral or lateral recumvincy, respiratory distress, cyanosis and convulsion. Delayed-type clinical signs including focal scabbing and depilation around nose were also observed 1 or 2 weeks after the start of administration of DA-5018. Only at the 50 mg/kg group, corneal opacities, reduced body weight gain (male) and death (male 6/17, female 3/17) were noted. In blood biochemical analysis, serum levels of glucose and triglyceride decreased at 10 and 50 mg/kg. In hematological examination, there were increases in the number of red blood cell, hemoglobin content and percent of hematocrit at 10 and 50 mg/kg. Pulmonary enlargement and hemorrhagic spot, focal scabbing and depilation around nose and corneal opacities were seen at the necropsy of the animals died during the dosing of DA-5018 50 mg/kg. Focal scabbing and depilation around nose were observed in the animals terminally necropsied at doses of 10 and 50 mg/kg. Histopathological examination revealed pulmonary hemorrhage, focal necrosis in the scabbed area, corneal necrosis, fibrosis and neovasculization in the stroma. At 0.4 and 2 mg/kg, there were no significant toxic changes attributable to the administration of DA-5018. In conclusion, target organs following to 4-week repeated dose of DA-5018 in the rat were determined to be lung, skin and eyes. Definite toxic dose and no-observed-adverse-effect-level (NOAEL) were estimated to be 50 and 2 mg/kg/day, respectively.

• Journal of Korean Society of Occupational and Environmental Hygiene
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• v.23 no.1
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• pp.1-10
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• 2013

Objectives: The present study investigated the potential subacute toxicity of 1,4-dichlorobutane (1,4-DCB) by a 2-week repeated oral dose in male Sprague-Dawley rats. Materials and Methods: The test chemical was administered once daily by gavage to male rats at dose levels of 0, 74, 222, 667, and 2000 mg/kg/day for 2 weeks. All rats were sacrificed at the end of treatment period. During the test period, clinical signs, mortality, body weights, food and water consumption, urinalysis, hematology, serum biochemistry, gross findings, and organ weights were examined. Results: At 2000 mg/kg/day, treatment-related clinical signs, as evidenced by hypothermia, decreased locomotor activity, piloerection, lying on side, and prone position were observed. All the rats were found dead on test day 2. At 667 mg/kg/day, polyuria, suppressed body weight gain, food consumption, and spleen and thymus weights, and increased adrenal gland and liver weights were observed.Hematological and serum biochemical investigations revealed increases in the alanine aminotransferase, alkaline phosphataseand total bilirubinand decreases in the serum $Na^+$ level, white blood cell count and lymphocyte ratio. There were no treatment-related adverse effects in the 74 and 222 mg/kg/day groups. Conclusions: In the present experimental conditions, target organs were determined to be spleen, thymus,and liver. The no-observed-adverse-effect level was considered to be 222 mg/kg/day in male rats.