• 대한본초학회지
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• 제36권6호
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• pp.27-37
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• 2021

Objectives : In the current study, we performed the 13-week repeated oral dose toxicity test and a 4-week recovery 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 no observed adverse effect level (NOAEL). Methods : The animal study was performed according to OECD guidelines for the testing of chemicals section 4 health effects test No.408 repeated dose 90-day oral toxicity study in rodents (03 October 2008). In the repeated dose toxicity study, SCP was orally administered to female and male rats at dose levels of 1,000, 2,000, and 4,000 mg/kg/day for 13-week. The control group and high dose (4,000 mg/kg/day) group were then monitored for 4 extra weeks to determine recovery time after the study period. 1) Results : Compared with the control group, there were no treatment-related adverse effects in clinical signs, body weight, hematology, serum biochemistry (Aspartate aminotransferase, Alanine aminotransferase, Alkaline phosphatase, 𝛾-Glutamyl transpeptidase, Blood urea nitrogen, Creatinine, Glucose, Total cholesterol, Total protein, Creatine phosphokinase, Albumin, Total bilirubin, Triglyceride, Inorganic phosphorus, Albumin/Globulin ratio, Calcium ion, Sodium ion, Potassium ion, Chloride ion), necropsy findings and organ weight (Ovary, Adrenal gland, Pituitary, Thymus, Prostate, Testis, Epididymis, Spleen, Kidney, Heart, Lung, Brain, Liver) at any dose tested. Conclusions : Taken together, these results suggest that the NOAEL of SCP in both genders was considered as over 4,000 mg/kg. Results from this study provide scientific evidence for the safety of SCP.

• 한국독성학회:학술대회논문집
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• 한국독성학회 2002년도 Molecular and Cellular Response to Toxic Substances
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• pp.158-158
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• 2002

The potential toxicological effects of aristolochic acid (AA), a natural component in Aristolochiaceae family, were investigated. The 13-week toxicity study consisted of groups of 10 SD rat/sex administrated water containing 0, 0.05, 0.5, or 5 mg/kg per day AA (Study 1). The tested groups were terminated on Test Day 90 due to mortality and overt clinical signs of toxicity.(omitted)

• Toxicological Research
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• 제31권4호
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• pp.393-402
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• 2015

This study was conducted to measure toxicity of 1-chloropropane (CAS No. : 540-54-5). According to the OECD Test Guideline 413 (Subchronic inhalation toxicity: 90-day study), SD rats were exposed to 0, 310, 1,250, and 5,000 ppm of 1-chloropropane for 6 h/day, 5 day/week for 13 weeks via whole-body inhalation. Mortality, clinical signs, body weights, food consumption, motor activity, ophthalmoscopy, hematology, serum chemistry, urinalysis, organ weights, gross and histopathological findings were compared between control and all tested groups. No mortality or remarkable clinical signs were examined during the study. No gross lesions or adverse effects on body weight, food consumption, motor activity, ophthalmoscopy, urinalysis, hematology, organ weights were observed in any of male or female rats in all tested groups. In serum biochemistry, glucose was significantly decreased in males of 1,250 and 5,000 ppm groups compared to control group in dose-dependent relationship. In histopathological examination, vacuolation of acinar cells was observed in pancreas of all male and female groups exposed to 1-chloropropane. In conclusion, no observable adverse effect level (NOAEL) was considered to be below 310 ppm/6 h/day, 5 day/week for rats.

• 대한본초학회지
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• 제25권3호
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• pp.43-51
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• 2010

Objectives : We investigated the repeated-dose toxicity of Wenpitang-Hab-Wulingsan(WHW), a Korean traditional medicine prescribed with twelve herbs, which has been used for the treatment of renal disease. Methods : WHW extract prepared by GLP company. WHW was supplemented by gavage at 0, 100, 500 and 1000 mg/kg/day for 13-week consecutive days. We recorded the clinical signs of toxicity, body weight, organ weights, hematology, gross and histological changes in target organs rats and clinical chemistry analysis for all rats. Results : WHW extract at all doses was shown no mortality or abnormal clinical signs in rats during at the observation period. Furthermore, there was no difference in body weight and food-take consumption, organ weight, gross pathological findings, and urine analysis among the groups of rats treated with different doses of WHW extract. The hematological analysis and clinical blood chemistry data were revealed no toxic effects from WHW-treated rats. Conclusions : The results suggest that WHW extract in rats is a wide margin of safety on a acute toxicity.

• Journal of Ginseng Research
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• 제44권2호
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• pp.222-228
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• 2020

Background: 20(S)-ginsenoside-Rg3 (C₄₂H₇₂O₁₃), a natural triterpenoid saponin, is extracted from red ginseng. The increasing use of 20(S)-ginsenoside Rg3 has raised product safety concerns. Methods: In acute toxicity, 20(S)-ginsenoside Rg3 was singly and orally administrated to Kunming mice and Sprague-Dawley (SD) rats at the maximum doses of 1600 mg/kg and 800 mg/kg, respectively. In the 26-week toxicity study, we used repeated oral administration of 20(S)-ginsenoside Rg3 in SD rats over 26 weeks at doses of 0, 20, 60, or 180 mg/kg. Moreover, a 4-week recovery period was scheduled to observe the persistence, delayed occurrence, and reversibility of toxic effects. Results: The result of acute toxicity shows that oral administration of 20(S)-ginsenoside Rg3 to mice and rats did not induce mortality or toxicity up to 1600 and 800 mg/kg, respectively. During a 26-week administration period and a 4-week withdrawal period (recovery period), there were no significant differences in clinical signs, body weight, food consumption, urinalysis parameters, biochemical and hematological values, or histopathological findings. Conclusion: The mean oral lethal dose (LD₅₀) of 20(S)-ginsenoside Rg3, in acute toxicity, is above 1600 mg/kg and 800 mg/kg in mice and rats, respectively. In a repeated-dose 26-week oral toxicity study, the no-observed-adverse-effect level for female and male SD rats was 180 mg/kg.

• Biomolecules & Therapeutics
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• 제2권2호
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• pp.161-172
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• 1994

This study was conducted to examine DA-3002, a biosynthetic human growth hormone, for its acute and subacute toxicities in mice and rats. The drug was administered subcutaneously and orally at a dose level of 1.0, 3.0, 8.9, 26.7 or 80.0 lU/kg once for single dose toxicity and given subcutaneously at a dose level of 0.34, 1.7 or 8.4 lU/kg daily for 13 weeks to investigate repeated dose toxicity. In the acute toxicity study, doses up to 80 lU/kg had no adverse effect on the behavior or body weight gain. Pathological examinations revealed no abnormal changes which could be attributed to toxic effect of DA-3002. In the subacute toxicity study, the growth hormone was tolerated well in broth mice and rats. No drug related deaths occurred and all animals appeared to be normal throughout the dosing period. Increases in body weight gain, food utilisation and absolute organ weights were observed in the rats in the high dose group. Mild changes in the blood chemical parameters were also seen in the treated groups. Histopathologically, however, no abnormal changes were observed in any organ. The changes noted during the treatment periods presumably represent exaggerated pharmacological effects of the growth hormone, and no observed adverse effect level (NOAEL) was considered to be more than 8.4 lu/kg/day.

• Toxicological Research
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• 제35권4호
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• pp.371-387
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• 2019

Although the dried root of Saposhnikovia divaricata (Turcz.) Schischk. (Umbelliferae) is a popular medicinal plant in East Asia, there has been no systemic toxicological evaluation of a water extract of Saposhnikoviae Radix (SRE). In this experiment, an oral acute and 13-week subchronic toxicological evaluations of SRE (500-5,000 mg/kg body weight) were performed in both sexes of Crl:CD(SD) rats. Based on the results from mortality, clinical signs, effects on body weight and organ weight, clinical biochemistry, hematology, urinalysis, and histopathology, significant acute, 4-week repeated dose range finding (DRF) and 13-week subchronic toxicity of SRE was not observed in either sex of rats; thus, the no observed adverse effect level (NOAEL) was 5,000 mg (kg/day). To identify anti-hyperuricemia potential of SRE, the suppressive effect of SRE was determined in mice challenged with potassium oxonate (PO; 250 mg/kg) via intraperitoneal injection for 8 days (each group; n = 7). SRE supplementation suppressed the uric acid level in urine through significant xanthine oxidase (XO) inhibitory activity. Kidney dysfunctions were observed in PO-challenged mice as evidenced by an increase in serum creatinine level. Whereas, SRE supplementation suppressed it in a dose-dependent manner. Collectively, SRE was safe up to 5,000 mg (kg/day) based on NOAEL found from acute and 13-week subchronic toxicological evaluations. SRE had anti-hyperuricemia effect and lowered the excessive level of uric acid, a potential factor for gout and kidney failure.

• 한국환경성돌연변이발암원학회:학술대회논문집
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• 한국환경성돌연변이발암원학회 2004년도 춘계학술대회
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• pp.102-103
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• 2004

• Biomolecules & Therapeutics
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• 제4권2호
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• pp.138-147
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• 1996

DWP401, a recombinant human epidermal growth factor, was subcutaneously administered to ICR mice at the dose levels of 0, 0.04, 0.2 and 1.0 mg/kg/day (15rats/sex/group) in order to evaluate the subchronic toxicity. General observations, examinations for food and water consumption, ophthalmoscopy and urinalysis were carried out during the study. For the complete gross and microscopic examinations, 10 mice/ sex/group were sacrificed at the ends of the dosing period, and the remaining animals were sacrificed with a 5 week recovery period. Examinations for hematology and blood biochemistry were also carried out at the time of recovery period. Based on the results, it was thought that the target tissue or organs were mesothelial cell, injection site, spleen, adrenal gland, ovary and transitional epithelial cell of urinary tract, and no observed toxic level of DWP401 was 0.04 mg/kg while definite toxic dose level might be 0.2 mg/kg.

• 대한약침학회지
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• 제17권4호
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• pp.27-35
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• 2014

Objectives: Mountain ginseng pharmacopuncture (MGP) is a pharmacopuncture made by distilling extract from mountain cultivated ginseng or mountain wild ginseng. This pharmacopuncture is injected intravenously, which is a quick, lossless way of strongly tonifying Qi function. The present study was undertaken to evaluate a 4-week, repeated, intravenous injection, toxicity test of MGP in Sprague-Dawley (SD) rats. Methods: Twenty male and female 6-week-old SD rats were used as subjects. We divided the SD rats into 4 groups: the high-dosage (10 mL/kg), medium-dosage (5 mL/kg), low-dosage (2.5 mL/kg) and control (normal saline) groups. MGP or normal saline was injected intravenously into the caudal vein of the rats once daily for 4 weeks. Clinical signs, body weights, and food consumption were monitored during the observation period, and hematology, serum biochemistry, organ weight, necropsy, and histological examinations were conducted once the observations had been completed. Results: No mortality was observed in any of the groups during the observation period. No changes due to MGP were observed in the experimental groups regarding clinical signs, body weights, food consumption, hematology, serum biochemistry, organ weight and necropsy. No histological changes due to MGP were observed in any of the male or female rats in the high-dosage group. Conclusion: During this 4-week, repeated, intravenous injection, toxicity test of MGP in SD rats, no toxic changes due to MGP were observed in any of the male or female rats in the high-dosage group. Thus, we suggest that the high and the low doses in a 13-week, repeated test should be 10 mL/kg and 2.5 mL/kg, respectively.