• Korean Journal of Veterinary Research
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• v.44 no.1
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• pp.49-55
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• 2004

The present study was carried out to investigate the potential acute toxicity of CKD-602 by a single intravenous dose in Beagle dogs. The test chemical was administered intravenously to male and female Beagle dogs at dose levels of 0.3, 0.5, or 2.5 mg/kg. Mortalities, clinical findings, and body weight changes were monitored for the 14-day period following the administration. At the end of 14-day observation period, all animals were sacrificed and complete gross postmortem examinations were performed. All males and females of the 2.5 mg/kg dose group were found dead between the fourth and seventh day after the injection. Treatment related clinical signs, including vomiting, anorexia, mucous stool, diarrhea, and no stool were observed. Decrease or suppression of body weight was observed in a dose-dependent manner. In autopsy, dark red discoloration of the gastrointestinal tract, atrophy of the thymus, paleness of the spleen, sporadic dark red spots of the lung and petechia of the heart were observed in dead animals of the 2.5 mg/kg dose group. There were no specific adverse effects on males and females of the 0.3 and 0.5 mg/kg dose groups, except for the transient clinical signs such as anorexia, vomiting, and mucus/no stool. On the basis of the results, it was concluded that a single intravenous injection of CKD-602 to Beagle dogs resulted in increased incidence of abnormal clinical signs and death, decreased body weight, and increased incidence of abnormal gross findings. The absolute toxic dose of this chemical was 2.5 mg/kg for both genders. The $LD_{50}$ value was 1.1 mg/kg (95% confidence limit not specified) for both genders. The no-observed-effect level (NOEL) was considered to be below 0.3 mg/kg for both genders.

• Journal of the Korean Society of Food Science and Nutrition
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• v.44 no.1
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• pp.24-28
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• 2015

The present study was carried out to investigate the in vivo single-dose acute toxicity of Bacillus subtilis JNS isolated from Cheonggukjang, which is a probiotic candidate showing strong and broad antibacterial activity. The test sample was orally administrated to male and female ICR mice at a highest dose of 2,000 mg/kg for 14 days. No significant change in general conditions, mortalities, body weight changes, clinical signs, autopsy findings, or presence of gross lesions was observed in either sex of mice. The results indicate that up to 2,000 mg/kg of B. subtilis JNS had no adverse effect on ICR mice.

• Natural Product Sciences
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• v.26 no.3
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• pp.252-258
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• 2020

This study investigated the biochemical and histological changes associated with the co-administration of cisplatin and methanolic extract of Portulaca oleracea (MEPO) in adult Wistar rats. Twenty-four (24) adult female Wistar rats were randomly divided into six (6) groups (A-F) (n = 4). Group A served as the control group for the experiment and received no treatment. Group B was given a single dose of cisplatin and served as the cisplatin control group. Group C and D received 400 mg/kg and 800 mg/kg of MEPO 6 hours after a single dose cisplatin injection respectively. Group E and F received 400 mg/kg and 800 mg/kg of MEPO 6 hours before cisplatin injection. The cisplatin injection was 2 mL/kg given intraperitoneally for all groups. There was a significant increase in the serum levels of ALT, ALP, AST, total bilirubin, and conjugated bilirubin following cisplatin treatment (p = 0.000, 0.000, 0.039, 0.000, 0.004 respectively) with a consequent reversal due to MEPO administration across all treated groups (p = 0.000, 0.000, 0.000, and 0.000) in a dose-dependent fashion. Cisplatin caused the expansion of the red and white pulp in the spleen which was attenuated by MEPO. MEPO demonstrated a protective effect against cisplatin-induced liver and spleen toxicity.

• Journal of Periodontal and Implant Science
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• v.25 no.3
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• pp.470-477
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• 1995

Flavonoids from Scutellariae Radix possessed a dual function both as an anti-inflammatory agent and an enhancer of cellular activity in gingival fibroblast. The purpose of this study was to evaluate on the toxicity of ethanolic extract from the root of Scutellariae Radix Georgi and its flavonoids, Wogonin, Baicalein, and Baicalin were isolated and purified by the following method. The crude drug was extracted with ethyl acetate and the residue was dissolved in ethyl alcohol. The ethyl alcohol soluble fraction was separated, concentrated, and then chromatographed on a silica gel column. The acute oral LD 50 in rats was determined for EtOH ex. of Scutellariae Radix and three compounds were evaluated with a single oral gavage at three graded dosage levels. The acute intravenous LD 50 was determined with a single intravenous injection via the jugular vein at three graded dosage levels. Groups of 5 male and 5 female rats, 6 week of age at the start of the study, were fed diets containing 3 graded dosage levels for 14 days. Groups of 5 male and 5 female hamster received O.5ml of the test article at once in a day for 5 days to the buccal cheek pouch for two minutes each. The acute oral LD50 for EtOH ex. of Scutellariae Radix is 1430mg/kg, and for Wogonin 1320mg/kg, for Baicalein 1250mg/kg, for Baicalin 1330mg/kg. The acute intravenous toxicity of EtOH ex. of Scutellariae Radix and its extracts was found to be 27mg/kg body weight No toxic effects were observed in rats fed up to 200mg/kg of EtOH ex. of Scutellariae Radix, Wogonin, Baicalein and Baicalin in the diet for 14 days. The acute Mucouse Membrane LD 50 in hamsters was found to be greater than 100mg/kg. These results suggested that EtOH ex. of Scutellariae Radix and its flavonoids are safe for oral care products using limited amount of extract.

• Molecular & Cellular Toxicology
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• v.1 no.4
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• pp.230-236
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• 2005

Formaldehyde is a common environmental contaminant found in tobacco smoke, paint, garments, diesel and exhaust, and medical and industrial products. Formaldehyde has been considered to be potentially carcinogenic, making it a subject of major environmental concern. However, only a little information on the mechanism of immunological sensitization and asthma by this compound has been known. So, we performed with Jurkat cell line, a human T lymphocyte, to assess the induction of DNA damage and to identify the DEGs related to immune response or toxicity by formaldehyde. In this study, we investigated the induction of DNA single strand breaks by formaldehyde using single cell gel electrophoresis assay (comet assay). And we compared gene expression between control and formaldehyde treatment to identify genes that are specifically or predominantly expressed by employing annealing control primer (ACP)-based $GeneFishing^{TM}$ method. The cytotoxicity ($IC_{30}$) of formaldehyde was determined above the 0.65 mM in Jurkat cell in 48 h treatment. Based on the $IC_{30}$ value from cytotoxicity test, we performed the comet assay in this concentration. From these results, 0.65 mM of formaldehyde was not revealed significant DNA damages in the absence of S-9 metabolic activation system. And the one differentially expressed gene (DEG) of formaldehyde was identified to zinc finger protein 292 using $GeneFishing^{TM}$ method. Through further investigation, we will identify more meaningful and useful DEGs on formaldehyde, and then can get the information on the associated mechanism and pathway with immune response or other toxicity by formaldehyde exposure.

• Biomolecules & Therapeutics
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• v.19 no.1
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• pp.38-44
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• 2011

Cisplatin is widely used for various types of cancers. However, its side effects, most notably, renal toxicity often limit its clinical utility. Although previous metabolomic studies reported possible toxicity markers, they used small number of animals and statistical approaches that may not perform best in the presence of intra-group variation. Here, we identified urinary biomarkers associated with renal toxicity induced by cisplatin using NMR-based metabolomics combined with Orthogonal Projections to Latent Structures-Discriminant Analysis (OPLS-DA). Male Sprague-Dawley rats (n=22) were treated with cisplatin (10 mg/kg single dose), and the urines obtained before and after treatment were analyzed by NMR. Multivariable analysis of NMR data presented clear separation between non-treated and treated groups. The OPLS-DA statistical results revealed that 1,3-dimethylurate, taurine, glucose, glycine and branched-chain amino acid (isoleucine, leucine and valine) were significantly elevated in the treated group and that phenylacetylglycine and sarcosine levels were decreased in the treated group. To test the robustness of the approach, we built a prediction model for the toxicity and were able to predict all the unknown samples (n=14) correctly. We believe the proposed NMR-based metabolomics with OPLS-DA approach and the resulting urine markers can be used to augment the currently available blood markers.

• Journal of Life Science
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• v.24 no.2
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• pp.191-195
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• 2014

Essential oils extracted or purified from various plants have shown various beneficial effects. Seed parts of Schizandra chinensis Baillon (Schisandrae Semen) have been used as a traditional medicine for thousands of years in parts of Asia, including Korea, China, and Japan. However, the pharmacological mechanisms of essential oils purified from S. fructus (S. chinensis Baillon) remain largely unresolved. The aim of this study was to investigate the safety of Schisandrae Semen essential oil (SSeo) by a single- dose toxicity study in mice. SSeo was orally administered at a dose of 5,000 mg/kg in ICR mice. All animals were sacrificed after 14 days of treatment. After a single administration, mortality, clinical signs, body weight changes, and gross pathological findings were observed for 14 days. We also measured parameters of organ weight, clinical chemistry, and hematology. No toxicological change related to the test substance or mortality was observed after administration of a single oral dose of SSeo. There were no adverse effects on clinical signs, body weight, or organ weight and no gross pathological findings in any treatment group. The clinical chemistry and hematological parameters were within the normal ranges except total bilirubin. Therefore, the approximate lethal dose for oral administration of SSeo in mice was considered to be over 5,000 mg/kg. The results on the single-dose toxicity of SSeo indicate that it is not possible to reach oral dose levels related to death or dose levels with any harmful side effects.

• Journal of Life Science
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• v.26 no.10
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• pp.1207-1213
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• 2016

Schisandrae fructus (SF) and Mori folium (MF) have been used as traditional medicines for thousands of years in parts of Asia, including Korea, China, and Japan. Recent researches on SF and MF have documented a wide spectrum of therapeutic properties, including anti-microbial, anti-inflammatory, anti-oxidative, immunomodulatory and anti-angiogenesis effects. However, the toxicity and safety of SF and MF, and their mixture (medicinal herber mixture, MHMIX) were not confirmed. Therefore, this study was performed to evaluate the acute toxicity and safety of SF, MF and MHMIX. SF, MF and MHMIX were orally administered at a dose of 5,000 mg/kg in ICR mice. Animals were monitored for the mortality and changes in the body weight, clinical signs and gross observation during the 14 days after dosing, upon necropsy. We also measured parameters of organ weight, clinical chemistry, and hematology. No dead and no clinical signs were found during the experiment period after administration of a single oral dose of SF, MF and MHMIX. There were no adverse effects on clinical signs, body weight, or organ weight and no gross pathological findings in any treatment group. Therefore, LD50 value of SF, MF and MHMIX may be over 5,000 mg/kg and it may have no side toxic effect to ICR mice. The results on the single-dose toxicity of SF, MF and MHMIX indicate that it is not possible to reach oral dose levels related to death or dose levels with any harmful side effects.

• Journal of Chest Surgery
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• v.17 no.1
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• pp.157-166
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• 1984

These biologic test procedures are designed to test the suitability of P.V.C. made in Korea intended for parenteral preparation, which were based on the U.S. Pharmacopeia XIX "Biologic Test-Plastic Container", Official from July 1, 1975. Healthy adult human blood and rabbits weighing 2\ulcorner.2Kg were used for test materials. Sample P.V.C. were sampled from the medical equipments made in Korea randomly and Control P.V.C. were sampled from the standardized Cobe and Polystan P.V.C. tubes. P.V.C. extract was prepared from a homogeneous P.V.C. samples by incubating 60 square centimeters of the sample per 20 millimeters of sterile pyrogen-free saline at 70\ulcorner for 72 hours or autoclaving at 120\ulcorner for 1 hour. The Implantation Test was designed to evaluate the reaction of living tissue to the plastic by the method of the implantation of the Sample itself into animal tissue. The Systemic Injection Test, the Intracutaneous Test, and the remainders were designed to determine the biological response of animals to plastics by the single-dose injection of specific extracts prepared from a Sample. The results are as follows; 1.Implantation Test - No significant difference for reactions was noted between the Sample treated animal and the Control after 72 hours of implantation. 2.Systemic Toxicity Injection Test - No sign of toxicity and/or death immediately after injection and at 4, 24, 48 hours respectfully after injection. 3.Intracutaneous Test - None of the animals treated with the Sample showed a significantly greater reaction than the observed in the animals treated with Blank. 4.Pyrogen Assay-Only one animal treated with the Sample showed the maximal rise of rectal temperature about 0.2\ulcorner after 3 hours of injection, but remainders showed no change. 5.Hemolytic Index - The positive Control tube of distilled water exhibited complete hemolysis while the negative Control tube and P.V.C. extract were negative demonstrating no hemolysis. 6.Cell Morphology of Erythrocytes and Leukocytes on Stored, Heparinized Human Blood -- There was no significant difference in the morphology of either the Control or Sample extract. 7.Clotting Mechanism of Human Blood in vitro - After allowing to the P.V.C. extract at room temperature for 5 Hours and at 10\ulcorner for 24 hours, there was no appreciable difference in Prothrombin Time under these conditions. 8.Clotting Mechanism of Rabbit in vivo - At the termination of 5 days after intraperitoneal injection of the P.V.C. extract, no significant changes in Clotting Time were observed. According to the above results, it could be concluded that the P.V.C. made in Korea was acceptable for parenteral preparation, especially treated with physiologic saline and/or human blood.man blood.

• Toxicological Research
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• v.14 no.3
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• pp.393-400
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• 1998

As a series of safety studies on DA-3585, a recombinant human erythropoietin, its local irritancy was examined in rabbits after the following treatments; application into the conjunctival sac of the eye(single), subcutaneous injection (single and -day repeated)and intravenous injection (7-day repeated.)In addition, perivascular irritation of DA-3585 was investigated in mice. In the result of ocular irritation test, 10,000IU/ml solution of DA-3585 could be considered as a non-irritating material. The local irritation of DA-3585 by a single and 7-day repeated subcutaneous injection was negligible and not so much different from that of saline. In the vascular irritancy test, macro-and microscopic observations revealed that local irritation of DA-3585 was comparable to that of saline when injected into retroauricular vein of rabbits for 7 consecutive days. Furthermore the perivascular administration of DA-3585 upto the concentration of 10,000 IU/ml did not induce any morphological abnormalities at injection sites. The results obtained from the present study suggest that the local irritancy of DA-3585 is not different from that of saline when injected through intravenous or subcutaneous route for clinical practice.