• Journal of The Korean Society of Clinical Toxicology
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• v.10 no.1
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• pp.22-32
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• 2012

Purpose: The purpose of this study was to examine the occurrence of toxic exposure cases in Korean emergency centers using a toxic exposure surveillance system-based report form and to provide guidelines for the prevention and treatment of toxic exposures. Methods: We retrospectively reviewed the medical records of toxic exposure patients who had visited emergency centers from January 2009 to December 2009. Epidemiology data points for the toxic exposure cases included age, gender, type of exposure, number and kind of substances involved, reason and route of poison exposure, management of the patients in the emergency departments, and the clinical outcome. Results: A total of 3,501 patients from 12 emergency departments were enrolled in the study. 50.0% of the total exposure patients were male and 63.0% of the total cases were fatal. Acute intoxication occurred in 91.3% of the total patients and suicidal intent was the most common (43.3%) reason for exposure. The most common route of exposure was ingestion (75.9%). Of the total cases, pesticides were involved in 26.3%, sedatives/hypnotics/antipsychotics were involved in 22.0%, and bites and envenomations were involved in 15.7%. Conclusion: We provided a database of patients who were admitted to emergency departments after poisoning incidents. We recommend that toxicology professionals develop a classification scheme for toxicants which is adequate for Korean domestic circumstances and initiate a toxic surveillance system for all types of exposures. With support of a psychiatric surveillance system for suicidal patients and establishment of social mediation for pesticide poisoning, major reductions in poison exposures can be achieved.

• International Journal of Oral Biology
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• v.37 no.2
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• pp.43-50
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• 2012

The use of high throughput screening (HTS) in drug development is principally for the selection new drug candidates or screening of chemical toxicants. This system minimizes the experimental environment and allows for the screening of candidates at the same time. Umbilical cord-derived stem cells have some of the characteristics of fetal stem cell and have several advantages such as the ease with which they can be obtained and lack of ethical issues. To establish a HTS system, optimized conditions that mimic typical cell culture conditions in a minimal space such as 96 well plates are needed for stem cell growth. We have thus established a novel HTS system using human umbilical cord derived-mesenchymal stem cells (hUC-MSCs). To determine the optimal cell number, hUC-MSCs were serially diluted and seeded at 750, 500, 200 and 100 cells per well on 96 well plates. The maintenance efficiencies of these dilutions were compared for 3, 7, 9, and 14 days. The fetal bovine serum (FBS) concentration (20, 10, 5 and 1%) and the cell numbers (750, 500 and 200 cells/well) were compared for 3, 5 and 7 days. In addition, we evaluated the optimal conditions for cell cycle block. These four independent optimization experiments were conducted using an MTT assay. In the results, the optimal conditions for a HTS system using hUC-MSCs were determined to be 300 cell/well cultured for 8 days with 1 or 5% FBS. In addition, we demonstrated that the optimal conditions for a cell cycle block in this culture system are 48 hours in the absence of FBS. In addition, we selected four types of novel small molecule candidates using our HTS system which demonstrates the feasibility if using hUC-MSCs for this type of screen. Moreover, the four candidate compounds can be tested for stem cell research application.

• Applied Microscopy
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• v.34 no.4
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• pp.241-254
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• 2004

Kidney had recovery functions against toxicants, ischemia, reperfusion-induced damage, acute-renal failure (ARF). Urinary epidermal growth factor (EGF) is produced by the juxtaglomerular apparatus. Kidney accumulates or excretes the EGF. In case of renal diseases, excreted EGF was decreased. The aim of this study is to evaluate the effects squalene (SQ) on the prevention of experimental acute renal failure induced by glycerol. In case of in vitro study, we investigated the expression of EGF by RT-PCR. After the proximal tubular cells was isolated, glycerol (1, 2, 4 mM) or glycerol plus squalene (0.1, 0.05 or 0.1%) was added. In case of in vivo study, we investigated the changes of BUN, creatine, and ultrastructure. Experimental groups were divided into four groups. Group 1 was normal mouse. Group 2 was injected with SQ only (180 mg/kg). Group 3 was not treated with squalene after intraperitoneal contamination of glycerol (50%, 8 ml/kg). And, Group 4 was treated with squalene (180 mg/kg) after intraperitoneal contamination of glycerol (50%, 8 ml/kg). All groups were used to 7 mice. In the results, we investigated the glycerol induced renal failure. The expression of EGF mRNA was decreased in renal proximal tubules when treated with only glycerol. SQ increased the mRNA expression of EGF in renal proximal tubules. SQ also quickly recovered the levels of BUN and creatine compared with those of mice treated with only glycerol (P<0.01). In case of ultrastructure, group 3 had heavily damaged mitochondria, but, mitochondria in group 4 had evidences of the recovery. It was concluded that SQ had the recovery effects for the glycerol-induced acute renal failure.

• Toxicological Research
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• v.20 no.1
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• pp.71-82
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• 2004

Changes in cell cycle control in the lungs and liver of the B6C3F1 mice (20 males per each group) exposed to ozone (0.5 ppm), 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK, 1.0 mg/kg), and dibutyl phthalate (DBP, 5,000 ppm) after 52 weeks were examined through Western, Northern blot, and immunohistochemistry based on alterations in protein expression levels of G1/S checkpoints (cyclin D1, cyclin E, and PCNA), G2/M checkpoints (cyclin B1, cyclin G, and cyclin A), negative regulators (p53, p21, GADD45, and p27), and positive regulator (mdm2). Expression levels of cyclins D1, E, G, PCNA, mutant p53, and mdm2 proteins were higher in the lungs and livers treated with combination of toxicants than in those treated with ozone only. Expression levels of the wild-type and mutant p53, p21, GADD45, p27, and mdm2 proteins and mRNAs were higher in toxicant-treated groups than those of the control. Immunohistochemical analysis revealed staining intensities of the PCNA, cyclin D1, c-myc and mdm2 protein- treated lungs and livers were stronger than those of the control group. Our results showed that combined treatment of ozone with NNK/DBP altered the cell cycle control through instability of the wild-type p53 gene. Such pivotal p53-mediated cell cycle alterations may be responsible for the toxicity observed under our experimental condition. These results may be applied to risk assessment of mixture-induced toxicity.

• Journal of Life Science
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• v.19 no.6
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• pp.799-803
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• 2009

The killing of male germ cells by radiation and other toxicants has recently been attributed to apoptosis, but a critical evaluation of the presence of the different features of apoptosis in each epithelial stage has not been performed. In this study, mouse testes exposed to radiation were examined by light microscopy and terminal transferase-mediated end labeling (TUNEL) with periodic acid-Schiff (PAS) stains to determine whether the cells were apoptotic according to several criteria. Apoptosis was easily recognized by the presence of peroxidase-stained, entirely apoptotic bodies. In the TUNEL-positive cells or bodies, the stained products correlated precisely with the typical morphologic characteristics of apoptosis as seen at the light microscopic level. The changes that occurred from 0 to 24 hours after exposing the mice to 2 Gy of gamma-rays (2 Gy/min) were examined. The numbers of apoptotic cells reached a peak at 12 hours after irradiation and then declined. The mice that received 0-8 Gy of gamma-rays were examined 8 hours after irradiation. Dose-response relationships were generated for each stage of the epithelial cycle by counting TUNEL-positive cells. The dose-response curves were linear- quadratic [y=(-0.014${\pm}$0.009)$D^{2}$+(0.31${\pm}$0.697)D+0.3575. Where y=the number of apoptotic cells per seminiferous tubule, and D=the irradiation dose in Gy, $r^{2}$=0.9] and there was a significant relationship between the frequency of apoptotic cells and the radiation dose. Although the maximum response was produced by 8 Gy, even 0.5 Gy induced marked changes. These changes were most pronounced in B spermatogonia of stage V and the spermatocyte at the mitotic cells of stage XII.

• Applied Biological Chemistry
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• v.31 no.3
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• pp.226-233
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• 1988

Some physico-chemical properties and biological activities of new fungicide formulations were tested to investigate a feasibility of water-floating formulation development for sheath blight control in rice. Pencycuron[1-(4-chlorobenzyl)-1-cyclopentyl-3-phenylurea] and flutolanil$({\alpha},{\alpha},{\alpha}$-trifluoro-3'-isopropoxy-O-toluanilide) were chosen as toxicants for the formulations. Vegetable oil and surface active agents were used as a floating agent and spreader, respectively. All the formulations tested showed an excellent spreadability on the water having over $35cm^2/mg$ and were chemically stable, which the degradation rates of active ingredients were less than 10% after 12 weeks of storage at $50^{\circ}C$. Most of the applied test formulation of pencycuron was retained within 0.5cm of the surface paddy water, while that of flutolanil was vertically dispersed in the water. Inhibition activity of the tested pencycuron formulation on the sclerotia germination of the pathogen in paddy water was maintained over 30 days after the formulation treatment. Control effect of 4% pencycuron water-floating formulated with surface active agent of hydro-lipophyllic balance 4.3 on the disease in rice was equal to the reference fungicide(pencycuron 25% WP) when the former was treated one day before the transplantation of rice seedlings. Overflowing the submerged paddy water after the formulation treatment resulted in a deterious effect on the disease control.

• Journal of Korean Society of Occupational and Environmental Hygiene
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• v.25 no.2
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• pp.134-145
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• 2015

Objectives: An objective of this study was to perform a risk assessment and social cost-benefit analysis for revising permissible exposure limits for seven substances: Nickel(Insoluble inorganic compounds), benzene, carbon disulfide, formaldehyde, cadmium(as compounds), trichloroethylene, touluene-2,4-diisocyanate. Materials and Methods: The research methods were divided into risk and hazard assessment and cost-benefit analysis. The risk and hazard assessment for the seven substances consists of four steps: An overview of GHS MSDS(1st), review of document of ACGIH's TLVs (2nd), comparison between international occupational exposure limits and domestic permissible exposure limits(3rd), and analysis of excess workplace and excess rate for occupational exposure limits based on previous work environment measurement data(4th). Total cost was estimated using cost of local exhaust ventilation, number of excess workplace and penalties for exceeding a permissible exposure limit. On the other hand, total benefit was calculated using the reduction rate of occupational disease, number of workplaces treating each substance and industrial accident compensation. Finally, the net benefit was calculated by subtracting total cost from total benefit. Results: All the substances investigated in this study were classified by CMR(Carcinogens, Mutagens or Reproductive toxicants) and their international occupational exposure limits were stricter than the domestic permissible exposure limits. As a result of excess rate analysis, trichloroethylene was the highest at 11%, whereas nickel was the lowest at 0.5%. The excess rates of all substances except for trichloroethylene were observed at less than 10%. Among the seven substances, the total cost was highest for trichloroethylene and lowest for carbon disulfide. The benefits for the seven substances were higher than costs estimated based on strengthening current permissible exposure limits. Thus, revising the permissible exposure limits of the seven substances was determined to be acceptable from a social perspective. Conclusions: The final revised permissible exposure limits suggested for the seven substances are as follows: $0.2mg/m^3$ for nickel, 0.5 ppm(TWA) and 2.5 ppm(STEL) for benzene, 1 ppm(TWA) for carbon disulfide, $0.01mg/m^3$(TWA) for cadmium, 10 ppm(TWA) and 25 ppm(STEL) for trichloroethylene, 0.3 ppm(TWA) for formaldehyde, and 0.005 ppm(TWA) and 0.02 ppm(STEL) for toluene diisocynate(isomers).

• Molecular & Cellular Toxicology
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• v.1 no.4
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• pp.256-261
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• 2005

The recent DNA microarray technology enables us to understand gene expression profiling in cell line and animal models. The technology has potential possibility to comprehend mechanism of multiple genes were related to compounds which have toxicity in biological system. So, microarray system has been used for the prediction of toxicity through gene expression induced by toxicants. It has been shown that compounds with similar toxic mechanisms produce similar changes in gene expression in vivo system. Here we focus on the use of toxicogenomics for the determination of gene expression analysis associated with hepatotoxicity in rat liver and cell line (WB-F344). Methotrexate (MTX) is a chemotherapy agent that has been used for many years in the treatment of cancer because it affects cells that are rapidly dividing. Also it has been known the toxicity of MTX, in a MTX abortion, it stops embryonic cells from dividing and multiplying and is a non-surgical method of ending pregnancy in its early stages. We have shown DNA microarray analyses to assess MTX-specific expression profiles in vivo and in vitro. Male Sprague-Dawely VAF+ albino rats of 5-6 weeks old and WB-F344 cell line have been treated with MTX. Total RNA was isolated from Rat liver and cell line that has treated with MTX. 4.8 K cDNA microarray in house has been used for gene expression profiling of MTX treatment. We have found quite distinct gene expression patterns induced by MTX in a cell line and in vivo system.

• Korean Journal of Environmental Agriculture
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• v.2 no.2
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• pp.108-113
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• 1983

There has been two kind of research fields in evaluating the ecotoxicity of chemicals The one is a bioassay and the other is an ecosystem analysis. The toxicants are transported into different biota, which have quite different environmental behaviour patterns and toxic properties. The effects of pesticides (butachlor, carbofuran, and tricyclazole) on periphyton community was studied by analyzing content of chlorophyll-a and autotrophic index (AI) that is a means of determining the trophic nature of the periphyton community. Results indicated that the content of chlorophyll-a was not influenced by the pesticides. The growth of algae was inhibited by sunshine period. And AI value is 43-2027: the large value indicates heterotrophic periphyton community, and was not affected by pesticides.

• Korean Journal of Veterinary Research
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• v.44 no.3
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• pp.379-387
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• 2004

When an organism is exposed to various toxicants chronically, reactive oxygen species(ROS) are accumulated and eventually result in several biological effects from gene expression to cell death. In the present study we investigated the oxidative damage of 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin(TCDD) and/or benzo(a)pyrene (B(a)P) in C100 cells. C100 cells treated with TCDD(30 nM) and B(a)P($3{\mu}M$) underwent diverse oxidative stress as determined through thiobarbituric acid-reactive substances(TBARS) formation, DNA fragmentation, DNA single strand break(SSB) assay, immunohistochemical staining of 8-hydroxy-2'-deoxyguanosine(8-OHdG), and mRNA expressions of antioxidant enzymatic genes such as Cu/Zn-SOD gene, GPx(glutathione peroxidase 5) gene, and catalase gene. Lipid peroxidation in C100 cells was determined through measuing the formation of TBARS. For theat, the cells were pretreated with TCDD(30 nM) and/or B(a)P($3{\mu}M$) for 0.5, 1, 2 and 4 days. TBARS formation was increased in TCDD(30 nM) and B(a)P($3{\mu}M$) and mixture($30nM\;TCDD+3{\mu}M\;B(a)P$) and positive control treatment groups comparing to the controls. Mixture treatment induced more DNA fragmentation than the single treatment group at day 6. Also, SSB in all treatment groups was clearly observed when compared with the negative control group. As with the expression of antioxidant enzyme, GPx 5mRNA, B(a)P alone and mixture($30nM\;TCDD+3{\mu}M\;B(a)P$) treatment were higher comparing to those of the negative control and TCDD treatment groups. Our results suggest that exposure of C100 cells to mixture of TCDD and B(a)P leads to significant oxidative damage comparing to the exposures to the individual chemicals. Mechanisms of action are discussed. Additional studies are needed to elucidate the detailed mechanism of mixture-induced toxicity.