• Toxicological Research
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• 제34권1호
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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.

• Korean Journal of Acupuncture
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• 제36권1호
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• pp.74-80
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• 2019

Objectives : TA, a polyherbal extract, typically is used for pharmacopuncture therapy on patients with traffic accident-related injuries and musculoskeletal diseases. This study was performed to evaluate the safety of the TA extract, using a micronucleus test. Methods : The dose range and sampling time were first established. An in vivo micronucleus test was then performed to determine the induction of micronuclei in mouse bone marrow cells after a single intramuscular administration of TA to 7-week-old ICR mice (0.2 ml/animal, at 24 hours post-dosing). Results : The incidence of micro-nucleated polychromatic erythrocytes (PCEs) in PCEs in the TA group was similar to that in the negative-control group, while that in the positive-control group was significantly greater. The positive- and negative-control groups did not differ in the ratio of PCEs to total erythrocytes. Conclusions : Our toxicity study indicates that the TA extract does not induce micronucleus formation in mouse bone marrow cells.

• 생약학회지
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• 제39권4호
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• pp.352-356
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• 2008

Acute toxicity of standardized extract of Salvia miltiorrhiza Bunge was examined using male and female ICR mice. Mice were treated with standardized extract the intragastrically at 5 mg/kg, 50 mg/kg, 500 mg/kg or 2,000 mg/kg and observed for two weeks. At the doses used, no mortality or abnormal clinical signs in animals were shown during at the observation period. Also there was no difference in net body weight gain, gross pathological findings at the terminal sacrifice among the groups mice treated with different doses of the test substance. The results suggested that acute oral toxicity of standardized extract of S. miltiorrhiza in mice is very low at the conditions employed in this study.

• 대한본초학회지
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• 제37권3호
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• pp.21-27
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• 2022

Objectives : Single oral dose toxicity test of Lythri Herba water extracts (LHWE) in Sprague-Dawley (SD) rat was performed to determine approximate lethal dose (ALD) of LHWE. Methods : This test was progressed according to OECD Guidelines for the Testing of Chemicals : acute oral toxicity. After adaptation of 7 days, SD rats were divided into 2 groups : vehicle control and 5000 mg/kg LHWE-treated group. Each group consisted of 5 female rats and 5 male rats. Vehicle or 5000 mg/kg LHWE was orally administrated once a day. Survival rates, general toxicity, and changes of body weight were investigated for 14 days after administration. On the last day of examination, the weight of all animals was measured and an autopsy was performed. All internal organ abnormalities were checked macroscopically and their findings were recorded. Results : In both groups, dead animals were not observed. During 14 days of administration, abnormal clinical signs were not detected. There was also no significant difference in weight gains between each group. Autopsy analysis showed that one case of the LHWE-treated female group had retention of clear fluid in the uterus; however, it was not considered to be affected by LHWE administration. Moreover, abnormal findings were not discovered in the control male group and the LHWE-treated male group. Conclusions : These results suggest that the ALD of LHWE exceed 5000 mg/kg and single oral administration of LHWE below 5000 mg/kg is nontoxic.

• Toxicological Research
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• 제18권1호
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• pp.87-98
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• 2002

This study was conducted to evaluate the safety of a recombinant human Factor VIII(GC-$\gamma$ AHF) manufactured by Korea Green Cross Company with different technology according to the Regulation of Korean Food and Drug Administration (l 998. 12. 3). In acute toxicity test, both genders of Sprague-Dawley rats and Beagle dogs were administered intravenously with GC-$\gamma$ AHF of three doses (3,125, 625 and 125 IU/kg), and single dose of 3,125 IU/kg, respectively. No dead animal and abnormal autopsy findings were found in Control and GC-$\gamma$ AHF treated group. Therefore, the 50% lethal dose ($LD_{50}$) of GC-$\gamma$ AHF was conidered to be higher than 3,125 IU/kg in rats and dogs. In the four weeks repeated intravenous toxicity study, GC-$\gamma$ AHF was administrated intravenosly to both genders of rats and dogs with 3 doses (500, 150, 50 IU/kg). There were neither dead animals nor significant changes of body weights during the experimental Period. In addition, no significant GC-$\gamma$ AHF related changes were found in clinical sign, urinalysis and other finding. Statistically changes were observed in hematological, biochemical and organ weight parameters of treated groups: however these changes were not dose dependent. No histopathological lesion were observed in both control and treated animals. Above data suggest that no observed adverse effect level of test materials in rats and dogs might be over 500 IU/kg/day in this study. In ocular irritation test, any injury on iris, conjunctiva and cornea in rabbits were not observed. The acute ocular irritation index (A.O.I.), mean ocular irritation index (M.O.I.) and Day-7 individual ocular irritation Index (I.O.I.) of GC-$\gamma$ AHF were 0. In the primary skin Irritation test, the primary irritation index (P.I.I.) oj GC-$\gamma$ AHF were 0. Therefore, the GC-$\gamma$ AHF is considered not to have the primary skin and eye toxicity in rabbits. In active systemic anaphylaxis (ASA) test, GC-$\gamma$ AHF and GC-$\gamma$ AHF emulsified with Freund's complete adjuvant (FCA) did not induce any symptom of anaphylactic shock in guinea pigs. In passive cutaneous anaphylxis (PCA) test, after sensitization with antisera of GC-$\gamma$ AHF sensitized mice, blue spots were observed on the hypodermis of back of rats, but diameter of each spot was smaller than 5 mm in each test groups except the positive control group. Based on the results of this study, GC-$\gamma$ AHF is not conidered to have any antigenic potential. In conclusion, at levels of up to 500 IU/kg, GC-$\gamma$ AHF did not produce treatment-related toxicity under the conditions of these acute-, four week repeated-toxicity, primary skin and eye toxicity, and antigenicity test.

• 대한약침학회지
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• 제17권1호
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• pp.27-34
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• 2014

Objectives: This experiment was conducted to examine the toxicity of Water soluble Carthmi-Flos herbal acupuncture (WCF) by administering a single intramuscular dose of WCF in 6-week-old, male and female Sprague-Dawley rats and to find the lethality dose for WCF. Methods: The experiment was conducted at Biotoxtech according to Good Laboratory Practices under a request by the Korean Pharmacopuncture Institute. This experiment was performed based on the testing standards of "Toxicity Test Standards for Drugs" by the Ministry of Food and Drug Safety. Subjects were divided into 4 groups: 1 control group in which normal saline was administered and 3 test groups in which 0.1, 0.5 or 1.0 mL of WCF was administered; a single intramuscular dose was injected into 5 males and 5 females in each group. General symptoms and body weights were observed/measured for 14 days after injection. At the end of the observation period, hematological and clinical chemistry tests were performed, followed by necropsy and histopathological examinations of the injected sections. Results: No mortalities were observed in any group. Also, symptoms, body weight, hematology, clinical chemistry and necropsy were not affected. However, histopathological examination of the injected part in one female in the 1.0-mL group showed infiltration of mononuclear cells and a multi-nucleated giant cell around eosinophilic material. Conclusion: Administration of single intramuscular doses of WCF in 3 groups of rats showed that the approximate lethal dose of WCF for all rats was in excess of 1.0 mL, as no mortalities were observed for injections up to and including 1.0 mL.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 2002년도 창립10주년기념 및 국립독성연구원 의약품동등성평가부서 신설기념 국재학술대회:생물학적 동등성과 의약품 개발 전략을 위한 국제심포지움
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• pp.219-219
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• 2002

The SPP003 is a mixture of water extract from Schizandrae Fructus, Poligoni multiflori Radix, Ginseng Radix Akba and Hoelen. The aim of this study was to investigate the anti-hyperglycemic effect of SPP003 in normal and streptozotocin (STZ)-induced diabetic rats, and to monitor the toxicity of SPP003. Oral glucose tolerance test (OGTT) was performed after oral administration of SPP003 100, 300, 600 and 900 mg/kg in normal rats. Blood glucese concentration was measured at -30 min (vehicle, SPP003 or tolbutamide 60 mg/kg, 0 min (glucose treatment), 60, 120 and 180 min. Rats were administerd STZ 65mg/kg (0.1M citrate buffer, pH 4.5) intraperitoneally to induce diabetes and administered vehicle, Spp003 (100, 300 and 600 mg/kg) or tolbutamide (60 mg/kg) orally once a day for 4 weeks. Blood glucose level was measured a 0, 4, 7, 14, 21 and 29 day after initial drug administration. A single oral toxicity of SPP003 was studied in Sprague-Dawley rats of both sexes. In this study, rats were administered with doses of 1, 2 and 5 g/kg of SPP003. In glucose tolerance test, SPP003 900 mg/kg markedly decreased glucose concentration at 1 hr after glucose treatment. Blood glucose levels were much higher in STZ-diabetic rats. These increases were significantly attenuated by SPP003 600 mg/kg. SPP003 did not show any signigicant toxicity. These findings suggest that SPP003 has hypoglycemic properties in STZ-diabetic rats.

• 대한약침학회지
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• 제18권3호
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• pp.57-62
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• 2015

Objectives: The purpose of this study was to examine the single-dose intravenous toxicity of Guseonwangdo-go glucose 5% pharmacopuncture (GWG5). Methods: Forty Sprague-Dawley rats were divided into four groups of five males and five females per group: an intravenous (IV) injection of 1.0 mL of normal saline solution per animal was administered to the control group; IV injections of 0.1, 0.5, and 1.0 mL of GWG5 per animal were administered to the experimental groups (G: 0.1, G: 0.5, and G: 1.0). Observation of clinical signs and body weight measurements were carried out for 14 days following the injections. At the end of the observation period, hematological, biochemical, and histopathological tests, as well as necropsy examinations, were performed on the injected parts. Results: No mortalities or adverse clinical signs were observed in any of the groups. The body weights of all groups continuously increased. In the hematological and the biochemical tests, females in G-0.1 had minimal changes, but those changes were not dose dependent. On necropsy examination, no abnormalities were observed. In the histopathological test, focal inflammatory cell infiltrations were observed in two female rats, one in the control group and one in G-1.0. Also, one female rat in the control group had an epidermis crust. These changes were concluded to have been caused by the insertion of the needle into a vein. Conclusion: The above findings suggest that the lethal dose of GWG5 administered via IV injection is more than 1.0 mL per animal in both male and female rats. Further studies are needed to establish more detailed evidence of its toxicity.

• 대한한방내과학회지
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• 제37권1호
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• pp.8-15
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• 2016

Objectives: To provide information on the safety of GST (Gami-Sasangja-tang), we carried out a single oral dose-increasing toxicity test of GST in beagle dogs.Materials and Methods: Six beagle dogs (three males and three females) were randomly assigned to two groups (experimental group: n=4, control group: n=2). The experimental group (two males, two females) was given oral doses of GST in increasing order (1,250, 2,500, and 5,000 mg/kg) at three-day intervals. After administration, the participants’ mortality, clinical signs, and body weight changes were monitored for two weeks. After two weeks, all dogs were sacrificed for autopsy.Results: Temporary vomiting was observed according to increasing dosage (n=1, 250 mg/kg; n=4, 2,500 and 5,000 mg/kg). Transient diarrhea was observed on the second and third dosing day (n=1, 2,500 mg/kg; n=2, 5,000 mg/kg). Temporary salivation was noted on the third dosing day (n=3, 5,000 mg/kg). Compound-colored stool was observed in all dogs fed the GST on all dosing days and also on the following days. We found no mortality and no abnormalities in the clinical signs, body weight, and gross findings in any of the dogs tested.Conclusions: The maximum tolerated dose was over 5,000 mg/kg for both male and female dogs.

• 대한약침학회지
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• 제17권3호
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• pp.31-39
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• 2014

Objectives: This study was performed to analyze the toxicity and to find the lethal dose of the test substance Water-soluble Carthami-flos pharmacopuncture (WCF) when used as a single intravenous-dose in 6-week-old, male and female Sprague-Dawley rats. Methods: The experiment was conducted at Biotoxtech according to Good Laboratory Practices. 20 female and 20 male Spague-Dawley rats were divided into 4 groups of 5 female and 5 male animals per group. The rats in the three experimental groups received single intravenous injections with 0.125-mL, 0.25-mL and 0.5-mL/animal doses of WCF, Groups 2, 3, and 4, respectively, and the control group, Group 1, received a single intravenous injection with a 0.5-mL dose of normal saline. Clinical signs were observed and body weight measurements were carried out for 14 days following the injections. At the end of the observation period, hematology, clinical chemistry, histopathological tests and necropsy were performed on the injected parts. Results: No deaths occurred in any of the groups. Also, no significant changes in body weight, hematological parameters or clinical chemistry test results between the control group and the experimental groups were observed. Visual inspection after necropsy showed no abnormalities. Histopathological tests on the injected parts showed no significant differences, except for Group 1 females; however, the result was spontaneous generation and had no toxicological meaning because it was not dose-dependent. Therefore, this study showed that WCF had no effect on the injected parts in terms of clinical signs, body weight, hematology, clinical chemistry, and necropsy. Conclusion: As a result of single intravenous-dose tests of the test substance WCF in 4 groups of rats, the lethal dose for both males and females exceeded 0.5 mL/animal. Therefore, WCF is a relatively safe pharmacopuncture that can be used for treatment, but further studies should be performed.