• Journal of Pharmacopuncture
• /
• v.18 no.3
• /
• pp.42-48
• /
• 2015

Objectives: The aim of the study is to investigate both the single-dose intramuscular injection toxicity and the approximate lethal dose of water-soluble Carthami-flos and Cervi cornu parvum pharmacopuncture (WCFC) in male and female Sprague-Dawley (SD) rats. Methods: The study was conducted at Biotoxtech Co. according to the Good Laboratory Practice (GLP) regulation and the toxicity test guidelines of the Ministry of Food and Drug Safety (MFDS) after approval of the Institutional Animal Care and Use Committee. Dosages for the control, high dose, middle dose and low dose groups were 0.5 mL/animal of saline and 0.5, 0.25 and 0.125 mL/animal of WCFC, respectively. WCFC was injected into the muscle of the left femoral region by using a disposable syringe (1 mL, 26 gauge). The general symptoms and mortality were observed 30 minutes, 1, 2, 4, and 6 hours after the first injection and then daily for 14 days after the injection. The body weights of the SD rats were measured on the day of the injection (before injection) and on the third, seventh, and fourteenth days after the injection. Serum biochemical and hematologic tests, necropsy examinations, and histopathologic examinations at the injection site were performed after the observation period. Results: No deaths, abnormal clinical symptoms, or significant weight changes were observed in either male or female SD rats in the control or the test (0.125, 0.25, and 0.5 mL/animal) groups during the observation period. No significant differences in hematology and serum biochemistry and no macroscopic abnormalities at necropsy were found. No abnormal reactions at injection sites were noted on the topical tolerance tests. Conclusion: The results of this single-dose toxicity study show that WCFC is safe, its lethal doses in male and female SD rats being estimated to be higher than 0.5 mL/animal.

• The Journal of Korean Medicine
• /
• v.32 no.1
• /
• pp.67-83
• /
• 2011

Objectives: The purpose of this study was to examine the single dose toxicity with oral administration and genotoxicities of Ssanghwa-tang fermented with Lactobacillus acidophyllus. Materials and Methods: Clinical signs, weight changes, lethal doses$(LD_{50})$, and postmortem evaluation were determined by Globally Harmonized Classification System(GHCS) in a single-dose oral toxicity study. In vitro mammalian chromosomal aberration test was conducted with Ames test by cell proliferation suppression assessment using the cultivated CHO-K1(Chinese hamster ovary fibroblast) origins. Bacterial reversion assay was performed using Salmonella typhimurium (TA98, TA100, TA1535, and TA1537) and Escherichia coli (WP2uvrA). In vivo micronucleus test was performed using ICR mouse bone marrow. Results: No clinical sign was observed and none of the groups with doses up to 2000 mg/kg showed significant acute oral toxicity in the single dose oral administration. None of the sample doses taken during the 6 to 18 hour groups showed significant aberrant metaphases comparing to the negative control group in the in vitro mammalian chromosomal aberration test. No evidence of mutagenicity was seen for Escherichia coli (WP2uvrA) or Salmonella typhimurium (TA98, TA100, TA1535, and TA1537). No significant increase in the frequency of micronuclei was seen in the micronucleus test. Conclusion: These results indicate that the $LD_{50}$ value of Ssanghwa-Tang fermented with Lactobacillus acidophyllus may be over 2000 mg/kg and it have no acute oral toxicity and genotoxicity.

• Toxicological Research
• /
• v.26 no.1
• /
• pp.53-59
• /
• 2010

This study was conducted to obtain acute information of the oral dose toxicity of DHU001, a polyherbal formula in male and female mice. In order to calculated 50% lethal dose ($LD_{50}$) and approximate lethal dose (LD), test material was once orally administered to male and female ICR mice at dose levels of 2000, 1000, 500, 250 and 0 (vehicle control) ml/kg (body weight). The mortality and changes on body weight, clinical signs, gross observation, organ weight and histopathology of principle organs were monitored 14 days after treatment with DHU001. We could not find any mortalities, DHU001 treatment-related clinical signs, changes on the body and organ weights, gross and histopathological findings. The results obtained in this study suggest that $LD_{50}$ and approximate LD in mice after single oral dose of DHU001 were considered over 2000 mg/kg in both female and male mice.

• Toxicological Research
• /
• v.17 no.4
• /
• pp.273-277
• /
• 2001

Though the bamboo salt, called as "JUKYUM" has been widely used in Korea as panacea, it's toxicity were not screened completely. To investigate the toxicity of bamboo salt, we compared with the toxicity of crude salt and reagent-grade NaCl by performing single dose oral toxicity test in SD rats. Crude salt, natural sun-dried salt (crude salt) production, was purchased from the western seashore of Korean peninsular, and reagent-grade NaCl was purchased from Sigma company. Results of the single dose oral toxicity tests on bamboo salt, crude salt and reagent-grade NaCl to SD rats are as follows, $LD_{50}$ of bamboo salt was 4174mg/kg (male) and 4074mg/kg (female), that of crude salt was 4871mg/kg (male) and 4898mg/kg (female) and that of reagent-grade NaCl was 4247mg/kg (male) and 4025mg/kg (female), respectively. There were little differences in clinical signs and gross legions among groups. Finding of gross autopsy and necropsy of bamboo salt treated group were similar to other groups.er groups.

• The Journal of Internal Korean Medicine
• /
• v.39 no.4
• /
• pp.676-685
• /
• 2018

Objectives: The aim of this study was to estimate the single oral toxicity of Peucedani Radix (PR) ethanol extracts. PR is one of the important herbs for removal of phlegm, the viscous turbid pathological product that can accumulate in the body and cause a variety of diseases. However, research on the pharmacologic toxicity of PR is lacking. Methods: In this study, PR was orally administered to 5-week-old male ICR mice at an oral dose of 2,000, 3,000, or 5,000 mg/kg. After a single-dose administration, the mortality and behavioral changes were observed daily and body weights were measured every two days. After 14 days, the organ weight, organ index, macroscopy, hematological analysis, and serum biochemistry analysis were determined. Results: No mortality, body weight changes, abnormal behavioral changes, or anatomical signs of toxicity were found. The organ weight, organ index, hematological analysis, and serum biochemistry analysis were also within the normal ranges. Conclusions: These results suggest that the 50% lethal dose of PR is more than 5,000 mg/kg. This could indicate that PR is a safe drug without acute toxicity and side effects.

• The Korean Journal of Community Living Science
• /
• v.27 no.3
• /
• pp.437-449
• /
• 2016

To provide information on the safety of crude antifungal compounds produced by Bacillus subtilus SN7 isolated from Meju, we carried out an acute (single) oral dose toxicity test and 4 week repeated oral dose determination test on crude antifungal compounds in male and female Sprague Dawley rats. In the acute toxicity test, rats were treated with crude antifungal compounds produced by Bacillus subtilus SN7 orally at increasing dose levels (500, 1,000, and 2,000 mg/kg) and observed for 2 weeks. In the repeated-dose 28-day oral dose determination study, rats were orally administered doses of 500, 1,000, and 2,000 mg/kg daily for 4 weeks. There were no test article-related deaths or abnormal clinical signs in the two studies. In the 4 week repeated oral dose determination test, there were also no significant differences in clinical signs, body and organ weight changes, or any other hematological and biochemical parameters between the control and treated groups. The results suggest that the crude antifungal compounds produced by Bacillus subtilus SN7 up to a dosage level of 2,000 mg/kg are not toxic in male and female rats.

• Journal of Pharmacopuncture
• /
• v.21 no.2
• /
• pp.104-111
• /
• 2018

Objective:This study is to evaluate both the single-dose intravenous injection toxicity and the approximate lethal dose of Water-soluble Danggui Pharmacopuncture (WDP) in Sprague-Dawley (SD) rats. Methods: Toxicity experiments were conducted at Good Laboratory Practice (GLP) laboratory in Biotoxtech Co., according to the regulations of GLP. WDP injection of dose 0.125, 0.25, and 0.5 mL/animal were experimental groups and normal saline injection group was control group. WDP and normal saline were injected once to 6- week old 5 male and 5 female SD rats at the tail veins at approximately 2 mL/min. During 14 days after the injection, general symptoms were observed and weight were measured. After the observation period, hematological and blood biochemical examination, macroscopic autopsy, topical resistance test at the injection area were performed. Results: RThe WDP 0.5 mL/animal injection group in 4 cases of male rats and all cases of female rats showed hematuria 30 minutes after the administration. However, after 1 hour, no more abnormal general symptoms were observed. The WDP did not affect weight, hematological and blood biochemical examination, macroscopic autopsy, and topical resistance test at the injection area. Conclusion: WDP single dose intravenous injection results showed that WDP have no toxic effects and a lethal dose of WDP should be over 0.5 mL/animal in male and female rats under the study condition. So WDP may be safe.

• Environmental Analysis Health and Toxicology
• /
• v.21 no.4 s.55
• /
• pp.331-335
• /
• 2006

The single dose toxicity of Buxus microphylla var koreana Nakai was evaluated in ICR mice. Twenty five mice of each sex were randomly assigned to five groups of 5 mice each and were administered singly by gavage at dose of 0, 222, 667, 2,000 and 5,000 mg/kg body weight. After single administration, signs of toxicity were observed every hour for the first 6 hours and every day for 14 days. At the end of 14-day observation period, all animals were sacrificed for gross postmortem examinations. Neither significant toxic signs nor death was observed during the observation period. In addition, no pathological changes were noticed in macroscopic examination at necropsy. These results indicate that the single oral administration of Buxus microphylla var. Koreana Nakai did not cause any toxic effect at the dose of 5,000 mg/kg body weight for both sexes and $LD_{50}$ of Buxus microphylla var. koreana Nakai is greater than 5,000 mg/kg body weight.

• Toxicological Research
• /
• v.20 no.2
• /
• pp.143-151
• /
• 2004

This study was to investigate single and repeated-dose toxicities of CJ-11555, an anticirrhotic agent, in Sprague-Dawley (SO) rats. In single-dose oral toxicity study, the test article were administered once by gavage to males and females at dose levels of 0 and 2,000 mg/kg. No dead animals and abnormal necropsy findings were found in control and CJ-11555 treated group. Therefore, the approximate lethal dose of CJ-11555 was considered to be higher than 2,000 mg/kg in rats. In the 4-week repeated oral toxicity study, the test article was administered once daily by gavage to male and female rats at dose levels of 0, 10, 50 and 200 mg/kg/day for 4-weeks. In clinical signs, yellow-colored urine and yellow hair coat were observed in the 50 and 200 mg/kg male and female groups. In hematology, erythrocyte count and hemoglobin were significantly decreased in the 200mg/kg male and female groups. In serum biochemistry, total cholesterol was significantly increased and aspartate aminotransferase (AST) was significantly decreased in the 50 or 200 mg/kg male and female groups. In histopathological examinations, centrilobular hepatocellular hypertrophy in the liver, congestion and pigmentation in the spleen, hyaline droplets in the kidney were observed in the 50 and 200 mg/kg male and female groups. In toxicokinetic study, CJ-11555 was dose-dependent in systemic exposure and showed better absorption in female with minimum accumulation after multidosing. Based on these results, it was concluded that the 4-week repeated oral dose of CJ-11555 resulted in the suppression of AST activity and centrilobular hepatocellular hypertrophy in both sexes at a dose level of 50 or 200 mg/kg/day. The target organ was estimated to be liver, spleen and male's kidney. The no-observed-adverse-effect level (NOAEL) for CJ-11555 in rats following gavage for at least 4-week is 10 mg/kg/day.

• Toxicological Research
• /
• v.23 no.4
• /
• pp.383-389
• /
• 2007

Recombinant human granulocyte-macrophage colony stimulating factor (hGM-CSF) regulates proliferation and differentiation of hematopoietic progenitor cells and modulates function of the mature hematopoietic cells. In the previous study, we reported that hGM-CSF could be produced in transgenic rice cell suspension culture, termed rhGM-CSF. In the present study we examined the single and repeated dose toxicity of rice cells-derived hGM-CSF in SD rats. During single dose toxicity study for 7 days, there were no any toxic effects at any dose of from 10 to $1000{\mu}g/kg$. The lethal dose ($LD_{50}$) was not found in this range. Moreover, repeated dose toxicity study of 14-days period and at the doses of 50 and $200{\mu}g/kg$ (i. v.) of rhGM-CSF did not show any changes in food and water intake. There were also no significant changes in both body and organ weights between the control and the test groups. The hematological and blood biochemical parameters were statistically not different in all the groups. These results suggest that rhGM-CSF has no toxicity in SD rats.