• Toxicological Research
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• v.21 no.3
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• pp.263-269
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• 2005

This study was performed to investigate repeated-dose toxicities of Clean natural, a new disinfectant, in Sprague-Dawley(SD) rats. In the 4-week repeated oral toxicity study, Clean Natural was orally administered once daily via gavage to male and female rats at dose levels of 0, 500, 1,000 and 2,000 mg/kg body weight for 4-weeks. There were no deaths and clinical signs during the dosing period. In both sexes, there were no statistically significant differences between the administered and control groups in urinalysis indicators and hematological parameters. In serum biochemistry, aspartate aminotransferase(AST) was significantly decreased and sodium content was increased in the 2,000 mg/kg male group, while chlorine was significantly decreased in the 2,000 mg/kg female group. Also, albumin, total cholesterol and total bilirubin were significantly increased in the 2,000 mg/kg male and female group. In histopathological examinations, centrilobular hepatocellular hypertrophy in the liver was observed in the 2,000 mg/kg male and female groups. And pigmentation in the spleen was observed in the 2,000 mg/kg male group. In conclusion, four-week repeated oral dose of Clean Natural to rats did not cause apparent toxicological change at the dose less than 2,000 mg/kg body weight. Thus it is suggested that no-observed adverse-effect level(NOAEL) for Clean Natural in rats was considered to be 1,000 mg/kg/day.

• The Korea Journal of Herbology
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• v.36 no.6
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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.

• Korean Journal of Pharmacognosy
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• v.50 no.3
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• pp.205-218
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• 2019

This study was conducted to investigate the toxicity symptoms and approximate lethal dose (ALD) of Oplopanax elatus (Nakai) Nakai hydrothermal extract powder by single oral dose toxicity and 4 weeks of repeated oral dose determination. The Sprague-Dawley (SD) male and female rats were treated with 1,250 (low- dosage group), 2,500 (medium- dosage group) and 5,000 (high- dosage group) mg/kg. In the single oral dose toxicity test, no dead animals and toxic symptoms were observed during the experiment. And there were no related with anomalies in normal weight changes and autopsy results. In the four-week repeated oral dose determination test, no death animals and toxicity symptoms were observed during the experiment, and there were no abnormal results in weight changes, feed and negative intake measurements. Results of eye examination, urinalysis, hematological values and serum biochemical values, gross findings and absolute organ were not of singularity. These result demonstrated that no toxic symptoms were observed by the test substance Oplopanax elatus (Nakai) Nakai hydrothermal extract powder under this test condition, and the non-toxic content is determined to be 5,000 mg/kg/day.

• 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.

• Journal of Pharmacopuncture
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• v.22 no.3
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• pp.192-199
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• 2019

Objectives: KCHO-1(Mecasin), also called Gamijakyakgamchobuja-tang originally, is a combination of some traditional herbal medicines in East Asia. This medicine has been used mainly for alleviating neuropathic pains for centuries in Korean traditional medicine. KCHO-1 was developed to treat pain, joint contracture and muscular weakness in patients with amyotrophic lateral sclerosis. This study was carried out to investigate the chronic toxicity of KCHO-1 oral administration in rats for 26 weeks. Methods: Sprague-Dawely rats were divided into four groups and 10 rats were placed in the control group and the high-dose group, respectively. Group 1 was the control group and the remaining groups were the experimental groups. In the oral toxicity study, 500 mg/kg, 1,000 mg/kg, and 2,000 mg/kg of KCHO-1 were administered to the experimental group, and 10 ml/kg of sterile distilled water was administered to the control group. Survival rate, body weight, feed intake, clinical signs, and visual findings were examined. Urinalysis, ophthalmologic examination, necropsy, organ weight, hematologic examination, blood chemical examination and histopathologic examination were performed. Results: Mortality and toxicological lesions associated with the administration of test substance were not observed in all groups. Conclusion: NOAEL(No observed adverse effect level) of KCHO-1 is higher than 2000 mg/kg/day. And, the above findings suggest that treatment with KCHO-1 is relatively safe.

• 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 Korean Society of Toxicology Conference
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• 2003.05a
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• pp.43-44
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• 2003

The subacute toxicity and toxicokinetics of a type IV phosphodiesterase inhibitor, CJ-10882, were evaluated after single (on the 1st day) and 4-week (on the 27th day) oral administration of the drug, in doses of 0 (to serve as a control), 2, 10 and 50 mg/kg/d, to male and female dogs (n = 3 for male and female dogs for each dose). During the test period, clinical signs, mortality, body weight, food consumption, ophthalmoscopy, urinalysis, hematology, serum biochemistry, gross findings, organ weight and histopathology were examined.(omitted)

• Toxicological Research
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• v.18 no.3
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• pp.241-248
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• 2002

The present study was conducted to investigate the potential subacute toxicity of CJ-10882 by a 4-week repeated oral dose in dogs. The test article was administered once dally by gavage to dogs at dose levels of 0, 2, 10, and 50 mg/kg/day for 4 weeks. During the test period, clinical signs, mortality, body weights, food consumption, ophthalmoscopy, urinalysis, hematology, serum biochemistry, gross finding, organ weight, and histopathology were evaluated. Several clinical sign were observed in treated dogs at 50 mg/kg, including salivation and vomiting. Increase in the serum level of ALT and albumin observed in the female 50 mg/kg group was considered as a toxic effect related to the test article since the histopathological change in Liver was accompanied. There were no treatment-related effects on mortality, food and water consumption, ophthalmoscopy, urinalysis, hematology, serum biochemistry, necropsy findings and organ weights in any treatment group. Based on these results, target organ was not observed and the no-observed-adverse-effect level (NOAEL) was 10 mg/kg/day and the absolute toxic dose was 50 mg/kg for both male and female dogs.

• Korean Journal of Veterinary Research
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• v.43 no.2
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• pp.195-202
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• 2003

Chitosan is known to have antibacterial, antitumorogenic, hypolipidemic and immunopotentiating activities, hence finding diverse uses as a component in varying functional foodstuffs. However, some investigators reported it caused mineral absoiption inhibition and excess coagulation. From the chemical viewpoint, conventional chitosans are high-molecule polymers lacking water solubility, which could be related with their possible toxicity. A newly developed low- molecule water soluble chitosan is thought to have low toxicity compared to conventional chitosans. But no investigation was carried out to evaluate its toxicity. In this study, a 28-day subacute oral toxicity study of the water-soluble chitosan was performed in Sprague-Dawley rats of both sexes. Each 36 male and female rats were orally administered with 500, 1,000 and 2,000 mg/kg/day for 28 consecutive days, respectively. Clinical parameters (growth rate, feed and water consumption, daily inspection, urine analysis) during the 28 days indicated the water-soluble chitosan did not induce any abnonnal changes. There were no abnormal findings due to the administration of the test substance in gross and microscopic findings. We had not found alteration in absolute and relative organ weight between the control and treated groups, with only exception in the liver but lacking dose-dependency. The results of hematology and serum biochemistry examination revealed that no treatment related changes were between control and all dose groups. In conclusion, it was suggested that subacute toxicity of the water-soluble chitosan was low and the no-observed adverse effect level was considered to be over 2,000 mg/kg in rats.

• Proceedings of the Korean Society of Toxicology Conference
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• 2003.10b
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• pp.132-132
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• 2003

In this GLP study, 4 study groups of 12 Sprague-Dawley (SD) rats/sex were given vehicle, or 1,000, 1,500, or 2,000 mg/kg/day Sophora Japonica Linne Seed Extract (SE) for 13 weeks. Standard endpoints in this study included mortality, clinical observations, body weight, food and water consumption, ophthalmoscopic examination, urinalysis, hematology, serum biochemistry, organ weights, gross anatomic pathology and histopathology.(omitted)