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REFERENCE LINKING PLATFORM OF KOREA S&T JOURNALS
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Journal DOI :
The Korean Society of Toxicology
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Volume & Issues
Volume 21, Issue 4 - Dec 2005
Volume 21, Issue 3 - Sep 2005
Volume 21, Issue 2 - Jun 2005
Volume 21, Issue 1 - Mar 2005
Selecting the target year
Recent Progress in Transgenic Mouse Models as an Alternative Carcinogenicity Bioassay
Son Woo-Chan ; Kim Bae-Hwan ; Jang Dong-Deuk ; Kim Chull-Kyu ; Han Beom-Seok ; Kim Jong-Choon ; Kang Boo-Hyon ; Lee Je-Bong ; Choi Yang-Kyu ; Kim Hyoung-Chin ;
Toxicological Research, volume 21, issue 1, 2005, Pages 1~14
Transgenic mouse models have been introduced and accepted by regulatory bodies as an alternative to carcinogenicity assay models to predict and evaluate chemical carcinogens. The recent research outcomes in transgenic mouse models have made progressive advances in the understanding of chemical carcinogenesis and the evaluation of potential human carcinogens. However, these models still remain to be insufficient assay systems although the insufficiencies have been recognised and are being resolved. Based on up to date information from literature, this review article intends to understand currently accepted transgenic mouse models, issues arising from study design, interpretation of the study, results of validation project and their cancer prediction rate, and further perspectives of cancer assay models from the regulatory view point.
Safety Evaluation of Water-soluble Chromium in Makeup Products
Jeong Hye-Jin ; Joo Kyung-Mi ; Kim Young-So ; Park Jeong-Eun ; Park Jin-Hee ;
Toxicological Research, volume 21, issue 1, 2005, Pages 15~21
There is now a growing concern about the possible toxicity of heavy metals in cosmetics. Heavy metals can be used as cosmetic ingredients or may be present as low level impurities in some of the raw materials. Chromium derivatives are used as pigments in cosmetics. Chromium is essential and toxic trace elements. Chromium may cause skin allergy. However, the regulations related to cosmetic products give no limit values for Chromium. Hexavalent chromium is significantly more toxic than trivalent chromium. Hexavalent chromium may present a carcinogenic risk at high concentrations. Therefore, it is important to consider oxidation state of chromium when analyze chromium. The purpose of this study is to determine the concentrations of water-soluble trivalent and hexavalent chromium in samples of makeup products, and to assess the safety of cosmetics on the basis of animal sensitization tests using guinea pig. The present study of chromium in 48 makeup products of 12 manufacturers provides a basis for assessing safety of makeup products. Water-soluble hexavalent chromium was not detected in any product. Water-soluble trivalent chromium was detected in only 9 eye shadows out of 48 makeup products, and could not be quantified 3 out of 9 eye shadows. The highest level of water-soluble trivalent chromium was about 10 mg/kg in spite of 90,000 mg/kg of total chromium. The results of animal sensitization tests show that 200 mg/kg of trivalent chromium and 5 mg/kg of hexavalent chromium have no harmful effect. No cross-reaction among these metals was found. Accordingly, the concentrations of water-soluble chromium in makeup products seemed to be safe. The overall results indicate that chromium in cosmetics probably have no significant toxicological effects. However, It is necessary to set guidelines on the maximum permissible concentration of water-soluble chromium in cosmetics.
Reproductive Toxicity Study of CONP01, a New Antiarthritic Agent: Developmental Study in Rats
Lee June-Suk ; Hong Dong Ho ; Kim Kwang-Ho ; Zhang Hu-Song ; Gil Gi Hyun ; Han Myong Kyu ; Yang Hyun Ju ; Bae Jin-Sook ; Kim Nam Du ; Song Si Whan ;
Toxicological Research, volume 21, issue 1, 2005, Pages 23~29
A developmental study of CONP01, a new antiarthritic agent, was conducted in Sprague-Dawley rats. Dosage of CONP01 0, 111, 333, and 1000 mg/kg/day were administered to dams orally from day 6 to day 16 of gestation. Two-third of dams per group were subjected to caesarean section on day day 20 of pregnancy for examination of their fetuses, and the remaining one-third of dams per group were allowed to deliver naturally for postnatal examination of their offspring. There was no change in the dams body weights, food consumptions, specific clinical sings and gross findings. There was significant decrease only in the absolute and relative weights of right ovary in 111 mg/kg treatment group, when compared with the vehicle control, whereas other organ weights were not changed. Moreover, no increase in the frequencies of external, visceral and skeletal malformation of fetuses were observed in the treated groups. These results suggest that the oral NOAEL (no observed adverse effect level) of CONP01 may be over 1,000 mg/kg in dams and fetuses of rats.
Protective Effect of the Stem Bark of Syringa velutina on Bisphenol-A in the Human Breast Cancer Cell Line and Immature Rat
Jo Eun-Hye ; Yang Se-Ran ; Cho Sung-Dae ; Jung Ji-Won ; Park Joon-Suk ; Hwang Jae-Woong ; Lee Seong-Hun ; Park Jung-Ran ; Lee Yong-Soon ; Kang Kyung-Sun ;
Toxicological Research, volume 21, issue 1, 2005, Pages 31~37
The inhibitory activity against bisphenol-A (BPA), one of well-known endocrine disrupters was examined with the water extracts prepared from the Stem Bark of Syringa velutina (SBS). In this study, we have investigated the effect of SBS on the toxicity caused by BPA in human breast cancer cell line, MCF-7 cells and immature Sprague-Dawley rats. In the estrogen receptor-mediated proliferation assay using MCF-7 cells, BPA (16 ng/ml) induced the cell proliferation, but the water extract of SBS inhibited BPA-induced cell proliferation in a dose-dependent manner. These results are associated with PARP degradation and specific cleavage of anti-apoptotic protein Bcl-2 of apoptotic regulatory factors. Additionally, the BPA (400 mg/100 g) significantly induced the increase of the uterine and virginal weights, while SBS (50 mg/100 g) showed the inhibitory action against BPA, i.e. caused the increase of estrogen-related organ weights in immature rat uterotrophic assay. Taken together, the present data suggest that SBS may have anti-toxicity activities against BPA in vitro and in vivo systems. SBS may be capable of inhibiting adverse effects of BPA such as reproductive disorder.
Antibacterial Activity In Vitro and Primary Dermal Irritation Test in Rabbits of Surfactin Produced Bacillus subtilus Complex BC2121
Hwang Mi-Hyun ; Yun Hyo-In ; Lim Jong-Hwan ; Kim Kil-Soo ; Rhee Man-hee ; Kim Nam-Woo ; Kim Jong-Choon ; Park Seung-Chun ;
Toxicological Research, volume 21, issue 1, 2005, Pages 39~43
The present study was carried out to investigate the antibacterial activity against Staphylococcus aureus with antibiotic-resistance in vitro and the skin irritation in rabbits with surfactin produced by Bacillus subtilus Complex BC1212. The antibacterial activities of selected antimicrobial agents (surfactin, amoxacillin, colistin, norfloxacin and streptomycin) were evaluated by using the broth microdilution method. As the results, the minimum inhibitory concentration (MIC) of the surfactin was less than 15.6 ㎍/ml. In the skin irritation test, two out of 4 rabbits showed very slight edema at 24 h after the administration of surfactin, and then recovered at 72 h. The change of body weight was normal during the skin irritation test. The primary irritation index in accordance with the Draize evaluation of topical reaction was calculated to be '0.125', which meant not irritating. Based on these results, it could be concluded that the test agent, surfactin, was a non-irritant. We could also think that the surfactin may be useful for the treatment of S. aureus infections such as bovine mastitis.
Antioxidative Activity and Irritation Test of a Complex Herbal Bath Extracted from Korean Traditional Plants
Chang Zhiqiang ; Kim Young-Hoan ; Song Jae-Chan ; Kim Nam-Woo ; Lee In-Seon ; Lee Sam-Pin ; Kim Jong-Choon ; Park Seung-Chun ;
Toxicological Research, volume 21, issue 1, 2005, Pages 45~49
The purpose of this study is to evaluate the free radical scavenging ability and xanthine oxidase inhibitory activity of a complex herbal bath consisted of Artemisiae argyi folium, Angelicae sinensis radix, Ligustici wallichii radix and Angelicae tuhuo radix, and its potential irritation response were also tested for safety use in the rabbits. For antioxidative activity, the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity of the complex herbal bath were examined at five different concentrations (0, 250, 500, 1000 and 2000 ㎍/ml). The concentration of the complex herbal bath required for scavenging DPPH free radical by 50% was 897.2 ㎍/ml. In the inhibition of xanthine oxidase (XO) activity, the concentration of the complex herbal bath required for 50% of inhibition was 221.4 ㎍/ml. In the skin irritation study in rabbit, all animals survived for the duration of the study and the examined skin exhibited no edema, erythema, and eschar formation. In the ocular irritation study in rabbit, after application of the sample to eyes, all of the eyes were normal. In summary, the complex herbal bath has potent antioxidant effects against the DPPH radical and XO and was considered to be a non-irritation bath for safety use.
Acute Oral Toxicity of Adventitious Roots Extract Derived from Wild Ginseng in Beagle Dogs
Song Si-Whan ; Yang Deok Chun ; Choung Se Young ;
Toxicological Research, volume 21, issue 1, 2005, Pages 51~55
To investigate the acute toxicity of adventitious roots extract derived from wild ginseng, it was orally administered to beagle dogs with a single dose. In acute toxicity test, three groups (9 beagle dogs of male) were administered with different dosages of adventitious roots extract (prepared by Biopia Corp.) 500 mg/kg (G2), 1,000 mg/kg (G3), 2,000 mg/kg (G4) and one group (G1, 2 beagle dogs of male) were received by only capsule without the extract according to the Regulation on Korea Food and Drug Administration (1999. 12. 22). There were vomitus for a time and mucous stool at the day, and anorexia and mucous stool at the first day in the group of 2,000 mg/kg administration. There were mucous stool in one and anorexia for a while in two beagle dogs at the first day in the 1,000 mg/kg administration. But no death or abnormal clinical sign was observed through the study period. Therefore, the adventitious roots extract derived from wild ginseng is considered not to have the acute toxicity in the beagle dogs. These results suggest that LD/sub 50/ value of the test substance was considered to be more than 2,000 mg/kg in the beagle dogs.
The Chromosomal Aberration Test of Wild Ginseng Culture Extract in Chinese Hamster Lung Cell
Song Si-Whan ; Yang Deok Chun ; Choung Se Young ;
Toxicological Research, volume 21, issue 1, 2005, Pages 57~62
To investigate the mutant induction of wild ginseng culture extract, we performed chromosomal aberration assay with chinese hamster lung cell in vitro. The test concentration of the extract was decided for the standard with the 50% suppression of cell propagation in the cell. The concentrations for the chromosome test were 1,250, 2,500 and 5,000 ㎍/ml with metabolic activation (+S, 6 hours treatment), 1,100, 2,200 and 4,400 ㎍/ml without metabolic activation (-S, 6 hours treatment) 800, 1,600 and 3,200 ㎍/ml without metabolic activation (-S, 24 hours treatment). No significant increase in chromosome aberrations was observed at any of these concentrations both in the absence and presence of metabolic activation system. Cyclophosphamide monohydrate (CPA) and ethylmethanesulfonate (EMS) caused a significant increase in chromosome aberration. These results may be concluded that wild ginseng culture extract is not capable of inducing chromosome aberration in cultured chinese hamster lung cell regardless of metabolic activation and genotoxicity of that is negative under the present experimental condition.
Acute Oral Toxicity Study of Standardized Gami-Honghwa-Tang (KH-19) in Rats and Beagle Dogs
Yu Young-Beob ; Sung Hyun Jea ; Yoon Yoo-Sik ;
Toxicological Research, volume 21, issue 1, 2005, Pages 63~70
Gami-Honghwa-Tang (KH-19), a herbal prescription for reducing the side effect of radiotherapy, is composed of eight crude herbs such as Rehmanniae Radix Preparata, Angelicae Gigantis Radix, Cnidii Rhizoma, Paeoniae Radix, Corni Fructus, Moutan Cortex Radicis, Lycii Fructus, Carthami Flos, and Glycyrrhizae Radix. In this study, marker substances in KH-19 were analyzed by high performance liquid chromatography-diode array detector (HPLC-DAD) and safety evaluation of standardized KH-19 was evaluated by good laboratory practices (GLP) guideline of Korea Food and Drug Administration. HPLC-DAD was employed to determine the quantities and the qualities of several marker substances such as 5-hydroxymethyl-2-furaldehyde (5-HMF), paeonol, loganin, paeoniflorin, glycyrrhizin, and decursin in the KH-19. In acute oral toxicity study on rat, transient inhibition of body weight was shown, but change in general symptom was not detected. No dead animal was observed up to 5,000 mg/kg in both male and female animals. In acute oral toxicity study on Beagle dog, transient vomiting, diarrhea, anorexia, and body weight reduction were observed, However, no dead animal was observed up to 2,000 mg/kg in both male and female animals.
Genotoxicity Studies of Chrysin
Jee Seungwan ; Kim Changhwan ; Park Misun ; Eom Miok ; Ryeom Taikyung ; Kim Okhee ; Kang Hoil ;
Toxicological Research, volume 21, issue 1, 2005, Pages 71~75
Chrysin (5,7-dihydroxyflavone) is a flavonoid compound contained in many fruits, vegetables and honey. In our experiment, we investigated genotoxicity of chrysin using bacterial reverse mutation assay, chromosomal aberration test, in vivo micronucleus test. In bacterial reverse mutation assay, chrysin did not induce mutagenicity in Salmonella typhimurium TA98, TA100, TA1535, TA1537, TA102 with and without metabolic activation. In chromosome aberration test, chrysin did not also induce structural and numerical abberations regardless of metabolic activation in Chinese hamster lung fibroblast cells. In mouse micronucleus test, no significant increase in the occurrence of micronucleated polychromatic erythrocytes (MNPCE) was observed in ICR male mice orally administered with chrysin at the dose of 0.5, 1.0, 2.0 g/kg body weight. Taken together these results, chrysin has no mutagenic potential in our experiment.
Cadmium Induces Cell Cycle Arrest and Change in Expression of Cell Cycle Related Proteins in Breast Cancer Cell Lines
Lee Young Joo ; Kang Tae Seok ; Kim Tae Sung ; Moon Hyun Ju ; Kang Il Hyun ; Oh Ji Young ; Kwon Hoonjeong ; Han Soon Young ;
Toxicological Research, volume 21, issue 1, 2005, Pages 77~85
Cadmium is an environmental pollutant exposed from contaminated foods or cigarette smoking and known to cause oxidative damage in organs. We investigated the cadmium-induced apoptosis and cell arrest in human breast cancer cells, MCF-7 cells and MDA-MB-231 cells. Obvious apoptotic cell death was shown in CdCl₂ 100 μM treatment for 12 hr, which were determined by DAPI staining and flow cytometric analysis. In cell cycle analysis, MCF-7 cells and MDA-MB-231 cells were arrested in S phase and G2/M phase respectively. These could be explained by the induction of cell cycle inhibitory protein, p21/sup Waf1/Cip1/ and p27/sup Kip1/, expression and reduction of cyclin/Cdk complexes in both cell lines. The decreased expression of cyclin A and Cdk2 in MCF-7 cells and cyclin B1 and Cdc2 in MDA-MB-231 cells were consistent with the flow cytometric observation. p-ERK expression was increased dose-dependent manner in both cell lines. It suggests that ERK MAPK pathway are involved in cadmium-induced cell cycle arrest and apoptosis. Moreover, cotreatment of zinc (100 μM, 12 hr) recovered the cadmium-induced cell arrest in both cells, which shows cadmium-induced oxidative stress mediates apoptosis and cell cycle arrest in human breast cancer cells.