• YAKHAK HOEJI
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• v.55 no.4
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• pp.352-360
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• 2011

Standard combination chemotherapy including isoniazid, rifampin, pyrazinamide, and ethambutol is very effective against tuberculosis. But, these medicines can cause hepatotoxicity which is the main reason for treatment interruption or change in drug regimen. In order to identify risk factors associated with hepatotoxcity in Koreans and assess elevated baseline LFTs' contributions to hepatotoxicity, a retrospective case control study was performed. The medical records of 277 patients who diagnosed with tuberculosis at a community hospital from January 1st, 2007 to June 30th, 2010 were reviewed. Patients were categorized into 3 groups (non toxic group, patients without increase in LFT levels; mild to moderate hepatotoxic group and severe hepatotoxic group). And the correlation between risk factors and hepatotoxicity was analyzed by using SPSS program. The overall incidence of hepatotoxicity was 18% and 8.7% of patients developed severe toxicity. Patients in the severe toxic group had the longest treatment period among the three groups. In 75% of severe toxic group, hepatotoxicity occurred within 18.3 days after starting medication. Hypoalbuminemia (serum albumin <3 g/dl) was a significant risk factor for development of severe toxicity. Elevated baseline transaminase (except ALT), total bilirubin, and preexisting hepatitis were also risk factors which were more than twice as likely to increase risk of severe hepatotoxicity (p>0.05). In conclusion, hypoalbuminemia (serum albumin level <3 g/dl) was a significant risk factor for anti-tuberculosis druginduced severe toxicity. Therefore, before starting antituberculosis chemotherapy, serum albumin level should be assessed at baseline. In high-risk patients (hypoalbuminemia, elevated LFTs) for hepatotoxicty, liver function should be closely monitored up to at least 21 days after taking medication.

• Fire Science and Engineering
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• v.14 no.4
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• pp.7-16
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• 2000

In the study, three criteria(toxicity, fire & explosion, environment) and damage prediction method for each case was set up, and all these criteria were applied to the subject substance that was selected as hazardous level by integrating all criteria through Algorithm. Particularly, the environment criterion is a comprehensive concept, environment index modeling by combining USCG(United State Coast Guard) & MSDS(Material Safety Data Sheet) environment criteria classifications and the environment part of MFPA's health hazardousnes(Nh). And for damage prediction method of each criterion were adopted and they were applied to hazardous chemical substances in use or stored by chemical substance related enterprises located in each region that made possible to set up total hazard level of used substances(inflammability, poisonousness and counteraction on a unit substance, and hazard level & display modeling on environment) & damage prediction in case of accident & solidity setup(CPQRA: Chemical Process Quantitative Risk Assessment, IAEA: International Atomic Energy Agency, VZ eq: Vulnerable Zone) risk counter. Thus it is deemed that it can be applied to toxic substance leakage that can happen during any chemical processing & storage, application as a tool for prior safety evaluation through potential dangerousness computation of fire & explosion.

• Journal of the Korea Society of Computer and Information
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• v.21 no.8
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• pp.57-64
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• 2016

Initial prevention activities and rapid propagation conditions is the most important to prevent diffusion of water pollution. If water pollutants flow into streams river or main stresm located in environmental conservation area or water intake facilities, we must predict immediately arrival time and the diffusion concentration to the proactive. National Institute of Environmental Research developed water pollution incident response prediction system linking dam and movable weir. the system is mathematical model which is updated daily. Therefore it can quickly predict the arrival time and the diffusion concentration when there are accident of oil spills and hazardous chemicals. Also we equipped with mathematical model and toxicity model of EFDC(Environmental Fluid Dynamics Code) to calculate the arrival time and the diffusion concentration. However these systems offer the services of an offline manner than real-time control services. we have ensured the reliability of data collection and have developed a real-time water quality measurement data transmission device by using the data linkage utilizing a mode bus communication and a commercial SCADA system, in particular, we implemented to be able to do real-time water quality prediction through information infrastructure of the water quality integrated management business created by utilizing the construction of the real-time prediction system that utilizes the data collected, the Open map, the visual representation using charts API and development of integrated management system development based on web maps.

• Korean Journal of Environmental Agriculture
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• v.12 no.1
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• pp.69-80
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• 1993

Environmental hazards of a chemical could be assessed by two different approaches : toxicity test and assessment of exposure potentials to human and environmental organisms. For the prediction of environmental fate of chemicals three available computer programs were compared each other and were verified. The results obtained by using these computer programs, PCHEM, EXAMS, and E4CHEM were summarized as follows. The estimated octanol/water partition coefficients by PCHEM were similar to the experimental values in the literature. But the other factors, water solubility and vapor pressure were different from the data in the literature. The simulation results of selected compounds by EXAMS showed similar tendency to the literature results of model field environment. Therefore, this computer program could be utilized to predict the environmental fate of chemicals. E4CHEM program is very simple and this program could predict the ultimate environmental fate of stable chemicals by input of two or three parameters. However, the validity should further be verified in the future field study using more compounds. It is suggested that these approaches could be fully utilized by understanding their limitations to predict the environmental fate of new chemicals under development, to screen the potential environmental pollutants among chemicals already-in use, and to devise measures to minimize the hazards to the environment.

• Biomolecules & Therapeutics
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• v.15 no.4
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• pp.252-260
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• 2007

As it is needed to assay possible feasibility of extrapolation between in vivo and in vitro systems and to develop a new in vitro method for toxicity testing, we investigated global gene expression from both animal and cell line treated with thioacetamide (TAA) and compared between in vivo and in vitro genomic profiles. For in vivo study, mice were orally treated with TAA and sacrificed at 6 and 24 h. For in vitro study, TAA was administered to a mouse hepatic cell line, BNL CL.2 and sampling was carried out at 6 and 24 h. Hepatotoxicity was assessed by analyzing hepatic enzymes and histopathological examination (in vivo) or lactate dehydrogenase (LDH) assay and morphological examination (in vitro). Global gene expression was assessed using microarray. In high dose TAA-treated group, there was centrilobular necrosis (in vivo) and cellular toxicity with an elevation of LDH (in vitro) at 24 h. Statistical analysis of global gene expression identified that there were similar numbers of altered genes found between in vivo and in vitro at each time points. Pathway analysis identified several common pathways existed between in vivo and in vitro system such as glutathione metabolism, bile acid biosynthesis, nitrogen metabolism, butanoate metabolism for hepatotoxicty caused by TAA. Our results suggest it may be feasible to develop toxicogenomics biomarkers by comparing in vivo and in vitro genomic profiles specific to TAA for application to prediction of liver toxicity.

• Journal of Environmental Health Sciences
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• v.50 no.2
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• pp.113-124
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• 2024

Background: The increasing need to minimize animal testing has sparked interest in alternative methods with more humane, cost-effective, and time-saving attributes. In particular, in silico-based computational toxicology is gaining prominence. Adverse outcome pathway (AOP) is a biological map depicting toxicological mechanisms, composed of molecular initiating events (MIEs), key events (KEs), and adverse outcomes (AOs). To understand toxicological mechanisms, predictive models are essential for AOP components in computational toxicology, including molecular structures. Objectives: This study reviewed the literature and investigated previous research cases related to AOP and in silico methodologies. We describe the results obtained from the analysis, including predictive techniques and approaches that can be used for future in silico-based alternative methods to animal testing using AOP. Methods: We analyzed in silico methods and databases used in the literature to identify trends in research on in silico prediction models. Results: We reviewed 26 studies related to AOP and in silico methodologies. The ToxCast/Tox21 database was commonly used for toxicity studies, and MIE was the most frequently used predictive factor among the AOP components. Machine learning was most widely used among prediction techniques, and various in silico methods, such as deep learning, molecular docking, and molecular dynamics, were also utilized. Conclusions: We analyzed the current research trends regarding in silico-based alternative methods for animal testing using AOPs. Developing predictive techniques that reflect toxicological mechanisms will be essential to replace animal testing with in silico methods. In the future, since the applicability of various predictive techniques is increasing, it will be necessary to continue monitoring the trend of predictive techniques and in silico-based approaches.

• Toxicological Research
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• v.30 no.1
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• pp.1-5
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• 2014

Xenograft models of human cancer play an important role in the screening and evaluation of candidates for new anticancer agents. The models, which are derived from human tumor cell lines and are classified according to the transplant site, such as ectopic xenograft and orthotopic xenograft, are still utilized to evaluate therapeutic efficacy and toxicity. The metastasis model is modified for the evaluation and prediction of cancer progression. Recently, animal models are made from patient-derived tumor tissue. The patient-derived tumor xenograft models with physiological characters similar to those of patients have been established for personalized medicine. In the discovery of anticancer drugs, standard animal models save time and money and provide evidence to support clinical trials. The current strategy for using xenograft models as an informative tool is introduced.

• Journal of The Korean Society of Clinical Toxicology
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• v.12 no.1
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• pp.14-21
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• 2014

Purpose: The objective of this study was to develop a new scoring tool that is comprehensively applicable and predicts fatality within 24 h of intoxication. Methods: This was a cohort study conducted in two emergency medical centers from 2011 to 2012. We identified factors associated with severe/fatality. Through a discriminant analysis, we devised the aBIG (age, Base deficit, Infection, and Glasgow coma scale) score. To compare the ability of aBIG to predict intoxication severity with that of previous scoring systems such as APACHE II, MODS, SAPS IIe, and SOFA, we determined the receiver operating characteristic curves of each variable in predicting severe-to-fatal toxicity. Results: Compared with the mild/moderate toxicity group (n=211), the severe/fatal group (n=143) had higher incidences of metabolic acidosis, infection, serious mental change, QTc prolongation and hepato-renal failure. Age, base deficit, infection-WBC count, and Glasgow Coma Scale were independently associated with severe/fatal poisoning. These variables were combined into the poisoning "aBIG" score [$0.28{\times}$Age group+$0.38{\times}WBC$ count/$10^3+0.52{\times}$Base deficit+$0.64{\times}$(15-GCS)], which were each calculated to have an area under the curve of 0.904 (95% confidence interval: 0.868-0.933). The aBIG poisoning score had an equivalent level of severity predictability as APACHE II and a superior than MODS, SOFA, and SAPS IIe. Conclusion: We developed a simplified scoring system using the four variables of age, base deficit, infected leukocytosis, and GCS. The poisoning aBIG score was a simple method that could be performed rapidly on admission to evaluate severity of illness and predict fatal severity in patients with acute intoxications.

• Journal of Soil and Groundwater Environment
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• v.22 no.5
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• pp.30-39
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• 2017

In this study, the predictive toxicity of barley Hordeum vulgare was estimated using a modified terrestrial biotic ligand model (TBLM) to account for the toxic effects of $CuOH^+$ and $CuCO_3(aq)$ generated at pH 7 or higher, and this was compared to that from the original TBLM. At pH values higher than 7, the difference in $EA_{50}\{Cu^{2+}\}$ (half maximal effective activity of $Cu^{2+}$) between the two models increased with increasing pH. As Mg concentration increased from 8.24 to 148 mg/L in the pH range of 5.5 to 8.5, the difference in $EA_{50}\{Cu^{2+}\}$ increased, and it reached its maximum at pH 8. The difference in $EC_{50}[Cu]_T$ (half maximal effective concentration of Cu) between the two models increased as dissolved organic carbon (DOC) concentration increased when pH was above 7. Thus, for soils with alkaline pH, the toxic effect of $CuOH^+$ and $CuCO_3(aq)$ are greater at higher salt and DOC concentrations. The acceptable Cu concentration in soil porewater can be estimated by the modified TBLM through deterministic method at pH levels higher than 7, while combination of TBLM and species sensitivity distribution through the probabilistic method could be utilized at pH levels lower than 7.

• Microbiology and Biotechnology Letters
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• v.27 no.1
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• pp.54-61
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• 1999

Measurement of inhibition of bioluminescence in Photobacterium phosphoreum has been porposed as a sensitive and rapid procedure to monitor toxic substances. However, at first, $EC_{50}$ which shows degree of toxicity to each toxic substances must be calculated. QSAR (Quantitative Structure Activity Relationship) model can be used to estimate $EC_{50}$ to save time and endeavor. Moderately high correlation coefficients ($r^2{\geq}$ 0.97) were calculated from the linear correlation between $EC_{50}$ and molecular connectivity indices of CAHs (chlorinated aliphatic hydrocarbons)such as $^0X$, $^0X^V$, $^1X$, $^2X$ and $^3X^v_c$ and quadratic correlation between $EC_{50}$ and $^0X$, $^0X^V$, $^2X^V$, $^3X_c$, $^3X^V_c$ and P. It shows that the molecular connection indices in carbon structure is contributed to biological characters with linear relation and that in the other one with quadratic relation. The $EC_{50}$ of chlorophenol derivatives had quadratic relation with the value of octanol/water prtition coefficients ($r^2$=0.99) and linear and quadratic relation with the number of chlorine compound (($r^2{\geq}$0.94). This confirms the already known trend of increasing toxicity with increasing ability of a compound to diffuse through cell membrane and number of chlorine substitution.