• Title/Summary/Keyword: Dose toxicity study

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Effect of p-Phenylenediamine to Rat Skin (p-Phenylenediamine이 흰쥐의 피부 조직에 미치는 영향)

  • Lee, SangHee;Cho, HyunGug;Lee, Sang-Il
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.34 no.9
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    • pp.1330-1335
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    • 2005
  • Red brownish p-pheylenediamine (PPD) has been widely used hair dye for women. The dye was known to cause systemic anaphylaxis, dermatitis and bladder cancer. But the effect of PPD toxicity with oxygen free radical has not been studied. This study investigated the degree of skin injury by PPD. PPD ($2.5\%$ PPD in $2\%\;NH_{4}OH$) was applied to the rat skin ($25 mg/16.5\;cm^2$) 3 or 5 times every other day. Histopathological findings demonstrated the proliferation of epithelial cells and the increased keratinization by PPD. The activities of glucose 6-phosphatase (G6Pase) was decreased and acid phosphatase (ACP) was increased in PPD-applied rat skin. Groups in which PPD was applied 5 times were more damaged than groups applied 3 times. To examine the relationship between tissue damage and oxygen free radicals, effect of PPD on xanthine oxidase (XO) activity was measured and XO activity was more significantly increased in the group treated with PPD 5 times than 3 times. However, reduced glutathione (GSH) content, and the activities of catalase (CAT), super-oxide dismutase (SOD) and glutathione S -transferase (GST) were more decreased in PPD-applied groups than in controls. Even though the activities of XOD was not changed in the group treated with PPD 3 times, the decreased activities of oxygen free radical system and the damaged skin tissue were observed. This result might be caused by the production of toxic PPD metabolites in rat skin. In conclusion, topical PPD application led to skin injury in a dose-dependent manner, probably due to the generation rate of oxygen free radical.

Estrogenic Activity, and Developmental Toxicity Studies of Pyrethroid Insecticides

  • Kim, Soon-Sun;Rhee, Gyu-Seek;Lee, Rhee-Da;Kwack, Seung-Jun;Lim, Kwon-Jo;Yhun, Hyo-Jung;Park, Kui-Lea
    • Proceedings of the Korea Society of Environmental Toocicology Conference
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    • 2003.10a
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    • pp.57-69
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    • 2003
  • It is well known that many pesticides possess hormonal activity, and affect the developments of wildlife and mammals including human. Currently, pyrethroid insecticides are in worldwide use to control in and outdoor pests, providing potential far environmental exposure. Hormonal activities of these pyrethroid insecticides, however, have been little studied, and the developmental effects of them were no reported. Therefore, we firstly examined the potential estrogenic activities of some pyrethroid insecticides (permethrin, cypermethrin, tetramethrin, deltamethrin, sumithrin, fenvalerate and bioallethrin) by immature rat uterotrophic assay, luciferase reporter gene assay and Calbindin-D$\sub$9k/ (CaBP-9k) gene expression assay. Uterine wet weights were increased by permethrin and the permethrin-induced weights were inhibited by ICI 182780 in the uterolrophic assay. On the other hand tetramethrin significantly reduced uterine and vaginal wet weights, and also inhibited the E2-induced weight increases at all doses tested. Cypermethrin and sumithrin had a tendency to increase uterine weights, although not statistically significant. Permethrin and cypermethrin dose-dependently increased the luciferase activity in reporter gene assay. Northern blot analysis showed that permethrin induced CaBP-9k mRNA expression whereas tetramethrin inhibted. Subsequent studies were conducted to investigate the possible developmental effects of four pyrethroid insecricides (permethrin, cypermethrin, sumithrin and teramethrin). Either diethlbestrol (DES) or 17${\beta}$ -estradiol (E2) was used as a reference control in this study. Pyrethroid insecticides were administered to Sprague Dawley rats via subcutaneous injection at 6 to 18 days of gestation or 1 to 5 days after birth. In utero treatment of permethrin (10mg/kg/day) in female rat resulted in significant increases in uterine and ovarian weights while significant decreases in serum E2 concentration, uterine and ovarian ER${\alpha}$ mRNA levels. Sumithrin and permethrin led to acceleration in vaginal opening of female rat, while delay in preputial separation of male after neonatal treatment. Anogenital distances of PND 18 were significantly reduced in sumthrin-treated, and permerhrin-treated male rats after neonatal treatment. All the pyrethroid insecticides tested caused significant increases in uterine weights on PND 18, while significant reductions in the first diestrus phase when neonataly treated. In addition, exposure to pyrethroids in neonatal period led to significant reduction in relative brain weight in female rat on PND 18, but its weight was recovered in diestrus phase. In summary, Our experimental data demonstrate the possibilities of developmental effects of pyrethroid insecticides via estrogenic or antiestrogenic activity.

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Evaluation of endocrine disrupting effect of the herbicide Alachlor on Japanese Medaka using short term reproduction assay (단기번식독성시험법을 이용한 제초제 Alachlor의 송사리 내분비계 영향 조사)

  • Lee, Je-Bong;Park, Yoen-Ki;Choi, Young-Woong;Kim, Byung-Seok;Kwon, Hye-Young;Jin, Yong-Duk;Im, Geon-Jae;Kang, Kyu-Young
    • The Korean Journal of Pesticide Science
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    • v.16 no.2
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    • pp.187-193
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    • 2012
  • Acute toxicity, water resolvability and short term reproduction test on Japanese medaka (Oriyzias latipes) for evaluating alachlor susceptibility to endocrine system were studied. Alachlor is known for suspected endocrine distruptors. As the results of tests, $LC_{50}$ (Median lethal concentration) was determined as 2.36 (1.994~2.805) mg/L, and test water replaced at 7 day intervals as its water resolvability was less than 20% in 7 days. The short term reproduction tests on Japanese medaka (Oriyzias latipes) were performed with a solvent control group, a treated group (alachlor concentrations of 0.02, 0.04, 0.11, 0.27, 0.68 ppm) and a positive control group (17 ${\beta}$ estradiol, 0.01, 0.1, 0.5 ppb). The number of spawning and embryo rates were declined in a alachlor-dose dependent manner, and the number of unfertilized eggs rates were in contrast increased depending on the concentrations. Further study should be needed to confirm whether the adverse effects may be effected by the concentrations. Additionally, alachlor was evaluated as a non-vitellogenin by the result of a test of significance of the vitellogenin content test for determination of the effect of estrogen among the endocrine disruptors.

The Effect of Tannic Acid to the Cadmium on Mouse (Tannic acid가 랫드의 카드뮴독성에 미치는 영향)

  • 김판기;안령미;황성희
    • Journal of Food Hygiene and Safety
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    • v.13 no.2
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    • pp.87-93
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    • 1998
  • The tannic acid (0.5 mg/ml, 1.0 mg/mi, 2.0 mg/ml) and/or cadmium (20 mg/kg) were administered by oral administration. The results were as follows: 1. There were adverse effects on the weight changes and water consumption. But, the extent of adverse changes were decreased by tannic acid administration. 2. Also, there were some significant changes in organ weight, especially relative liver weight and relative brain weight by cadmium administration, but Ta1.0 group was significant changes in relative liver weight, relative lung weight and relative thymus weight compared with control group. 3. In the hematological patterns of administered mice, there were significant changes between cadmium treated groups and control group. Hemoglobin contents, packed cell volume, platelet count and neutrophill count were significantly change compared with control group. These changes were not shown in tannic acid treated group. 4. There were serological enzymatic changes in the cadmium treated mouse. In the tannic acid treated group 0.5, 1.0, 2.0 mg/ml, ALT, AST, BUN and creatinine were recovered to the extent of control group. From the above results, the tannic acid has some possible alleviative effects of cadmium toxicity upto the 2.0 mg/ml/day of oral dose for 4 weeks. But we need further study of mechanism for toxicty alleviating action of tannic acid to the heavy metals like cadmium.

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Combined Modality Treatment in Head and Neck Cancer (국소 진행된 두경부암의 병합요법 : 치료 방법에 따른 비교)

  • Park In-Kyu;Lee Ho-Jun;Yun Sang-Mo;Kim Jae-Chul
    • Korean Journal of Head & Neck Oncology
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    • v.17 no.1
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    • pp.32-37
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    • 2001
  • Objectives: We performed this study to compare the short term results of induction chemotherapy and radiotherapy versus concurrent chemoradiotherapy in patients with locally advanced head and neck cancer. Materials and Methods: From Oct. 1985 to May 1998, 121 patients with locally advanced head and neck cancer were treated with induction chemotherapy and radiotherapy (induction group) or concurrent chemoradiotherapy (concurrent group), and a retrospective analysis was done. Induction chemotherapy was done for 97 patients, and concurrent chemotherapy for 24 patients. Age, sex, performance status, and pathologic types were evenly distributed between two groups. Primary site showed nasopharynx(72.2%), oropharynx(27.8%) in induction group, and nasopharynx(50%), oropharynx(50%) in concurrent group. Chemotherapy regimen was CF(cisplatin and 5-fluorouracil) for 67 patients and CVB (cisplatin, vincristine, bleomycin) for 30 patients in induction group, and CF for all of 24 patients in concurrent group. Proportion of patients treated with more than 2 cycles of planned chemotherapy was 94.8% in induction group and 87.5% in concurrent group. Conventionally fractionated radiotherapy with daily fraction size of 1.8-2.0Gy and 5 fractions/week was done. Total dose was 61-95Gy (median 73.4Gy) for induction group, and 69.4-75.4Gy (median 69.4Gy) for concurrent group. Follow-up time was 4-161 months (median 38 months) for induction group, 7-35 months (median 21.5 months) for concurrent group, respectively. Results: According to treatment modality, overall 2-year survival rates were 68.0% for induction group, 74.3% for concurrent group (p>0.05). two-year disease-free survival rates were 51 % and 74% (p=0.05). Complete response rates were 67.4% for induction group and 83.3% for concurrent group (p=0.09). The incidence of grade 3-4 hematologic toxicity (2.1% vs. 25%, p=0.001) and grade 3-4 mucositis (9.3% vs. 37.5%, p=0.002) during radiotherapy was higher in concurrent group. Conclusion: Concurrent chemoradiotherapy showed a trend of improvement in short-term survival and treatment response when compared with induction chemotherapy and radiotherapy in locally advanced head and neck cancer. A more controlled randomized trial is needed.

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Effect of Diallyl Disulfide on Heme Oxygenase-1 Expression in Human Hepatoma Cell Line HepG2 (인간 간암세포주 HepG2에서 heme oxygenase-1 발현에 대한 diallyl disulfide의 효과)

  • Kim, Kang-Mi;Lee, Sang-Kwon;Park, Young-Chul
    • Journal of Life Science
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    • v.21 no.7
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    • pp.1046-1051
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    • 2011
  • Diallyl disulfide (DADS), the most prevalent oil-soluble organosulfur compound in garlic, is known to have diverse biological activities, including anticarcinogenic, antiatherosclerotic, antiinflammatory, and antioxidant actions. In this study, we investigated the effect of DADS on the expression of heme oxygenase-1 (HO-1) in human liver hepatoma cell line HepG2. Treatment of HepG2 cells by DADS evoked a dose-dependent growth inhibition without significant toxicity to the cells, and also induced the expression of transcription factor Nrf2. However, DADS did not have any enhancing effect on transcription and translation of HO-1 expression in HepG2 cells. In addition, DADS efficiently blocked protein synthesis of HO-1 in HepG2 cells stimulated by CoPP or hemin. But, DADS did not decrease the content of transcripts of HO-1 gene stimulated by CoPP, with accumulation of Nrf2 and small Maf in the nucleus. Based on these results, we conclude that DADS inhibits HO-1 expression by modulation of translational level of CoPP or hemin-induced HO-1 expression in HepG2 cells.

Evaluation of Phototoxicity for Cosmetics and Alternative Method (화장품 광독성 평가와 동물대체시험법)

  • Lee, Jong-Kwon;Sin, Ji-Soon;Kim, Jin-Ho;Eom, Jun-Ho;Kim, Hyung-Soo;Park, Kui-Lea
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.31 no.3 s.52
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    • pp.245-251
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    • 2005
  • Safety is one of the key issue in the regulation of cosmetics. Cosmetic Act deals with it in Korea. The guidance for the testing cosmetic ingredients and their safety evaluation are prepared by Korea Food and Drug Administration. Ultraviolet radiation could Induce skin damage, edema, erythema, photoaging, immune dysfunction and skin cancer. Ultraviolet radiation is classified as Group 2A(probably carcinogenic to humans) by International Agenry for Reaserch on Cancer(IARC). The in vitro methodologies for evaluating the toxic potential of ingredients reported in the literature have not yet been sufficiently validated for use in areas other than the study for mutagenicity/genotoxicity, for pre-screening for severe irritancy, for screening of phototoxicity and for evaluating the percutaneous absorption. The 3T3 neutral red uptake photoxicity test (3T3 NRU PT) was accepted as OECD toxicity guideline in 2002. The 3T3 NRU PT is an in vitro method based on a comparison of the cytotoxicitv of a chemical when tested in the presence and in the absence of exposure to a non-cytotoxic dose of UVA/visible light.

Antioxidative Effects of Red Ginseng Saponins on Paraquat-induced Oxidative Stress (Paraquat 유도 산화적 스트레스에 대한 홍삼 사포닌의 항산화 효과)

  • Kim, Dong-Jo;Seong, Kum-Soo;Kim, Dong-Won;Kim, Seong-Ruyong;Chang, Che-Chul
    • Journal of Ginseng Research
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    • v.28 no.1
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    • pp.5-10
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    • 2004
  • This study was carried out to investigate the effect of the active ingredients from ginseng on paraquat(PQ) toxicity. Oxidative stress was induced by intraperitreatneal injection of PQ at a single dose of 25 mg/kg. Saponin treated groups were given protopanaxadiol saponins(PPD) or protopanaxatriol saponins(PPT)(5 mg/kg, orally) per day for 1, 3, & 7 days. We also investigated the relationship between lipid peroxidation and ginseng saponins by measuring the levels of superoxide dismutase(SOD), catalase(CAT), glutathione peroxidase (GPx), reduced glutathione(GSH), malondialdehyde (MDA), and hydrogen peroxide(H$_2$O$_2$) in liver tissue. The activities of SOD, CAT, and GPx were generally high in the PPD group; the SOD activity on each day was the highest in the PPD group. The H$_2$O$_2$ content was the lowest in the PPD group. The GSH levels were significantly increased in the PPD. The levels of MDA(the end product of lipid peroxidation) were significantly lower in the red ginseng component groups than in the PQ group; the levels were especially low in the PPD groups. These results led us to conclude that the antioxidant effects of extracts from red ginseng prevent oxidative damage by direct antioxidant effects involving SOD, CAT, & GPx, and increasing the ability of the body to synthesize endogenous antioxidants.

Anti-inflammatory Effect of Onion (Allium cepa) Peel Hot Water Extract in vitro and in vivo (양파껍질 열수추출물의 in vitro 및 in vivo 항염증 효과)

  • Kang, Bo-Kyeong;Kim, Koth-Bong-Woo-Ri;Ahn, Na-Kyung;Choi, Yeon-Uk;Kim, Min-ji;Bark, Si-Woo;Pak, Won-Min;Kim, Bo-Ram;Park, Ji-Hye;Bae, Nan-Young;Ahn, Dong-Hyun
    • KSBB Journal
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    • v.30 no.4
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    • pp.148-154
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    • 2015
  • Onion (Allium cepa) is one of the flavonoids-rich materials in human diet and onion peel, which is the onion by-products, contains over 20 times more quercetin than the flesh. In this study, to examine the anti-inflammatory effects of onion peel hot water extract (OPHWE), the cell viability, nitric oxide (NO), pro-inflammatory cytokines, such as interluekin-6 (IL-6), tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), and IL-$1{\beta}$, were measured using the murine macrophage cell line RAW 264.7 cells. The Balb/c mice were used for an in vivo acute toxicity test and ICR mice were used for measurement of inhibition effects of croton oil-induced mouse ear edema. As a result, NO levels decreased in a dose-dependent manner. The production of IL-6, TNF-${\alpha}$, and IL-$1{\beta}$ was suppressed by 38%, 41%, and 34% respectively, compared with that of the LPS only group, without any cytotoxicity. The edema formation in the ICR mouse ear was also reduced compared to that in control. Moreover, there were no mortalities occurred in mice administered 5,000 mg/kg body weight of OPHWE. These results suggest that OPHWE has considerable anti-inflammatory activities and can be regarded as a potent candidate material to treat inflammatory diseases.

Evaluating the Micronucleus Induction Potential for the Genotoxicity Assay Using the Human Skin Model, KeraSkinTM (인공피부모델 KeraSkinTM을 이용한 유전독성 평가)

  • Lee, Su-Hyon;Jung, Haeng-Sun;Kim, Seol-Yeong;Kim, Hye Soo;Lim, Kyung-Min;Chung, Young-Shin;Choe, Tae-Boo
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.42 no.3
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    • pp.211-216
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    • 2016
  • Micronucleus test is genotoxicity assay for detection of micronuclei in the cytoplasm of interphase cells. The reduction and replacement of in vivo toxicity testing on animals require the development of in vitro models to predict the genotoxicity or other tests for cosmetic products. In this study, we evaluated a genotoxicity assay for topically applied chemicals using a three-dimensional human reconstructed skin model, KeraSkin$^{TM}$. Two genotoxins, mitomycin C (MMC) and methyl methanesulfonate (MMS), induced significant dose-related increases in cytotoxicity and micronuclei induction in the skin model. In contrast, two non-genotoxins, 4-nitrophenol (4-NP) and trichloroethylene (TCE), induced cytotoxicity but not micronucleus formation. In conclusion, micronucleus test using human skin model may be useful for predicting in vitro genotoxic potentials of cosmetic products.