• Title/Summary/Keyword: toxicological data

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Toxicological Aspects of Carboxylesterases -A Sensitive Biomarker of Organophosphate Toxicity-

  • Satoh, Tetsuo;Suzuki, Satoshi;Hosokawa, Masakiyo
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1998.11a
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    • pp.108-113
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    • 1998
  • Egasyn is accessory protein of ${\beta}$-glucuronidase(${\beta}$-G) in the liver microsomes. Liver microsomal ${\beta}$-G is stabilized within the luminal site of the microsomal vesicles by complexation with egasyn which is one of carboxylesterase isozymes. We investigated the effects of organophosphorus compounds(OPs) such as insecticides on the dissociation of egasyn-${\beta}$-glucuronidase(EG) complex. The EG complex was easily dissociated by administration of OPs, i.e., Fenitrothion, EPN, Phenthionate, and bis-p-nitrophenyl phosphate(BNPP), and resulting ${\beta}$-G dissociated was released into blood, leading to the rapid and transient increase of plasma ${\beta}$-G level with a concomitant decrease of liver microsomal ${\beta}$-G level. In a case of phenthionate treatment, less increase in plasma ${\beta}$-G level was observed, as compared with those of other OPs. This may be explained by a fact that phenthionate was easily hydrolyzed by carboxylesterase. Similarly, carbamate insecticides such as Carbaryl caused rapid increase of plasma ${\beta}$-G level. In contrast, no significant increase of plasma ${\beta}$-G level was observed when pyrethroid insecticides were administered to rats. This is due to a fact that pyrethroids such as Phenthrin and Allethrin were easily hydrolyzed by A-esterase as well as carboxylesterase. On the other hand, addition of OPs to the incubation mixture containing liver microsomes caused the release of ${\beta}$-G from microsomes to the medium. From these in vivo and in vitro data, it is concluded that increase of the plasma ${\beta}$-G level after OPs administration is much more sensitive biomarker than cholinesterase inhibition to acute intoxication of OPs and carbamates.

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Anti-aging Effect and Gene Expression Profiling of Aged Rats Treated with G. bimaculatus Extract

  • Ahn, Mi Young;Hwang, Jae Sam;Yun, Eun Young;Kim, Min-Ji;Park, Kun-Koo
    • Toxicological Research
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    • v.31 no.2
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    • pp.173-180
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    • 2015
  • Extract from Gryllus bimaculatus crickets inhibits oxidation at the DNA level, with reduced production of 8-hydroxy-2'-deoxyguanosine (8-OHdG). Microarray analyses were performed with a rat 28K cDNA clone set array to identify the gene expression profiles of aged (10 months old) Wistar Kyoto rats treated for one month with 100 mg/kg G. bimaculatus ethanol extract to assess the effects. The extract produced a meaningful anti-edema effect, evident by the inhibition of creatinine phosphokinase activity. The weights of abdominal and ovarian adipose tissues were reduced and the proportion of unsaturated fatty acids in adipose tissues was increased in an extract dose-dependent manner. Compared with untreated control rats, rats treated with the extract displayed the upregulation of 1053 genes including Fas (tumor necrosis factor receptor superfamily, member 6), Amigo3 (adhesion molecule with an immunoglobulin-like domain), Reticulon 4, 3-hydroxy-3-methylglutaryl-coenzyme (Hmgcr; a reductase), related anti-fatigue (enzyme metabolism), and Rtn antioxidant, and the downregulation of 73 genes including Ugt2b (UDP glycosyltransferase 2 family), Early growth response 1, and Glycoprotein m6a. Data suggest that G. bimaculatus extract may have value in lessening the effects of aging, resulting in a differential gene expression pattern indicative of a marked stress response and lower expression of metabolic and biosynthetic genes.

The Environmental Impact Quotient on Fruit and Vegetables Pesticides in Korea (국내 과채류에 등록된 농약에 대한 환경영향지수)

  • Oh, Kyeong-Seok;Lee, Byung-Moo;Sung, Ha-Jung;Oh, Hong-Gyu;Ihm, Yang-Bin;Kyung, Kee-Sung
    • The Korean Journal of Pesticide Science
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    • v.7 no.2
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    • pp.123-130
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    • 2003
  • The Environmental Impact Quotient(EIQ) has been used to organize the extensive toxicological and soil residue data available on some fruit vegetables pesticides into a usable form for field use. It addresses a majority of the environmental concerns that are encountered in agricultural systems including farm worker, consumer, ecological and environmental safety. The EIQ made use of the rating system by using the EIQ equation. The EIQ of pesticides registered for oriental melon was higher than that of other in terms of farm worker, consumer and environmental safety. Pesticides registered for red pepper showed highest EIQ in ecosystem. The EIQ decreased in order of insecticide> fungicide> herbicide> plant growth regulator. The environment Impact Quotient for the pesticides registered in fruit and vegetables decrease gradually.

Life-Cycle Assessment (LCA) for Eco-Design in a Wastewater Reuse Facility (친환경 설계를 위한 하수처리수 재이용시설의 전과정 평가)

  • Lee, Sin-Won;Kim, Sung-Keun
    • KSCE Journal of Civil and Environmental Engineering Research
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    • v.31 no.2D
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    • pp.255-266
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    • 2011
  • In order to evaluate the environmental load occurring from the whole life cycle of a facility, LCA (Life Cycle Assessment) adopted by ISO is not only applied as an individual product but rather a complicated system involving buildings and/or infrastructure in a wide range of scope. The introducing of LCA to a wastewater reuse facility will assist to understand not only the treatment of water contaminants but also the overall system related to the interaction of involved, potential issues. This research implemented LCA for the establishment of the wastewater reuse facility. The results show that a fresh water aquatic Eco-toxicological Impact (88.3%) is the largest environment concern and the maintenance & operation phase has the most impact on the environment utilizing life cycle for the wastewater reuse facility. The civil works and chemical treatments in the maintenance & operation phase led to the biggest environmental impact. The results of this research can provide pertinent data of investigating opportunities for environmental improvement not limited to public officers regulating environmental policies, and could be used to make decisions for an environmentally sound and sustainable design in the initial phase of construction.

Prediction of Photo-Carcinogenicity from Photo-Ames Assay (Photo-Ames Assay를 이용한 광발암성 예측)

  • Hong Mi Young;Kim Ji Young;Chung Moon Koo;Lee Michael
    • Environmental Mutagens and Carcinogens
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    • v.25 no.1
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    • pp.6-12
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    • 2005
  • Many compounds might become activated after absorption of UV light energy. In some cases, the resulting molecule may undergo further biological reaction of toxicological relevance related especially to the photo-carcinogenicity resulting from photo-genotoxicity. However, no regulatory requirements have been issued with the exception of guideline issued by the Scientific Committee of Cosmetology, Commission of the European Communities (SCC/EEC) on the testing of sunscreens for their photo-genotoxicity. Thus, the objectives of this study are to investigate the utility of photo-Ames assay for detecting photo-mutagens, and to evaluate its ability to predict rodent photo-carcinogenicity. Photo-Ames assay was performed on five test substances that demonstrated positive results in photo-carcinogenicity tests: 8-methoxypsoralen (photoactive substance that forms DNA adducts in the presence of ultraviolet A irradiation), chlorpromazine (an aliphatic phenothiazine an a-adr-energic blocking agent), lomefloxacin (an antibiotic in a class of drugs called fluoroquinolones), anthracene (a tricyclic aromatic hydrocarbon a basic substance for production of anthraquinone, dyes, pigments, insecticides, wood preservatives and coating materials) and retinoic acid (a retinoid compound closely related to vitamin A). Out of 5 test substances, 3 showed a positive outcome in photo-Ames assay. With this limited data set, an investigation into the predictive value of this photo-Ames test for determining the photo-carcinogenicity showed that photo-Ames assay has relatively low sensitivity (the ability of a test to predict carcinogenicity). Thus, to determine the use of in vitro genotoxicity tests for prediction of carcinogenicity,' several standard photo-genotoxicity assays should be compared for their suitability in detecting photo-genotoxic compounds.

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Chemical Risk Assessment Screening Tool of a Global Chemical Company

  • Tjoe-Nij, Evelyn;Rochin, Christophe;Berne, Nathalie;Sassi, Alessandro;Leplay, Antoine
    • Safety and Health at Work
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    • v.9 no.1
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    • pp.84-94
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    • 2018
  • Background: This paper describes a simple-to-use and reliable screening tool called Critical Task Exposure Screening (CTES), developed by a chemical company. The tool assesses if the exposure to a chemical for a task is likely to be within acceptable levels. Methods: CTES is a Microsoft Excel tool, where the inhalation risk score is calculated by relating the exposure estimate to the corresponding occupational exposure limit (OEL) or occupational exposure band (OEB). The inhalation exposure is estimated for tasks by preassigned ART1.5 activity classes and modifying factors. Results: CTES requires few inputs. The toxicological data, including OELs, OEBs, and vapor pressure are read from a database. Once the substance is selected, the user specifies its concentration and then chooses the task description and its duration. CTES has three outputs that may trigger follow-up: (1) inhalation risk score; (2) identification of the skin hazard with the skin warnings for local and systemic adverse effects; and (3) status for carcinogenic, mutagenic, or reprotoxic effects. Conclusion: The tool provides an effective way to rapidly screen low-concern tasks, and quickly identifies certain tasks involving substances that will need further review with, nevertheless, the appropriate conservatism. This tool shows that the higher-tier ART1.5 inhalation exposure assessment model can be included effectively in a screening tool. After 2 years of worldwide extensive use within the company, CTES is well perceived by the users, including the shop floor management, and it fulfills its target of screening tool.

Evaluation of the in vitro biological activity of selected 35 chemicals (35종의 특정 화학성분들의 in vitro 활성 평가)

  • Shin, Han-Jae;Sohn, Hyung-Ok;Park, Chul-Hoon;Lee, Hyeong-Seok;Min, Young-Keun;Hyun, Hak-Chul
    • Journal of the Korean Society of Tobacco Science
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    • v.29 no.1
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    • pp.30-40
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    • 2007
  • The objective of this study was to investigate the contribution of various smoke constituents to the toxicological activity of total particulate matter(TPM) or the gas/vapor phase(GVP). These components included phenol compounds, aromatic amines, polycyclic aromatic hydrocarbons, heterocyclic amines, and carbonyl compounds. The mutagenic and cytotoxic potencies were assessed using the Salmonella mutagenicity assay with S. typimurium TA98 strain and the neutral red uptake cytotoxicity assay(NRU) with BALB/c 3T3 fibroblast cells, respectively. The Salmonella mutagenicity test showed that heterocyclic amines exhibited significantly higher levels of toxicity compared to other smoke constituents. Among them, 2-amino-3,4-dimethylimidazo[4,5-f]quinoline(MeIQ) was shown the most mutagenic compound with a specific mutagenicity of $7.9{\times}10^5\;revertants/{\mu}g$. An analysis of the possible contribution revealed that MeIQ account for only 0.85% of the 2R4F-TPM mutagenicity in TA98. NRU data demonstrated that high cytotoxic activity was obtained for hydroquinone, formaldehyde, and acrolein. Based on the results of the present study, the contribution of acrolein to the cytotoxicity of the GVP fraction was calculated as 61%. Thus, a large proportion of the cytotoxic activity of this complex mixture, cigarette smoke gas phase, can be attributed to the acrolein.

Roles of Matrix Metalloproteinase-2 and -9 on the H-ras-Induced Invasive Phenotype in Human Breast Epithelial Cells and Human Fibrosarcoma Cells

  • Kim, Mi-Sung;Won, Ju-Hye;Aree Moon
    • Toxicological Research
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    • v.14 no.4
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    • pp.569-575
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    • 1998
  • One of the most frequent dejects in human cancer is the uncontrolled activation of the ms-signaling pathways. Significant evidence has accumulated to directly implicate members of the matrix metalloproteinases (MMPs) in tumor invasion and metastasis formation. We have previously shown that MMP-9 expression was significantly enhanced in the ras-tranfected HT1080 human fibrosarcoma cells at the mRNA level. In the present study, we investigated the roles of MMP-2 and -9 on the H-ras-induced invasive phenotypes of MCF 10A human breast epithelial cells and HT 1080 human fibrosarcoma cells. We show that H-ras is able to induce or enhance a signaling pathway leading to the enhancement of an invasive phenotype in both MCF10A and HT1080 cells as determined by matrigel invasion assay. We then examined the effect of H-ras activation on the expression of MMP-2 and -9 by measuring enzymatic activities and mRNA levels. Our data clearly demonstrated that H-ras prominently induces expression of MMP-2 in MCF10A cells, while it efficiently up regulates MMP-9 in HT1080 cells. Taken together, these findings suggest that the correlation between ras-mediated invasiveness and enhanced expression of MMPs may be cell type-specific: MMP-9 is closely associated with the invasive phenotype induced by ras activation in fibrosarcoma cells, whereas MMP-2 is more likely associated with it in epithelial cells.

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Comparison Between TCDD and 3MC Action on CYP1A1 Expression and EROD Activity in the Isolated Perfused Female Rat Liver

  • Ahn, Mee R.;Sheen, Yhun Y.
    • Toxicological Research
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    • v.14 no.4
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    • pp.587-594
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    • 1998
  • In order to understand the mechanism if the regulation of CYP 1A1 gene expression and ethoxyresorufin deethylase (EROD) activity in ex vivo system, we have studied the action of TCDD and 3MC in the isolated perfused female rat liver. CYP1A1 mRNA level and EROD activity were measured in rat liver that was isolated and perfused with various chemicals such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 3-methylcholanthrene (3MC), 17$\beta$-estradiol (E$_2$), morin. TCDD or 3MC alone perfusion into female rat liver resulted in increase of CYP 1A1 mRNA level and the magnitude of stimulation was six times higher with TCDD treatment than 3MC treatment. However E$_2$ perfusion into female rat liver showed inhibition of CYP 1A1 mRNA level. When 10$^{-8}$ M E$_2$ was administered concomitantly with either 10$^{-9}$ M TCDD or 10$^{-9}$ M 3MC, stimulated CYP 1A1 mRNA by either TCDD or 3MC was inhibited. Morin was examined for its effects on CYP 1A1 mRNA level and result was similar to that was observed with estrogen. EROD activity was also stimulated with either TCDD or 3MC perfusion, and the magnitude of EROD stiumlation was smaller than that of CYP 1A1 mRNA stimulation in response to TCDD or 3MC perfusion. Unlike CYP1A1 mRNA level, stimulation of EROD activity was greater with 3MC than TCDD. Concomitant perfusion either E$_2$ or morin with TCDD or 3MC inhibited 3MC perfusion or TCDD perfusion stimulated EROD activity. These data suggested that TCDD and 3MC might act diffrently in terms of regulation of CYP 1A1 gene expression in rat liver.

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Time-dependent Changes of Cadmium and Metallothionein after Short-term Exposure to Cadmium in Rats

  • Cho, Mi-Ran;Kang, Hwan-Goo;Jeong, Sang-Hee;Cho, Myung-Haing
    • Toxicological Research
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    • v.26 no.2
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    • pp.131-136
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    • 2010
  • The time-dependent changes in cadmium (Cd) concentration were studied in Female Sprague-Dawley (SD) rats during and after Cd exposure via drinking water (10 and 50 ppm) for 30 days. The cadmium concentration in muscle, liver, kidney, blood plasma, and urine, and the metallothionein concentration in blood plasma were determined every 10 days during exposure and every 7 days after exposure for 3 weeks. The muscle Cd concentration did not change during, and neither after, exposure. The liver Cd concentration increased from 1.4 to 3.3 (at 10 ppm) and from 6.1 to 10.1 folds (at 50 ppm) during exposure and remained higher than those of controls in both groups even during post-exposure period. The kidney Cd concentrations were 2.3 to 5.1 (at 10 ppm) and 4.9-14.0 folds (at 50 ppm) higher than those of controls during exposure and also remained elevated during the post-exposure period. Plasma Cd concentrations were not significantly different from those of controls in both groups. Urine Cd concentrations were more than 2 folds (at 10 ppm) and 6.5 to 12.6 folds (at 50 ppm) higher than those of controls but rapidly decreased over the 7 days of withdrawal. Blood plasma metallothionein concentrations were more than 2.4 folds (at 10 ppm) and 3.1 to 7.4 folds (at 50 ppm), and they remained elevated till 7 days (10 ppm) and 14 days (at 50 ppm) after exposure. Our data support that Cd in urine could be a useful biomarker during Cd exposure period and metallothionein in blood plasma could be as a supportive biological marker for during and post Cd exposure.