• Journal of Korean Society of Occupational and Environmental Hygiene
• /
• v.31 no.3
• /
• pp.185-193
• /
• 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.

• Journal of Environmental Health Sciences
• /
• v.40 no.2
• /
• pp.105-113
• /
• 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.

• Environmental Mutagens and Carcinogens
• /
• v.25 no.1
• /
• pp.6-12
• /
• 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.

• Journal of Microbiology and Biotechnology
• /
• v.28 no.4
• /
• pp.645-651
• /
• 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.

• Proceedings of the Korean Society of Toxicology Conference
• /
• 2003.10b
• /
• pp.95-95
• /
• 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)

• Proceedings of the Korea Environmental Mutagen Society Conference
• /
• 2003.10a
• /
• pp.95-95
• /
• 2003

• Journal of Korean Society of Occupational and Environmental Hygiene
• /
• v.29 no.2
• /
• pp.141-158
• /
• 2019

Objectives: An adverse outcome pathway is a biological pathway that disturbs homeostasis and causes toxicity. It is a conceptual framework for organizing existing biological knowledge and consists of the molecular initiating event, key event, and adverse output. The AOP concept provides intuitive risk identification that can be helpful in evaluating the carcinogenicity of chemicals and in the prevention of cancer through the assessment of chemical carcinogenicity predictions. Methods: We reviewed various papers and books related to the application of AOPs for the prevention of occupational cancer. We mainly used the internet to search for the necessary research data and information, such as via Google scholar(http://scholar.google.com), ScienceDirect(www.sciencedirect.com), Scopus(www.scopus. com), NDSL(http: //www.ndsl.kr/index.do) and PubMed(http://www.ncbi.nlm.nih.gov/pubmed). The key terms searched were "adverse outcome pathway," "toxicology," "risk assessment," "human exposure," "worker," "nanoparticle," "applications," and "occupational safety and health," among others. Results: Since it focused on the current state of AOP for the prediction of toxicity from chemical exposure at work and prospects for industrial health in the context of the AOP concept, respiratory and nanomaterial hazard assessments. AOP provides an intuitive understanding of the toxicity of chemicals as a conceptual means, and it works toward accurately predicting chemical toxicity. The AOP technique has emerged as a future-oriented alternative to the existing paradigm of chemical hazard and risk assessment. AOP can be applied to the assessment of chemical carcinogenicity along with efforts to understand the effects of chronic toxic chemicals in workplaces. Based on these predictive tools, it could be possible to bring about a breakthrough in the prevention of occupational and environmental cancer. Conclusions: The AOP tool has emerged as a future-oriented alternative to the existing paradigm of chemical hazard and risk assessment and has been widely used in the field of chemical risk assessment and the evaluation of carcinogenicity at work. It will be a useful tool for prediction, and it is possible that it can help bring about a breakthrough in the prevention of occupational and environmental cancer.

• Toxicological Research
• /
• v.21 no.2
• /
• pp.99-105
• /
• 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.

• Toxicological Research
• /
• v.32 no.4
• /
• pp.289-300
• /
• 2016

Non-genotoxic carcinogens are substances that induce tumorigenesis by non-mutagenic mechanisms and long term rodent bioassays are required to identify them. Recent studies have shown that transcription profiling can be applied to develop early identifiers for long term phenotypes. In this study, we used rat liver expression profiles from the NTP (National Toxicology Program, Research Triangle Park, USA) DrugMatrix Database to construct a gene classifier that can distinguish between non-genotoxic carcinogens and other chemicals. The model was based on short term exposure assays (3 days) and the training was limited to oxidative stressors, peroxisome proliferators and hormone modulators. Validation of the predictor was performed on independent toxicogenomic data (TG-GATEs, Toxicogenomics Project-Genomics Assisted Toxicity Evaluation System, Osaka, Japan). To build our model we performed Random Forests together with a recursive elimination algorithm (VarSelRF). Gene set enrichment analysis was employed for functional interpretation. A total of 770 microarrays comprising 96 different compounds were analyzed and a predictor of 54 genes was built. Prediction accuracy was 0.85 in the training set, 0.87 in the test set and increased with increasing concentration in the validation set: 0.6 at low dose, 0.7 at medium doses and 0.81 at high doses. Pathway analysis revealed gene prominence of cellular respiration, energy production and lipoprotein metabolism. The biggest target of toxicogenomics is accurately predict the toxicity of unknown drugs. In this analysis, we presented a classifier that can predict non-genotoxic carcinogenicity by using short term exposure assays. In this approach, dose level is critical when evaluating chemicals at early time points.

• Toxicological Research
• /
• v.21 no.1
• /
• pp.1-14
• /
• 2005

Transgenic mouse models have been introduced and accepted by regulatory bodies as an alternative to carcinogenicity assay models to predict and evaluate chemical carcinogens. The recent research outcomes in transgenic mouse models have made progressive advances in the understanding of chemical carcinogenesis and the evaluation of potential human carcinogens. However, these models still remain to be insufficient assay systems although the insufficiencies have been recognised and are being resolved. Based on up to date information from literature, this review article intends to understand currently accepted transgenic mouse models, issues arising from study design, interpretation of the study, results of validation project and their cancer prediction rate, and further perspectives of cancer assay models from the regulatory view point.