• Title/Summary/Keyword: Carcinogens

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Thresholds of Genotoxic and Non-Genotoxic Carcinogens

  • Nohmi, Takehiko
    • Toxicological Research
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    • v.34 no.4
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    • pp.281-290
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    • 2018
  • Exposure to chemical agents is an inevitable consequence of modern society; some of these agents are hazardous to human health. The effects of chemical carcinogens are of great concern in many countries, and international organizations, such as the World Health Organization, have established guidelines for the regulation of these chemicals. Carcinogens are currently categorized into two classes, genotoxic and non-genotoxic carcinogens, which are subject to different regulatory policies. Genotoxic carcinogens are chemicals that exert carcinogenicity via the induction of mutations. Owing to their DNA interaction properties, there is thought to be no safe exposure threshold or dose. Genotoxic carcinogens are regulated under the assumption that they pose a cancer risk for humans, even at very low doses. In contrast, non-genotoxic carcinogens, which induce cancer through mechanisms other than mutations, such as hormonal effects, cytotoxicity, cell proliferation, or epigenetic changes, are thought to have a safe exposure threshold or dose; thus, their use in society is permitted unless the exposure or intake level would exceed the threshold. Genotoxicity assays are an important method to distinguish the two classes of carcinogens. However, some carcinogens have negative results in in vitro bacterial mutation assays, but yield positive results in the in vivo transgenic rodent gene mutation assay. Non-DNA damage, such as spindle poison or topoisomerase inhibition, often leads to positive results in cytogenetic genotoxicity assays such as the chromosome aberration assay or the micronucleus assay. Therefore, mechanistic considerations of tumor induction, based on the results of the genotoxicity assays, are necessary to distinguish genotoxic and non-genotoxic carcinogens. In this review, the concept of threshold of toxicological concern is introduced and the potential risk from multiple exposures to low doses of genotoxic carcinogens is also discussed.

Exposure of Carcinogens in Electronics Industries and Strategy for Control of Carcinogens: Using Work Environment Measurement Database (2013-2017) in Korea (한국 전자산업에서 작업환경측정을 통해 파악된 발암물질들 노출 특성과 발암물질관리 방안: 작업환경측정자료(2013-2017)를 중심으로)

  • Mia, Son;Jaewon, Yun;Yu Seoung, Hwang;Mijin, Park;MinSeo, Choi;Mi-Young, Lee;Domyung, Paek
    • Journal of Korean Society of Occupational and Environmental Hygiene
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    • v.32 no.4
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    • pp.302-324
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    • 2022
  • Objectives: The objective of this study is to investigate exposure to occupational carcinogens in the nationwide electronics industries and to establish a strategy for control of occupational carcinogens in South Korea. Methods: We evaluated occupational carcinogens as defined by International Agency for Research on Cancer (IARC) using a nationwide work environment measurement database on the electronics industry in South Korea measured between 2013 and 2017 in accordance with the Occupational Safety and Health Act. Results: The number of occupational carcinogens found in the electronics industry in South Korea were: 20 for IARC Group 1, 14 for Group 2A, and 30 for Group 2B. The occupational carcinogens (Group 1) most frequently exposed were strong-inorganic-acid mists containing sulfuric acid (sulfuric acid), welding fumes, mineral oils (untreated or mildly treated), nickel compounds, silica dust, crystalline substances in the form of quartz or cristobalite, formaldehyde, arsenic and inorganic arsenic compounds, chromium (VI) compounds, trichloroethylene, cadmium and cadmium compounds, vinyl chloride, ethylene oxide, wood dust, beryllium and beryllium compounds, 1,3 butadiene, benzene, and others. Among them, the carcinogens (Group 1) exceeding the acceptable standard were trichloroethylene, formaldehyde, and ethylene oxide. The working environment measurement system as regulated by Occupational Safety and Health Act is not properly assessed and managed for occupational carcinogens in South Korea. A component analysis for all materials used should be set up to practically reduce occupational carcinogens. A ban on the use of occupational carcinogens and the development of alternative materials are needed. The occupational carcinogens below the acceptable standards should be carefully examined and a new standard for exposure needs to be established. Conclusions: The Occupational Safety and Health Act should be improved to identify and monitor occupational carcinogens at work sites. A strategy for occupational safety and health systems should be provided to give direction to workers' needs and right to know.

Application of Molecular Orbital Theory to Biological chemistry (II). Interactions of Chemical Carcinogens with DNA Bases (分子軌道論의 生物化學에의 應用 (第 2 報). 發癌物質과 DNA 鹽基와의 相互作用)

  • Ho-Soon Kim;Yoon-Yul Park;Byung-Kak Park
    • Journal of the Korean Chemical Society
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    • v.24 no.4
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    • pp.280-287
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    • 1980
  • The interactions of chemical carcinogens, such as polycyclic aromatic hydrocarbons, dimethylaminoazobenzene (DAB) and its derivatives and heterocyclic compounds with tissue components, especially with deoxyribonucleic acid (DNA), were examined by means of simple Huckel method. Assuming that the formations of a loose molecular complex between the carcinogens and the tissue components are the first step of chemical carcinogenesis, the most proble orientation between the chemical carcinogens and adenine-thymine (A=T) pair or guanine-cytosine $(G\equivC)$ pair is determined. It has been found that, in the case of the formation of molecular complex between chemical carcinogens and A=T pair, the two atoms of K-region of the carcinogens and the atom of L-region in the proximity of their K-region are combined correspondingly with C-l' carbon atom in the sugar that is attached to thymine, N-1 nitrogen atom and C-5 carbon atom in the thymine part of A=T pair, while, in the case of that between the carcinogens and $G\equivC$ pair, the above three atoms of the carcinogens are combined correspondingly with C-8 carbon atom, N-9 nitrogen atom and N-3 nitrogen atom in the guanine part of $G\equivC$ pair.

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Effect of Chemical Carcinogens on the Replication, Cytolyticity, DNA Synthesis, and Protein Expression of Herpes Simplex Virus in Viral Infected Cells (발암성 화학물질들이 Herpes Simplex Virus의 복제, 세포융해, DNA 합성 및 단백질 합성에 미치는 효과)

  • Chun, Yeon-Sook
    • The Korean Journal of Pharmacology
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    • v.28 no.2
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    • pp.213-222
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    • 1992
  • We investigated effects of several chemical carcinogens, i.e., $benzo({\alpha})pyrene$ (BP),7,12-dimethylbenz(a)anthracene (DMBA), nitrosomethyl urea (NMU), and nicotine on the replication, cytolyticity, DNA synthesis, and protein synthesis of type 1 herpes simplex virus (HSV-1) in viral infected Vero cell monolayers. We observed that the BP and DMBA did not show such activity. All chemical carcinogens did not inhibit the synthesis of viral DNA, but the expression of gamma viral proteins that are expressed from the newly synthesized progeny viral DNA was somewhat notably inhibited by BP and DMBA. However, the synthesis of alpha and beta viral proteins was not altered by the chemical carcinogens. These data indicate that the gamma viral proteins expressed from the newly synthesized DNA in the presence of chemical carcinogens in the culture medium may be defective. This is further supported by the fact that the virus fail to replicate in the presence of these chemical carcinogens, in spite of viral DNA and proteins are somewhat normally synthesized.

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Effect of Genotoxicity or Carcinogenecity Chemicals on the ROS Production (유전독성, 발암성 화학물질이 ROS 생성에 미치는 영향)

  • Go, Seo-Youn;Sheen, Yhun-Yhong
    • Environmental Analysis Health and Toxicology
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    • v.23 no.1
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    • pp.23-32
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    • 2008
  • In the present study, ROS detection of L5178Y cells that were treated with twenty test compounds in order to find out hydrogen peroxide ($H_2O_2$) induction for genotoxicity and carcinogenic toxicity. Twenty test compounds were consist of four classes, such as genotoxic carcinogens, genotoxic noncarcinogens, nongenotoxic carcinogens, and nongenotoxic noncarcinogens. Genotoxic carcinogens are 1,2-dibromoethane, glycidol, melphalan, diethylstilbestrol and urethane. Genotoxic noncarcinogens are 8-hydroxyquinoline, emodin, acetonitrile and diallylphthalate, L-ascorbic acid. Nongenotoxic carcinogens are methyl carbamate, O-nitrotoluene, 1,4-dioxane, tetrachloroethylene and 2,3,7,8-tetrachlorodibenzo-p-dioxin. And nongenotoxic noncarcinogens are D-mannitol, 1,2-dichlorobenzene, caprolactam, bisphenol A and chlorpheniramine maleate.

QSAR Approach for Toxicity Prediction of Chemicals Used in Electronics Industries (전자산업에서 사용하는 화학물질의 독성예측을 위한 QSAR 접근법)

  • Kim, Jiyoung;Choi, Kwangmin;Kim, Kwansick;Kim, Dongil
    • Journal of Environmental Health Sciences
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    • v.40 no.2
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    • pp.105-113
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    • 2014
  • Objectives: It is necessary to apply quantitative structure activity relationship (QSAR) for the various chemicals with insufficient toxicity data that are used in the workplace, based on the precautionary principle. This study aims to find application plan of QSAR software tool for predicting health hazards such as genetic toxicity, and carcinogenicity for some chemicals used in the electronics industries. Methods: Toxicity prediction of 21 chemicals such as 5-aminotetrazole, ethyl lactate, digallium trioxide, etc. used in electronics industries was assessed by Toxicity Prediction by Komputer Assisted Technology (TOPKAT). In order to identify the suitability and reliability of carcinogenicity prediction, 25 chemicals such as 4-aminobiphenyl, ethylene oxide, etc. which are classified as Group 1 carcinogens by the International Agency for Research on Cancer (IARC) were selected. Results: Among 21 chemicals, we obtained prediction results for 5 carcinogens, 8 non-carcinogens and 8 unpredictability chemicals. On the other hand, the carcinogenic potential of 5 carcinogens was found to be low by relevant research testing data and Oncologic TM tool. Seven of the 25 carcinogens (IARC Group 1) were wrongly predicted as non-carcinogens (false negative rate: 36.8%). We confirmed that the prediction error could be improved by combining genetic toxicity information such as mutagenicity. Conclusions: Some compounds, including inorganic chemicals and polymers, were still limited for applying toxicity prediction program. Carcinogenicity prediction may be further improved by conducting cross-validation of various toxicity prediction programs, or application of the theoretical molecular descriptors.

Development of Korean CARcinogen EXposure: Assessment of the Exposure Intensity of Carcinogens by Industry

  • Koh, Dong-Hee;Park, Ju-Hyun;Lee, Sang-Gil;Kim, Hwan-Cheol;Jung, Hyejung;Kim, Inah;Choi, Sangjun;Park, Donguk
    • Safety and Health at Work
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    • v.13 no.3
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    • pp.308-314
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    • 2022
  • Background: Occupational cancer is a global health issue. The Korean CARcinogen EXposure (K-CAREX), a database of CARcinogen EXposure, was developed for the Korean labor force to estimate the number of workers exposed to carcinogens by industry. The present study aimed to estimate the intensity of exposure to carcinogens by industry, in order to supply complementary information about CARcinogen EXposure intensity to the K-CAREX. Methods: We used nationwide workplace monitoring data from 2014 to 2016 and selected target carcinogens based on the K-CAREX list. We computed the 95th percentile levels of measurements for each industry by carcinogens. Based on the 95th percentile level relative to the occupational exposure limit, we classified the CARcinogen EXposure intensity into five exposure ratings (1-5) for each industry. Results: The exposure ratings were estimated for 21 carcinogenic agents in each of the 228 minor industry groups. For example, 3,058 samples were measured for benzene in the manufacturing industry of basic chemicals. This industry was assigned a benzene exposure rating of 3. Conclusions: We evaluated the CARcinogen EXposure ratings across industries in Korean workers. The results will provide information on the exposure intensity to carcinogens for integration into the K-CAREX. Furthermore, it will aid in prioritizing control efforts and identifying industries of concern.

Suggestion for the Prevention of Occupational Cancer in Korea (한국에서의 직업성 암 예방을 위한 제언)

  • Kim, Won;Kim, Shin-Bum;Choi, In-Ja;Kwag, Hyun-Seok
    • Journal of Environmental Health Sciences
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    • v.36 no.6
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    • pp.518-526
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    • 2010
  • There are millions of deaths from cancer worldwide every year. Among them, 4~10% are considered to be attributable to occupational factors and 0.6 million workers die annually from work-related cancers. Occupational cancers are relatively preventable compared with the cancers associated with other factors. In the developed countries, especially in Europe, there have been hundreds of occupational cancers reported annually in the respective nation-states. However, there were only 35 cases reported in Korea in the 1990s which were accepted as being work-related cancers. This difference might be related to a low level of recognition, detection, and acceptance of occupational cancer and carcinogens in Korea. To prevent the risk of exposure to carcinogens a comprehensive list of carcinogens must be prepared. This should be followed by timely dissemination of information which will enable fundamental controls to be implemented, such as the imposition of ban, substitution, and engineering controls. This will require setting up procedures to record the past use and exposure data and carrying out robust statistical analyses of that data on occupational cancers and carcinogens.

Estimation of Human Carcinogenic Potency (HCP) of Carcinogens in Risk Assessment and Management. (위해성 평가 및 관리에 있어서 발암물질의 인체발암능력 평가)

  • 이병무;김대영;김세기;김근종
    • Environmental Mutagens and Carcinogens
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    • v.19 no.1
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    • pp.39-45
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    • 1999
  • Human Carcinogenic Potency (HCP) can be estimated based on human daily exposure dose to carcinogen (Dh), body weight (Wh), 10% tumorigenic dose (TD10), and slope factor at TD10 (Q10) from 2-yr bioassay data. This approach is more relevant to humans generally exposed to low doses of carcinogens and can reduce more of extrapolation errors from high dose in animal experiments to low dose in humans than HERP (human exposure dose/rodent potency dose) proposed by Ames et al. (Science, 236, 271-280, 1987). TD50 and HERP have been routinely used to compare rodent carcinogenic potency and human carcinogenic potency, but those approaches have had limitations in extrapolation of high dose to low dose in humans. The advantages of HCP are to estimate human exposure dose (Dh) by human monitoring instead of environmental monitoring, to consider slope factor (Q10) which reflects the tendency of curve at low dose, and to use TD10 which represents much lower dose thant TD50 or HERP. HCP will be a useful parameter for the estimation of human carcinogenic potency in risk assessment and management of carcinogens.

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.