• 한국미생물·생명공학회지
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• 제22권3호
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• pp.290-295
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• 1994

Micelle, liposome and polyethylene glycol(PEG) were employed to reduce the cell mem- brane toxicity of Amphotericin B(Amp. B). Cholesterol-sulfate which can form a mixed micelle with Amp. B molecules was found very effective for the reduction of Amp. B toxicity. 0.01% of cholesterol-sulfate could reduce the toxicity of 5X 10$^{-6}$ M Amp. B by 90%. The required concent- ration of cholesterol-sulfate for the toxicity reduction was proportionally increased with increasing Amp. B concentration. PEG was also effective on the reduction of Amp. B toxicity. 2% PEG was required for the reduction of toxicity by 50%, regardless of Amp. B concentration. The liposome system showed an effective reduction of Amp. B toxicity on RBC, maintaining the antibiotic effect on Candida albicans as free drugs. This seems to be due to the fact that liposome bilayer plays a role of buffer system between ergosterol of fungi cell membrane and cholesterol of red blood cell membrane, which leads the redistribution of Amp. B between them, as the result, the reduction of drug toxicity on cell membrane.

• Toxicological Research
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• 제35권4호
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• pp.343-351
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• 2019

Many in vitro developmental toxicity assays have been proposed over several decades. Since the late 1980s, we have made intermittent attempts to introduce in vitro assays as screening tests for developmental toxicity of inhouse candidate products. Two cell-based assays which were developed two decades apart were intensively studied. One was an assay of inhibitory effects on mouse ascites tumor cell attachment to a concanavalin A-coated plastic sheet surface (MOT assay), which we studied in the early days of assay development. The other was an assay of inhibitory effects on the differentiation of mouse embryonic stem cell to beating heart cells (EST assay), which we assessed more recently. We evaluated the suitability of the assays for screening in-house candidates. The concordance rates with in vivo developmental toxicity were at the 60% level. The EST assay classified chemicals that inhibited cell proliferation as embryo-toxic. Both assays had a significant false positive rate. The assays were generally considered unsuitable for screening the developmental toxicity of our candidate compounds. Recent test systems adopt advanced technologies. Despite such evolution of materials and methods, the concordance rates of the EST and MOT systems were similar. This may suggest that the fundamental predictivity of in vitro developmental toxicity assays has remained basically unchanged for decades. To improve their predictivity, in vitro developmental toxicity assays should be strictly based on elucidated pathogenetic mechanisms of developmental toxicity.

• 대한약침학회지
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• 제5권1호
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• pp.61-79
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• 2002

Objective: The purpose of this study was to investigate acute and subacute toxicity and sarcoma-180 anti-cancer effects of Herbal acupuncture with Anneniacae amarum semen (Haeng-in) in mice and rats. Method: Balble mice were injected intraperitoneany with Haeng-In extract for $LD_{50}$ and acute toxicity test. Sprague-Dawley rats were injected intraperitoneally with Haeng-In extract for subacute toxicity test. TheAnneniacae amarum semen Herbal-Acupuncture was injected on Chung-wan (CV12) of mice with Sarcoma-180 cancer cell line. Results: 1. $LD_{50}$ was uncountable as none of the subjects expired from the treatment groups during the test. 2. The clinical signs and the body weight of mice treated with 0.1cc and 0.2cc Haeng-In extract were not affected during the acute toxicity test. 3. In acute toxicity test of serum biochemical values of mice, total protein and albumin were decreased in treatment group Ⅰ. Glucose was increased, and total cholesterol was decreased in treatment groups. GPT was increased in treatment group Ⅰ. 4. In subacute toxicity test, toxic symptoms were not detected in the treatment groups. 5. In subacute toxicity test, the body weight was increased in treatment groups on 14th and 21st day. 6. In subacute toxicity test. liver weight was increased in treatment group Ⅱ, and spleen weight was increased in treatment group Ⅱ. Lung weight was increased in an the treatment groups.(p<0.05) 7. In subacute toxicity test, severe tissue injury was found in lung and liver, especially treatment group Ⅰshowed more significant lung damage compared to treatment group l. 8. In subacute toxicity test, WBC. MCH and MCHC were increased in an the treatment groups, RBC, HGB and HCT were decreased in treatment group H(p<0.05). 9. In subacute toxicity test of serum biochemical values of rats, triglyceride was decreased in all the treatment groups. ALP was decreased in treatment group Ⅰ. and creatinine was decreased in treatment group Ⅱ. BUN/CR was increased in treatment group Ⅱ(p<0.05). 10. Median survival time of Sarcoma-180 cancer cell treated with Haeng-In was increased in all the treatment groups by twenty percent, compared to the control group(p<0.05). 11. Natural killer cell activity about the Sarcoma-180 cell was decreased at the ratio of 100:1 but was increased at the ratio of 10:1. In treatment group Ⅱ, increase was found at the ratio of 100:1 and 50:1 (p<0.05). 12. Interleukin-2 productivity of the Sarcoma-180 cell was decreased in treatment group I, but was increased in treatment group Ⅱ(p<0.05). Conclusion: According to the results, we can conclude Herbal-acupuncture with Anneniacae amarum semen caused toxicity, and had effects in Sarcoma-180 cancer cell.

• 대한본초학회지
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• 제20권2호
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• pp.1-6
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• 2005

Objectives : The purpose of this study is to investigate genetic toxicity of Cervi pantotrichum Cornu herbal acupuncture solution(CPCHA). Methods : In this study, a series of investigation have been carried out to analyze the effects of Cervi pantotrichum Cornu herball acupuncture solution(CPCHA) on colony forming ability of NIH3T3cells, Hela cells and adrenorectal coloncell for genetic toxicity test. Results and Conclusions : From the above results, it is suggested that Cervi pantotrichum Cornu herball acupuncture solution(CPCHA) was limited 0.5-10ug/ml by test. Cervi pantotrichum Cornu herball acupuncture solution(CPCHA) did not exert the protective role to the genetic toxicity in kinds of cell lines used in this study. From these results, Cervi pantotrichum Cornu herbal aqua-acupuncture solution needs further study to prove it's function in cell culture system.

• Toxicological Research
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• 제17권4호
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• pp.267-272
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• 2001

This study was carried out to assess the reproductive toxicity of 2-bromopropane (S-BP) using spermatogenesis stage classification and Sertoli cell indices (SCI).Vehicle control olive oil and 2-BP doses of 125, 250 and 500 mg/kg of body weight were injected in the interaperitoneum of 12 weeks male Sprague-Dawley rats for 28 days respectively of SCI on germ cells including the spermatogonia of stages II-III, Ⅵ,Ⅹ, XII, ⅩIII, and spermatocytes of stages VIII (preleptotene), Ⅹ (leptotene), XII (leptotene), V and Ⅵ (pachytene), and the round spermatids of stage Ⅵ. Considering the process of maturation depletion in spermatonesis, spermatogonia may be the primary target cells of 2-BP toxicity.

• 한국독성학회:학술대회논문집
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• 한국독성학회 2006년도 추계학술대회
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• pp.95-101
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• 2006

Compare to the toxicity tests using experimental animals, the GLP application and compliance in toxicity studies using cell culture systems may be less straightforward elucidated in the two documents published by the OECD Working Croup on GLP 'The Application of the GLP Principles to Short Term Studies (1999)' and 'The Application of the Principles of GLP to in vitro Studies (2004)' The object of this presentation is to show how to interpret the GLP principles and to apply with actual performances in a well known toxicity test using cell culture, chromosome aberration study. The presentation will cover test substance, test system (cell line), study environment management, documentation, quality assurance, and study protocol and report.

• 대한약침학회지
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• 제5권1호
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• pp.7-26
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• 2002

Objective: The purpose of this study was to investigate acute and subacute toxicity and sarcoma-180 anti-cancer effects of herbal acupuncture with Carthami- Tinctorii fructus (CF) in mice and rats. Method: Balb/c mice were injected intraperitoneally with Carthami - Tinctorii fructus (CF) for $LD_{50}$ and acute toxicity test. Sprague Dawley rats were injected intraperitoneally with Carthami- Tinctorii fructus (CF) for subacute toxicity test. The Carthami- Tinctorii fructus herbal-acupuncture was injected on Chung-wan (CV12) of mice with Sarcoma-180 cancer cell line. Results: 1. $LD_{50}$ was uncountable as none of the subjects expired during the test. 2. In acute toxicity test, toxic symptoms were not detected, but the body weight of mice was increased in treatment Ⅰ, treatment Ⅱ groups, compared to the normal group.(p<0.05) 3. In acute toxicity test of serum biochemical values of mice, glucose was increased in treatment Ⅰ and treatment Ⅱ groups, total cholesterol was increased in treatment I group, GOT was decreased in treatment Ⅱ group, and GPT was decreased in treatment Ⅰ group, compared to the normal group.(p<0.05) 4. The clinical signs and the body weight of mice treated with 0.1 cc, 0.2cc Carthami- Tinctorii fructus (CF) were not affected during the subacute toxicity test. 5. In subacute toxicity test, treatment groups didn't show significant changes in complete blood count test (CBC) of rats, compared to the nonnal group.(p<0.05) 6. In subacute toxicity test of serum biochemical values of rats, uric acid was decreased in treatment Ⅰ and treatment Ⅱ groups, compared to the nonnal group, triglyceride was decreased in treatment I group, compared to the normal group, GOT and GPT were decreased in treatment I and treatment Ⅱ groups, and alkaline phosphatase was decreased in treatment Ⅰ and treatment Ⅱ groups, compared to the normal group.(p<0.05) 7. Median survival time was increased in all the treatment groups for Sarcoma-180 cancer cell treated with Carthmni- Tinctorii fructus (CF).(p<0.05) 8. Natural killer cell activity was significantly increased in all the treatment groups compared to the normal group.(p<0.05) 9. Interleukin-2 productivity was decreased in treatment Ⅰ and treatment Ⅱ groups.(p<0.05) Conclusion: According to the results, we can conclude herbal-acupuncture of Carthami-Tinctoriifructus (CF) caused negligible toxkity, and had anti-tumor effects in mice.

• 대한약침학회지
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• 제5권2호
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• pp.120-136
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• 2002

Objectives : The purpose of this study is to investigate Acute and Subacute Toxicity, and Anti-cancer Effect of H Herbal-acupuncture on mice and rats. Methods : Balb/c mice were injected intraperitoneally with H Herbal-acupuncture for $LD_{50}$ and acute toxicity test. Sprague-Dawley rats were experimented in the same way for subacute toxicity test. H Herbal-acupuncture was injected into abdomen of mice having S-180 cancer cell line. Result : 1. During the test, $LD_{50}$ could not be counted since there was no expired subjects. 2. In an acute toxicity test, the loss of motility and reflex action was observed, but weight increased in the treatment group, compared with those in the normal group (P<0.05). 3. In an acute toxicity test of serum biochemical values of mice, glucose increased in the treatment group II while total cholesterol was increased in the all treatment groups (P<0.05). 4. In a subacute toxicity test, a little loss of motility and reflex action was observed in the treatment group. Weight of mice in the treatment group decreased on the 28th day. 5. In a subacute toxicity test, liver weight was decreased but lung weight of mice increased in the all treatment groups (P<0.05). 6. As a result of measuring Complete Blood Count test (CBC) of rat, HCT was decreased in treatments even though it was not significant, compared with the normal group (P<0.05). 7. In a serum biochemical value test of subacute toxicity, total protein and albumin decreased in the all treatment groups. Creatinine, glucose, GOT increased in the treatment group I compared with the control group. Alkaline phos-phatase decreased in treatment II group, compared with the control group (P<0.05). 8. Median survival time that was measured in the rats treated with sarcoma-180 cancer cell Median decreased in the treatment group, compared with the control group (P<0.05). 9. Natural killer cell activity showed significant reduction at 100:1 and 10:1 E/T ratio while it increased at 50:1 E/T ratio. It is inferred that there was an error in the experiment (P<0.05). 10. In an interleukin-2 productivity test, even though it decreased in lung cancer, and increased in abdomen cancer, but it was only a small difference (P<0.005). 11. After injecting B16F10 cell into a capillary vessel of C57BL/6 mice and generating metastasized lung cancer, the lung was examined with the naked eye. It was not possible to see metastasized cancer in the all groups on the seventh day but the cancer was viewed on the fourteenth day. The number and volume of metastasized cancer in the treatment group enlarged in the treatment group, compared with the control group. Conclusion : According to the results, H herbal-acupuncture took no effects in cancer.

• 대한한의학회지
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• 제21권3호
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• pp.199-208
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• 2000

Objectives : In order to investigate the toxicity of rats after oral administration of Eumcheonyijin-tang extract. Methods : The experimental animals were subdivided into control, short term administration group, and long term administration group. With changes of gross appearance, the histological changes of liver and kidney were observed. Blood chemical indexes used in this study were AST, ALT, total bilirubin, albumin, BUN and creatinine in serum. Results : In the long term administration group, histological changes were detected in the liver as centrolobular disposition of fatty tissue(adipose cell), and in serum test, AST, ALT increased at 21 days after administration group, serum total bilirubin were increased 21, 28 and 35 days after administration group. So it seems to induce toxicity. Kidneys of the long term administration group revealed histological changes : increasing of connective tissue and pyknosis of glomerulus cell were observed at 28 days after administration group, and in serum test, significant changes of albumin, BUN, and creatinine were admitted. So it seems to induce toxicity. Conclusions : In long term administration of Eumcheonyijin-tang toxicity was induced.

• 상하수도학회지
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• 제19권5호
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• pp.639-646
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• 2005

In this research, we tried to develop the application method to water management and treatment using toxicity test method. When we measure the toxicity of environmental samples, we have to decide whether we take some countermeasures to reduce the toxicity or not. The first issue is how to set these action levels in each bioassays. A new idea was attempted to authorize indirect approach of each bioassays through the response characteristics against mixture of chemicals in water quality standard. The significant response in the cell-growth-inhibition bioassay was detected for standards-mixture(STDs). For acute toxicity assay, STDs-based implicit correlation between risks to humans and bioassay data showed a rational approach to set action levels in practical management. A simple model was proposed to describe and predict the changes in the total toxicity based on the concentrations of toxic-controlling chemicals during the ozonation of landfill leachates. On the basis of this simple model, toxicity reduction was predicted for pre-aggregation treatment before ozonation and ozone concentration during the ozonation. The method proposed in this study would be useful in optimizing water treatment processes and their running conditions in terms of the toxicity reduction efficacy.