• 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.

• Biomolecules & Therapeutics
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• v.4 no.4
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• pp.354-363
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• 1996

This study was conducted to investigate the repeated dose toxicity of DA-9601, an antiulcer agent of Artemisia app. extract, in rats. DA-9601 was administered orally once a day for 4 weeks to 10 males and 10 females per group at doses of 0(vehicle control), 125, 500 or 2000 mg/kg/day. Throughout the study, no treatment-related deaths and clinical signs were observed. In female rats receiving 125 mg/kg of DA-9601, water consumption increased slightly on day 4, 11 and 25. Hematological examination showed a decrease of MCV and an increase of PLT in male rats at the doses of 500 and 2000 mg/kg groups. Blood biochemistry revealed slight decreases of cholesterol, BUN and Na in male rats and decreases of total bilirubin and creatinine and slight increases of globulin and Cl in female rats. The organ weights at the end of 4 weeks showed slight changes in some organs of treated groups. But, all these changes were not considered to be of toxicological importance, because they did not show dose-response relationship and relevance to gross and microscopic findings. Histopathologically, abnormal treatment-related changes were not observed in any organ and target organs were not detected. On the basis of these results, the NOAEL(no-observed-adverse-effect level) of DA-9601 was estimated to be more than 2000 mg/kg/day under the conditions tested.

• The Korea Journal of Herbology
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• v.35 no.2
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• pp.47-53
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• 2020

Objectives : Bombyx batryticatus L. is the dried larval form of the silkworm (Bombyx mori L.) infected by Beauveria bassiania (Bals.) Vuill. It is used as a food and medicinal resource to treat asthma, headaches, epilepsy, and convulsions in traditional Korean and Chinese medicines. However, the research of the toxicity about B. batryticatus is not enough yet. Here, we investigate the effects of potential subacute toxicity following the repeated oral administration of B. batryticatus water extract to C57BL/6 mice, at various doses of 0, 50, 150, and 450 mg/kg/day during a two-week period. Methods : The following parameters were examined during the study period: body weight, gross findings, clinical signs, organ weight, hematology, serum biochemistry, histopathology, and mortality. At the end of the treatment period, all the mice were euthanized. Results : No changes were observed in the body weights, gross findings, clinical signs, organ weights, and mortality after two weeks of administration of the B. batryticatus extract. In addition, compared with the normal control group, no noticeable treatment-related changes were observed in the hematological, serum biochemical, and histopathological parameters in the treated group following treatment with doses of up to 450 mg/kg/day. Conclusion : Based on these findings, we conclude that the treatment of mice with the water extract of B. batryticatus did not cause considerable C57BL/6 toxicity, and therefore, it could be considered safe for further pharmacological studies.

• Journal of the Korean Society of Food Culture
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• v.34 no.6
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• pp.801-809
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• 2019

Abeliophyllum distichum Nakai is a deciduous shrub of a flowering plant in Oleaceae. It is an important plant resource and consists of only one species in the entire world. A. distichum Nakai is well known an edible, medicinal herb in its habitat districts, but the toxicological evaluation for the safe use of its extract is still insufficient. The study characterized the toxicity of an Abeliophyllum distichum Nakai ethanol extract in Sprague-Dawley (SD) rats and determined the safe dosage levels in a 13 weeks toxicity study. Abeliophyllum distichum Nakai ethanol extract was orally administered once daily for 2 weeks at 0, 500, 1,000 and 2,000 mg/kg/day to male and female SD rats. while recording the clinical signs of toxicity, body weight, food intake/consumption, eye test and urine analysis. Only the total protein frequency in the urine of male SD rats (p<0.05), the right ovary of the 500 mg/kg group (p<0.01) and the right adrenal gland of the 1,000 mg/kg group (p<0.05) in the female rats showed statistically significant changes. But no toxic effects were noted from repeated-dose administration of the Abeliophyllum distichum Nakai ethanol extract in the SD rats during the observation period. The post-mortem examinations showed no test substance-mediated changes. The hematological analysis and clinical blood chemistry data demonstrated no toxic effects from repeated-dose administration of Abeliophyllum distichum Nakai ethanol extract in the SD rats during the observation period. Based on these results, this data suggests that a dose of 1,000 mg/kg/day is a highest treatment to administer when conducting a further 13 weeks toxicity study.

• Preventive Nutrition and Food Science
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• v.11 no.2
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• pp.115-119
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• 2006

The object of this study was to examine whether the germanium fortified yeast administered to SD rat is accumulated in the liver and kidney. The administration doses were within 2,000 mg/kg which is the level of NOAEL (no observed adverse effect level) proved through the previous study of single/consecutive oral toxicity test. There were no significant clinical symptoms and mortality following the administration of organic germanium-fortified yeast (0, 500, 1,000, 2,000 mg/kg) during the whole test period, and also no difference in the consumed amount of feed and water for each group. No significant abnormalities of hematology and blood chemistry parameters were found in all groups of organic germanium-fortified yeast (0, 500, 1,000, 2,000 mg/kg). The amount of germanium accumulated in liver and kidney was 0 g/kg by ICP-AES method in the group of organic germanium-fortified yeast. In the positive control group of $GeO_2$ (150 mg/kg), the amount of accumulation was shown to 3135.0 and 4277.2 g/kg in each female and male kidney and 1044.3 and 2135.8 g/kg in each female and male liver, respectively. Organic germanium-fortified yeast, a biosynthetic product resulting from putting germanium into yeast, did not show any clinical symptoms, blood chemical significance, and residues in kidney and liver. It could be inferred that the non-toxic amount of organic germanium-fortified yeast was up to 2,000 mg/kg.

• 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.

• Herbal Formula Science
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• v.31 no.4
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• pp.327-339
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• 2023

Objectives : This study conducted a repeated dose 90-day oral toxicity test in order to up-cycling Schisandra fruit extract powder(SFEP) using discarded Schisandra chinensis by-products and evaluated the NOAEL of SFEP. Methods : SD-rats were orally administered SFEP at concentrations of 0, 62.5, 125, and 250 mg/kg once daily for 90 days. Body weights and clinical signs were observed during the administration period. After completion of the experiment, the experimental animals were autopsied to observe necropsy findings and organ weights changes, and hematological parameters and blood chemistry values were measured. Results : During the SFEP administration period, clinical signs such as salivation, wounds, and erosion were sporadically observed in 1 to 2 animals. In the SFEP 250 mg/kg administered group, weights of the liver and thyroid gland significantly increased compared to the control group, but no significant changes were observed in organ weights according to body weights. As a result of measuring hematological parameters and blood chemistry values, a decrease in RDW, T-BIL, and TBA, and an increase in TP, ALB, and Ca were observed due to SFEP administration. However, these changes following SFEP administration were accidental and not dose-dependent. Additionally, no correlation was found between gender and other parameters. Conclusions : Therefore, the NOAEL of SFEP was confirmed to be 250 mg/kg.

• Journal of Applied Biological Chemistry
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• v.58 no.2
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• pp.139-143
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• 2015

In the present study, we investigated the oral toxicity of Amomum tsao-ko Crevost et Lemaire, (Zingiberaceae) extract in Balb/c mice (BALB, n=60) for 3 weeks. Balb/c mice (10 mice/group, 6 group, $20{\pm}2g$, 6 weeks) were orally administered for 21 days, with dosage of 250, 500, 1000, 2000 mg/kg/day. Ethanol extract of A. tsao-ko did not affect any significant change of mortality, clinical signs, organs and body weights. Also, there were not significantly difference from the naive group (control) in hematological and serum biochemical examination. Consequently, these findings indicate that 3-week treatment with the ethanol extract of A. tsao-ko was not any toxic effects in Balb/c mice and the no-observed adverse effect level (NOAEL) for oral toxicity was determined to be 2000 mg/kg/day under our experimental conditions.

• Journal of Oriental Neuropsychiatry
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• v.23 no.2
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• pp.99-120
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• 2012

Objectives : The oriental medicine Jangwonhwan, a boiled extract of 12 medicinal herbs/mushrooms, has been prescribed to patients with cognitive dysfunction, as originally described in the Korean medical text, DonguiBogam(amnesia chapter). Recently, a modified formula of Jangwonhwan (LMK02-Jangwonhwan) consisting of seven medicinal plants/mushrooms, was shown to reduce the ${\beta}$-amyloid deposition in the brain of Tg-APPswe/PS1dE9 mouse model for Alzheimer's disease. The toxicity of LMK02-Jangwonhwan was investigated in SD rats, by a daily oral administration for 13 weeks and NOAEL(No observed adverse effect dose), a definite toxic dose and target organ, as well. Methods : Quality control of the tablet form of LMK02-Jangwonhwan was established by estimating the indicative components, Ginsenoside Rg3 of Red Ginseng and Decursin of Angelicagigas Nakai. The toxicity of LMK02-Jangwonhwan was investigated in 6 week old, specific pathogen free (SPF), Sprageu-Dawley rats by oral administration. Each test group consisted of 10 male and 10 female rats. The groups received doses of 500, 1,000 or 2,000 mg/kg/day of test substance for 13 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 the control group. Results : The 13-week repeated oral treatment doses didn't result in any specific symptoms or death. There were no significant changes in the rat's weight and food consumption. Further, ophthalmic examination, urinalysis, hematological, serum biochemistry test and organ weight revealed no significant differences. Conclusions : The no-observed-adverse-effect level(NOAEL) of LMK02 for male and female Sprague-Dawley rats was determined as 2,000mg/kg/day and the target organ wasn't confirmed. Because no significant adverse effects were observed, the target organ could not be determined.

• Journal of Pharmacopuncture
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• v.25 no.4
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• pp.364-368
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• 2022

Objectives: Verbenalin is a compound found in herbs such as Cornus officinalis and Verbena officinalis. This study investigated whether verbenalin is safe by analyzing its mutagenicity. Methods: To examine the mutagenic potential of verbenalin, a bacterial reverse mutation test (Ames test) was conducted with Salmonella typhimurium and Escherichia coli strains. Experiments with and without metabolic activity were performed. Results: The mean colony number was less than double that of the control. Growth inhibition and precipitation of verbenalin were not apparent in all strains at different concentrations regardless of metabolic activity. Conclusion: Verbenalin did not show any signs of mutagenicity in this study. Additional toxicity studies including repeated oral toxicity, reproductive toxicity, and carcinogenicity tests are needed.