• Title/Summary/Keyword: Human toxicity

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Toxicogenomics and Cell-based Assays for Toxicology

  • Tong, Weida;Fang, Hong;Mendrick, Donna
    • Interdisciplinary Bio Central
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    • v.1 no.3
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    • pp.10.1-10.5
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    • 2009
  • Toxicity is usually investigated using a set of standardized animal-based studies which, unfortunately, fail to detect all compounds that induce human adverse events and do not provide detailed mechanistic information of observed toxicity. As an alternative to conventional toxicology, toxicogenomics takes advantage of currently advanced technologies in genomics, proteomics, metabolomics, and bioinformatics to gain a molecular level understanding of toxicity and to enhance the predictive power of toxicity testing in drug development and risk/safety assessment. In addition, there has been a renewed interest, particularly in various government agencies, to prioritize and/or supplement animal testing with a battery of mechanistically informative in vitro assays. This article provides a brief summary of the issues, challenges and lessons learned in these fields and discuss the ways forward to further advance toxicology using these technologies.

Application of Toxicogenomic Analysis to the Monitoring of Environmental Toxicity Using Recombinant Bioluminescent Bacteria and Cultured Mammalian Cells

  • Choi, Sue Hyung;Gu, Man Bock;Yasuyuki, Sakai
    • Proceedings of the Korean Society for Applied Microbiology Conference
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    • 2003.06a
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    • pp.129-131
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    • 2003
  • Recombinant bioluminescent bacteria and cultured human cells were applied for toxicogenomic analysis of environmentally hazardous chemicals. Recombinant bioluminescent biosensing cells were used to detect and classify the toxicity caused by various chemicals. Classification of toxicity was realized based upon the chemicals' mode of action using DNA-, oxidative-, protein, and membrane-damage sensitive strains. As well, a simple double-layered cell culture system using Caco-2 cells and Hep G2 cells, which mimic the metabolic processes occurring in humans, such as adsorption through the small intestine and biotransformationin both the small intestine and the liver, was developed to investigate the toxicity of hazardous materials to humans. For a more in-depth analysis, a DNA microarray was used to study the transcriptional responses of Caco-2 and Hep G2 cells to benzo〔a〕pyrene.

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Trichloroethylene and tetrachloroethylene contamination: A review of toxicity, analytical methods, occurrence in foods, and risk assessment

  • Adebayo J. Akinboye;Hyegyeong Lee;Joon-Goo Lee
    • Food Science and Preservation
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    • v.31 no.3
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    • pp.360-373
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    • 2024
  • Polychlorinated hydrocarbons are continuously released into the environment from various industrial processes. Trichloroethylene (TCE) and tetrachloroethylene (perchloroethylene, PCE) are of primary concern because of their large-scale production, wide industrial application, poor biodegradability, and tendency to circulate in the air and water. The common routes of human exposure to these compounds include inhalation, ingestion, and dermal adsorption. Additionally, they have been detected in various plant foods. Prolonged exposure to these contaminants is associated with certain risks. They are carcinogenic and have other toxic effects, including gastrointestinal, developmental, neurological, and hematological toxicity. To analyze these contaminants, they are generally extracted from various matrices, followed by instrumental analysis. Gas chromatography, often in combination with different detectors, is the most widely used analytical method. This review covers the toxicity, analytical methods, occurrence in foods, and risk assessment of these contaminants.

Assessment of Environmental Impacts and $CO_2$ Emissions from Soil Remediation Technologies using Life Cycle Assessment - Case Studies on SVE and Biopile Systems - (전과정평가(LCA)에 의한 토양오염 정화공정의 환경영향분석 및 $CO_2$ 배출량 산정 - SVE 및 Biopile 시스템 중심으로 -)

  • Jeong, Seung-Woo;Suh, Sang-Won
    • Journal of Korean Society of Environmental Engineers
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    • v.33 no.4
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    • pp.267-274
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    • 2011
  • The environmental impacts of 95% remediation of a total petroleum hydrocarbon-contaminated soil were evaluated using life cycle assessment (LCA). LCA of two remediation systems, soil vapor extraction (SVE) and biopile, were conducted by using imput materials and energy listed in a remedial system standardization report. Life cycle impact assessment (LCIA) results showed that the environmental impacts of SVE were all higher than those of biopile. Prominent four environmental impacts, human toxicity via soil, aquatic ecotoxicity, human toxicity via surface water and human toxicity via air, were apparently found from the LCIA results of the both remedial systems. Human toxicity via soil was the prominent impact of SVE, while aquatic ecotoxicity was the prominent impact of biopile. This study also showed that the operation stage and the activated carbon replacement stage contributed 60% and 36% of the environmental impacts of SVE system, respectively. The major input affecting the environmental impact of SVE was electricity. The operation stage of biopile resulted in the highest contribution to the entire environmental impact. The key input affecting the environmental impact of biopile was also electricity. This study suggested that electricity reduction strategies would be tried in the contaminated-soil remediation sites for archieving less environmental impacts. Remediation of contaminated soil normally takes long time and thus requires a great deal of material and energy. More extensive life cycle researches on remedial systems are required to meet recent national challenges toward carbon dioxide reduction and green growth. Furthermore, systematic information on electricity use of remedial systems should be collected for the reliable assessment of environmental impacts and carbon dioxide emissions during soil remediation.

Toxicity of Organophosphorus Flame Retardants (OPFRs) and Their Mixtures in Aliivibrio fischeri and Human Hepatocyte HepG2 (인체 간세포주 HepG2 및 발광박테리아를 활용한 유기인계 난연제와 그 혼합물의 독성 스크리닝)

  • Sunmi Kim;Kyounghee Kang;Jiyun Kim;Minju Na;Jiwon Choi
    • Journal of Environmental Health Sciences
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    • v.49 no.2
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    • pp.89-98
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    • 2023
  • Background: Organophosphorus flame retardants (OPFRs) are a group of chemical substances used in building materials and plastic products to suppress or mitigate the combustion of materials. Although OPFRs are generally used in mixed form, information on their mixture toxicity is quite scarce. Objectives: This study aims to elucidate the toxicity and determine the types of interaction (e.g., synergistic, additive, and antagonistic effect) of OPFRs mixtures. Methods: Nine organophosphorus flame retardants, including TEHP (tris(2-ethylhexyl) phosphate) and TDCPP (tris(1,3-dichloro-2-propyl) phosphate), were selected based on indoor dust measurement data in South Korea. Nine OPFRs were exposed to the luminescent bacteria Aliivibrio fischeri for 30 minutes and the human hepatocyte cell line HepG2 for 48 hours. Chemicals with significant toxicity were only used for mixture toxicity tests in HepG2. In addition, the observed ECx values were compared with the predicted toxicity values in the CA (concentration addition) prediction model, and the MDR (model deviation ratio) was calculated to determine the type of interaction. Results: Only four chemicals showed significant toxicity in the luminescent bacteria assays. However, EC50 values were derived for seven out of nine OPFRs in the HepG2 assays. In the HepG2 assays, the highest to lowest EC50 were in the order of the molecular weight of the target chemicals. In the further mixture tests, most binary mixtures show additive interactions except for the two combinations that have TPhP (triphenyl phosphate), i.e., TPhP and TDCPP, and TPhP and TBOEP (tris(2-butoxyethyl) phosphate). Conclusions: Our data shows OPFR mixtures usually have additivity; however, more research is needed to find out the reason for the synergistic effect of TPhP. Also, the mixture experimental dataset can be used as a training and validation set for developing the mixture toxicity prediction model as a further step.

Analysis of Toxicity in Escherichia coli from the Expression of Human Purinergic Receptor $P2X_4$ (인간 퓨린수용체 $P2X_4$를 발현시킬 때 나타나는 대장균 독성의 원인분석)

  • Yu, Yon-Joo;Jung, Yun-A;Lim, Dong-Bin
    • Korean Journal of Microbiology
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    • v.47 no.1
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    • pp.7-13
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    • 2011
  • In general, expression of membrane protein in Escherichia coli is very toxic to the host organism, but the mechanism for the toxicity is not clear yet. Expression of human purinergic receptor $P2X_4$ was found to be extremely toxic to the host E. coli. We examined this toxicity by isolation and analysis of less toxic mutant proteins. We could isolate 30 less toxic mutants of $P2X_4$ after hydroxylamine mutagenesis. Western blot showed that all of them produced proteins smaller than the wild type $P2X_4$. DNA sequencing of two largest mutant proteins showed that they were lost its second transmembrane domain. Localization analysis of these mutant proteins showed that they are not in cytoplasmic membrane, but in inclusion bodies. These data showed that inactive truncated $P2X_4$ is not toxic to E. coli and membrane integration and functionality of $P2X_4$ may be needed to show host toxicity.

Combined Toxic Effects of Polar and Nonpolar Chemicals on Human Hepatocytes (HepG2) Cells by Quantitative Property - Activity Relationship Modeling

  • Kim, Ki-Woong;Won, Yong Lim;Park, Dong Jin;Kim, Young Sun;Jin, Eun Sil;Lee, Sung Kwang
    • Toxicological Research
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    • v.32 no.4
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    • pp.337-343
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    • 2016
  • We determined the toxicity of mixtures of ethyl acetate (EA), isopropyl alcohol (IPA), methyl ethyl ketone (MEK), toluene (TOL) and xylene (XYL) with half-maximal effective concentration ($EC_{50}$) values obtained using human hepatocytes cells. According to these data, quantitative property-activity relationships (QPAR) models were successfully proposed to predict the toxicity of mixtures by multiple linear regressions (MLR). The leave-one-out cross validation method was used to find the best subsets of descriptors in the learning methods. Significant differences in physico-chemical properties such as boiling point (BP), specific gravity (SG), Reid vapor pressure (rVP) and flash point (FP) were observed between the single substances and the mixtures. The $EC_{50}$ of the mixture of EA and IPA was significantly lower than that of contained TOL and XYL. The mixture toxicity was related to the mixing ratio of MEK, TOL and XYL (MLR equation $EC_{50}=3.3081-2.5018{\times}TOL-3.2595{\times}XYL-12.6596{\times}MEK{\times}XYL$), as well as to BP, SG, VP and FP (MLR equation $EC_{50}=1.3424+6.2250{\times}FP-7.1198{\times}SG{\times}FP-0.03013{\times}rVP{\times}FP$). These results suggest that QPAR-based models could accurately predict the toxicity of polar and nonpolar mixtures used in rotogravure printing industries.