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REFERENCE LINKING PLATFORM OF KOREA S&T JOURNALS
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The Korean Society of Toxicology
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Volume 18, Issue 4 - Dec 2002
Volume 18, Issue 3 - Sep 2002
Volume 18, Issue 2 - Jun 2002
Volume 18, Issue 1 - Mar 2002
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Safety and Risk Assessment of Arsenic in Drinking Water
Toxicological Research, volume 18, issue 2, 2002, Pages 107~116
Arsenic (As) is a ubiquitous element found in several forms in foods and water. Although certain foods, such as marine fish, contain substantial levels of organic arsenic forms, they are relatively low in toxicity compared to inorganic forms. in contrast, arsenic in drinking water is predominantly inorganic and highly toxic. Chronic ingestion of arsenic-contaminated drinking water is therefore the major pathway posing potential risk to human hearth. since the early 1990s in Bangladesh ozone, arsenic exposure has caused more than 7,000 deaths and uncounted thousands shout symptoms of long-term arsenic poisoning. Significant portion of world populations are exposed to low to moderate levels of arsenic of parts per billion (ppb) to hundreds of ppb. As a consequence, the World Health Organization (WHO) and U.S. environmental health agencies, such as the Environmental Protection Agency (EPA) made arsenic their highest priority. Recently, the WHO, European Union (EU), and US. EPA lowered an acceptable level of 10 ppb for arsenic in drinking water In this article, various health effects of arsenic in drinking water were reviewed and the current status for risk assessment to regulate arsenic in drinking water was discussed.
Saururus chinenesis Extracts Scavenge Reactive Oxygen Species and Modulate Nitric Oxide Production in Raw 264.7 Macrophages
Oh, Jang-Hee ; Shon, Hee-Kyoung ; Oh, Moon-You ; Chung, An-Sik ;
Toxicological Research, volume 18, issue 2, 2002, Pages 117~127
Saururus chinensis Baill has been used in Korean folk medicine for the treatment of various diseases such as edema, Jaundice, and furuncle. The components of this plant were extracted into four fraction. Among the four fraction, hexane and ethyl acetate fraction were highly toxic to 3T3 mouse embryo fibroblast and Raw 264.7 mouse macrophage, but n-butanol and residue fraction did not show any toxic effect to those cell lines. n-Butanol and residue fraction exhibited antioxidant effects on hydro-gen peroxide, hydroxyl radical, and superoxide anion directly in vitro and in the 3T3 fibroblasts. All the four fractions inhibited lipid peroxidation measured by thiobarbituric acid reactive substances (TBARS) formation. In addition, n-butanol and residue fraction showed inhibitory effects on lipopolysaccharide (LPS)-induced nitric oxide production, and also down-regulated inducible nitric oxide synthase (iNOS) mRNA transcription 6 h after LPS stimulation in Raw 204.7 cells. Only n-butanol fraction, which mainly consists of flavonoids, inhibited NF-kB activation by decreasing IkBa degradation 90 min after LPS stimulation. horn the results, it is suggested that this plant could be a good candidate material for drug development based on its antioxidant and/or anti-inflammatory constituents.
Comparison of L5178Y tk
Mouse Lymphoma Assay and In vitro Chromosome Aberration Test
Lee, Michael ; Jung Kwon ; Cho, Ji-Hee ; Hong, Mi-Young ; Kim, Eun-Joo ; Junghee Han ; Chung, Moon-Koo ; Han, Sang-Seop ;
Toxicological Research, volume 18, issue 2, 2002, Pages 129~138
The mouse lymphoma assay (MLA) has been recently validated as a sensitive and specific test system to determine the genotoxic potential for a chemical. The objective of this study is to evaluate the utility of MLA for detecting mutagens. Especially, to compare MLA with the in vitro chromosomal aberration test (CA), we performed MLA using the microwell method with three chemicals (hydroxyurea, theophylline and amino acid copper complex), which were reportedly positive in the CA. In cell treated with hydroxyurea, anti-neoplastic agent that blocks DNA replication, evidence of a positive response was obtained without S9 mix for 4 h and 24 h. In addition, analysis of colony size distribution at concentration that gave an elevated mutant fraction showed that hydroxyurea induced a high proportion of small type colonies, indicating that hydroxyurea-induced mutation is associated with large chromosomal deletion. Conversely, negative MLA result was obtained for theophylline, which was wed as central nervous system stimulator. Although theophylline increased the mutant frequency at concentration of 1250
with S9 mix for 4 h, a concentration-related increase in mutant frequency was not observed. The MLA result of amino acid copper complex was considered equivocal because the positive result was obtained at concentration showing 10% or less RS or RTG. Thus, among 3 CA-positive chemicals, positive MLA result was obtained for one. The other two chemicals were negative and equivocal. However MLA, which evaluates mutagenic potential of chemicals through colony formation by cell grouth, may provide a higher predictivity of carcinogenesis than CA.
Subcutaneous Toxicity Evaluation of a Combination Vaccine against Hantaan and Puumala Viruses in Rats for 4 Weeks
Lee, Su-Hae ; Jung, Eun-Yong ; No, Kyong-Ok ; Sin, Ji-Soon ; Ahn, Chang-Nam ; Kim, Dae-Joong ; Nam, Sang-Yoon ; Kang, Jong-Koo ;
Toxicological Research, volume 18, issue 2, 2002, Pages 139~147
Hantaan (HTNV) and Puumala (PUUV) viruses cause hemorrhagic fever with renal syndrome in human. In the present study, the repeated dose toxicity of the HTNV-PUUV combination vaccine was evaluated in Sprague-Dawley rats. Animals were injected subcutaneously for 28 days with dosages of 0, 0.017, 0.17 and 1.7 dose/kg body weight per day, respectively. No any significant changes of body weight, food and water consumptions were shown. There were no death and clinical findings during the experimental period. In both male and female rats, there were not significant changes in hematological and serum biochemical analysis, urinalysis, and ophthalmoscopic and histopathological examination. These results indicate that the HTNV-PUUV combination vaccine may have no toxic effects and no observed adverse effect level (NOAEL) may be over 1.7 dose/kg/day at subcutaneous route in rats.
3 Months Repeated Dose Toxicity Studies of the Bamboo Salt(Jukyum) in Rats
Toxicological Research, volume 18, issue 2, 2002, Pages 149~157
Though the bamboo salt, called as "JUKYUM" has been widely used in Korea as panacea, it's toxicity was not screened completely. To investigate the toxicity of bamboo salt, we compared with the toxicity of crude salt and reagent-grade NaCl by performing repeated dose (3 month's) oral toxicity test in SD rats. Crude salt, natural sun-dried salt (crude salt) production, was purchased from the western seashore of Korean peninsular and reagent-grade NaCl was purchased from Sigma company. Results of repeated dose oral toxicity tests for 3 months (bamboo salt; 750, 1500, 3000 mg/kg/day, crude salt : 3000 mg/kg/day, reagent-grade NaCl; 3000 mg/kg/day) suggested that the bamboo salt treated group show no significant toxicological findings with body weights and organ weighs changes, and hematological, serum bio-chemical and histopathological findings compared with other groups.er groups.
Mechanism of Lung Damage Induced by Cyclohexane in Rats
Toxicological Research, volume 18, issue 2, 2002, Pages 159~165
Recently, we reported (korean J. Biomed. Lab. Sci., 6(4): 245-251, 2000) that cyclohexane (l.56 g/kg of body wt., i.p.) administration led to lung injury in rats. However the detailed mechanism remain to be elucidated. This study was designed to clarify the mechanism of lung damage induced by cyclohexane in rats. First, lung damage was assessed by quantifying bronchoalveolar lavage fluid (BAL) protein content as well us by histopathological examination. Second, activities of serum xanthine oxidase (XO), pulmonary XO and oxygen free radical scavenging enzymes. XO tope conversion (O/D + O, %) ratio and content of reduced glutathione (GSH) were determined. In the histopathological findings, the vasodilation, local edema and hemorrhage were demonstrated in alveoli of lung. And vascular lumens filled with lipid droplets, increased macrophages in luminal margin and increased fibroblast-like interstitial cells in interstitial space were observed in electron micrographs. The introperitoneal treatment of cyclohexane dramatically increased BAL protein by 21-fold compared with control. Cyclohexane administration to rats led to a significant rise of serum and pulmonary XO activities and O/D + O ratio by 47%,30% and 24%, respectively, compared witれ control. Furthermore, activities of pulmonary oxygen free radical scavenging enzymes such as superoxide dismutase, glutathione peroxidase and glutathione S-transferase, and GSH content were not found to be statistically different between control and cyclohexane-treated rats. These results indicate that intraperitoneal injection of cyclohexane to rats may induce the lipid embolism in pulmonary blood vessel and lead to the hypoxia with the ensuing of oxygen free radical generation, and which may be responsible for the pulmonary injury.
Background Data for Fertility and Early Embryonic Development Study in Sprague-Dawley Rats
Toxicological Research, volume 18, issue 2, 2002, Pages 167~174
Historical control data have been shown to be valuable in the proper interpretation and validation of reproductive toxicology studies. The present data were compiled from rat fertility and early embryonic development studies conducted at Korea Institute of Toxicology during the 1994∼2001 period. These data were assembled in order to provide background information for the general and reproductive data collected in 11 fertility and early embryonic development studies using Sprague-Dawley rats obtain-ing from the Breeding Facility, Korea Institute of Toxicology, Korea. A total of 274 males and 274 females were used in these studies during the eight-year period. Parameters of fertility and early embryonic development included clinical sign, body weights, food consumption, organ weights, estrus cycle, copulation index, precoital time, fertility index, pregnancy index, sperm parameters, and early embryonic development parameters. Most of the values were comparable to the previous historical control data reported by other investigators. These data can be wed not only as a historical data base for the meaningful interpretation of data from reproductive and developmental toxicity studies, but also as a contribution to biological characterization of Sprague-Dawley rats.
Evaluation of Local Lymph Node Assay as an Alternative Method for Skin Sensitization Potential in Baltic Mice
Toxicological Research, volume 18, issue 2, 2002, Pages 175~181
Allergic contact dermatitis (skin sensitization) may be caused by a wide variety of chemicals. A murine local lymph node assay (LLNA) has been developed as an alternative to guinea pig models for assessing the contact sensitization potential of chemical. This study was carried out to evaluate the skin sensitization potential for chemicals in Balb/c mice by LLNA. Contact allergen, dinitrochlorobenzene (DNCB), respiratory allergen, toluene diisocyanate (TDI) and a weak allergen,
-hexlycinnamaldehyde (HCA) were wed as positive chemicals and irritant, sodium lauryl sulfate(SLS) also wed as a reference chemical in this study. The weights of lymph node in the mice treated with DNCB, TDI, and HCA were increased compared to vehicle control. There was a significant increase in lymph node weight of mice treated with high concentration of SLS compared to vehicle control. The stimulation index (SI) of Lymph node cell in the mice treated with DNCB, TDI, and HCA revealed over three-fold increase compared to vehicle control by
-thymidine uptake. All allergens correctly identified in this LLNA study wing Balb/c mice. These results suggest that LLNA wing Balb/c mice could be a useful method for screening the allergenic potential of chemicals. The expression of IL-2 mRNA was slightly increased in draining auricular lymph node cell of the mice treated with TDI and HCA by RT-PCR. However the IL-2 levels in DNCB and SLS of treated animals were not significantly changed.
Green Tea (-) Epigallocatechin-gallate Induces the Apoptotic Death of Prostate Cancer Cells
Toxicological Research, volume 18, issue 2, 2002, Pages 183~190
The mechanism by which catechin-mediated cytotoxicity against tumor cells remains to be elusive. To elucidate the mechanical mights of anti-tumor effects, (-)epigallocatechin-gallate (EGCG) of catechin was applied to human prostate cancer DU 145 cells. Cell viability was measured by crystal violet staining. Cell lysates were wed to measure the catalytic activity of caspases by using fluorogenic peptide: Ac-DEVD-AMC for caspase-3 protease, Z-IETD-AFC for caspase-8 protease, Ac-LEHD-AFC for caspase-9 protease as substrates. The equal amounts of protein from cell lysate was separated on SDS-PAGE and analyzed by western blotting with anti-Fas antibody, anti-FasL antibody, anti-BCL2 antibody and anti-Bax antibody. (-)EGCG induced the death of DUl45 cells, which was revealed as apoptosis shown by DNA fragmentation. (-)EGCG induced the activation of caspase family cysteine proteases including caspase-3, -8 and -9 proteases in DU145 cells. Also, (-)EGCG increased the expression of Fas and Fas ligand (FasL) protein in DU145 colls. The expression level of BCL2 was decreased in (-)EGCG treated DU145 cells, whereas Bax protein was increased in a time-dependent manner. We suggest that (-)EGCG-induced apoptosis of DU145 cells is mediated by signaling pathway involving caspase family cysteine protease, mitochondrial BCL2-family protein and Fas/FasL.
Analysis of 3-Monochloro-1,2-Propanediol (3-MCPD) in Soy Sauce Products in Korea
Toxicological Research, volume 18, issue 2, 2002, Pages 191~194
3-Monochloro-1,2-propanediol(3-MCPD) was analyzed in soy sauce products commercially available in Korea. A total of 24 samples were collected and 3-MCPD was determined by GC/MS. Sources of 24 samples were classified by manufacturing methods as naturally brewed(NB), acid hydrolyzed (AH) and mixed (M = NB + AH) soy sauces. 3-MCPD was not detected in NB soy sauce products (< 0.01 ppm, mg/kg) whereas AH and M soy sauce products showed a wide range of 3-MCPD contamination (0.0l ∼ 2.038 ppm). The contaminated levels of 3-MCPD in soy sauce products were higher than the permissible or tentative permissible level of 3-MCPD in both European Community (0.02 ppm) and Korea (0.3 ppm). These data suggest that 3-MCPD levels contaminated in soy sauce products in Korea were shown to be too high and should be reduced to as low a level technologically feasible to protect Korean from the exposure to toxic chemical, 3-MCPD.
Single and Four-Week Intravenous Toxicity Studies of a Novel Cephalosporin Antibiotic Agent, IDC-7181, in Rats
Toxicological Research, volume 18, issue 2, 2002, Pages 195~203
This study was performed to evaluate single and repeated-dose toxicities oj a new cophalosporin antibiotic agent IDC-7l81 in Sprague-Dawley rats. IDC-7181 was injected intravenously to rats at dose levels of 0, 3.2, 16, 80, 400 and 2,000 mg/kg/day for single-dose toxicity study and at dose levels of 0, 10, 50 and 250 mg/kg/day for 4-week repeated-dose toxicity study. In both studies, there were no dose-related changes in mortality clinical signs, body weight changes, food and water consumption, opthalmoscopy, organ weights, urine analysis, biochemical examination, and hematological findings of all animals treated with IDC-7l8l. Gross and histopathological findings revealed no evidence of specific toxicity related to IDC-7181. These results suggest that the intravenous maximum tolerated dose value of IDC-7181 may be over 250 mg/kg and
value may be over 2,000 mg/kg in rats.
Development of Subacute Animal Model to Predict Occurrence of Systemic Anaphylaxis Following Vaccination and Evaluation of Various Immunotoxicological Parameters
Toxicological Research, volume 18, issue 2, 2002, Pages 205~213
This study was undertaken to develop a subacute murine model for predicting occurrence of systemic anaphylaxis and to evaluate efficacy of various immunological parameters as the monitoring indices for the occurrence of anaphyalxis. The murine anaphyalxis model was developed through intraperitoneally sensitizing 100
ovalbumin (OVA) in the presence of 1 mg alum and 300 ng cholera toxin twice a week interval followed by challenging 500
. OVA intravenously. Typical anaphylaxis symptoms were demonstrated at the both BALB/c mice, a strain prone to type-2 response, and C57BL/6 mice. a strain prone to type-1 response. Level of plasma histamine was approximately 50-fold or 30-fold higher in the mice sensitized with OVA than the mice sensitized with alum plus cholera toxin or the saline-treated mice after OVA challenge, respectively. Sensitization and challenge with OVA significantly enhanced plasma leukotriene
level but not IgE levels in comparison with the control mice, which indicated the role of leukotriene
for progression of anaphyalxis. Furthermore, among mice suffered from anaphylaxis, levels of OVA-specific IgGl were significantly higher in the BALB/c mice than in the C57BL/6 mice, which implied the genetic susceptibility for the induction of systemic anaphylaxis. Conclusively, simultaneous evaluation of histamine, leukotriene
, and allergen-specific IgG isotype may serve as more efficient monitoring tool for vaccine-related anaphyalxis.