• Journal of Korean Society on Water Environment
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• v.29 no.2
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• pp.176-183
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• 2013

The variation of the stable region of arsenic compounds in aqueous environment with temperature has been investigated by constructing the Pourbaix diagram of arsenic at different temperatures. The standard potential corresponding to the boundary between arsenic compounds with different charge valence was estimated to be decreased with temperature, which means the stability of arsenic compound with +5 charge valence increases. The distribution diagram of the most highly oxidized arsenic compound showed that arsenic acid is formed at higher pH and arsenate is generated at lower pH as temperature rises. The aquatic toxicity due to arsenic compounds was considered to be decreased with temperature in the neutral pH condition based on the $LD_T$ value defined in this study.

• Analytical Science and Technology
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• v.24 no.6
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• pp.544-555
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• 2011

The acute toxicity in the rainbow trout (Oncorhynchus mykiss) was analyzed and predicted using quantitative structure-activity relationships (QSAR). The aquatic toxicity, 96h $LC_{50}$ (median lethal concentration) of 275 organic pesticides, was obtained from EU-funded project DEMETRA. Prediction models were derived from 558 2D molecular descriptors, calculated in PreADMET. The linear (multiple linear regression) and nonlinear (support vector machine and artificial neural network) learning methods were optimized by taking into account the statistical parameters between the experimental and predicted p$LC_{50}$. After preprocessing, population based forward selection were used to select the best subsets of descriptors in the learning methods including 5-fold cross-validation procedure. The support vector machine model was used as the best model ($R^2_{CV}$=0.677, RMSECV=0.887, MSECV=0.674) and also correctly classified 87% for the training set according to EU regulation criteria. The MLR model could describe the structural characteristics of toxic chemicals and interaction with lipid membrane of fish. All the developed models were validated by 5 fold cross-validation and Y-scrambling test.

• Toxicological Research
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• v.35 no.3
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• pp.257-270
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• 2019

Silver nanoparticles (AgNPs) have been widely used in a variety of applications in innovative development; consequently, people are more exposed to this particle. Growing concern about toxicity from AgNP exposure has attracted greater attention, while questions about nanosilver-responsive genes and consequences for human health remain unanswered. By considering early detection and prevention of nanotoxicology at the genetic level, this study aimed to identify 1) changes in gene expression levels that could be potential indicators for AgNP toxicity and 2) morphological phenotypes correlating to toxicity of HepG2 cells. To detect possible nanosilver-responsive genes in xenogenic targeted organs, a comprehensive systematic literature review of changes in gene expression in HepG2 cells after AgNP exposure and in silico method, connection up- and down-regulation expression analysis of microarrays (CU-DREAM), were performed. In addition, cells were extracted and processed for transmission electron microscopy to examine ultrastructural alterations. From the Gene Expression Omnibus (GEO) Series database, we selected genes that were up- and down-regulated in AgNPs, but not up- and down-regulated in silver ion exposed cells, as nanosilver-responsive genes. HepG2 cells in the AgNP-treated group showed distinct ultrastructural alterations. Our results suggested potential representative gene data after AgNPs exposure provide insight into assessment and prediction of toxicity from nanosilver exposure.

• Fire Science and Engineering
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• v.29 no.2
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• pp.73-78
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• 2015

Fire in the risk management subject belongs to high risk disaster which accompanies personnel and materiel loss. So, management of disaster and safety is required to include fire prevention activities, fire risk prediction and investment of safety management expense. Combustion toxicity is required by gas toxicity test (KS F 2271), to minimize human damage. In this study, gas toxicity test were experimented with regard to urethane sample (Depth 5~25 mm) to obtain basic data. Fire effluent exposing to experimental animal were analyzed by FT-IR (Fourier transform infrared spectroscopy). Combustion toxicity index Lethal Fractional Effective Dose ($L_{FED}$) of ISO 13344 was calculated. According to the result of calculating Lethal Concentration 50% ($LC_{50}$) based on $L_{FED}$, $LC_{50}$ of urethane sample containing certain level of fire load is confirmed as $118{\sim}129g/m^3$. Through this study, applicability of this method was confirmed for fire risk assessment. This method can provide information to predict human damage by toxicity combustion gas for securing safety.

• Korean Chemical Engineering Research
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• v.54 no.5
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• pp.621-629
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• 2016

Recently, the researches on quantitative structure activity relationship (QSAR) for describing toxicities or activities of chemicals based on chemical structural characteristics have been widely carried out in order to estimate the toxicity of chemicals in multiuse facilities. Because the toxicity of chemicals are explained by various kinds of molecular descriptors, an important step for QSAR model development is how to select significant molecular descriptors. This research proposes a statistical selection of significant molecular descriptors and a new QSAR model based on partial least square (PLS). The proposed QSAR model is applied to estimate the logarithm of partition coefficients (log P) of 130 polychlorinated biphenyls (PCBs) and lethal concentration ($LC_{50}$) of 14 PCBs, where the prediction accuracies of the proposed QSAR model are compared to a conventional QSAR model provided by OECD QSAR toolbox. For the selection of significant molecular descriptors that have high correlation with molecular descriptors and activity information of the chemicals of interest, correlation coefficient (r) and variable importance of projection (VIP) are applied and then PLS model of the selected molecular descriptors and activity information is used to predict toxicities and activity information of chemicals. In the prediction results of coefficient of regression ($R^2$) and prediction residual error sum of square (PRESS), the proposed QSAR model showed improved prediction performances of log P and $LC_{50}$ by 26% and 91% than the conventional QSAR model, respectively. The proposed QSAR method based on computational toxicology can improve the prediction performance of the toxicities and the activity information of chemicals, which can contribute to the health and environmental risk assessment of toxic chemicals.

• Environmental Mutagens and Carcinogens
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• v.21 no.2
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• pp.118-121
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• 2001

The predictive screening of various molecular descriptors for predicting carcinogenic, mutagenic, teratogenic and alkylation activity of chlorinated disinfection byproducts (DBPs) has been investigated for the application of quantitative structure-activity relationships (QSAR). The toxicity index for 29 compounds were computed by the PASS program and active values were employed in this study. Studies show that different descriptors account for the model equation of each genotoxic endpoint and that thermodynamic descriptors significantly played a major role on prediction of endpoints of chlorinated aliphatic compounds.

• CELLMED
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• v.3 no.2
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• pp.12.1-12.4
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• 2013

Identification of target protein is an important procedure in the course of drug discovery. Because of complexity, action mechanisms of herbal medicine are rather obscure, unlike small-molecular drugs. Inverse docking simulation is a reverse use of molecular docking involving multiple target searches for known chemical structure. This methodology can be applied in the field of target fishing and toxicity prediction for herbal compounds as well as known drug molecules. The aim of this review is to introduce a series of in silico works for predicting potential drug targets and side-effects based on inverse docking simulations.

• YAKHAK HOEJI
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• v.59 no.5
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• pp.201-206
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• 2015

The aim of the present study was to optimize in vitro method for the prediction of drug-induced liver injury using human liver microsomes (HLM). Cytotoxicity test of cyclophosphamide and acetaminophen in HepG2 cells cultured with HLM showed that the newly established condition using 0.375 mg/ml HLM for 24 hr incubation was comparable or more sensitive than the previously established condition using 0.75 mg/ml HLM for 12 hr incubation. Although the cytotoxic effect of troglitazone was completely attenuated by 0.75 mg/ml HLM, it was augmented by 0.375 mg/ml HLM in the presence of the NADPH-generating system. The cytotoxic effect of chlormezanone, a withdrawn drug due to hepatotoxicity in human, was increased by HLM in the presence of the NADPH-generating system. In contrast, the cytotoxic effect of methapyrilene, a withdrawn drug due to hepatotoxicity in rats, was decreased by HLM in the presence of the NADPH-generating system. The present study suggests that the optimized in vitro method using HLM can be useful for the prediction of drug-induced hepatotoxicity.

• Journal of the Korea Safety Management & Science
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• v.26 no.3
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• pp.59-70
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• 2024

This study aims to estimate the scope of damage impact with a real-life explosion case and a damage prediction program (ALOHA) and suggest measures to reduce risk by comparing and analyzing the results using a Probit model. After applying it to the ALOHA program, the toxicity, overpressure, and radiant heat damage of 5 tons of storage scopes between 66 to 413 meters, and the real-life case also demonstrated that most of the damage took place within 300 meters of the LPG gas station. In the Probit analysis, the damages due to radiant heat were estimated as first-degree burns (13-50%), while structural damage (0-75%) and glass window breakage (94-100%) were expected from overpressure, depending on the storage volume. After comparing the real-life case and the damage prediction program, this study concluded that the ALOHA program could be used as the scope of damage impacts is nearly the same as the actual case; it also concluded that the analysis using the Probit model could reduce risks by applying calculated results and predicting the probability of human casualties and structural damages.

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