• Journal of Physiology & Pathology in Korean Medicine
• /
• v.25 no.1
• /
• pp.100-108
• /
• 2011

The object of this study was two. One was if Polygonati Rhizoma preparata had a benzo(a)pyrene, the other was to evaluate the single dose toxicity of 9 repetitive steaming and fermenting processed Polygonati Rhizoma, dried root parts of Polygonati Rhozoma preparata extract, in male and female mice. We measured a content of benzo(a)pyrene in Polygonati Rhozoma preparata using a method with HPLC/FLD. And for single dose toxicity, aqueous extracts of Polygonati Rhozoma preparata (EPP; Yield = 35.4 %) was administered to female and male ICR mice as an oral dose of 2,000, 1,000 and 500 mg/kg (body weight) according to the recommendation of Korea Food and Drug Administration (KFDA) Guidelines. Animals were monitored for the mortality and changes in body weight, clinical signs and gross observation during 14 days after dosing, upon necropsy; organ weight and histopathology of 12 principle organs were examined. As results, we could not find any mortality, clinical signs, and changes in the body and organ weight except for slight soft feces sporadically detected in EPP treated male mice at 1 day after administration. In addition, no EPP-treatment related abnormal gross findings and changes in histopathology of principle organs were detected except for some sporadic accidental findings. The results obtained in this study suggest that benzo(a)pyrene was not existed in Polygonati Rhozoma preparata and the 50% lethal dose and approximate lethal dose of EPP aqueous extracts in both female and male mice were considered as over 2,000 mg/kg, the limited highest dosage recommended by KFDA Guidelines. However, it also observed that the possibilities of digestive disorders, like soft feces when administered over 500 mg/kg of EPP aqueous extracts in the present study.

• Biomolecules & Therapeutics
• /
• v.17 no.3
• /
• pp.325-331
• /
• 2009

The object of this study was to evaluate the single oral dose toxicity of Low Molecular Weight Fucoidan (LMF) in male and female rats. LMF was administered to female and male SD rats as an oral dose of 2,000, 1,000 and 500 mg/kg (body wt.). Animals were monitored for the mortality and changes in body weight, clinical signs and gross observation organ weight and histopathology of 14 principle organs were examined upon necropsy. As the results, no LMF treatment related mortalities, clinical signs, changes on the body and organ weights, gross and histopathological observations against 14 principle organs were detected up to 2,000 mg/kg in both female and male rats except for some sporadic findings not LMF treatment related toxicological signs. Therefore, $LD_{50}$ (50% lethal dose) and approximate LD of LMF after single oral treatment in female and male rats were considered over 2,000 mg/kg - the limited dosages recommended by KFDA Guidelines [2005-60, 2005], respectively.

• Toxicological Research
• /
• v.27 no.4
• /
• pp.217-224
• /
• 2011

The object of this study was to evaluate the single oral dose toxicity of platycodin D, a saponin from the root of Platycodon grandiflorum in male and female mice. Platycodin D was administered to female and male mice as an oral dose of 2000, 1000, 500, 250 and 125 mg/kg (body wt.). Animals were monitored for the mortality and changes in body weight, clinical signs and gross observation during 14 days after treatment, upon necropsy, organ weight and histopathology of 14 principle organs were examined. As the results, no platycodin D treatment related mortalities, clinical signs, changes on the body and organ weights, gross and histopathological observations against 14 principle organs were detected up to 2000 mg/kg in both female and male mice. Therefore, $LD_{50}$ (50% lethal dose) and approximate LD of playtcodin D after single oral treatment in female and male mice were considered over 2000 mg/kg - the limited dosages recommended by KFDA Guidelines [2009-116, 2009], respectively.

• Journal of Physiology & Pathology in Korean Medicine
• /
• v.24 no.1
• /
• pp.134-142
• /
• 2010

Although BinSo-San(BSS), a mixed herbal formula consisted of 11 types of medicinal herbs and have been used as anti-inflammatory agent, In the present study, the acute toxicity (single oral dose toxicity) of lyophilized BSS aqueous extracts was monitored in male and female mice after oral administration according to Korea Food and Drug Administration (KFDA) Guidelines (2005-60, 2005). In order to observe the 50% lethal dose ($LD_{50}$), approximate lethal dosage (ALD), maximum tolerance dosage (MTD) and target organs, test articles were once orally administered to female and male ICR mice at dose levels of 2000, 1000, 500, 250 and 0 (control) mg/kg (body wt.) according to the recommendation of KFDA Guidelines (2005-60, 2005). The mortality and changes on body weight, clinical signs and gross observation were monitored during 14 days after dosing according to KFDA Guidelines (2005-60, 2005) with organ weight and histopathology of 12 types of principle organs. We could not find any mortality, clinical signs and changes in the body weights except for dose-independent increases of body weight and gains restricted in 1000 mg/kg of BSS extracts-dosing female group. Hypertrophic changes of lymphoid organs.thymus, spleen and popliteal lymph nodes were detectedat postmortem observation with BSS extracts dose-dependent increases of lymphoid organ weights, and hyperplasia of lymphoid cells in these all three lymphoid organs at histopathological observations. These changes are considered as results of pharmacological effects of BSS extracts or their components, immunomodulating effects, not toxicological signs. In addition, some sporadic accidental findings such as congestion spots, cyst formation in kidney, atrophy of thymus and spleen with depletion of lymphoid cells, and edematous changes of uterus with desquamation of uterus mucosa as estrus cycles were detected throughout the whole experimental groups including both male and female vehicle controls. The significant (p<0.01) increases of absolute weights of kidney and pancreas detected in BSS extracts 1000 mg/kg-treated female group are considered as secondary changes from increases of body weights. The results obtained in this study suggest that the BSS extract is non-toxic in mice and is therefore likely to be safe for clinical use. The LD50 and ALD of BSS aqueous extracts in both female and male mice were considered as over 2000 mg/kg because no mortalities were detected upto 2000 mg/kg that was the highest dose recommended by KFDA and OECD. In addition, the MTD of BSS extracts was also considered as over 2000 mg/kg because no BSS extracts-treatment related toxicological signs were detected at histopathological observation except for BSS or their component-related pharmacological effects, the immunomodulating effects detected in the present study.

• Safety and Health at Work
• /
• v.2 no.3
• /
• pp.290-300
• /
• 2011

Objectives: There is limited data regarding the toxicity of methylcyclohexane, despite its wide use in rubber adhesives, paint diluents, and cleansing agents. This study aimed to verify the toxicity and influence on the reproductive system of methylcyclohexane after its repeated injection in Sprague Dawley (SD) rats. Methods: Methylcyclohexane was injected subcutaneously into male and female SD rats once a day, five times a week, for 13 weeks at different doses (0, 10, 100, and 1,000 mg/kg/day) for each group. The toxicity of testing material was verified by observing the change in body and organ weight, hematological change, pathological findings, and effect on the reproductive system at each different concentration. Results: In the 1,000 mg/kg/day group, there were cases of animal deaths. In animals that survived, hematological changes, including a decrease in the red blood cell count, were observed. A considerable weight gain or loss and pathological abnormalities in the liver, kidney, and other organs were found. However, the 10 and 100 mg/kg/day groups did not cause deaths or other specific abnormalities. In terms of reproductive toxicity, there were changes in hormone levels, including a significant decrease in hormones such as estradiol and progesterone (p < 0.001) in male animals. Menstrual cycle change for female animals did not show concentration dependency. Conclusion: When injected repeatedly for 13 weeks, methylcyclohexane proved to be toxic for the liver, heart, and kidney at a high dose. The absolute toxic dose was 1,000 mg/kg/day, while the no observed adverse effect level was less than 100 mg/kg/day. The substance exerted little influence on the reproductive system.

• Journal of Ginseng Research
• /
• v.14 no.3
• /
• pp.357-363
• /
• 1990

When mice irradiated by neutron (Be) are fed with ginseng concentrate, ginseng powder, and adaptagen of which the major ingredient is ginseng alkaloid to neutron (Be source) irradiated mouse, the following results are obtained. 1. The 50% lethal dose (LD50) for the neutron irradiation were 4 days at 600 rad, 7 days at 500 rad, 16 days at 400 rad, 33 days at 375 rad, and 55 days at 350 rad. In thistest, the standard amollntofirradiation was set at 375 rad/8 min. 2. Some spots appeared in the tail of the neutron-irradiated mouse because of blood congestion, and some had its tip tails cut. But the group administered with adaptagen did not show any of these symptoms. 3. The neutron irradiated mouse showed darkening the color of their lung-chloasmas while none of the adaptagen group had this symptom. 4. The lung tissue of the neutron irradiated mouse showed an increase of the karyolysis and cytoplasmic vacuole. 5. When both neutron irradiation and the ginseng sllbstances were given to the mouse at the same day, the 50% lethal days were increased to 29-33 days for the group administered with ginseng extract. 67 days for the group given with the ginseng powder. and 80 days for the groilp arith the adaptagen. 6. The survival rate of those fed with adaptagen for 33 days before the neutron-irradiation was 100%, while the 50% lethal daysofthe group fed with ginsengextract were 39 days and that of the group fed with ginseng powder were 69 days. 7. The serum valued of ${\gamma}$-globulin, IgG, and albumin were returned to normal condition in the group fed with adaptagen for 33 days before the neutron-irradiation. But those of the group which were given the irradiation and the ginseng substances at the same day did not show such a recovery.

• Journal of Pharmacopuncture
• /
• v.18 no.2
• /
• pp.42-50
• /
• 2015

Objectives: The aims of the study were to test the single- dose intravenous toxicity of Daebohwalryeok pharmacopuncture (DHRP) in Sprague-Dawley (SD) rats and to estimate the crude lethal dose. Methods: The experiments were conducted at Biotoxtech Co., a Good Laboratory Practice (GLP) laboratory, according to the GLP regulation and were approved by the Institutional Animal Care and Use Committee of Biotoxtech Co. (Approval no: 110156). The rats were divided into three groups: DHRP was injected into the rats in the two test groups at doses of 10 mL/kg and 20 mL/kg, respectively, and normal saline solution was injected into the rats in the control group. Single doses of DHRP were injected intravenously into 6 week old SD rats (5 male and 5 female rats per group). General symptoms were observed and weights were measured during the 14 day observation period after the injection. After the observation period, necropsies were done. Then, histopathological tests were performed. Weight data were analyzed with a one-way analysis of variance (ANOVA) by using statistical analysis system (SAS, version 9.2). Results: No deaths and no statistical significant weight changes were observed for either male or female SD rats in either the control or the test groups during the observation period. In addition, no treatment related general symptoms or necropsy abnormalities were observed. Histopathological results showed no DHRP related effects in the 20 mL/kg DHRP group for either male or female rats. Conclusion: Under the conditions of this study, the results from single-dose intravenous injections of DHRP showed that estimated lethal doses for both male and female rats were above 20 mL/kg.

• Journal of Acupuncture Research
• /
• v.40 no.4
• /
• pp.344-350
• /
• 2023

Background: 4-carvomenthenol[4-methyl-1-(1-methylethyl)-3-cyclohexen-1-ol] is a main component of Origanum vulgare L., Zanthoxylum piperitum (L.) DC., and other plants. It has been reported to exhibit anti-inflammatory, antibacterial, and anti-tumor effects. Furthermore, it is necessary to conduct a toxicity test on 4-carvomenthenol to ensure its safety. Methods: This study included 5-week-old Institute of Cancer Research mice that were categorized into 3 treatment groups (12, 25, and 50 mg/kg 4-carvomenthenol dose levels) and a control group (10% dimethyl sulfoxide, 40% polyethylene glycol 300, 5% Tween 80, and 45% normal saline injection of the final volume), with 5 male mice and 5 female mice per group. All groups were observed for clinical symptoms and body weight in a period of 14 days and were subjected to gross necropsy after euthanasia. Results: No deaths were recorded. No test substance-related clinical signs in the female mice of the 12 mg/kg dose group were observed. Abnormal gait was observed in 1 male from day 1 to day 3 in the 12 mg/kg dose group; 1-3 males from day 1 to day 7 and 1-5 females from day 1 to day 15 in the 25 mg/kg dose group; and 2-5 males and 2-5 females from day 1 to day 15 in the 50 mg/kg dose group. No test substance-related effect on the body weight and necropsy findings was observed. Conclusion: The results of this study suggested that the lethal dose of 4-carvomenthenol could be greater than 50 mg/kg. However, further research is needed, especially repeated-dose toxicity studies, to confirm the efficacy and safety of 4-carvomenthenol.

• The Journal of Internal Korean Medicine
• /
• v.27 no.1
• /
• pp.102-113
• /
• 2006

Objectives & Methods : To obtain the 50% lethal dose(LD50), approximated lethal dose(ALD) and approximated target organs of 'Mahwangyounpae-tang' for further study into such things as repeated dose toxicity, genotoxicity and reproductive toxicity, single dose toxicity was tested in male SD rats according to KFDA Guideline 1999-61[KFDA, 1999] at dosage levels of 2,000, 1,000, 500, 250 and 125 mg/kg/$10m{\ell}$. In this study, mortalities, clinical signs, body weight changes and body weight gains, gross findings and weight of principal organs were detected during and/or after 14 days of single dosing. Results & Conclusions : After 2 or 3 days of dosing, 1 or 2 animals in 2,000 mg/kg-dosing groups died. Excitation and leaping response were observed as test article-treatment related clinical signs. These abnormal signs were restricted to 2,000 and 1,000 mg/kg-dosing groups and survivors recovered to normal within 3 or 4 days after dosing. Significant decrease in body weight were observed in some periods of observation in 2,000 and 1,000 mg/kg-dosing group, from 1 days after dosing compared to those of vehicle control group. Significantly diminished body weight gains were observed in observation periods in 2,000 and 1,000 mg/kg-dosing group compared to those of vehicle control group. Hypertrophy and hemorrhage of heart and decoloration of kidney were observed as test article-treatment related gross findings. These abnormal findings were restricted to 2,000 and 1,000 mg/kg-dosing groups. A significant increase of absolute and relative heart and kidney weight were demonstrated in 2,000 mg/kg-dosing groups. The value for LD50 found in this study was 2,218.57 mg/kg. ALD in this study was 2,000 mg/kg, and the target organs are considered to be the heart and the kidney.

• Journal of Physiology & Pathology in Korean Medicine
• /
• v.20 no.2
• /
• pp.442-448
• /
• 2006

To obtain the 50% lethal dose (LD50), approximated lethal dose (ALD) and approximated target organs of 'Mahwangyounpae-tang' for further study like repeat dose toxicity, genotoxicity and reproductive toxicity, single dose toxicity was tested in male ICR mouse according to KFDA Guideline 1999-61 [KFDA, 1999] at a dosage level of 2,000, 1,000, 500, 250 and $125\;mg/kg/10m{\ell}$. In this study, mortalities, clinical signs, body weight changes and body weight gains, gross findings and weight of principal organs were detected during and/or after 14 days of single dosing. After 2 or 3 days of dosing, 1 or 2 animals in 2,000 and 1,000 mg/kg-dosing groups were died. Excitation and leaping response were observed as test article-treatment related clinical signs. These abnormal signs were restricted to 2,000 and 1,000 mg/kg-dosing groups and they were recovered to normal within 4 days after dosing in case of survivors. A significant decrease of body weight were observed in some periods of observation in 2,000 and 1,000 mg/kg-dosing group from 1 days after dosing compared to those of vehicle control group. A significant decrease of body weight gains were observed in observation periods in 2,000 and 1,000 mg/kg-dosing group compared to those of vehicle control group. Hypertrophy of heart and decoloration of kidney were observed as test article-treatment related gross findings. These abnormal findings were restricted to 2,000 and 1,000 mg/kg-dosing groups. A significant increase of absolute and relative heart and kidney weight were demonstrated in 2,000 mg/kg-dosing groups. LD50 in this study was detected as 2,242.42 mg/kg. ALD in this study was detected as 1,000 mg/kg and the target organ was considered as the heart and kidney.