• Journal of The Korean Society of Clinical Toxicology
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• v.10 no.2
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• pp.103-110
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• 2012

Purpose: The aim of this study was to evaluate the cardiovascular manifestations and clinical course in patients with acute carbon monoxide poisoning. Methods: A retrospective study was conducted over a 36 month period on consecutive patients who visited an emergency medical center and were diagnosed with acute carbon monoxide poisoning. A standardized data extraction protocol was performed on the selected patients. Results: A total of 293 patients were selected during the study period. Cardiac manifestations were observed in 35.2% (n=103) of the patients: hypotension in 11 patients (3.8%), ECG abnormalities in 44 patients (15.0%) and cardiac enzyme abnormalities in 103 patients (35.2%). Echo cardiography was performed on 56 patients with cardiac toxicity: 12 patients had abnormal results (5 patients with global hypokinesia and 7 patients with regional wall akinesia). Five patients died within 3 hours after ED admission, and the remaining patients were discharged alive. At 3 months after discharge, none of these patients had died.The SOFA scores in the severe cardiac toxicity group and non-severe cardiac toxicity group at the time of arrival were $2.53{\pm}2.29$ and $2.19{\pm}2.12$, respectively (p=0.860). Conclusion: Cardiovascular manifestations occur after acute CO poisoning at arateof 35.2%. Even those with severe cardiovascular toxicity recovered well within 10 days after admission. Therefore, the importance of cardiac toxicity after acute CO poisoning is not significant in itself in the clinical course, and the short-term prognosis of cardiac toxicity is unlikely to be unfavorable in acute CO poisoning.

• Journal of Biomedical Engineering Research
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• v.40 no.5
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• pp.143-150
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• 2019

To evaluate the toxicity of ophthalmic drug, the Draize test and Bovine Corneal Opacity and Permeability (BCOP) test commonly used. In Draize test, experimental animals were under stress and pain due to long-term exposure of drug. In addition, regarding physiological functions, animal model is not perfectly reflected a human eye condition. Although some models such as $EpiOcular^{TM}$, HCE model, LabCyte Cornea-Model, and MCTT $HCE^{TM}$ were already presented advanced cornea ex-vivo model to replace animal test. In this sense, cornea tissue structure mimicked ex-vivo toxicity model was fabricated in this study. The corneal epithelial cells (CECs) and keratocytes (CKs) isolated from rabbit eyeball were seeded on non-patterned silk film (n-pSF) and patterned silk film (pSF) at $32,500cells/cm^2$ and $6,500cells/cm^2$. Sequentially, n-pSF and pSF were stacked to mimic a multi-layered stroma structure. The thickness of films was about $15.63{\mu}m$ and the distance of patterns was about $3{\mu}m$. H&E stain was performed to confirm the cell proliferation on silk film. F-actin of CKs was also stained with Phalloidin to observe the cytoskeletal alignment along with patterns of the pSF. In the results, CECs and CKs were shown the good cell attachment on the n-pSF and pSFs. Proliferated cells expressed the specific phenotype of cornea epithelium and stroma. In conclusion, we successfully established the ex-vivo cornea toxicity model to replace the eye irritation tests. In further study, we will set up the human ex-vivo cornea toxicity model and then will evaluate the drug screening efficacy.

• Entomological Research
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• v.48 no.6
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• pp.533-539
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• 2018

The RNA interference (RNAi) has been considered as an important genetic tool and applied to develop a new living modified (LM) crop trait which is an improvement of nutrient quality or pest management. The RNAi of DvSnf7 has been used for resistance to LM maize and the Western Corn Rootworm which is a major agricultural pest for the US Corn Belt. Most of the environmental risk assessments (ERA) of double strand RNA (dsRNA) have been performed using in vitro transcript products, and not in vivo expressed product. A large amount of dsRNA was required for the acute toxicity assay of water fleas. Therefore development of massive dsRNA purification techniques is critical. Daphnia, a freshwater microcrustacean, is a model organism for studying cellular and molecular mechanism involved in life history traits and ecotoxicology. In this study, we established the massive dsRNA purification method using Escherichia coli and implemented acute toxicity assays to Daphnia magna. As a result, the present RNase A and DNase I, dsRNA was efficiently purified without any special techniques or equipment. Even though purified dsRNA existed during the acute toxicity test, lethality or abnormal behavior were not observed in D. magna. These results indicated that GFP and DvSnf7 dsRNA were not significantly affected to D. magna due to their lack of sequence matching in its genome. The purification method of dsRNA and the acute toxicity assay of water fleas using purified dsRNA would be suitable for the toxicological studies of LMOs to aquatic non-target organisms.

• Korean Journal of Pharmacognosy
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• v.50 no.3
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• pp.205-218
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• 2019

This study was conducted to investigate the toxicity symptoms and approximate lethal dose (ALD) of Oplopanax elatus (Nakai) Nakai hydrothermal extract powder by single oral dose toxicity and 4 weeks of repeated oral dose determination. The Sprague-Dawley (SD) male and female rats were treated with 1,250 (low- dosage group), 2,500 (medium- dosage group) and 5,000 (high- dosage group) mg/kg. In the single oral dose toxicity test, no dead animals and toxic symptoms were observed during the experiment. And there were no related with anomalies in normal weight changes and autopsy results. In the four-week repeated oral dose determination test, no death animals and toxicity symptoms were observed during the experiment, and there were no abnormal results in weight changes, feed and negative intake measurements. Results of eye examination, urinalysis, hematological values and serum biochemical values, gross findings and absolute organ were not of singularity. These result demonstrated that no toxic symptoms were observed by the test substance Oplopanax elatus (Nakai) Nakai hydrothermal extract powder under this test condition, and the non-toxic content is determined to be 5,000 mg/kg/day.

• 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.

• The Korean Journal of Pesticide Science
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• v.12 no.4
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• pp.382-390
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• 2008

This study was performed to evaluate the acute toxicity and residual toxicity of the 69 kinds of agrochemicals (41 insecticides, 18 fungicides, and 10 acaricides) against honeybee, Apis mellifera and bumblebee, Bombus terrestris. According to the IOBC standard, the toxicity showed below 30% was classified as non-toxic. Among 41 insecticides, five insecticides (acetamiprid, chlorfenapyr, thiacloprid, milbemectin, and buprofezin+amitraz) against the honeybee; eight insecticides (methomyl, thiodicarb, acetamiprid, chlorfenapyr, thiacloprid, abamectin, spino sad, buprofezin+amitraz) against the bumblebee did not show any toxic effect. Therefore, it thought to being safe. Other 18 fungicides and 10 acaricides were safe against the honeybee and bumblebee. In residual toxicity against the honeybee, eight insecticides (dichlorvos, methomyl, imidachlorprid, emamectin benzoate, spinosad, cartap hydrochloride, chlorfenapyr, and endosulfan) among 41 insecticides tested were safe at three days after treatment; however, sixteen insecticides (dimethoate, fenitrothion, fenthion, methidathion, phenthoate, pyraclofos, fenpropathrin, clothianidin, dinotefuran, thiamethoxam, abamectin, acetamiprid+ethofenprox, acetamiprid+indoxacarb, bifenthrin+imidacloprid, ethofenprox+phenthoate, imidacloprid+methiocarb) still remain high toxicity at eleven days after treatment. Against the bumblebee, residual toxicity showed as safe in seven insecticides (dimethoate, methidation, a-cypermethion, ethofenprox, indoxcarb, chlorpyrifos+a-cypennethrin, esfenvalerate+fenitrochion) at three days after treatment; however, eight insecticides (fenitrothion, pyraclofos, clothianidin, fipronil, acetamiprid+ethofenprox, chlorpyrifos+bifenthrin, ethofenprox+phenthoate, imidacloprid+methiocarb) still showed high toxicity at seven days after treatment. From above results, it will be useful information to select insecticides being safe and effective against the honeybee and bumblebee.

• Tuberculosis and Respiratory Diseases
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• v.67 no.2
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• pp.121-126
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• 2009

Background: Pemetrexed has been prescribed newly as a second line chemotherapy in advanced non-small cell lung carcinoma (NSCLC). The aim of study was to determine the efficacy and toxicity of pemetrexed in advanced NSCLC. Methods: Patients with histologically or cytologically confirmed NSCLC were evaluated from June 2006 to December 2008. The patients had relapsed or progressed after prior chemotherapy treatment. They were treated with intravenous pemetrexed $500mg/m^2$ for 10 min on Day 1 of each 21-day cycle. Results: A total of 89 patients were eligible for analysis. The response rate and disease control rate were 11% and 66%. Non-squamous cell carcinoma histology was significantly associated with a superior response rate (p=0.035) and disease control rate (p=0.009) than squamous cell carcinoma histology. The median survival time was 13 months and the median progression free survival time was 2.3 months. The median survival time of patients with ECOG PS 0~1 was 13.2 months, whereas median survival time was 11.6 months for patients with PS 2 (p=0.002). The median progression free survival time of patients with PS 0~1 were 3.8 months, but 2.1 months for patients with PS 2 (p=0.016). The median progression free survival time of smokers with non-squamous cell carcinoma was 3.4 months, which was significant (p=0.014). Grade 3~4 neutropenia were seen in 7.9% patients. Conclusion: Pemetrexed has efficacy in patients who had prior chemotherapy with advanced NSCLC and less hematologic toxicity.

• Korean Journal of Environmental Biology
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• v.23 no.2 s.58
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• pp.98-105
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• 2005

The relative sensitivity of two freshwater non- biting midges, Chironomus yoshimatsui Martin and Sublette and C. riparius Meigan, was examined for lead, cadmium, and mercury in water- only exposures. Two endpoints were compared to assess toxicity 48 h and 96 h after exposure: Acute toxicity ($50\%$ lethal concentration: $LC_50$) and behavioral toxicity ($50\%$ effective concentration: $EC_{50}$). for the behavioral toxicity, reduction of swimming performance of two midge species in the treated conditions was compared to that in the untreated control. The sensitivities differed depending on the species and heavy metals, although some trends emerged. $LC_50$ values in C. yoshimatsui to cadmium and lead were always higher than those in C. riparius with increasing toxicity, regardless of the exposure times. The opposit was true for the mercury treatment. Similar trends were observed in the $EC_{50}$ values. The $EC_{50}$ values were always lower than the $LC_50$ values in all the treatment cases (midge species, heavy metals, and exposure times). These results indicate that the two midge species respond to the heavy metals differently: C. riparius is sensive to cadmium and lead and C. yoshimatsui to mercury. Behavioral toxicity such as swimming performance can be an effective endpoint for assessing heavy metal toxicity in water.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.16
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• pp.7331-7335
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• 2015

Background: Concurrent chemoradiation with three weekly high dose cisplatin is the non-surgical standard of care for the treatment of locally advanced head and neck cancers. Although this treatment regime is efficacious, it has high acute toxicity, which leads not only to increased treatment cost, but also to increased overall treatment time. Hence, the current study was undertaken to evaluate the acute toxicity and tumor response in head and neck cancer patients treated with concurrent chemoradiation using $40mg/m^2$ weekly cisplatin, which has been our institutional practice. Materials and Methods: This single institution retrospective study included data for 287 head and neck cancer patients treated with concurrent chemoradiation from 2012 to 2014. Results: The mean age of the patients was 48.8 years. The most common site of involvement was oral cavity. Most of the study patients presented with advanced stage disease. The mean overall treatment time was 56.9 days. Some 67.2% had overall complete response to treatment as documented till 90 days from the start of treatment. According to the Radiation Therapy Oncology Group (RTOG) acute radiation morbidity scoring criteria, mucositis was seen in 95.1% of the patients. Dermatitis and emesis were observed in 81.9% and 98.6%, respectively. Regarding haematological toxicity, 48.8% and 29.6% suffered from anaemia and leukopenia, respectively, during treatment. Acute kidney injury was assessed using the Common Terminology Criteria for Adverse Events (CTCAE), and was found in 18.8% of the patients. Conclusions: Concurrent chemoradiotherapy with weekly cisplatin is an effective treatment regime for head and neck cancers with reasonable toxicity which can be used in developing countries, where cost of treatment is so important.

• Journal of Korean Society on Water Environment
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• v.34 no.1
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• pp.77-83
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• 2018

This paper aims to evaluate the results of toxicity testing with Daphnia magna and Vibrio fischeri on wastewater samples which might be influenced by ion imbalance. The effluents from factories were found to be more toxic with high salinity levels than those from public wastewater treatment plant (WTP) and sewage treatment plant (SWP). Clion composition was highest in the effluent, in terms of percentage, which was followed by $Na^+$, $SO_4^{2-}$ and $Ca^{2+}$. $K^+$ and $Mg^{2+}$ ion was relatively low. The sensitivity of D. magna test results was higher than V. fischeri. Among samples which were proved by V. fischeri testing to be nontoxic, the composition ratio of each ion whether toxic samples or nontoxic samples which were decided by D. magna toxicity testing, were compared. $Na^+$, $K^+$, $Ca^{2+}$, $Mg^{2+}$ ion composition ratio showed high level in nontoxic samples whereas $SO_4^{2-}$ and $Cl^-$ ion composition ratio was high in toxic samples. Accordingly, $SO_4^{2-}$ and $Cl^-$ ion seemed to be considered the ions causing toxicity in effluent. Toxicity from some categories of industries (Mining of non-metallic minerals, Manufacture of basic organic petrochemicals, Manufacture of other basic organic chemicals, Manufacture of other chemical products etc.) seemed to be influenced by salinity. The Ion concentration in influent and effluent were similar. Concentration of $Na^+$, $Cl^-$, $K^+$, $Ca^{2+}$ ions were high in influent, however $Mg^{2+}$ and $SO_4^{2-}$ ions were high in effluent.