• Natural Product Sciences
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• v.21 no.1
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• pp.34-41
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• 2015

The objective of this study is to characterize a toxicity of Epimedii Herba (EH) in F344 rats and to find a dose levels for the 13 weeks toxicity study. EH is well known as medicinal herb in many Asian countries for traditional medicines of antibacterial and antiviral effects, estrogenic and antiestrogenic effects, and for treatment of osteoporosis, hypotensives, fatigue, kidney disorders, and related complications. However, the indispensable and basic information of toxicological evaluation of EH extract is insufficient to support its safe use. Therefore, we conducted toxicological evaluation of this drug in compliance with OECD and MFDS guideline in this study. The extract of EH was administered orally to F344 rats at dose levels of 0, 500, 1000, 2000, 3500, and 5000 mg/kg/day for 2 weeks. Each group was composed of 5 male and female rats. In this study, there were no treatment of EH-related adverse changes in clinical observations, mortality, body weights, food consumption, urinalysis, gross finding at necropsy, and organ weight examination. Total red blood cell count, hematocrit, mean corpuscular hemoglobin concentration, total cholesterol, and phospholipid were decreased in males and females at 5000 mg/kg/day compared to the control animals. Mean corpuscular volume and reticulocyte counts were increased in males and females at 5000 mg/kg/day compared to control animals. Therefore, we recommend that dose level of 5000 mg/kg/day is a highest treatment group in 13-week EH extract exposure study for further toxicity assessment.

• Journal of Acupuncture Research
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• v.39 no.4
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• pp.310-316
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• 2022

Background: Verbenalin is an iridoid glucoside, which is among the active components of some medicinal herbs such as Verbena officinalis Linn, and Cornus officinalis Siebold and Zucc. Previous studies have confirmed the antioxidant activity and neuroprotective potential of verbenalin. To confirm the safety of verbenalin, an approximate lethal dose was determined based on a single oral dose toxicity study. Methods: Institute of Cancer Research mice were randomly assigned to three verbenalin exposure groups (250, 500, and 1,000 mg/kg) and a control group (5% methylcellulose solution). There were (5 male and 5 female mice per group). Mortality, clinical signs, and body weight were monitored for 14 days, and necropsies were conducted. Results: No mortalities were observed in the control group or the verbenalin 250 mg/kg group, whereas mortalities were observed in the 500 mg/kg and 1,000 mg/kg verbenalin groups. During the observation period, stool abnormalities such as mucous stools were observed. Clinical signs such as loss of locomotor activity were observed in the 500 mg/kg and 1,000 mg/kg verbenalin groups. During the study period, significant changes in body weight were observed in the 500 mg/kg and 1,000 mg/kg verbenalin groups; however, no gross abnormalities were observed at necropsy. Overall, no toxicity was found in the 250 mg/kg group. Conclusion: The approximate lethal dose of verbenalin was estimated to be 500 mg/kg. For a more accurate assessment of the safety of verbenalin, other types of studies such as repeated-dose toxicity studies should also be conducted.

• The Korean Journal of Pesticide Science
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• v.15 no.3
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• pp.278-288
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• 2011

This study was conducted to evaluate the safety of ${\beta}$-carotene biofortified rice, a genetically modified organism (GMO) developed by Rural Development Administration. ${\beta}$-carotene biofortified rice were exposed on Sprague-Dawley rats for 13 weeks. All rats survived until the end of the exposure period. There were no biologically significant differences in body weight, feed and water consumption, weight gains and feed efficiency. There were no clinical signs of toxicity attributable to exposure to GM rice. Mild decreases in AST, ALT, TG levels were observed in Group II (25% GM rice (w/w) and Group III (50% GM rice (w/w), both in females and males. Results of histopathological changes treated with the ${\beta}$-carotene biofortified rice had no significant differences between the control and treatment groups. Based on these results, we deemed that genetically modified ${\beta}$-carotene biofortified rice was as safe as conventional rice.

• Journal of the Korean Society of Food Science and Nutrition
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• v.40 no.6
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• pp.824-831
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• 2011

This study was to investigate 90-day repeated-dose toxicities of 50 kGy irradiated methanol extract powder of red ginseng in ICR mice. The test materials (methanol extract powder of red ginseng with or without 50 kGy irradiation) were administered by gavage to male and female ICR mice at dose levels of 0, 125, 250 and 500 mg/kg/day for 90 days. In the results, no abnormality was observed in mortality, clinical findings, body weight changes, food consumptions, opthalmoscopic findings, necropsy findings and histopathological findings. Although the minor changes in blood and biochemical parameters were observed, they were not dose dependent and not affected by gamma irradiation. In conclusion, 90-day repeated oral dose of the methanol extract powder of red ginseng and 50 kGy irradiated methanol extract powder of red ginseng to ICR mice did not cause apparent toxicological change at the dose of 125, 250 and 500 mg/kg body weight.

• Biomolecules & Therapeutics
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• v.10 no.2
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• pp.117-123
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• 2002

CJ-10882, (E)-[(3-Cyclopentyloxy-4-methoxyphenyl)methylene]hydrazine-carboxamide, is a newly developed type IV phosphodiesterase isozyme (PDE IV) inhibitor. To investigate the subacute toxic effects of CJ-10882, it was administered to both male and female dogs at 0, 25, 50, 100 or 200 mg/kg/day orally for up to 2 weeks. During the test period, clinical signs, mortality, body weight, food consumption, ophthalmoscopy, urinalysis, hematology, serum biochemistry, gross finding, organ weight, and histopathology were evacuated. Several clinical signs were observed in treated dogs at above 25 mg/kg, including salivation and vomiting. A reduction in the body weight was observed in both sexes at above 50 mg/kg. There were no treatment-related effects on mortality, ophthalmoscopy, urinalysis, hematology, sect biochemistry, necropsy findings, and histopathology in any treatment group. The results of this study demonstrate that CJ-10882, a selective Inhibitor of the type IV class of PDE, may cause effects on gastrointestinal tract and salivary glands. Therefore, these organs should be closely examined in studies with other PDE IV inhibitors.

• Journal of Pharmacopuncture
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• v.25 no.4
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• pp.354-363
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• 2022

Objectives: This study aimed to assess the adverse effects of Rasaraj Rasa tablets after repeated oral administration for 180 days in Wistar rats. Methods: Wistar rats were divided into five groups, of which three were treated with 54, 162, and 270 mg/kg body weight of Rasaraj Rasa, respectively, which correspond to one, three, and five times the proposed human therapeutic dose, for 180 days consecutively. The fifth group (satellite) also received 270 mg/kg body weight of Rasaraj Rasa for 180 days. Body weight and food intake were measured weekly. At the end of the study, all rats were sacrificed, and their blood, serum, and organs were collected and examined using hematology, serum biochemistry, gross pathology, and histopathology tests. In contrast, the satellite group was kept for 4 weeks after treatment. Results: No significant treatment-related toxicological findings were observed in the clinical features, body weight, laboratory findings, and pathological findings of the high-dose treated groups, when compared to those of the control group. Conclusion: The no-observed-adverse-effect-level for Rasaraj Rasa in Wistar rats is set at 270 mg/kg body weight.

• Toxicological Research
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• v.35 no.4
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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.

• Journal of the Korean Society of Food Science and Nutrition
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• v.36 no.8
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• pp.975-982
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• 2007

The purpose of this study was to investigate repeated-dose toxicity in male and female rats orally administered with Pediococcus pentosaceus MD1, an anti-Helicobacter pyroli producing lactic acid bacteria isolated from kimchi. Sprague-Dawley rats were divided into 4 groups, 10 animals in each group. The test article was administered once daily by gavage to rats at dose levels of 0, 500, 1,000 and 2,000 mg/kg for 4 weeks. No test article-related deaths and clinical findings in both sexes of rats during the study period were resulted. In addition, no differences were found between control and treated groups in body weight changes, food intake consumption and water consumptions. Hematological parameters, serum biochemical analysis and any other findings did not also show any significant or dose-dependent alterations. There were no alterations in absolute and relative organ weights by the administration of Pediococcus pentosaceus MD1. These results suggest that no-observed-adverse-effect level (NOAEL) of Pediococcus pentosaceus MD1 is considered to be more than 2 g/kg in male and female rats.

• Korean Journal of Pharmacognosy
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• v.50 no.4
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• pp.260-271
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• 2019

This study aimed to evaluate the safety of Oplopanax elatus (Nakai) Nakai hydrothermal extract powder. It was conducted using male and female Sprague-Dawley (SD) rats. The test group was established with dose of 500 (low-dosage group), 1,000 (medium- dosage group), and 2,000 (high- dosage group) mg/day. These are investigated that number of dead animals, general symptoms, weight changes, food consumption, ophthalmological examination, urinalysis, urine volume, hematological values, plasma coagulation time values, serum biochemical values, absolute organ weight, relative organ weight and histopathological finding during the experiment. As a result of the above, toxicological changes were not observed. Therefore, the non-toxic content of Oplopanax elatus (Nakai) Nakai hydrothermal extract powder is determined to be 2,000 mg/kg/day, and target organ was not observed.

• Journal of Veterinary Clinics
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• v.38 no.1
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• pp.7-15
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• 2021

Kyungokgo-gamibang, Kyungokgo with Iksuyongjingo and Sparassis crispa, is a traditional Korean medicine used for restorative effects. This study aimed to evaluate the safety of Kyungokgo-gamibang in healthy beagle dogs. In the single-dose oral toxicity study, three beagle dogs were orally administered 2,000, 1,000, and 500 mg/kg of Kyungokgo-gamibang and were observed for 14 days. In the repeated-dose oral toxicity study, nine healthy dogs were orally administered 0.2g/kg of Kyungokgo-gamibang (n = 3, low-dose group), 1 g/kg of Kyungokgo-gamibang (n = 3, high-dose group), or normal saline (n = 3, control group) twice a day for 8 weeks. The hematological, serum biochemical, urine, protein, and lipid profiles were evaluated to investigate the adverse effects of the Kyungokgo-gamibang. During the study period, the dogs demonstrated no clinical signs and the hematological, serum biochemical, urine, protein, and lipid analyses revealed unremarkable findings. The study results suggest that Kyungokgo-gamibang can be safely administered to dogs without any adverse effects.