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REFERENCE LINKING PLATFORM OF KOREA S&T JOURNALS
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Journal DOI :
The Korean Society of Toxicology
Editor in Chief :
Volume & Issues
Volume 26, Issue 4 - Dec 2010
Volume 26, Issue 3 - Sep 2010
Volume 26, Issue 2 - Jun 2010
Volume 26, Issue 1 - Mar 2010
Selecting the target year
Toxicological Mechanism of Endocrine Disrupting Chemicals: Is Estrogen Receptor Involved?
Jeung, Eui-Bae ; Choi, Kyung-Chul ;
Toxicological Research, volume 26, issue 4, 2010, Pages 237~243
DOI : 10.5487/TR.2010.26.4.237
Endocrine disrupting chemicals (EDCs) have been shown to interfere with physiological systems, i.e., adversely affecting hormone balance (endocrine system), or disrupting normal function, in the female and male reproductive organs. Although endocrine disruption is a global concern for human health, its impact and significance and the screening strategy for detecting these synthetic or man-made chemicals are not clearly understood in female and male reproductive functions. Thus, in this review, we summarize the interference of environmental EDCs on reproductive development and function, and toxicological mechanism(s) of EDCs in in vitro and in vivo models of male and female reproductive system. In addition, this review highlights the effect of exposure to multiple EDCs on reproductive functions, and brings attention to their toxicological mechanism(s) through estrogen receptors.
Epithelial-mesenchymal Transition and Cell Invasion
Son, Hwa-Jin ; Moon, Aree ;
Toxicological Research, volume 26, issue 4, 2010, Pages 245~252
DOI : 10.5487/TR.2010.26.4.245
Epithelial-mesenchymal transition (EMT) is a complex process in which epithelial cells acquire the characteristics of invasive mesenchymal cells. EMT has been implicated in cancer progression and metastasis as well as the formation of many tissues and organs during development. Epithelial cells undergoing EMT lose cell-cell adhesion structures and polarity, and rearrange their cytoskeletons. Several oncogenic pathways such as transforming growth factor (TGF)-
, Wnt, and Notch signaling pathways, have been shown to induce EMT. These pathways have activated transcription factors including Snail, Slug, and the ZEB family which work as transcriptional repressors of E-cadherin, thereby making epithelial cells motile and resistant to apoptosis. Mounting evidence shows that EMT is associated with cell invasion and tumor progression. In this review, we summarize the characteristic features of EMT, pathways leading to EMT, and the role of EMT in cell invasion. Three topics are addressed in this review: (1) Definition of EMT, (2) Signaling pathways leading to EMT, (3) Role of EMT in cell invasion. Understanding the role of EMT in cell invasion will provide valuable information for establishing strategies to develop anti-metastatic therapeutics which modulate malignant cellular processes mediated by EMT.
Research Trends of Ecotoxicity of Nanoparticles in Soil Environment
Lee, Woo-Mi ; Kim, Shin-Woong ; Kwak, Jin-Il ; Nam, Sun-Hwa ; Shin, Yu-Jin ; An, Youn-Joo ;
Toxicological Research, volume 26, issue 4, 2010, Pages 253~259
DOI : 10.5487/TR.2010.26.4.253
We are consistently being exposed to nanomaterials in direct and/or indirect route as they are used in almost all the sectors in our life. Nations across the worlds are now trying to put global regulation policy on nanomaterials. Sometimes, they are reported to be more toxic than the corresponding ion and micromaterials. Therefore, safety research of nanoparticles has huge implications on a national economics. In this study, we evaluated and analyzed the research trend of ecotoxicity of nanoparticles in soil environment. Test species include terrestrial plants, earthworms, and soil nematode. Soil enzyme activities were also discussed. We found that the results of nanotoxicity studies were affected by many factors such as physicochemical properties, size, dispersion method and test medium of nanoparticle, which should be considered when conducting toxicity researches. In particular, more researches on the effect of physicochemical properties and fate of nanoparticles on toxicity effect should be conducted consistently.
Inhalation Toxicity of Particulate Matters Doped with Arsenic Induced Genotoxicity and Altered Akt Signaling Pathway in Lungs of Mice
Park, Jin-Hong ; Kwon, Jung-Taek ; Minai-Teherani, Arassh ; Hwang, Soon-Kyung ; Chang, Seung-Hee ; Lim, Hwang-Tae ; Cho, Hyun-Seon ; Cho, Myung-Haing ;
Toxicological Research, volume 26, issue 4, 2010, Pages 261~266
DOI : 10.5487/TR.2010.26.4.261
In the workplace, the arsenic is used in the semiconductor production and the manufacturing of pigments, glass, pesticides and fungicides. Therefore, workers may be exposed to airborne arsenic during its use in manufacturing. The purpose of this study was to evaluate the potential toxicity of particulate matters (PMs) doped with arsenic (PMs-Arsenic) using a rodent model and to compare the genotoxicity in various concentrations and to examine the role of PMs-Arsenic in the induction of signaling pathway in the lung. Mice were exposed to PMs
(high concentration) doped with arsenic
(high concentration) for 4 wks (6 h/d, 5 d/wk), respectively in the whole-body inhalation exposure chambers. To determine the level of genotoxicity, Chromosomal aberration (CA) assay in splenic lymphocytes and Supravital micronucleus (SMN) assay were performed. Then, signal pathway in the lung was analyzed. In the genotoxicity experiments, the increases of aberrant cells were concentration-dependent. Also, PMs-arsenic caused peripheral blood micronucleus frequency at high concentration. The inhalation of PMs-Arsenic increased an expression of phosphorylated Akt (p-Akt: protein kinase B) and phpsphorylated mammalian target of rapamycin (p-mTOR) at high concentration group. Taken together, inhaled PMs-Arsenic caused genotoxicity and altered Akt signaling pathway in the lung. Therefore, the inhalation of PMs-Arsenic needs for a careful risk assessment in the workplace.
Induction of Inflammatory Responses by Carbon Fullerene (C60) in Cultured RAW264.7 Cells and in Intraperitoneally Injected Mice
Park, Eun-Jung ; Roh, Jin-Kyu ; Kim, Young-Hun ; Park, Kwang-Sik ;
Toxicological Research, volume 26, issue 4, 2010, Pages 267~273
DOI : 10.5487/TR.2010.26.4.267
As the use of carbon fullerene increases in the chemical industry, the concern over its biological and toxicological effects is also increasing. In this study, the suspension of carbon fullerene (C60) in phosphate buffered saline was prepared and toxicity was investigated using cultured RAW 264.7 and in intraperitoneally injected mice, respectively. The average size of carbon fullerene in the suspension was
when determined by particle size analyzer. Cell viability was significantly decreased by the exposure of carbon fullerene (
) for 96 hrs in the cultured RAW 264.7 cells. Intracellular reduced glutathione (GSH) level was also decreased compared to the level of the non-treated control group during the exposure period, while the level of nitric oxide was increased. When mice were intraperitoneally injected with carbon fullerene, serum cytokine levels of IL-1 and IL-6 were increased with the increased expression of inflammatory genes in peritoneal macrophage and T cell distribution in blood lymphocytes. The results suggested inflammatory responses were induced by carbon fullerene.
Placenta Transfer and Toxicokinetics of Valproic Acid in Pregnant Cynomolgus Monkeys
Jeong, Eun-Ju ; Yu, Wook-Joon ; Kim, Choong-Yong ; Chung, Moon-Koo ;
Toxicological Research, volume 26, issue 4, 2010, Pages 275~283
DOI : 10.5487/TR.2010.26.4.275
Placenta transfer study in non-human primate (NHP) is one of the crucial components in the assessment of developmental toxicity because of the similarity between NHP and humans. To establish the method to determine placenta transfer in non-human primate, toxicokinetics of valproic acid (VPA), a drug used to treat epilepsy in pregnant women, were determined in pregnant cynomolgus monkeys. After mating, pregnancy-proven females were daily administered with VPA at dose levels of 0, 20, 60 and 180 mg/kg by oral route during the organogenesis period from gestation day (GD) 20 to 50. Concentrations of VPA and its metabolite, 4-ene-VPA, in maternal plasma on GDs 20 and 50, and concentrations of VPA and 4-ene-VPA in placenta, amniotic fluid and fetus on GD 50 were analyzed using LC/MS/MS. Following single oral administration of VPA to pregnant monkeys, concentrations of VPA and 4-ene-VPA were generally quantifiable in the plasma from all treatment groups up to 4-24 hours post-dose, demonstrating that VPA was absorbed and the monkeys were systemically exposed to VPA and 4-ene-VPA. After repeated administration of VPA to the monkeys, VPA was detected in amniotic fluid, placenta and fetus from all treatment groups, demonstrating that VPA was transferred via placenta and the fetus was exposed to VPA, and the exposures were increased with increasing dose. Concentrations of 4-ene-VPA in amniotic fluid and fetus were below the limit of quantification, but small amount of 4-ene-VPA was detected in placenta. In conclusion, pregnant monkeys were exposed to VPA and 4-ene-VPA after oral administration of VPA at dose levels of 20, 60 and 180 mg/kg during the organogenesis period. VPA was transferred via placenta and the fetus was exposed to VPA with dose-dependent exposure. The metabolite, 4-ene VPA, was not detected in both amniotic fluid and fetus, but small amount of 4-ene-VPA was detected in placenta. These results demonstrated that proper procedures to investigate placenta transfer in NHP, such as mating and diagnosis of pregnancy via examining gestational sac with ultrasonography, collection of amniotic fluid, placenta and fetus after Caesarean section followed by adequate bioanalysis and toxicokinetic analysis, were established in this study using cynomolugus monkeys.
Establishment of the Korean Tolerable Daily Intake of Bisphenol A Based on Risk Assessments by an Expert Committee
Choi, Chan-Woong ; Jeong, Ji-Yoon ; Hwang, Myung-Sil ; Jung, Ki-Kyung ; Lee, Kwang-Ho ; Lee, Hyo-Min ;
Toxicological Research, volume 26, issue 4, 2010, Pages 285~291
DOI : 10.5487/TR.2010.26.4.285
Recently, reproductive and neurobehavioral effects of bisphenol A (BPA) have been documented, and thus a review was requested for BPA management direction by the government. Therefore, this study was performed to establish a Korean tolerable daily intake (TDI) for BPA. An expert committee, consisting of specialists in fields such as toxicology, medicine, pharmacology, and statistics, was asked to evaluate BPA health based guidance values (HbGVs). Although many toxicological studies were reviewed to select a point of departure (POD) for TDI, rat and mouse reproductive studies by Tyl et al. (2002, 2006), which were performed according to GLP standards and OECD guidelines, were selected. This POD was the lowest value determined from the most sensitive toxicological test. The POD, a NOAEL of 5 mg/kg bw/day, was selected based on its systemic toxicity as critical effects. An uncertainty factor of 100 including interspecies and intraspecies differences was applied to calculate the TDI. According to the evaluation results, a TDI of BPA for Korean was suggested at 0.05 mg/kg bw/day. In addition, the BPA exposure level based on food consumption by the Korean population was estimated as 1.509
bw/day, and the HI was evaluated at 0.03 when the TDI of 0.05 mg/kg bw/day was applied. This HI value of 0.03 indicated that hazardous effects would not be expected from BPA oral exposures. Although highly uncertain, further studies on low dose neurobehavioral effects of BPA should be performed. In addition, it is recommended that the 'as low as reasonably achievable' (ALARA) principle be applied for BPA exposure from food packaging materials in newborn infants and children.
Determination of tert-Butyl Acetate using a Nose Only Inhalation Exposure in Rats
Yang, Young-Su ; Lee, Jin-Soo ; Kwon, Soon-Jin ; Seo, Heung-Sik ; Choi, Seong-Jin ; Yu, Hee-Jin ; Song, Jeong-Ah ; Lee, Kyu-Hong ; Lee, Byoung-Seok ; Heo, Jeong-Doo ; Cho, Kyu-Hyuk ; Song, Chang-Woo ;
Toxicological Research, volume 26, issue 4, 2010, Pages 293~300
DOI : 10.5487/TR.2010.26.4.293
tert-Butyl acetate (TBAc) is an organic solvent, which is commonly used in architectural coatings and industrial solvents. It has recently been exempted from the definition of a volatile organic compound (VOC) by the Air Resources Board (ARB). Since the use of TBAc as a substitute for other VOCs has increased, thus its potential risk in humans has also increased. However, its inhalation toxicity data in the literature are very limited. Hence, inhalation exposure to TBAc was carried out to investigate its toxic effects in this study. Adult male rats were exposed to TBAc for 4 h for 1 day by using a nose-only inhalation exposure chamber (low dose,
(500 ppm); high dose,
(2000 ppm)). Shamtreated control rats were exposed to clean air in the inhalation chamber for the same period. The animals were killed at 2, 7, and 15 days after exposure. At each time point, body weight measurement, bronchoalveolar lavage fluid (BALF) analysis, histopathological examination, and biochemical assay were performed. No treatment-related abnormal effects were observed in any group according to time course. Based on those findings, the median lethal concentration (
) of TBAc was over
in this study. According to the MSDS, the 4 h
for TBAc for rats is over
. We suggested that this value is changed and these findings may be applied in the risk assessment of TBAc which could be beneficial in a sub-acute study.
Risk Assessment of Growth Hormones and Antimicrobial Residues in Meat
Jeong, Sang-Hee ; Kang, Dae-Jin ; Lim, Myung-Woon ; Kang, Chang-Soo ; Sung, Ha-Jung ;
Toxicological Research, volume 26, issue 4, 2010, Pages 301~313
DOI : 10.5487/TR.2010.26.4.301
Growth promoters including hormonal substances and antibiotics are used legally and illegally in food producing animals for the growth promotion of livestock animals. Hormonal substances still under debate in terms of their human health impacts are estradiol-
, progesterone, testosterone, zeranol, trenbolone, and melengestrol acetate (MGA). Many of the risk assessment results of natural steroid hormones have presented negligible impacts when they are used under good veterinary practices. For synthetic hormonelike substances, ADIs and MRLs have been established for food safety along with the approval of animal treatment. Small amounts of antibiotics added to feedstuff present growth promotion effects via the prevention of infectious diseases at doses lower than therapeutic dose. The induction of antimicrobial resistant bacteria and the disruption of normal human intestinal flora are major concerns in terms of human health impact. Regulatory guidance such as ADIs and MRLs fully reflect the impact on human gastrointestinal microflora. However, before deciding on any risk management options, risk assessments of antimicrobial resistance require large-scale evidence regarding the relationship between antimicrobial use in food-producing animals and the occurrence of antimicrobial resistance in human pathogens. In this article, the risk profiles of hormonal and antibacterial growth promoters are provided based on recent toxicity and human exposure information, and recommendations for risk management to prevent human health impacts by the use of growth promoters are also presented.
Toluene Induces Depression-Like Behaviors in Adult Mice
Yang, Mi-Young ; Kim, Sung-Ho ; Kim, Jong-Choon ; Shin, Tae-Kyun ; Moon, Chang-Jong ;
Toxicological Research, volume 26, issue 4, 2010, Pages 315~320
DOI : 10.5487/TR.2010.26.4.315
It has been clinically reported that toluene causes mental depression in humans. However, the detrimental effects of toluene exposure on brain function and the relation between features of mental depression and toluene exposure are poorly understood. This study evaluated depression-like behaviors in adult C57BL/6 mice after administration of toluene, and elucidated the effects of classical antidepressants on the depression-like behaviors. For the estimation of depression-like behaviors, tail suspension test (TST) and forcedswim test (FST) were performed 1, 4 and 16 days after toluene (0~1000 mg/kg bw) treatment. In addition, classical antidepressants such as fluoxetine (FLX, 20 mg/kg bw) and imipramine (IMI, 40 mg/kg bw) were administered 12 h and 1 h before the tests. In the TST and FST, toluene-treated mice exhibited a longer duration of immobility than vehicle-treated mice 1 and 4 days after toluene treatment. The depression-like behaviors were significantly reversed by FLX and IMI. The weight of the adrenal gland and the size of adrenocortical cells were significantly higher in toluene-treated mice compared to vehicle-treated controls. It is suggested that acute toluene exposure of adult mice is sufficiently detrimental to induce depression. In addition, this study has established a mouse model for a depressive state induced by toluene treatment.
Comparison of Hydroxyl Radical, Peroxyl Radical, and Peroxynitrite Scavenging Capacity of Extracts and Active Components from Selected Medicinal Plants
Kwon, Do-Young ; Kim, Sun-Ju ; Lee, Ju-Won ; Kim, Young-Chul ;
Toxicological Research, volume 26, issue 4, 2010, Pages 321~327
DOI : 10.5487/TR.2010.26.4.321
The ability of 80% ethanol extracts from five medicinal plants, Aralia continentalis, Paeonia suffruticosa, Magnolia denudata, Anemarrhena asphodeloides, and Schizonepeta tenuifolia, to neutralize hydroxyl radical, peroxyl radical and peroxynitrite was examined using the total oxyradical scavenging capacity (TOSC) assay. Peroxyl radical was generated from thermal homolysis of 2,2'-azobis(2-methylpropionamidine) dihydrochloride (ABAP); hydroxyl radical by an iron-ascorbate Fenton reaction; peroxynitrite by spontaneous decomposition of 3-morpholinosydnonimine N-ethylcarbamide (SIN-1). The oxidants generated react with
-methiolbutyric acid (KMBA) to yield ethylene, and the TOSC of the substances tested is quantified from their ability to inhibit ethylene formation. Extracts from P. suffruticosa, M. denudata, and S. tenuifolia were determined to be potent peroxyl radical scavenging agents with a specific TOSC (sTOSC) being at least six-fold greater than that of glutathione (GSH). These three plants also showed sTOSCs toward peroxynitrite markedly greater than sTOSC of GSH, however, only P. suffruticosa revealed a significant hydroxyl radical scavenging capacity. Seven major active constituents isolated from P. suffruticosa, quercetin, (+)-catechin, methyl gallate, gallic acid, benzoic acid, benzoyl paeoniflorin and paeoniflorin, were determined for their antioxidant potential toward peroxynitrite, peroxyl and hydroxyl radicals. Quercetin, (+)-catechin, methyl gallate, and gallic acid exhibited sTOSCs 40~85 times greater than sTOSC of GSH. These four components also showed a peroxynitrite scavenging capacity higher than at least 10-fold of GSH. For antioxidant activity against hydroxyl radical, methyl gallate was greatest followed by gallic acid and quercetin. Further studies need to be conducted to substantiate the significance of scavenging a specific oxidant in the prevention of cellular injury and disease states caused by the reactive free radical species.
Levels of Exhaled Breath Condensate pH and Fractional Exhaled Nitric Oxide in Retired Coal Miners
Lee, Jong-Seong ; Shin, Jae-Hoon ; Lee, Joung-Oh ; Lee, Kyung-Myung ; Kim, Ji-Hong ; Choi, Byung-Soon ;
Toxicological Research, volume 26, issue 4, 2010, Pages 329~337
DOI : 10.5487/TR.2010.26.4.329
Inhaled inorganic dusts, such as coal, can cause inflammation and fibrosis in the lungs, known as pneumoconiosis. Diagnosis of pneumoconiosis depends on morphological changes by radiological findings and functional change by pulmonary function test (PFT). Unfortunately, current diagnostic findings are limited only to lung fibrosis, which is usually irreversibly progressive. Therefore, it is important that research on potential and prospective biomarkers for pneumoconiosis should be conducted prior to initiation of irreversible radiological or functional changes in the lungs. Analytical techniques using exhaled breath condensate (EBC) or exhaled gas are non-invasive methods for detection of various respiratory diseases. The objective of this study is to investigate the relationship between inflammatory biomarkers, such as EBC pH or fractional exhaled nitric oxide (
), and pneumoconiosis among 120 retired coal miners (41 controls and 79 pneumoconiosis patients). Levels of EBC pH and FENO did not show a statistically significant difference between the pneumoconiosis patient group and pneumoconiosis patients with small opacity classified by International Labor Organization (ILO) classification. The mean concentration of
in the low percentage
(< 80%) was lower than that in the high percentage (80%
) (p = 0.023). The mean concentration of
in current smokers was lower than that in non smokers (never or past smokers) (p = 0.027). Although there was no statistical significance, the levels of
in smokers tended to decrease, compared with non smokers, regardless of pneumoconiosis. In conclusion, there was no significant relationship between the level of EBC pH or
and radiological findings or PFT. The effects between exhaled biomarkers and pneumoconiosis progression, such as decreasing PFT and exacerbation of radiological findings, should be monitored.