• Journal of Pharmacopuncture
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• v.13 no.4
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• pp.43-61
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• 2010

Objectives : This study was performed to analyse single dose toxicity of Sweet Bee Venom(Sweet BV) extracted from the bee venom in Beagle dogs. Methods : All experiments were conducted under the regulations of Good Laboratory Practice (GLP) at Biotoxtech Company, a non-clinical study authorized institution. Male and female Beagle dogs of 5-6 months old were chosen for the pilot study of single dose toxicity of Sweet BV which was administered at the level of 9.0 mg/kg body weight which is 1300 times higher than the clinical application dosage as the high dosage, followed by 3.0 and 1.0 mg/kg as midium and low dosage, respectively. Equal amount of excipient(normal saline) to the Sweet BV experiment groups was administered as the control group. Results : 1. No mortality was witnessed in all of the experiment groups. 2. Hyperemia and movement disorder were observed around the area of administration in all the experiment groups, and higher occurrence in the higher dosage treatment. 3. For weight measurement, Neither male nor female groups showed significant changes. 4. To verify abnormalities of organs and tissues, thigh muscle which treated with Sweet BV, brain, liver, lung, kidney, and spinal cords were removed and histologocal observation using H-E staining was conducted. In the histologocal observation of thigh muscle, cell infiltration, inflammation, degeneration, necrosis of muscle fiber, and fibrosis were found in both thigh tissue. And the changes depend on the dose of Sweet BV. But the other organs did not showed in any abnormality. 5. The maximum dose of Sweet BV in Beagle dogs were over 9 mg/kg in this study. Conclusions : The above findings of this study suggest that Sweet BV is a relatively safe treatment medium. Further studies on the toxicity of Sweet BV should be conducted to yield more concrete evidences.

• Journal of Applied Biological Chemistry
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• v.59 no.3
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• pp.227-231
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• 2016

Deep sea water (DSW) is located 100 to 500 m below the sea surface. DSW is widely used in various fields, and is an important source of minerals that can be used to treat mineral deficiency. In the present study, the oral toxicity of DSW-mineral extracts was determined using single-dose and 14-day repeated dose oral toxicity tests in ICR mice. For the single-dose oral toxicity tests, mineral extracts of magnesium (Mg) and calcium (Ca) at doses of 0, 6, 270, 810, and 1,350 mg/kg, respectively, were orally administered to mice once at the beginning of the experiment, and the mice were observed for 14 days. For the 14-day repeated dose oral toxicity tests, Mg and Ca mineral extracts at doses of 0, 3, 135, 405, 675 mg/kg, respectively, were orally administered to mice daily, and the mice were observed for 14 days. Various tests were performed including visual observation; analysis of relative organ weight, food intake, and organ weight; biochemical analysis, and histopathology. The results indicated that mortality and changes in appearance were not observed among differentially administered groups of male and female ICR mice during the experimental period. Differences in body weight gain, food intake, organ weight, and histopathology parameters were not significant between the control and mineral-administered groups. Some results of the biochemical analyses were significantly different, but showed no specific tendencies. Overall, no evidence of toxicity was observed from the oral administration of DSW extracts of Ca and Mg in ICR mice.

• Journal of Acupuncture Research
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• v.40 no.4
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• pp.344-350
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• 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 Korean Medicine
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• v.35 no.2
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• pp.28-33
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• 2014

Background: Samul-tang (Si-Wu-Tang, SMT) is a traditional herbal formula, which has been widely used to treat various diseases such as menstrual irregularity, bleeding and leucorrhea. Although many studies have investigated the pharmacological properties of SMT, its toxicity information has not yet been fully elucidated. Methods: Five Sprague Dawley (SD) rats of each sex were given a single dose (5000 mg/kg) of SMT by gavage; control rats received the vehicle only. After the single administration, mortality, clinical signs, body weight changes and gross findings were monitored for 15 days in accordance with Good Laboratory Practice (GLP) principles. Results: In a single oral dose toxicity study, there was no adverse effect on mortality, clinical sign, body weight change or gross finding in any treatment group. Conclusions: The results indicate that SMT did not induce toxic effects at a dose level up to 5000 mg/kg in rats and its median lethal dose ($LD_{50}$) was considered to be over 5000 mg/kg/day body weight for both genders.

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

• Proceedings of the Korean Society of Toxicology Conference
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• 2002.11b
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• pp.171-171
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• 2002

This study was carried out by an Korean GLP laboratory to assess the combined repeated dose, reproduction and developmental toxicity of benzoyl peroxide for OECD SIDS(Screening Information Data Set) program. Male and female Sprague Dawley rats were exposed to benzoyl peroxide at levels of 0, 250, 500 and 1,000 mg/kg/day for 29 days for male and for 41-51 days for female.(omitted)

• Toxicological Research
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• v.12 no.2
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• pp.323-330
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• 1996

Subacute toxicity study was performed in Sprague-Dawley rats after daily oral administration of KDRD-002 0.23, 0.7, 2.1 g/kg for one month. There were no clinical signs and pathological changes compared with control group but slight decrease in spontaneous motor activities and locomotions at high dose group of KDRD-002. Body weights were not significantly changed between control and KDRD-002 treated groups. In histopathological examinations, however, two animals (1 male, 1 female) showed abnormal increases in the weights of spleen tissues at middle dose group of KDRD-002. Also, there were some hemorrhages in lung tissues at low dose group of KDRD-002, but it was not considered to be caused by KDRD-002. These results suggest that KDRD-002 does not induce any significant subacute oral toxicity in Sprague-Dawley rats.

• Communications for Statistical Applications and Methods
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• v.29 no.2
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• pp.239-250
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• 2022

In many applications, we frequently encounter correlated multiple outcomes measured on the same subject. Joint modeling of such multiple outcomes can improve efficiency of inference compared to independent modeling. For instance, in developmental toxicity studies, fetal weight and number of malformed pups are measured on the pregnant dams exposed to different levels of a toxic substance, in which the association between such outcomes should be taken into account in the model. The number of malformations may possibly have many zeros, which should be analyzed via zero-inflated count models. Motivated by applications in developmental toxicity studies, we propose a Bayesian joint modeling framework for continuous and count outcomes with excess zeros. In our model, zero-inflated Poisson (ZIP) regression model would be used to describe count data, and a subject-specific random effects would account for the correlation across the two outcomes. We implement a Bayesian approach using MCMC procedure with data augmentation method and adaptive rejection sampling. We apply our proposed model to dose-response analysis in a developmental toxicity study to estimate the benchmark dose in a risk assessment.

• The Korea Journal of Herbology
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• v.35 no.4
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• pp.45-50
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• 2020

Objective : This study was performed to evaluate the toxicity after a single oral administration of black raspberry extract to male and female Sprague-Dawley (SD) rats and to determine the approximate lethal dose (ALD). Methods : We previously showed that the black raspberry extract repressed the simvastatin-mediated expression of Proprotein convertase subtilisin/kexin type 9 (PCSK9) and improved Low-Density Lipoprotein cholesterol (LDL-C) uptake by hepatocytes through the induction of the Low-Density Lipoprotein Receptor expression in hepatocytes. The groups consisted of black raspberry extract groups, as an oral dose of 2,000 mg/kg and a control group. 5 weeks SD rats were randomly assigned to 4 groups of 5 rats. Each male and female SD rats were administered orally once. For 14 days after the administration, mortality, clinical signs, changes in body weight, and necropsy findings were observed according to the "Standard for Toxicity Study of Pharmaceuticals" of Korea Food and Drug Administration (KFDA) guideline and "Acute Oral Toxicity- Fixed Dose Procedure" of OECD Test Guideline. Results : There were no cases of mortality in the group administered with 2,000 mg/kg of male and female, and no abnormalities in body weight change and clinical signs. Also, no gross abnormalities were observed at the autopsy. Conclusions : As a result of a single oral administration of the black raspberry extract to SD rats, the ALD was determined to exceed 2,000 mg/kg for both male and female SD rats.

• Journal of Society of Preventive Korean Medicine
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• v.15 no.2
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• pp.21-38
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• 2011

Objective : This study was to evaluate the single dose toxicity of Bojungikki-tang(Buzhongyiqi-tang, BJIKT) in male and female mice. Method : Aqueous extracts of BJIKT were 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. Results : we could not find any mortality, clinical signs, and changes in the body and organ weight. In addition, no BJIKT-treatment related abnormal gross findings and changes in histopathology of principle organs were detected except for some sporadic accidental findings. Conclusion : The results obtained in this study suggest that the 50% lethal dose and approximate lethal dose of BJIKT aqueous extracts in both female and male mice were considered as over 2,000 mg/kg, the limited highest dosage recommended by KFDA Guidelines, and can be safety used in clinics.