• Title/Summary/Keyword: Toxic model

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Effect of Diazinon on the Cytoplasmic Organelles of Hepatocytes in Albino Mice (Diazinon이 Mouse의 간세포내 미세구조에 미치는 영향)

  • Kim, Y.H.;Chung, H.S.;Lee, K.S.
    • Applied Microscopy
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    • v.14 no.2
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    • pp.66-80
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    • 1984
  • The organic phosphorus compounds have been widely used as an insecticide, since toxicity of these compounds is especially drastic to the insects than to men and other mammals. The organic phosphates are rapidly hydrolized and hence have little cumulative and ecologic effects. However, due to their acute toxic effects organophosphate have recorded rather high fatalities in men and domestic animals. The organic phosphorus compounds are powerful inhibitors to the carboxylic esterase enzymes such as acetylcholinesterase and pseudocholinesterase. As a result of firm binding characteristics of phosphate radicals to the active sites of enzyme, the activities of these enzymes are inhibited by the organophosphates. The organophosphates such as diazinon is easily observed from skin, gastrointestinal tract, conjunctivas and respiratory tract, and it is converted to more toxic form during metabolism in the liver The present study was carried out in order to investigate the hepatotoxicity of diazinon by observing the changes in the ultrastructure of cytoplasmic organelles of hepatic cells in albino mice. The animals were killed at 6, 12 and 24 hours after administration of 25mg/kg diazinon. The piece of hepatic tissue obtained from each animal was ultrathinly sectioned. The specimens stained by uranyl acetate and lead citrate double contrast methods were observed with JEM model 100B electron microscope. The results obtained were as follows: 1) A prominent dilatation and sacculation of the cisternae of rough endoplasmic reticulum associated with detachment of membrane bound-ribosomes, and disaggregation of the free ribosomes were recognized. 2) The hypertrophy of the smooth endoplasmic reticulum associated with depletion of the glycogen particles was observed. 3) The atrophy of cisternae of Golgi complex was observed. 4) A large number of secondary lysosomes (autophagic vacuoles and residual bodies) were formed. Consequently it is suggested that diazinon would induce disorganization of the cytoplasmic organelles of hepatocytes in albino mice.

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Prediction of $EC_{50}$ of Photobacterium phosphoreum for CAHs and Chlorophenol Derivatives Using QSAR (QSAR방법을 이용한 CAHs와 Chlorophenol 유도체에 대한 $EC_{50}$값 예측)

  • Lee, Hong-Joo;Yoo, Seung-O;Lee, Jeong-Gun;Kim, Byung-Yong;Chun, Uck-Han
    • 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.

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Screening of toxic potential of graphene family nanomaterials using in vitro and alternative in vivo toxicity testing systems

  • Chatterjee, Nivedita;Yang, Ji Su;Park, Kwangsik;Oh, Seung Min;Park, Jeonggue;Choi, Jinhee
    • Environmental Analysis Health and Toxicology
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    • v.30
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    • pp.7.1-7.7
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    • 2015
  • Objectives The widely promising applications of graphene nanomaterials raise considerable concerns regarding their environmental and human health risk assessment. The aim of the current study was to evaluate the toxicity profiling of graphene family nanano-materials (GFNs) in alternative in vitro and in vivo toxicity testing models. Methods The GFNs used in this study are graphene nanoplatelets ([GNPs]-pristine, carboxylate [COOH] and amide [$NH_2$]) and graphene oxides (single layer [SLGO] and few layers [FLGO]). The human bronchial epithelial cells (Beas2B cells) as in vitro system and the nematode Caenorhabditis elegans as in vivo system were used to profile the toxicity response of GFNs. Cytotoxicity assays, colony formation assay for cellular toxicity and reproduction potentiality in C. elegans were used as end points to evaluate the GFNs' toxicity. Results In general, GNPs exhibited higher toxicity than GOs in Beas2B cells, and among the GNPs the order of toxicity was pristine > $NH_2$ > COOH. Although the order of toxicity of the GNPs was maintained in C. elegans reproductive toxicity, but GOs were found to be more toxic in the worms than GNPs. In both systems, SLGO exhibited profoundly greater dose dependency than FLGO. The possible reason of their differential toxicity lay in their distinctive physicochemical characteristics and agglomeration behavior in the exposure media. Conclusions The present study revealed that the toxicity of GFNs is dependent on the graphene nanomaterial's physical forms, surface functionalizations, number of layers, dose, time of exposure and obviously, on the alternative model systems used for toxicity assessment.

A study on combustion gas toxicity of polymeric materials using FTIR gas analysis (FTIR 가스분석에 의한 고분자재료의 연소가스독성 평가)

  • Lee, Doo-Hyung;Kong, Young-Kun
    • Journal of the Korean Society of Hazard Mitigation
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    • v.5 no.4 s.19
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    • pp.79-84
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    • 2005
  • When polymeric materials are exposed to fire condition, a lot of heat and toxic gases evolved and cause damage to property and human being. Especially toxic gases are major hazard to life safety. This study FTIR(Fourier Transform Infrared) spectrometer analysis was performaed to etermine the gas analysis and the concentration of gases evolved from PVC, FRP, SMC and Ureathane foam using ASTM E 1678 fire model. And FED toxicity index calculated from FTIR data also presented. By the comparison of animal test adopted in KS F 2271 and FTIR gas analysis method, FTIR gas analysis method can replace current animal toxicity test and produce precise and quantitative combustion gas data.

Effects of Pahs and Pcbs and Their Toxic Metabolites on Inhibition of Gjic and Cell Proliferation in Rat Liver Epithelial Wb-F344 Cells

  • Miroslav, Machala;Jan, Vondracek;Katerina, Chramostova;Lenka, Sindlerova;Pavel, Krcmar;Martina, Pliskova;Katerina, Pencikova;Brad, Upham
    • Environmental Mutagens and Carcinogens
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    • v.23 no.2
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    • pp.56-62
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    • 2003
  • The liver progenitor cells could form a potential target cell population fore both tumor-initiating and -promoting chemicals. Induction of drug-metabolizing and antioxidant enzymes, including AhR-dependent CYP1A1, NQO-1 and AKR1C9, was detected in the rat liver epithelial WB-F344 "stem-like" cells. Additionally, WB-F344 cells express a functional, wild-type form of p53 protein, a biomarker of genotoxic events, and connexin 43, a basic structural unit of gap junctions forming an important type of intercellular communication. In this cellular model, two complementary assays have been established for detection of the modes of action associated with tumor promotion: inhibition of gap junctional intercellular communication (GJIC) and proliferative activity in confluent cells. We found that the PAHs and PCBs, which are AhR agonists, released WB-F344 cells from contact inhibition, increasing both DNA synthesis and cell numbers. Genotoxic effects of some PAHs that lead to apoptosis and cell cycle delay might interfere with the proliferative activity of PAHs. Contrary to that, the nongenotoxic low-molecular-weight PAHs and non-dioxin-like PCB congeners, abundant in the environment, did not significantly affect cell cycle and cell proliferation; however both groups of compounds inhibited GJIC in WB-F344 cells. The release from contact inhibiton by a mechanism that possibly involves the AhR activation, inhibition of GJIC and genotoxic events induced by environmental contaminants are three important modes of action that could play an important role in carcinogenic effects of toxic compounds. The relative potencies to inhibit GJIC, to induce AhR-mediated activity, and to release cells from contact inhibition were determined for a large series of PAHs and PCBs and their metabolites. In vitro bioassays based on detection of events on cellular level (deregulation of GJIC and/or proliferation) or determination of receptor-mediated activities in both ?$stem-like^{\circ}{\times}$ and hepatocyte-like liver cellular models are valuable tools for detection of modes of action of polyaromatic hydrocarbons. They may serve, together with concentration data, as a first step in their risk assessment.

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Some nanotoxicity effects of copper (60-80 nm) and copper oxide (40 nm) nanoparticles on Artemia salina

  • Isil Canan Cicek Cimen;Durali Danabas;Mehmet Ates
    • Advances in nano research
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    • v.16 no.5
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    • pp.501-508
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    • 2024
  • In this study, nanotoxicity tests were made by exposure of Artemia salina to copper (Cu 60-80 nm) and copper oxide (CuO 40 nm) nanoparticles (NPs) at different concentrations (0.2, 1, 5, 10, 25, and 50 mg/L). The LC50 value of Cu (60-80 nm) NPs on the A. salina individuals at the beginning (0), 24th, 48th and 72nd hours and elimination period was 52.37 mg/L while the LC50 value of CuO (40 nm) NPs was 55.39 mg/L. The results of UV-Vis absorbance values showed that all statistical data revealed that maximum effect was observed between 24-30 hours and 25 ppm absorbance concentration was more effective. The multiple R, correlation coefficient (R2) and adjusted R2 values of Cu NP for the suitable Quadratic model were, respectively; 92.96 %, 86.42 % and 76.71 % while they are 98.31 %, 96.64 % and 94.25 % for CuO NP. Also, the data, was indicated effect size significantly changed based on the type and size of NP. Considering the microscope results, it was clearly noticed that A. salina organisms took the NPs in to their body. The accumulation in the gut of A. salina was observed and the images were taken with phase contrast microscope for both of NPs. The highest decrease for survival rates of A. salina individuals exposed to Cu NP was observed in the 10 ppm concentration (43.47 %) and in the 5 ppm concentration (46.20 %) for CuO NP. The results revealed that Cu and CuO NPS showed different toxic effects and that Cu NPs were more toxic than CuO.

Use of n Mathematical Model to Assess the Effects of Dissolved Organic Phosphorus on Species Competition Among the Dinoflagellates Alexandrium tamarense and Gymnodinium catenatum and the Diatom Skeletonema costatum (수치모델을 이용한 와편모조류 Alexandrium tamarense, Gymnodinium catenatum 및 규조류 Skeletonema costatum의 종간 경쟁에 미치는 용존태 유기인의 영향)

  • Oh, Seok-Jin;Yang, Han-Soeb;Yamamoto, Tamiji
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.40 no.1
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    • pp.39-49
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    • 2007
  • Species competition among the toxic dinoflagellates Alexandrium tamarense and Gymnodinium catenatum and the diatom Skeletonema costatum was simulated using a mathematical model. Prior to the model simulation competition experiments using the three species were conducted to obtain data for validation by the simulation model. S. costatum dominated at a density of ${\sim}10^{4}\;cells/mL$ compared to the other species in the medium with dissolved inorganic phosphorus (DIP). The growth of S. costatum was also stimulated by the addition of dissolved organic phosphorus (DOP), such as uridine-5-monophosphate (UMP) or glycerophosphate (Glycero-P), although this species is unable to take up DOP. This implies that the growth of S. costatum may be supported by DIP, which is hydrolyzed by alkaline phosphatase produced from A. tamarense and G. catenatum. The species competition model was run assuming the environmental conditions of northern Hiroshima Bay, Japan, during spring and summer. G. catenatum increased in cell density and neared the level of S. costatum at the end of the calculation. In the sensitivity analyses by means of doubling and halving parameters, depleted DIP had little effect on the cell density of G. catenatum. However the growth of A. tamarense and S. costatum was significantly affected by changes in the parameter values. These results indicate that if DIP depletion is ongoing, species that have a large phosphate pool in their cells, such as G. catenatum, will predominate in the community.

Dispersion Model of Initial Consequence Analysis for Instantaneous Chemical Release (순간적인 화학물질 누출에 따른 초기 피해영향 범위 산정을 위한 분산모델 연구)

  • Son, Tai Eun;Lee, Eui Ju
    • Journal of the Korean Society of Safety
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    • v.37 no.2
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    • pp.1-9
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    • 2022
  • Most factories deal with toxic or flammable chemicals in their industrial processes. These hazardous substances pose a risk of leakage due to accidents, such as fire and explosion. In the event of chemical release, massive casualties and property damage can result; hence, quantitative risk prediction and assessment are necessary. Several methods are available for evaluating chemical dispersion in the atmosphere, and most analyses are considered neutral in dispersion models and under far-field wind condition. The foregoing assumption renders a model valid only after a considerable time has elapsed from the moment chemicals are released or dispersed from a source. Hence, an initial dispersion model is required to assess risk quantitatively and predict the extent of damage because the most dangerous locations are those near a leak source. In this study, the dispersion model for initial consequence analysis was developed with three-dimensional unsteady advective diffusion equation. In this expression, instantaneous leakage is assumed as a puff, and wind velocity is considered as a coordinate transform in the solution. To minimize the buoyant force, ethane is used as leaked fuel, and two different diffusion coefficients are introduced. The calculated concentration field with a molecular diffusion coefficient shows a moving circular iso-line in the horizontal plane. The maximum concentration decreases as time progresses and distance increases. In the case of using a coefficient for turbulent diffusion, the dispersion along the wind velocity direction is enhanced, and an elliptic iso-contour line is found. The result yielded by a widely used commercial program, ALOHA, was compared with the end point of the lower explosion limit. In the future, we plan to build a more accurate and general initial risk assessment model by considering the turbulence diffusion and buoyancy effect on dispersion.

Evaluation of Stability in the Purified Wood Vinegar and Its Hair Growth Effect (목초액의 안정성 및 모발 성장 촉진 효과)

  • Cho, Young-Ho;Lee, Ju-Yeon;Lee, Jong-Hwa;Cho, Jae-Su;Lee, Gye-Won
    • Journal of Life Science
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    • v.19 no.10
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    • pp.1389-1395
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    • 2009
  • Generally, it takes a long time to purify wood vinegar, and it contains toxic compounds such as tar, methanol, phenol and benzopyrene. To reduce the toxicity of wood vinegar itself, we have developed a new purification method of wood vinegar using an oxidation-cohesion reaction and distillation with an active carbon. We have investigated the physico-chemical change (pH, specific gravity, refractive index and dissolved tar), the change of amount of toxic compounds (carbonyl group, phenol, benzopyrene and residual solvents) and organic acids (formic acid (FA), acetic acid (AA), propionic acid (PA)) of the purified wood vinegar under the long term and accelerated storage conditions. Also, we have evaluated the effect of the purified wood vinegar on hair growth using an alopecia model of C57BL/6 mice. As a result, we could find out that the purified wood vinegar was stable and remained without decay under the storage conditions and benzopyrene, a carcinogenic agent, was not detected in the purified wood vinegar. After topical treatment of the purified wood vinegar solution or minoxidil (MXD) for 2 weeks to dorsal skin, the hair regrowth of the mice accelerated faster than that of the control, with no clinical signs. In conclusion, we could suggest a guideline for quality control of process to reduce the toxic compounds in wood vinegar and it might be a useful hair growth promoter in the treatment of baldness or alopecia.

MPTP-induced vulnerability of dopamine neurons in A53T α-synuclein overexpressed mice with the potential involvement of DJ-1 downregulation

  • Lee, Seongmi;Oh, Seung Tack;Jeong, Ha Jin;Pak, Sok Cheon;Park, Hi-Joon;Kim, Jongpil;Cho, Hyun-seok;Jeon, Songhee
    • The Korean Journal of Physiology and Pharmacology
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    • v.21 no.6
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    • pp.625-632
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    • 2017
  • Familial Parkinson's disease (PD) has been linked to point mutations and duplication of the ${\alpha}$-synuclein (${\alpha}$-syn) gene. Mutant ${\alpha}$-syn expression increases the vulnerability of neurons to exogenous insults. In this study, we developed a new PD model in the transgenic mice expressing mutant hemizygous (hemi) or homozygous (homo) A53T ${\alpha}$-synuclein (${\alpha}$-syn Tg) and their wildtype (WT) littermates by treatment with sub-toxic (10 mg/kg, i.p., daily for 5 days) or toxic (30 mg/kg, i.p., daily for 5 days) dose of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Tyrosine hydroxylase and Bcl-2 levels were reduced in the ${\alpha}$-syn Tg but not WT mice by sub-toxic MPTP injection. In the adhesive removal test, time to remove paper was significantly increased only in the homo ${\alpha}$-syn Tg mice. In the challenging beam test, the hemi and homo ${\alpha}$-syn Tg mice spent significantly longer time to traverse as compared to that of WT group. In order to find out responsible proteins related with vulnerability of mutant ${\alpha}$-syn expressed neurons, DJ-1 and ubiquitin enzyme expressions were examined. In the SN, DJ-1 and ubiquitin conjugating enzyme, UBE2N, levels were significantly decreased in the ${\alpha}$-syn Tg mice. Moreover, A53T ${\alpha}$-syn overexpression decreased DJ-1 expression in SH-SY5Y cells. These findings suggest that the vulnerability to oxidative injury such as MPTP of A53T ${\alpha}$-syn mice can be explained by downregulation of DJ-1.