• Title/Summary/Keyword: Carcinogenicity

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A Study on the Selection of Reliable Carcinogenic Inhalation Toxicity Test Substances (발암성 흡입독성 시험물질선정 신뢰도 향상방안에 관한 연구)

  • Cho, Jung-Rae;Rim, Kyung-Taek;Lee, Jong-Ho
    • Journal of Korean Society of Occupational and Environmental Hygiene
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    • v.31 no.3
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    • pp.185-193
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    • 2021
  • Objectives: Inhalation toxicity testing of chemical substances to identify carcinogenicity requires a long time and considerable cost, so the selection of test candidates is a very important aspect. This study was performed to determine optimal procedures for selecting carcinogenic inhalation toxicity test substances as conducted by the Occupational Safety and Health Research Institute (OSHRI). Methods: At the beginning, a database was constructed containing complex information such as usage amount, hazard, carcinogenicity prediction, and testability in order to select chemicals requiring carcinogenicity testing. Selection of test substances was carried out with priority given to usage, carcinogenicity, and testability. Results: Chemicals used in large quantities in industrial fields and strongly suspected of carcinogenicity were winnowed down to 12 substances, and these substances were scheduled for future testing by OSHRI. Conclusions: For the stable and reliable operation of carcinogenicity tests as conducted by OSHRI, this study standardized the procedures for selecting carcinogenicity test substances and suggested the introduction of various carcinogenicity prediction techniques.

Comparison of Notation Items for Chemical Occupational Exposure Limits (화학물질에 대한 직업적 노출기준의 표기 항목 비교)

  • Phee, Young Gyu;Kim, Seung Won;Ha, Kwonchul
    • Journal of Korean Society of Occupational and Environmental Hygiene
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    • v.30 no.2
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    • pp.226-235
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    • 2020
  • Objectives: This study was to investigate the signs and notations of skin absorption, carcinogenicity, germ cell mutagenicity, and reproductive toxicity in the occupational exposure limits of Korea and of other advanced countries. Methods: Information on occupational exposure limits in Korea, the USA, the UK, Germany, and Japan was investigated through the Internet, and items marked as carcinogenicity and skin absorption were compared by country. Results: Legal occupational exposure limits have been greatly simplified. However, in the case of HSE WEL, skin absorption, carcinogenicity classification, sensitization, and in the case of DFG MAK, skin absorption, carcinogenicity, pregnancy risk group, germ cell mutagenicity, airway and skin sensitization, photo contact sensitization, and vapor pressure were provided. Conclusions: It is desirable to indicate the carcinogenicity and skin absorption within permissible limits, and to include information on critical effects in chemical substance exposure limits to uphold the right to know of industrial hygienists and workers in Korea. It is also necessary to clarify the precautions, limitations and protections for skin absorption.

CB6F1-Tg rasH2 Mouse Carrying Human Prototype c-Ha-ras Gene As an Alternative Model For Carcinogenicity Testing For Pharmaceuticals

  • Usui, T.;Urano, K.;Suzuki, S.;Hioki, K.;Maruyama, Ch.;Tomisawa, M.;Ohnishi, Y.;Suemizu, H.;Yamamoto, S.
    • Toxicological Research
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    • v.17
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    • pp.293-297
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    • 2001
  • The international pharmaceutical and regulatory communities had been recognizing the limited utility of conventional rodent carcinogenicity study particularly on the second species, mouse, after intense investigation of carcinogenicity data base worldwide, and a new scheme for carcinogenicity testing for pharmaceuticals was proposed at the Expert Working Group on Safety in the International Conference on Harmonization (ICH) in 1996. CB6F 1-Tg rasH2 mouse carrying human prototype c-Ha-ras gene with its own promoter/enhancer is one oj the new carcinogenicity assay model for human cancer risk assessment. Studies have been conducted since 1992 to validate the transgenic (Tg) mice for rapid carcinogenicity test-ing, short term (26 weeks) studies with genotoxic (by Salmonella), non-genotoxic carcinogens, genotoxic non-carcinogens, non-genotoxic non-carcinogens revealed relatively high concordance oj the response of the Tg mouse with classical bioassay across classes of carcinogenic agents. Mechanistic basis for carcinogensis in the model are being elucidated in terms of the role of overexpression and/or point mutation of the transgene. This report review the initial studies of validation of the model and preliminary results of on-going ILSI HESI ACT project will be presented.

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Prediction of Photo-Carcinogenicity from Photo-Ames Assay (Photo-Ames Assay를 이용한 광발암성 예측)

  • Hong Mi Young;Kim Ji Young;Chung Moon Koo;Lee Michael
    • Environmental Mutagens and Carcinogens
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    • v.25 no.1
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    • pp.6-12
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    • 2005
  • Many compounds might become activated after absorption of UV light energy. In some cases, the resulting molecule may undergo further biological reaction of toxicological relevance related especially to the photo-carcinogenicity resulting from photo-genotoxicity. However, no regulatory requirements have been issued with the exception of guideline issued by the Scientific Committee of Cosmetology, Commission of the European Communities (SCC/EEC) on the testing of sunscreens for their photo-genotoxicity. Thus, the objectives of this study are to investigate the utility of photo-Ames assay for detecting photo-mutagens, and to evaluate its ability to predict rodent photo-carcinogenicity. Photo-Ames assay was performed on five test substances that demonstrated positive results in photo-carcinogenicity tests: 8-methoxypsoralen (photoactive substance that forms DNA adducts in the presence of ultraviolet A irradiation), chlorpromazine (an aliphatic phenothiazine an a-adr-energic blocking agent), lomefloxacin (an antibiotic in a class of drugs called fluoroquinolones), anthracene (a tricyclic aromatic hydrocarbon a basic substance for production of anthraquinone, dyes, pigments, insecticides, wood preservatives and coating materials) and retinoic acid (a retinoid compound closely related to vitamin A). Out of 5 test substances, 3 showed a positive outcome in photo-Ames assay. With this limited data set, an investigation into the predictive value of this photo-Ames test for determining the photo-carcinogenicity showed that photo-Ames assay has relatively low sensitivity (the ability of a test to predict carcinogenicity). Thus, to determine the use of in vitro genotoxicity tests for prediction of carcinogenicity,' several standard photo-genotoxicity assays should be compared for their suitability in detecting photo-genotoxic compounds.

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IARC Carcinogenicity Assessment for 2-Bromopropane: 28 Years after Outbreak of Reproductive Toxicity (집단생식독성 발생 28년 후 원인물질 2-bromopropane에 대한 IARC 발암성평가)

  • Il Je Yu
    • Journal of Korean Society of Occupational and Environmental Hygiene
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    • v.33 no.1
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    • pp.1-2
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    • 2023
  • 2-Bromopropane, a causative chemical that caused the outbreak of reproductive toxicity 28 years ago, was classified as Group 2A in the recently held IARC monograph 133 meeting. Korean research data were used as supporting data in the carcinogenicity evaluation of 2-bromopropane and other carcinogens. I would like to share my memories with the researchers at the Occupational Safety and Health Research Institute who worked hard to identify the cause.

A study on the criteria and supply status of information for managing carcinogens in domestic and foreign (국내외 발암성물질의 관리기준과 정보제공 현황에 관한 연구)

  • Lee, Kwon Seob;Lee, Jong Han;Lee, Hye Jin
    • Journal of Korean Society of Occupational and Environmental Hygiene
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    • v.21 no.1
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    • pp.40-48
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    • 2011
  • This study was intended to resolve problems caused by different classification criteria and management methods of carcinogenicity, which have made industrial safety & health institutions and business employers difficult to execute projects or to carry out occupational safety and health related works, and have affected how civic groups perceive carcinogens. The content of this study contained the comparison of management and categorization standards for carcinogens between Korea and other countries as well as the current carcinogenicity-related information supply status of each professional institution. Furthermore, this research examined the current state of supplying information on carcinogenicity among major institutional information supply according to the categorization standard for carcinogens by UN GHS, Ministry of Employment and Labor in Korea(KMoEL), and GHS MSDS provided by Korea Occupational Safety & Health Agency(KOSHA). Now, professional agency provide 927 kinds of IARC, 237 kinds of NTP, 351 kinds of ACGIH and 1,006 kinds of EU ECHA information on carcinogenic agents. KMoEL provides carcinogenicity-related information of 58 chemical agents in accordance with the category of carcinogens guided by ACGIH. KOSHA offers 13,232 kinds of GHS MSDS information including 2,484 carcinogenic substances. Therefore, carcinogenicity-related information of chemical substances, which are not available on the existing GHS MSDS DB, should be updated for the future reference.

Alternative Carcinogenicity Screening Assay Using Colon Cancer Stem Cells: A Quantitative PCR (qPCR)-Based Prediction System for Colon Carcinogenesis

  • Bak, Yesol;Jang, Hui-Joo;Shin, Jong-Woon;Kim, Soo-Jin;Chun, Hyun woo;Seo, Ji-Hye;No, Su-Hyun;Chae, Jung-il;Son, Dong Hee;Lee, Seung Yeoun;Hong, Jintae;Yoon, Do-Young
    • Journal of Microbiology and Biotechnology
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    • v.28 no.4
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    • pp.645-651
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    • 2018
  • The carcinogenicity of chemicals in the environment is a major concern. Recently, numerous studies have attempted to develop methods for predicting carcinogenicity, including rodent and cell-based approaches. However, rodent carcinogenicity tests for evaluating the carcinogenic potential of a chemical to humans are time-consuming and costly. This study focused on the development of an alternative method for predicting carcinogenicity using quantitative PCR (qPCR) and colon cancer stem cells. A toxicogenomic method, mRNA profiling, is useful for predicting carcinogenicity. Using microarray analysis, we optimized 16 predictive gene sets from five carcinogens (azoxymethane, 3,2'-dimethyl-4-aminobiphenyl, N-ethyl-n-nitrosourea, metronidazole, 4-(n-methyl-n-nitrosamino)-1-(3-pyridyl)-1-butanone) used to treat colon cancer stem cell samples. The 16 genes were evaluated by qPCR using 23 positive and negative carcinogens in colon cancer stem cells. Among them, six genes could differentiate between positive and negative carcinogens with a p-value of ${\leq}0.05$. Our qPCR-based prediction system for colon carcinogenesis using colon cancer stem cells is cost- and time-efficient. Thus, this qPCR-based prediction system is an alternative to in vivo carcinogenicity screening assays.

Enhanced Prediction of Potential Rodent Carcinogenicity by Utilizing Comet Assay and Apoptotic Assay in Combination

  • Lee, Michael
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2003.10b
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    • pp.95-95
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    • 2003
  • The comet assay has been recently validated as a sensitive and specific test system for the quantification of DNA damage. with 11 substances that demonstrated positive results in at least one test among 4 standard short-term genotoxicity tests, and to evaluate its ability to predict rodent carcinogenicity.(omitted)

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Assessment of Sensitivity of Photo-Chromosomal Assay in the Prediction of Photo-carcinogenicity (광염색체이상시험의 광발암성 예측능력에 대한 평가)

  • Hong Mi-Young;Kim Ji-Young;Lee Young Mi;Lee Michael
    • Toxicological Research
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    • v.21 no.2
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    • pp.99-105
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    • 2005
  • Photo-mutagenic compounds have been known to alter skin cancer rates by acting as initiators or by affecting subsequent steps in carcinogenesis. The objectives of this study are to investigate the utility of photo-chromosomal aberration (photo-CA) assay for detecting photo-clastogens, and to evaluate its ability to predict rodent photocarcinogenicity. Photo-CA assay was performed with five test substances that demonstrated positive results in photo-carcinogenicity tests: 8-Methoxypsoralen (photoactive substance that forms DNA adducts in the presence of ultraviolet A irradiation), chlorpromazine (an aliphatic phenothiazine an alpha-adrenergic blocking agent), lomefloxacin (an antibiotic in a class of drugs called fluoroquinolones), anthracene (a tricyclic aromatic hydrocarbon a basic substance for production of anthraquinone, dyes, pigments, insecticides, wood preservatives and coating materials) and Retinoic acid (a retinoid compound closely related to vitamin A). For the best discrimination between the test substance-mediated genotoxicity and the undesirable genotoxicity caused by direct DNA absorption, a UV dose-response of the cells in the absence of the test substances was firstly analyzed. All 5 test substances showed a positive outcome in photo-CA assay, indicating that the photo-CA test is very sensitive to the photo-genotoxic effect of UV irradiation. With this limited data-set, an investigation into the predictive value of this photo-CA test for determining the photo-carcinogenicity showed that photo-CA assay has the high ability of a test to predict carcinogenicity. Therefore, the photo-CA test using mammalian cells seems to be a sensitive method to evaluate the photo-carcinogenic potential of new compounds.

The carcinogenicity study of Folpet in rats (랫드에서 Folpet의 발암성에 관한 연구)

  • Lee, Yong-soon;Cho, Jae-jin;Kang, Kyung-sun;Kim, Bae-hwan;Nam, Ki-hoan;Seo, Kwang-won;Kang, Seong-keun;Lim, Yun-kyu;Heo, Kang-jun
    • Korean Journal of Veterinary Research
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    • v.34 no.3
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    • pp.609-617
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    • 1994
  • This study was performed for assessing carcinogenicity of Folpet using medium-term carcinogenicity bioassay. Sprague-Dawley rats aged six weeks divided into four grout's and were initially given an intraperitoneal injection of diethylnirosamine at 200mg/kg body weight. Two weeks later, group 1(negative control) was treated with basal diet. A Folpet was given per oral administration to group 2(100 ppm) and goup 3(1,000 ppm). Group 4 was fed on water containing 0.05% phenobarbital sodium as a promtor for six weeks. At three weeks after beginning of the experiment, partial hepatectomy was performed in all rats. The tumor-promoting effects were examined by the numbers and areas per $cm^2$ of induced glutathion S-tranferase placetal form(GST-P) positive foci in liver, and silver stained nucleolar organizer regions(AgNORs) which have recently introduced as one of the indicators for the cell proliferative activity. As the results, Folpet didn't have tumor-promoting effects on GST-P positive foci developement and AgNORs during promoting stage after initiation, whereas phenobarbital sodium treatment group showed promoting effect. It was concluded that Folpet didn't have promoting effect at 500, 1,000 ppm using this midium-term carcinogenicity bioassay model.

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