• Journal of Oriental Neuropsychiatry
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• v.24 no.1
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• pp.131-144
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• 2013

Objectives : To provide information on the safety of ACM, we carried out a single oral dose-increasing toxicity and 4-weeks repeated oral dose determining test of ACM in beagle dogs. Methods : In a single oral dose-increasing toxicity test, beagles were treated with ACM orally increasing dose level (1,000, 2,000, 5,000 mg/㎏) at interval of 3 days. After administration, signs of toxicity were observed for two weeks. In 4-weeks repeated oral dose determinating test, beagles were treated with ACM with oral dose 500, 1,000, 2,000 mg/kg for 4 weeks. Mortality, clinical signs, body weight changes, food consumption, urinalysis, hematological and biochemical parameters, organ weights, necropsy findings, and histological findings were monitored during the study period. Results : In a single oral dose-increasing toxicity test, we found no mortality, abnormalities in clinical signs, body weight, and necropsy findings during the study period. In 4-weeks repeated oral dose determinating test, we found no mortality, abnormalities in clinical signs, body weight, food consumption, urinalysis, hematological and biological parameters, gross findings, organ weights, necropsy findings, and histopathological findings in any of the beagles tested. Conclusions : The results obtained in these studies suggest that maximum tolerated dose (MTD) of ACM in male and female beagle dogs was supposed to be over 5,000 mg/kg. For the future studies of toxicity, it is advisable that high dose and low dose are set at 2000 mg/kg and 500 mg/kg, respectively.

• Environmental Mutagens and Carcinogens
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• v.22 no.2
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• pp.97-105
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• 2002

Nowadays a huge variety of products that aim to assist to quit smoking or reduce addictive symptoms are developed and manufactured with safety evaluation, but the safety of the most recent products of interest which do not contain tobacco and nicotine, and shape cigarettes is not evaluated and guaranteed relatively. This study was carried out to evaluate the single and repeated dose inhalation toxicity and genotoxicity of H menthol (Nicotine free-tobacco free) herbal cigarettes provided by Cigastop Ltd. in ICR mice. In this study, doses which we determined to expose to mice were 40 cigarettes for 6 hours a day to mice in single dose and 20 (high dose), 10 (middle dose) and 5 cigarettes (low dose) a day for 28 days in repeated dose inhalation toxicity, in vivo chromosome aberration test and micronucleus test. The particulate substances from H menthol herbal cigarettes also were gathered and used in the Salmonella typhimurium/microsome assay (Salmonella test; Ames test). We could find neither significant changes between control and treatment groups nor dose-response effects of test material at all except serum Ca level of female middle dose treatment group in repeated dose inhalation toxicity test. In conclusion, H menthol herbal cigarettes, when applied clinically intended dose we used, might not show any toxic and/or mutagenic effect.

• Biomolecules & Therapeutics
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• v.16 no.1
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• pp.61-68
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• 2008

In order to develop an improved paclitaxel formulation vehicle, a micelle forming solubilizer, Aceporol 330 was synthesized. It was previously reported that Aceporol 330 provided the linearity of paclitaxel plasma pharmacokinetics. In this study, the single dose toxicity test and 2-week repeated dose toxicity test of Aceporol 330 was performed in beagle dogs after intravenous administration. Single dose and 2-week repeated dose toxicity test of Aceporol 330 showed fever/generalized erythema, severe vomiting, and diarrhea in beagle dogs. However, those toxicities were less severe than those of Cremophor EL. Blood chemistry analysis of 2-week repeatedly treated beagle dogs with Aceporol 330 showed significant elevation of total cholesterol (TCHO) and triglyceride (TG) compared to that of control group. Cremophor EL also significantly increased total cholesterol (TCHO) and triglyceride (TG) as much as Aceporol 330. Results from this study indicated that Aceporol 330 was less toxic than Cremophor EL. Based on the pharmacokinetic advantages and the low toxicity of Aceporol 330 in single dose and 2-week repeated dose toxicity test, Aceporol 330 has a potential for use as a safer solubilizer for paclitaxel than Cremophor EL.

• The Korea Journal of Herbology
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• v.34 no.3
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• pp.31-36
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• 2019

Objectives : In this animal study, we performed the single oral dose toxicity 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 approximate lethal dose (ALD). Methods : According to OECD guidelines for the testing of chemicals section 4 health effects test No. 420 acute oral toxicity study - fixed dose procedure (17 December 2001), single oral dose toxicity test was performed. Animals were divided into two groups: Group 1, vehicle-treated rats (Control); Group 2, SCP 5000 mg/kg treated rats. SCP is composed of two medicinal herbs: Cornus officinalis Sieb. et Zucc. (650 g) and Psoralea corylifolia L. (350 g) in 30% ethanol. SCP was once orally administered to female and male SD rats at dose levels of 5000 mg/kg. Animals were monitored on the mortality, clinical signs, body weight changes and necropsy findings for 14 days. Results : After single oral treatment of SCP, we could not find any mortality up to 5000 mg/kg. Compared with the control group, there were also no significant differences in clinical sign, weight change, weight gain and gross abnormalities in SCP 5000 mg/kg-treated group. Conclusions : Taken together, these results suggest that the ALD of SCP in both female and male SD rats were considered as over 5000 mg/kg. Results from this study provide scientific evidence for the safety of SCP.

• The Korea Journal of Herbology
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• v.33 no.4
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• pp.53-58
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• 2018

Objectives : Kaempferia parviflora Rhizome is black ginger indigenous to Laos and Thailand. It has been used as a folk medicine to improve blood flow and promote vitality and longevity with good health and well being. For these reasons, Kaempferia parviflora Rhizome has been focused on developing it as a food or food supplement. In addition, Kaempferia parviflora Rhizome could be under consideration of new prescription based on its characteristic compounds, polymethoxyflavonoids. However, it needs to be certified as safe before it can be used. Here, a single-oral toxicity test and safety classification was carried out to identity acute information of the toxicity of Kaempferia parviflora Rhizome powder and to make sure of its safety in clinical applications. Methods : Test substance was orally administered to male and female SD-rat at dose levels of 5000 mg/kg to estimate approximate lethal dose(ALD). Based on the acute information of the toxicity, the safety classification was estimated using the HED(human equivalent dose)-based MOS(margin of safety). Results : At 14 days after treatment with test substance. there were no of test substance related with mortalities and clinical signs. In addition, no changes in the body or organ weights and no gross or histopathological findings were observed. Thus, the ALD of Kaempferia parviflora Rhizome powder was considered over 5,000 mg/kg in both female and male mice. Conclusions : Based on the single oral toxicity test using the highest and limit dose, 5,000 mg/kg and the decision guideline for safety classification based on HED-based MOS, it was estimated that Kaempferia parviflora Rhizome powder is classified as "Specified class B" indicating that clinical dose is not limited to patients as safe as food.

• 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.

• Journal of Pharmacopuncture
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• v.22 no.3
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• pp.171-175
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• 2019

Objectives: TA is a polyherbal extract comprising seven herbs, typically used for the pharmacopuncture treatment of patients with traffic accident- related injuries and musculoskeletal diseases. This animal study was conducted to evaluate the safety of the TA extract, using a single-dose toxicity test. Methods: The dose range and sampling time were first established. Six- week-old Sprague-Dawley rats were administered 1.0 mL of TA or normal saline (control), intramuscularly, for the single-dose toxicity test. The general condition, mortality, and histology of all rats were observed for 2 weeks. Results: No abnormal symptoms or deaths were observed in any group. The body weights of the rats in the TA and control groups were similar. No significant differences in histopathology were observed between the groups. Conclusion : Our study indicates that 1.0 mL of TA extract may be safely administered for pharmacopuncture for treatment of patients in traditional medicine clinics.

• Toxicological Research
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• v.32 no.2
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• pp.159-173
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• 2016

Crickets have been attracting considerable interest in the field of nutrition and toxicology due to the global exhaustion of food resulting from a growing population. The cricket is normally eaten in several countries after roasting, similar to the grasshopper; however, safety evaluation data on cricket powder is limited. Here, we performed general toxicity studies of cricket powder including a single, 2-week repeated dose range evaluation test, a 13-week repeated oral dose toxicity test in Sprague-Dawley rats, a single oral dose toxicity test in Beagle dogs, and a skin sensitization test in guinea pigs following the Organization for Economic Cooperation and Development test guidelines 406 and 408 in addition to Good Laboratory Practice. To investigate the NOAEL and target organs of cricket powder, Sprague-Dawley rats were allocated to 4 groups: vehicle control, 1,250 mg/kg, 2,500 mg/kg, 5,000 mg/kg dose test groups and cricket powder was administered over 13 weeks after single dose and dose range finding studies in rats based on the results of the single oral administration toxicity study in rats and Beagle dogs. The results of the study showed that the NOAEL of cricket powder was over 5,000 mg/kg for both sexes of rats without adverse effects in a 13-week repeated oral toxicity study and there was no skin hypersensitivity reaction. Therefore, our results reveal that crickets can be widely used as a new substitute food or nutrient resource.

• Journal of Haehwa Medicine
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• v.22 no.1
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• pp.171-184
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• 2013

Single-and repeated-dose toxicities of Compound K (CK) were evaluated according to Toxicity Test Guidelines of Korea Food and Drug Administration using Sprague-Dawley rats. For single-dose toxicity study, CK was dissolved in drinking water, orally administered and examined for 14 days. As results, CK up to a dose of 5,000 mg/kg, the limited dose, neither induced death, clinical signs and necropsy findings, nor affected body weight gain and organ weights, in which 10% lethal dose could not be estimated. Based on the results of single-dose toxicity test, CK was administered at doses of 500, 1,000 or 2,000 mg/kg for 28 days for the evaluation of repeated-dose toxicity. All doses including the limited dose (2,000 mg/kg) of CK did not cause any abnormalities of rats, including mortality, clinical signs, body weight gain, feed/water consumption, necropsy findings, organ weights, hematology, blood biochemistry. Rather, high doses (1,000 - 2,000 mg/kg) of CK reduced the serum levels of alanine transaminase (ALT), aspartate transaminase (AST), creatinine phosphokinase (CPK), lactate dehydrogenase (LDH) and triglycerides, in addition to an increase in glucose, indicative of protective effects on hepatic and muscular injuries. Thus, both maximum tolerable dose (MTD) and no observed adverse effect level (NOAEL) were not determined. The results indicate that long-term intake of high-dose CK might not induce general adverse effects.

• Toxicological Research
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• v.18 no.1
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• pp.73-77
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• 2002

The single dose toxicity of Hwangiaegongjinbo, an invigorator developed by Korea Medical Science Institute was evaluated in ICR mice and Sprague-Dawley rats. The aqueous solution of freeze-dried powder of Hwangiaegongjinbo or its original solution was once administrated orally to both sexes of mice and rats at dose of 2000 mg/kg, the recommended upper limit dose for acute toxicity. Water was administered to another group as control. after single adminstration, sign of toxicity were observed every hour for the first 6 hours and every day for 14 days. Neither sign그cant toxic sign nor death was observed during the observation period. In addition, no pathological changes were noticed in macroscopic examination at necropsy in those treated group. These results indicated that $LD_{50}$ of Hwangiaegongjinbo is greater than 2000 mg/kg in ICR mice and Sprague-Dawley rats.