• Title/Summary/Keyword: 독성시험 방법

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A Study on DNA Degeneration by Comet Assay & Pathological Observation for Mouse Which were Exposed HCN Gases from Fire (화재로 인한 HCN 가스에 노출된 마우스의 병리학적 관찰 및 단세포 전기영동법을 사용한 DNA 변성 추적에 관한 연구)

  • Cho, Nam-Wook;Oh, Eun-Ha;Hwang, Sung-Kwy
    • Journal of the Korean Institute of Gas
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    • v.16 no.6
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    • pp.7-16
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    • 2012
  • Combustion Toxic Effects among several factors of risk encountered during fire are important in the evacuation and final survival, and they are broader and fatal than the direct damages caused by flame. Most studies on fire toxicity until the present are limited to fatality, mainly deaths by fire through pathological research. In this study, it is conducted as a fundamental experiment to address 3 principles of animal experiment and to provide an alternative test to animal testing that is regulated by national building codes and it was conducted through approval by the animal testing ethics committee. Hence, in this study average time of activity stop was measured after directly inhaling toxic gases (HCN) to laboratory animals (mice) through gas toxicity test (KS F 2271) for major asphyxiating gases(HCN) which are produced during fire combustion. effects of Combustion toxic gases on body were quantitatively analyzed through changes in internal organs and hematological analysis, and electrophoresis of a single cell of these laboratory animals. Biological conclusion of combustion toxicology is drawn through approaches (pathological examination, blood test, blood biochemical test, electrophoresis analysis of single cell) which could not confirmed in existing gas toxicity test.

Issues in 2-year Long-term in vivo Carcinogenicity Assay (2년 장기 발암성 검색법의 이슈)

  • Son, Woo-Chan;Kim, Bae-Hwan;Jang, Dong-Deuk;Han, Beom-Seok;Kim, Jong-Choon;Lee, Je-Bong;Shin, Jin-Sup;Kim, Hyoung-Chin
    • The Korean Journal of Pesticide Science
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    • v.8 no.4
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    • pp.239-254
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    • 2004
  • It has been debating about conducting and interpretating of 2-year rodent carcinogenicity bioassay. Although some criticisms arising in usefulness, it has been still known that long-term carcinogenicity studies using rodents would be the only assay system to predict any possible human risks, which would not be replaced. Both regulatory agencies and academies have developed some assay models, however, there have been controversy whether those study designs and interpretations are based on sound scientific rationale and validated data. Such kinds of issues including choice of species/strain, dose level selection, duration of study, number of animals per group, historical control data, monitoring parameters, terminal investigations, peer review, statistics, alternative assay models, interpretation of neoplastic lesions, and risk assessments, were reviewed.

Genome Type Analysis of Human Adenoviruses Associated with Pediatric Gastroenteritis in Korea (소아장염을 유발하는 한국형 아데노바이러스들의 지놈형별)

  • Kim, Hee-Jin;Yang, Jai-Myung;Kim, Kyung-Hee
    • The Journal of Korean Society of Virology
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    • v.26 no.1
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    • pp.23-30
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    • 1996
  • 대략 36,000 base pairs (bp)의 두 가닥짜리 DNA를 지놈으로 가진 사람 아데노바이러스 (Ad)는 DNA 상동성(相同性) 및 생물학적/생화학적 성격이 특이한 49개의 혈청형이 알려져 있는데, 이들 대부분의 Ad가 영유아군 및 면역능이 저하된 성인에서 치사적 결과를 초래할 수 있다. Ad의 세포향성(向性)(tropism)은 매우 다양하여 종류에 따라 상기도 감염, 각결막염, 영유아 장염등을 유발하는데 최근 Ad의 다양한 병원성에 대한 원인을 분자생물학적 수준에서 규명하려는 노력의 일환으로 지역에 따라 주되게 출현하는 Ad형 규명이 활발히 이루어지고 있다. Ad 동정/확인은 표면을 이루고 있는 group 공통항원인 hexon 단백질을 탐지하는 효소면역 측정법 (EIA)에 의하며, Ad형별은 Ad fiber의 세포독성 중화시험에의 한다. 그러나, 세포독성 중화시험이 엄청난 노동력 및 시간을 요구하면서도 민감도/특이도가 만족스럽지 못하여 이를 개선하기 위하여 검체 또는 세포배양에서 Ad DNA를 추출하여 제한효소 절단형태를 비교하는 방법이 개발되었는데 이는 세포배양에 잘 자라지 않는 바이러스주의 형별뿐만 아니라 지역 분리주들의 지놈 변형주를 관찰하는 분자생물학적/분자역학적 연구에도 도움이 되고 있다. 국내에는 Ad와 관련된 소아장염의 빈도가 rotavirus에 의한 것 다음으로 빈번한데도 Ad40/41외에 주되게 출현하는 장내 Ad형들이 전혀 규명된 바 없고, 한국형 Ad들의 지놈형태가 전혀 보고된 바가 없다. 또한 세계적으로 Ad형별 조사지역이 늘어감에 따라 유아장염과 연관된 Ad 역시 Ad40, 41이 외의 형들이 Ad40, 41을 능가하는 것으로 보고되고 있는 지역도 있으나 국내에서는 Ad40, 41이외의 형들은 그 역학적 중요도가 전혀 알려져 있지 않다. 이로서 본 연구의 목적은 Ad주들에 특이 중화항체를 이용한 세포독성 중화시험과 Ad DNA 절단법을 적용하여 한국형 장내 Ad주들의 형별을 처음으로 시도함과 동시에 1989-1991사이 출현한 Ad들의 유전적 변형을 관찰하려는 것이었다. 두 방법 모두 사용하였을 때 주되게 출현하는 장내 Ad형들은 Ad4l, Ad2, Ad7, Ad5, 및 Ad40이었다. Ad40/41-양성 검체를 제외한 Ad hexon-EIA양성들의 77.5%를 형별 할 수 있었던 Ad DNA의 제한효소 절단방법은 형들간의 교차중화로 특이성이 낮았던 중화방법 (47.5%)보다 매우 효율적이어서 두 가지 방법을 함께 적응하였을 때는 40주중의 81.5%인 35주를 형별 할 수 있었다. 또한Ad DNA 제한 효소 절단방법은 Ad7 변이주 (Ad7b)도 탐지 할 수 있었다.

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Stability in Effects of ${\gamma}$-Irradiated Chinese Medicinal Prescriptions on Protection of Mice from Radiation (감마선조사 한약의 방사선방호 효능 안정성)

  • 양정아;김성호;김세라;유영법;조성기
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.29 no.3
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    • pp.506-512
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    • 2000
  • 건조 농산물을 비롯한 식품에 대한 방사선 조사가 허가, 시행되고 있으며, 그 적용 범위도 확대되고 있다. 이에 따라 건조 생약재의 위생화의 대체방법으로 방사선 조사 기술의 적용이 산업계로부터 요구되고 있다. 본 연구는 감마선 조사 생약재의 효능 변화 유무를 확인하기 위한 일환으로 수행되었다. 저자 등은 사물탕, 보중익기탕 및 삼령백출산 등이 방사선 방호 효과를 보이는 것으로 이미 보고한 바 있다. 본 실험에서는 감마선 조사(10 kGy)한 이들 한약제 각각의 방사선 방호 효과를 비조사 시료와 비교 평가하였다. 효과평가를 위하여 방사선 조사 마우스에서 소장움 생존시험, 내재성 비장집락 형성시험 및 apoptosis 측정을 시행하였다. 각 한약제의 감마선 조사 시료는 3가지 시험 모두에서 비조사 시료와 유사한 효과를 나타내었으며(p<0.05), 생체내 독성도 나타내지 않았다. 이는 생약재의 여러 가지 고유 효능 중 일부의 안정성으르 확인한 것으로 생각되며, 이 결과로 미루어 보아 감마선 조사 생약재의 효능 안정성은 한의학적 고유의 효능 비교 평가를 통하여 확인될 수 있을 것으로 사료된다. 한편, 저자 등은 감마선 조사 생약재의 유효성분 안정성 및 유전 독성학적 안전성을 확인하여 보고한 바 있다. 이들 결과를 토대로 향후 감마선 조사 행약재의 고유 효능의 안정성에 관한 체계적인 연구결과를 얻는다면 생약재의 위생화 수단으로 감마선 조사기술의 이용이 실용화될 수 있을 것으로 사료된다.

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Adjusted maximum tolerated dose estimation by stopping rule in phaseⅠclinical trial (제 1상 임상시험에서 멈춤 규칙을 이용한 수정된 최대허용용량 추정법)

  • Park, Ju Hee;Kim, Dongjae
    • Journal of the Korean Data and Information Science Society
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    • v.23 no.6
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    • pp.1085-1091
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    • 2012
  • Phase I clinical trials are designed to identify an appropriate dose; the maximum tolerated dose, which assures safety of a new drug by evaluating the toxicity at each dose-level. The adjusted maximum tolerated dose estimation is presented by stopping rule in phase I clinical trial on this research. The suggested maximum tolerated dose estimation is compared to the standard method3 and NM method using a Monte Carlo simulation study.

A Study on the Toxic Gases and Smoke Hazard of PASCON Trough (파스콘 트로프의 연기유독성에 관한 연구)

  • Lee, Chang-Woo;Hyun, Seong-Ho;Choi, Don-Mook
    • Fire Science and Engineering
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    • v.20 no.2 s.62
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    • pp.1-7
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    • 2006
  • The aim of the research is to estimate the effect of smoke and combustion gases on humane body indirectly through measuring the toxicity of those. For this purpose, the toxic index of smoke and combustion gases was investigated by smoke hazard test and analysis of smoke which were conducted by KS F 2271 and NES 713 method respectively. It i s proved by KS F 2271 method that PASCON trough is suitable to the testing standard of interior material and construction of building. In addition, it is identified by NES 713 method that combustion gases occurring in PASCON product were only carbon dioxide and carbon monoxide, and the smoke index of those was 0.944. This value means that the hazard effect of smoke gases on humane ! body can possibly happens when exposed to the smoke gases for more than 30 min. In aspect of the domestic situation that have not regulated the hazard estimation and the emissions of smoke when the flame retarding ability of the products have been requested, the toxic indexes of PASCON products are comparatively low.

Development and Research into Functional Foods from Hydrolyzed Whey Protein Powder with Sialic Acid as Its Index Component - I. Repeated 90-day Oral Administration Toxicity Test using Rats Administered Hydrolyzed Whey Protein Powder containing Normal Concentration of Sialic Acid (7%) with Enzyme Separation Method - (Sialic Acid를 지표성분으로 하는 유청가수분해단백분말의 기능성식품 개발연구 - I. 효소분리로 7% Siailc Acid가 표준적으로 함유된 유청가수분해단백분말(7%)의 랫드를 이용한 90일 반복경구투여 독성시험 평가 연구 -)

  • Noh, Hye-Ji;Cho, Hyang-Hyun;Kim, Hee-Kyong
    • Journal of Dairy Science and Biotechnology
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    • v.34 no.2
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    • pp.99-116
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    • 2016
  • We herein performed animal safety assessment in accordance with Good Laboratory Practice (GLP) regulations with the aim of developing sialic acid from glycomacropeptide (hereafter referred to as "GMP") as an index ingredient and functional component in functional foods. GMP is a type of whey protein derived from milk and a safe food, with multiple functions, such as antiviral activity. A test substance was produced containing 7% (w/w) sialic acid and mostly-hydrolyzed whey protein (hereafter referred to as "7%-GNANA") by enzymatic treatment of substrate GMP. The maximum intake test dose level was selected based on 5,000 mg/kg/day dose set for male NOEL (no-observed-effect-level) and female NOAEL (no-observed-adverse-effect-level) determined by a dose-range finding (DRF) test (GLP Center of Catholic University of Daegu, Report No. 15-NREO-001) that was previously conducted with the same test substance. To evaluate the toxicity of a repeated oral dose of the test substance in connection with the previous DRF study, 1,250, 2,500, and 5,000 mg/kg of the substance were administered by a probe into the stomachs of 6-week-old SPF Sprague-Dawley male and female rats for 90 d. Each test group consisted of 10 male and 10 female rats. To determine the toxicity index, all parameters, such as observation of common signs; measurements of body weight and food consumption; ophthalmic examination; urinalysis, electrolyte, hematological, and serum biochemical examination; measurement of organ weights during autopsy; and visual and histopathological examinations were conducted according to GLP standards. After evaluating the results based on the test toxicity assessment criteria, it was determined that NOAEL of the test substance, 7%-GNANA, was 5,000 mg/kg/day, for both male and female rats. No animal death was noted in any of the test groups, including the control group, during the study period, and there was no significant difference associated with test substance, as compared with the control group, with respect to general symptoms, body weight changes, food consumption, ophthalmic examination, urinalysis, hematological and serum biochemical examination, and electrolyte and blood coagulation tests during the administration period (P<0.05). As assessed by the effects of the test substance on organ weights, food consumption, autopsy, and histopathological safety, change in kidney weight as an indicator of male NOAEL revealed up to 20% kidney weight increase in the high-dose group (5,000 mg/kg/day) compared with the change in the control group. However, it was concluded that this effect of the test substance was minor. In the case of female rats, reduction of food consumption, increase of kidney weight, and decrease of thymus weight were observed in the high-dose group. The kidney weight increased by 10.2% (left) and 8.9% (right) in the high-dose group, with a slight dose-dependency compared with that of the control group. It was observed that the thymus weight decreased by 25.3% in the high-dose group, but it was a minor test substance-associated effect. During the autopsy, botryoid tumor was detected on the ribs of one subject in the high-dose group, but we concluded that the tumor has been caused by a naturally occurring (non-test) substance. Histopathological examination revealed lesions on the kidney, liver, spleen, and other organs in the low-dose test group. Since these lesions were considered a separate phenomenon, or naturally occurring and associated with aging, it was checked whether any target organ showed clear symptoms caused by the test substance. In conclusion, different concentrations of the test substance were fed to rats and, consequently, it was verified that only a minor effect was associated with the test substance in the high-dose (5,000 mg/kg/day) group of both male and female rats, without any other significant effects associated with the test substance. Therefore, it was concluded that NOAEL of 7%-GNANA (product name: Helicobactrol) with male and female rats as test animals was 5,000 mg/kg/day, and it thus was determined that the substance is safe for the ultimate use as an ingredient of health functional foods.

Invirto alternatives to photosensitization Test (광감작성 시험에서의 동물대체 시험법)

  • Lee, Ho;Nam, Ki-Taek;Koh, Jae-Sook;Park, Won-Jae
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.22 no.1
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    • pp.84-101
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    • 1996
  • To minimize the use of animals in toxicity testing, and to reduce the cost in vivo test, more rational test method was described which determines, in the same animal, photoxic and photoallergic potential of a substance, and is daptable to routine testing. The other purpose of this study was to investigate the usefulness of in vivo alternatives ; photostability and spectrophotometric carbonyl assay. In this modified photosensitization model, animal numbers and resting periods, the number and method of topical application were simplified. Two positive photoreactive agents, Benzocaine and 6-methyl coumarine, showed a similar photoallergic potential to that of Ichikawa's method. Two sunscreens, Octyl methoxy cinnamate, Butyl methoxyl dibenzoyl methane, hardly showed photoallergic potentials. The photostability test could be used in the step of prescreening of photosensitization potential because most of the photoreactive agents represented the reduction of more than 20% in the absorbance. And photoreactive agents have a high potential of photosensitization in the sddessment of spectrophotometric carbonyl level although two sunscreens have a low possibility of photosensitization. Therefore this method was assumed as a valuable in vivo alternatives in the respect even in the very low concentrations which phototoxicity test using almonella showed no phototoxic potential.

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Comparison of the performance of classification algorithms using cytotoxicity data (세포독성 자료를 이용한 분류 알고리즘 성능 비교)

  • Yoon, Yeochang;Jeung, Eui Bae;Jo, Na Rae;Ju, Su In;Lee, Sung Duck
    • The Korean Journal of Applied Statistics
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    • v.31 no.3
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    • pp.417-426
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    • 2018
  • An alternative developmental toxicity test using mouse embryonic stem cell derived embryoid bodies has been developed. This alternative method is not to administer chemicals to animals, but to treat chemicals with cells. This study suggests the use of Discriminant Analysis, Support Vector Machine, Artificial Neural Network and k-Nearest Neighbor. Algorithm performance was compared with accuracy and a weighted Cohen's kappa coefficient. In application, various classification techniques were applied to cytotoxicity data to classify drug toxicity and compare the results.

STUDIES ON CYTOTOXICITY AND ANTITUMOR ACTIVITY OF KOREAN PHARMACEUTICAL HERBS

  • Ryeom, Kon;Lee, Young-Kee;Shin, Suck-Woo;Jung, Byung-Ki
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1995.04a
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    • pp.62-62
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    • 1995
  • 한국산 천연자원중 한방이나 민간요법에서 항종양제로 빈번히 사용되어온 생약들 중에서 103종을 선정하여 이들 성분들을 추출하고 시험관내에서 항종양성이 우수하고 정상세포에 손상을 적게 주는 생약 6종을 선별하여 암세포주에 대한 독성능 (in vitro)과 항종양성 면역감시기구(in vivo)및 LD$_{50}$등을 측정하여 항종양제로의 신약개발을 목적으로 수행하였다. 방법: 선별된 6종의 생약유효성분을 METHANOL로 추출하여 조추출물을 얻었으며 이물질들을 순차적으로 각각의 유기용매로 추출, column chromatography법으로 분획하였으며 분획분에 대한 암세포독성능은 MTT colorimetric 검정법을 이용하여 IC$_{50}$값을 구하였다. 면역감시기구 측정방범으로는 Balb/c mouae암,수 각 10수씩에 P388암세포주를 접종한군과 접종하지 않은 실험군에 생약추출분획물 8.6mg/0.2ml씩 20일간 매일 경구 투여시키고 대조군에는 생리식염수 0.2ml씩을 매일 경구 투여시켜 NK cell의 활성 MIF Recombinant IL-2로 유도시킨 NK cell활성능, chemotaxis등을 측정하였다. 생체내 항종양능 시험은 tumor panel system에 따라 mouse leukemia cell을 사용하여 측정하였다. 각분획성분의 투여용량은 실험동물에서 독성실험결과로 LD$_{50}$량을 구해 항암효과 평가시에 Maximum dose로 하였고 최고용량을 기준으로 일정한 공비를 적응하여 3단계의 투여량을 설정하였다. (중략)

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