• 한국식품위생안전성학회지
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• 제26권4호
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• pp.377-382
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• 2011

살균소독제, 라미아-킬(benzalkonium chloride(20%), citric acid(20%))에 대하여 랫드와 토끼를 이용하여 급성경구독 성과 피부 자극성 평가를 각각 수행하였다. 랫드에 라미아-킬 2,000 mg/kg 농도를 최고농도로 하여 단회 투여 후, 14일간 관찰한 결과, 사망, 이상증상 및 체 중변화 등은 관찰되지 않아, 라미아-킬의 $LD_{50}$은 2,000 mg/kg 이상으로 추정되었다. 토끼의 등 부위의 털을 제거하고 찰과부위와 비찰과 부위에 여러 농도로 라미아-킬을 도포 한 후, 피부 자극성을 확인한 결과, 라미아-킬의 l차 자극 지수가 0.50으로 비자극성 물질로 분류되었다. 따라서, 본 연구를 통하여, 라미아-킬은 급성경구독성 시 안전한 물질이며, 피부 자극성을 야기하지 않는 물질로 평가되었다.

• 한국식품영양과학회지
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• 제42권6호
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• pp.892-897
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• 2013

본 연구는 김치로부터 항진균 활성을 보이는 유산균인 Lactobacillus(Lb.) plantarum AF1이 생산하는 조항진균 물질의 부분 정제물이 천연 식품보존제 및 사료보존제로서 사용 가능성을 알아보기 위하여 안전성을 평가하고자 단회 급성독성시험을 실시하였다. 급성독성시험을 위하여 경구로 1회 시험물질을 최고 용량(2,000 mg/kg)으로 하여 ICR계통 암수 마우스에게 용량별 각 군당 10 마리씩 투여한 후 14일간의 일반증상, 사망률, 체중, 임상증상 및 육안적 소견을 관찰하였다. 단회 경구투여한 후 모든 시험군에서 사망례가 관찰되지 않았으며, 시험동물은 시험 종료 시까지 계속 생존하여 평균치사량을 산출할 수 없었다. 경구투여한 후 마우스의 체중변화에 있어서도 암수 모두 대조군과 시료물질 투여군 사이에 유의성 있는 차이는 보이지 않았으며, 용량 의존적인 차이도 볼 수 없었다. 경구투여한 후 시험 종료한 다음 생존동물 모두를 부검하여 주요 장기의 육안적 소견을 관찰한 결과 대조군과 시료투여군 모두에서 외관상이나 내부 장기에 어떠한 이상소견이나 병변이 관찰되지 않았다. 이상의 결과로부터 시험물질인 Lb. plantarum AF1이 생산한 조항진균 물질을 경구투여 시 ICR계통 암수 마우스에서 독성학적인 변화가 관찰되지 않았으며, $LD_{50}$은 경구투여 시 2,000 mg/kg 이상인 저독성의 안전한 물질로 사료된다.

• 대한약침학회지
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• 제26권1호
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• pp.27-37
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• 2023

Objectives: Moroccan Arbutus unedo is an essential medicinal plant; however, little is known about the biological properties of its leaves mentioned in Moroccan traditional medicine. Methods: Various standard experiments were performed to evaluate the phytochemical, antidiabetic, antioxidant, antibacterial, and acute and sub-chronic toxicity characteristics of A. unedo leaves. Results: Phytochemical screening led to the identification of several phytochemical classes, including tannins, flavonoids, terpenoids, and anthraquinones, with high concentrations of polyphenols (31.83 ± 0.29 mg GAEs/g extract) and flavonoids (16.66 ± 1.47 mg REs/g extract). Further, the mineral analysis revealed high levels of calcium and potassium. A. unedo extract demonstrated significant antioxidant and anti-diabetic activities by inhibiting α-amylase (1.350 ± 0.32 g/mL) and α-glucosidase (0.099 ± 1.21 g/mL) compared to the reference drug Acarbose. Also, the methanolic extract of the plant exhibited significantly higher antibacterial activity than the aqueous extract. Precisely, three of the four examined bacterial strains exhibited substantial susceptibility to the methanolic extract . Minimum bactericidal concentration (MBC)/minimum inhibitory concentration (MIC) values indicated that A. unedo harbor abundant bactericidal compounds. For toxicological studies, mice were administered with A. unedo aqueous extract at single doses of 2,000 and 5,000 mg/kg. They did not exhibit significant abnormal behavior, toxic symptoms, or death during the 14-day acute toxicity test and the 90-day sub-chronic toxicity test periods. The general behavior, body weight, and hematological and biochemical status of the rats were assessed, revealing no toxicological symptoms or clinically significant changes in biological markers observed in the mice models, except hypoglycemia, after 90 days of daily dose administration. Conclusion: The study highlighted several biological advantages of A. unedo leaves without toxic effects in short-term application. Our findings suggest that conducting more comprehensive and extensive in vivo investigations is of utmost importance to identify molecules that can be formulated into pharmaceuticals in the future.

• Biomolecules & Therapeutics
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• 제19권1호
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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 Chest Surgery
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• 제17권1호
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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.

• 한국식품저장유통학회지
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• 제20권1호
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• pp.121-126
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• 2013

본 연구는 김치에서 분리한 우수한 항균활성을 나타내는 Leuc. citreum GR1을 분리하여 단기투여에 의한 안전성을 확인하고자 식품의약품안전청의 의약품 등의 독성시험기준에 따라 실시하였다. 시험물질인 Leuc. citreum GR1의 임상적용 경로가 구강이므로 경구투여용 존데를 사용하여 단회 경구 투여를 수행하였으며, 투여용량은 단회 경구투여 최고용량인 5,000 mg/kg을 고농도로 설정하였다. 급성독성시험을 위하여 경구 1회 시험물질을 625, 1,250, 2,500 및 5,000 mg/kg 투여 용량으로 하여 ICR계 암 수 마우스에게 용량별 각 군당 10마리씩 시험물질을 투여한 후 14일간의 일반증상, 사망률, 체중, 임상증상 및 육안적 소견을 관찰하였다. 단회 경구투여한 후 모든 시험군에서 사망례가 관찰되지 않았으며, 시험동물은 시험 종료 시까지 계속 생존하여 평균치사량을 산출할 수 없었다. 경구투여한 후 마우스의 체중변화에 있어서도 암 수 모두 대조군과 시료물질 투여군 사이에 유의성 있는 차이는 보이지 않았으며, 용량 의존적인 차이도 볼 수 없었다. 단회 경구구투여 후 시험 종료한 다음 생존동물 모두를 부검하여 주요 장기의 육안적 소견을 관찰한 결과 대조군과 시료투여군 모두에서 외관상이나 내부 장기에 어떠한 이상소견이나 병변이 관찰되지 않았다. 이상의 결과로부터 시험물질인 Leuc. citreum GR1는 경구투여 시 ICR계 암 수 마우스에서 독성학적인 변화가 관찰되지 않았으며, 경구투여가 5,000 mg/kg 이상인 저독성의 안전한 물질로 사료된다.

• 대한약침학회지
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• 제18권1호
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• pp.63-71
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• 2015

Objectives: This study was carried out to analyze the single-dose toxicity of Eun-Bi San pharmacopuncture injected into the muscle of Sprague-Dawley (SD) rats. Methods: All experiments were performed at Biotoxtech, an institution certified to conduct non-clinical studies under the Good Laboratory Practice (GLP) regulations. Six week old SD rats reared by ORIENTBIO were chosen for this pilot study. The reason SD rats were chosen is that they have been widely used in safety tests in the field of medicine, so the results can be easily compared with many other databases. The Eun-Bi San pharmacopuncture was made in a clean room at the Korean Pharmacopuncture Institute (KPI, K-GMP). The constituents of the Eun-Bi San pharmacopuncture are Angelicae gigantis radix, Strychni semen and Glycyrrhizae radix. These were extracted at low temperature and low pressure in an aseptic room at the KPI. Doses of Eun-Bi San pharmacopuncture, 0.25, 0.5 and 1.0 mL, were administered to the experimental groups, and a dose of normal saline solution, 1.0 mL, was administered to the control group. This study was performed under the approval of the Institutional Animal Ethics Committee of Biotoxtech Co., Ltd. Results: No deaths or abnormalities occurred in any of the four groups. No significant changes in weight, hematological parameters or clinical chemistry between the control group and the experimental groups were observed. To determine if abnormalities existed in any organs and tissues, we used microscopy to examine representative histological sections of each specified organ; the results showed no significant differences in any of the organs or tissues. Conclusion: The results of this study suggest that treatment with Eun-Bi San pharmacopuncture is relatively safe and that its clinical use may be beneficial. Further evaluations and studies on this subject will be needed to provide more concrete evidence in support of these conclusions.

• 대한본초학회지
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• 제24권3호
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• pp.1-12
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• 2009

Objectives : The objective of this study was to compare, the potency of toxicity of Cantharidin containing dried Mylabis phalerata (MP) extract and it's modifier. Methods ： They were monitored at dosage level 2,000, 1,000, 500, 250 and 125 mg/kg, respectively. Changes of body weight, clinical signs, mortality, LD50, macroscopic changes of gastrointestinal tract and liver were observed after single oral dose of test articles with changes of serum Gastrin and Somatostatin levels. Results ： Dosage-dependent decrease of body weight and/or gains were demonstrated in dried MP extract-dosing groups, were also detected in modified and dried MP extract-dosing groups at 2,000 and 1,000 mg/kg-dosing group. However, below 500 mg/kg-dosing group, the body weights were significantly increased compared to that of equal dosage group of dried MP extract-dosing group. Dosage-dependently detected clinical signs in dried MP extract-dosing groups, were also detected in modified and dried MP extract-dosing groups at 2,000 and 1,000 mg/kg-dosing group. However, below 500 mg/kg-dosing group, these clinical signs dramatically were decreased compared to that of equal dosage group of dried MP extract-dosing group. Dosage-dependent increase of mortality rates were observed in dried MP extract-dosing groups, were also detected in modified and dried MP extract-dosing groups at 2,000 and 1,000 mg/kg-dosing group. However, below 500 mg/kg-dosing group, the mortalities were significantly decreased compared to that of equal dosage group of dried MP extract-dosing group. The LD50 of dried MP extract in male mice was dramaticlly increased in their modify, 265.86 vs 426.99 mg/kg. Dosage-dependently increase of number of hemorrhagic and/or erythematous spots detected in the gastrointestinal tracts of dried MP extract-dosing groups, were also detected in modified and dried MP extract-dosing groups at 2,000 and 1,000 mg/kg-dosing group. However, below 500 mg/kg-dosing group, these abnormal spots were dramatically decreased compared to that of equal dosage group of dried MP extract-dosing group. Dosage-dependently increase of degrees of enlargement and congestion detected in the liver of dried MP extract-dosing groups, were also detected in modified and dried MP extract-dosing groups at 2,000 and 1,000 mg/kg-dosing group. However, below 500 mg/kg-dosing group, these abnormal signs were dramatically decreased compared to that of equal dosage group of dried MP extract-dosing group. Dosage-dependently increase of serum gastrin levels of dried MP extract-dosing groups, were also detected in modified and dried MP extract-dosing groups at 2,000 and 1,000 mg/kg-dosing group. However, below 500 mg/kg-dosing group, these abnormal increase were dramatically decreased compared to that of equal dosage group of dried MP extract-dosing group. Dosage-dependently increase of serum somatostatin levels of dried MP extract-dosing groups, were also detected in modified and dried MP extract-dosing groups at 2,000 and 1,000 mg/kg-dosing group. However, below 500 mg/kg-dosing group, these abnormal increase were dramatically decreased compared to that of equal dosage group of dried MP extract-dosing group. Conclusions ： The toxicity of dried MP extract was reduced by their modify.

• 혜화의학회지
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• 제22권1호
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• pp.119-128
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• 2013

Objectives: Yijin-tang-gamibang has been used in the Korean Medicine for treating various digestive disease. This study was aimed to investigate the effects and safety of Yijin-tang-gamibang in reflux esophagitis through the analysis of articles. Method: A total of 9 articles about Yijin-tang-gamibang and reflux esophagitis were used to develop this article. Results: According to basic research and clinic research data, it is supported that Yijin-tang-gamibang was useful prescription in reflux esophagitis. Yijin-tang-gamibang has favorable protective effects on the reflux esophagitis induced by pylorus and forestomach ligation in rats. After treatment with Yijin-tang-gamibang, patients showed improvement in all symptoms associated with reflux esophagitis and functional dyspepsia, including general condition. And Yijin-tang-gamibang did not show any toxic effect in single oral dose toxicity test. Conclusion: The results of this study suggest that Yijin-tang-gamibang showed favorable protective effects on the reflux esophagitis. However, it proved insufficient to confirm its efficacy owing to lack of clinical studies of high quality. So, we need well designed studies to verify clinical efficacy of Yijin-tang-gamibang hereafter.

• Applied Biological Chemistry
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• 제18권2호
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• pp.71-97
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• 1975

To improve the food qualities in Korea, two hundred and fourtynine kinds of food additives have been allowed in food processing, of which one hundred and nineteen kinds could be used under the limitted conditions. Hence, in practical uses in food processing, many kinds of them are mixed at random within the permitted amounts for their special purposes. For last several years, many kinds of the food additives were prohibited because they have been proved to be toxic even with the single dose. Until recently a few studies on the toxicity in the mixture of food additives were reported, however, they were shown to be no severe additional effect on the animal. This study was performed to see if any elevation of chronic or subacute toxicity of food additives occur especially when they are mixed with each other, using three kinds of food additives (DHA, AF-2, BHT) most widely used as food preservatives, antiseptics and antioxidants. One hundred and fifty young male rats were taken and divided into ten feeding groups, one first control group (food additives blank), three second control groups (DHA 0.1%, AF-2 0.1%, BHT 0.5%), three mixture groups of low level (mixture of each 60% of two second control level) and three mixture groups of high level (mixture of each 90% of two second control level). As the methods of biological and clinical tests, the change of body weight (growth rate), daily intake of diets, organ to body weight ratio, histopathological findings of organs, hematological observation, liver and kidney function tests were checked three times during the periods of 24 weeks. The following results were obtained. 1. The low level group of DHA, AF-2 mixture and DHA, BHT mixture revealed a little retardation in growth rate than the first control group, however, they were similar to the second controls, while all the mixture groups of high level showed a more remarkable retardation than the first and second controls. 2. Average daily intake of the diets was the same in each group, showing a similar decreasing tendency (70-100g/kg of body weight) in accordance with the growth rate. It was observed that there are no differences in the taste and appetite in each group of rats. 3. Abnormal enlargements of kidney and lung were not seen in all the mixture groups compared with the controls, while a slight hepatomegaly was observed in all mixture groups of low level as in the second controls. Significant differences (almost 1% level) were observed between the high level groups and the first control group. 4. Histopathological effects of the food additives on lung, kidney and liver tissues were found in all mixture group of high level. The less frequencies of the same effects were also seen in the low level groups. 5. The esterified cholesterol to total cholesterol ratio in the mixture groups of high level showed a little lower values, and the activities of serum glutamate oxaloacetate transaminase and alkaline phosphatase decreased almost with significance of 5% level compared with the first control group. The serum A/G ratio in the mixture groups also decreased. The results demonstrated that the liver function was decreased in the mixture groups compared with the controls. 6. In all groups throughout the test period, kidney functions (concentration of protein and creatinine excreated per hour in urine and renal filtration rate) were shown almost as normal as the first control. 7. Average values of hematocrit, erythrocytes and leucocytes in the mixture groups were in the normal ranges as in the controls, which denotes that the production of blood cells in bone marrow were also normal in all groups. With the above results, it is concluded that when the food additives (DHA, AF-2, BHT) were given together to the rats in several combinations even in less amount, they showed more toxic signs than the single doses.