• Title/Summary/Keyword: dose toxicity

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The effects of selenium on fetal growth and development in CD-1 mice exposed with mercury for the gestation period (임신 중 수은을 섭취한 CD-1 마우스 태아의 성장발육과 기형발생에 미친 셀레늄의 효과)

  • Kim, Jin-suk;Lee, Sang-mok;Choi, Seok-wha;Lee, Won-chang
    • Korean Journal of Veterinary Research
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    • v.34 no.2
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    • pp.361-368
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    • 1994
  • Teratogenic and embryotoxic effects of mercury have been reported, however, there is little information about possible antidotes against mercury exposure during gestation. In order to evaluate therapeutic effects of selenium as an antidote against mercury poisoning, pregnant CD-1 mice were exposed to methylmercury chloride(20ppm) through the drinking water with treatment of sodium selenite (1.0mg, 2.0mg or 3.0mg/kg b.w., subcutaneously) or BAL(5.0mg/kg b.w., subcutaneously) under the single or combination base as the therapeutic agents from day 6 to 15 of gestation. Fetal growth parameters such as body weight and crown-rump length in the mice exposed to mercury, were reduced as was placental weight compared to those in the control. Treatment of selenium(alone, combination with BAL) reduced the harmful effects induced by mercury on the fetal growth parameters even though no specific relationship between dose and therapeutic effect. The incidence of dead fetuses/resorptions and malformed fetuses(especially cleft palate) was also increased in the mercury only treated group. Selenium treatment demonostrated reduced the incidence of abnormal fetuses under the exposure of mercury. Relative maternal organ weights(liver, kidney, spleen) were increased significantly but relative brain weight was decreased as evidenced by decreased in the mercury treated mice compared to that in the control. A subtle indication of maternal mercury toxicity evidenced by changes of relative maternal organ weights, decreased water and feed consumption were also prevented efficiently by selenium treatment. The present study suggests that methylmercuric chloride is embrytoxic and teratogenic in CD-1 mice when exposured during organogenesis and that selenium administration may have therapeutic application for the treatment of mercury poisoning although more applicable study in human should be performed with caution in the future.

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Gemcitabine-induced Cell Death in Lung Cancer Cells : the Role of p53 (폐암 세포에서 Gemcitabine에 의한 세포 사멸과 p53의 역할)

  • Kim, Doh-Hyung;Bae, Gang-U;Yong, Wha-Shim;Choi, Eun-Kyung;Kim, Youn-Seup;Park, Jae-Seuk;Jee, Young-Koo;Lee, Kye-Young
    • Tuberculosis and Respiratory Diseases
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    • v.53 no.3
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    • pp.275-284
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    • 2002
  • Background : Gemcitabine is a new anti-cancer agent for treating non-small cell lung cancer. Functioning as an antimetabolite, it induces anti-cancer effects by suppressing DNA synthesis after being incorporated into the DNA as a cytosine arabinoside analogue. When Gemcitabine is incorporated into the DNA, the p53 gene may be activated by induction of the DNA defect. However, there are a few studies on the molecular mechanisms of Gemcitabine-induced cell death. This study examined the role of p53 in Gemcitabine-induced cell death. Methods : A549 and NCl-H358 lung cancer cells were used in this study. The cell viability test was done using a MTT assay at Gemcitabine concentrations of 10nM, 100nM, 1uM, 10uM and 100uM. A FACScan analysis with propium iodide staining was used for the cell cycle analysis. Western blot analysis was done to investigate the extent of p53 activation. For the functional knock-out of p53, stable A549-E6 cells and H358-E6 cells were transfected pLXSN-16E6SD which is over expresses the human papilloma virus E6 protein that constantly degrades p53 protein. The functional knock out of p53 was confirmed by Western blot analysis after treatment with a DNA damaging agent, doxorubicine. Results : Gemcitabine exhibited cell toxicity in dose-dependent fashion. The cell cycle analysis resulted in an S phase arrest. Western blot analysis significant p53 activation in time-dependent manner. Gemcitabine-induced cytotoxicity was reduced by 20-30% in the A549-E6 cells and the 30-40% in H358-E6 cells when compared with the A549-neo and H358-neo control cells. Conclusion : Gemcitabine induces an S phase arrest, as expected for the anti-metabolite, and activates the p53 gene, Furthermore, p53 might play an important role in Gemcitabine-induced cell death. Further investigation into the molecular mechanisms on how Gemcitabine activates the p53 gene and its signaling pathway are recommended.

Phase II Trial of Irinotecan plus Cisplatin Combination as First Line Therapy for Patients with Small cell Lung Cancer (소세포폐암 환자에서 1차 항암 치료제로서 Irinotecan 과 Cisplatin 병합요법에 관한 2상 연구)

  • Jeong, Hye Cheol;Lee, Sang Yeub;Kim, Jung Ha;Ha, Eun Sil;Jung, Jin Yong;Lee, Kyung Ju;Lee, Seung Hyeun;Kim, Se Joong;Lee, Eun Joo;Hur, Gyu Young;Lee, Sung Yong;Kim, Je Hyeong;Shin, Chol;Shim, Jae Jeong;In, Kwang Ho;Kang, Kyung Ho;Yoo, Se Hwa
    • Tuberculosis and Respiratory Diseases
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    • v.60 no.1
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    • pp.57-64
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    • 2006
  • Background : Recently, there have been several studies showing that irinotecan hydrochloride, a topoisomerase I inhibitor, is effective against extensive disease(ED) small cell lung cancer (SCLC). We conducted a phase II trial to evaluate the efficacy and toxicity of irinotecan plus cisplatin as a 1st line therapy for both limited and extensive disease SCLC. Methods : The study was conducted between January 2002 and June 2004. Patients were treated with $60mg/m^2$ irinotecan on day 1, 8, 15 and $60mg/m^2$ cisplatin on day 1, every 4 weeks. During concurrent thoracic irradiation for limited disease (LD)-SCLC patients, dose of irinotecan was reduced to $40mg/m^2$. Prophylactic cranial irradiation was given to patients with complete remission (CR) after chemotherapy. Results : Median ages of LD- and ED- SCLC were 64 years and performance status (PS) was 0-2. In patients with LD-SCLC, the response rate after concurrent chemoradiotherapy was 85% (CR, 6; Partial response [PR], 11). The median survival was 20 months (95% CIs, 15.6 to 24.4) with 1-and 2-year survival rates of 85% and 35%, respectively. Median progression free survival (PFS) was 12 months (95% CIs, 6.2 to 18.1) with 1- year PFS of 36%. In ED-SCLC, the response rate was 83.4% (CR, 1; PR, 14). The median survival was 14.5 months (95% CIs, 8.8 to 20.1) with 1-year survival rates of 75%. Median PFS was 6.3 months (95% CIs, 5.6 to 7.1) with 1- year PFS of 20%. The major toxicities (grade 3 or 4) of this regimen included leukopenia, anemia, thrombocytopenia, nausea/vomiting, and diarrhea without life threatening complication. Conclusion : Our data shows that the combination of irinotecan plus cisplatin as a first line therapy is effective and tolerable in the treatment of both LD- and ED- SCLC.

Multidisciplinary Management of the Locally Advanced Unresectable Non-Small Cell Lung Cancer (수술 불가능한 국소 진행 비소세포성 폐암의 집합적 요법)

  • Cho, Kwan-Ho
    • Radiation Oncology Journal
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    • v.22 no.1
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    • pp.1-10
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    • 2004
  • Locally advanced (Stage III) non-small cell lung cancer (NSCLC) accounts for approximately one third of all cases of NSCLC. Few patients with locally advanced NSCLC present with disease amenable to curative surgical resection. Historically, these patients were treated with primary thoracic radiation therapy (RT) and had poor long term survival rates, due to both progression of local disease and development on distant metastases. Over the last two decades, the use of multidisciplinary approach has improved the outcome for patients with locally advanced NSCLC. Combined chemoradiotherapy is the most favored approach for treatment of locally advanced unresectable NSCLC. There are two basic treatment protocols for administering combined chemotherapy and radiation, sequential versus concurrent. The rationale for using chemotherapy is to eliminate subclinical metastatic disease while improving local control. Sequential use of chemotherapy followed by radiotherapy has improved median and long term survival compared to radiation therapy alone. This approach appears to decrease the risk of distant metastases,, but local failure rates remain the same as radiation alone. Concurrent chemoradiotherapy has been studied extensively. The potential advantages of this approach may include sensitization of tumor cells to radiation by the administration of chemotherapy, and reduced overall treatment time compared to sequential therapy; which is known to be important for improving local control in radiation biology. This approach Improves survival primarily as a result of improved local control. However, it doesn't seem to decrease the risk of distant metastases probably because concurrent chemoradiation requires dose reductions in chemotherapy due to increased risks of acute morbidity such as acute esophageal toxicity. Although multidisciplinary therapy has led to improved survival rates compared to radiation therapy alone and has become the new standard of care, the optimal therapy of locally advanced NSCLC continues to evolve. The current issues in the multidisciplinary management of locally advanced NSCLC will be reviewed in this report.

The Results of Curative Concurrent Chemoradiotherapy for Anal Carcinoma (항문암 환자에서 근치적 목적의 동시 항암화학 방사선치료의 결과)

  • Jeong, Jae-Uk;Yoon, Mee-Sun;Song, Ju-Young;Ahn, Sung-Ja;Chung, Woong-Ki;Nah, Byung-Sik;Nam, Taek-Keun
    • Radiation Oncology Journal
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    • v.28 no.4
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    • pp.205-210
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    • 2010
  • Purpose: To evaluate the predictive factors for treatment response and prognostic factors affecting survival outcomes after concurrent chemoradiotherapy (CCRT) for patients with anal squamous cell carcinoma. Materials and Methods: Medical records of forty two patients with histologically confirmed analsquamous cell carcinoma, who had complete CCRT between 1993 and 2008, were reviewed retrospectively. Median age was 61.5 years (39~89 years), and median radiotherapy (RT) dose was 50.4 Gy (30.0~64.0 Gy). A total of 36 patients had equal to or less than T2 stage (85.7%). Fourteen patients (33.3%) showed regional nodal metastasis, 36 patients (85.7%) were treated with 5-fluorouracil (5-FU) plus mitomycin, and the remaining patients were treated by 5-FU plus cisplatinum. Results: The median follow-up time was 62 months (2~202 months). The 5-year overall survival, loco regional relapse-free survival, disease-free survival, and colostomy-free survival rates were 86.0%, 71.7%, 71.7%, 78.2%, respectively. Regarding overall survival, the Eastern Cooperative Oncology Group (ECOG) performance status and complete response were found to be significant prognostic factors on univariate analysis. For multivariate analysis, only the ECOG performance status was significant. No significant factor was found for locoregional relapse-free survival or disease-free survival and similarly for treatment response, no significant factor was determined on logistic regression analysis. There were 7 patients who had local or regional recurrences and one patient with distant metastasis. The only evaluable toxicity in all patients was radiation dermatitis of perianal skin (grade 3), which developed in 4 patients (9.5%) and grade 2 in 22 patients (52.4%). Conclusion: This study revealed that patients with a performance score of ECOG 0-1 survived significantly longer than those with a poorer score. Finally, there was no significant predicting factors tested for treatment response.

Photocatalytic Oxidation of Arsenite Using Goethite and UV LED (침철석과 자외선 LED를 이용한 아비산염의 광촉매 산화)

  • Jeon, Ji-Hun;Kim, Seong-Hee;Lee, Sang-Woo;Kim, Soon-Oh
    • Journal of Korean Society of Environmental Engineers
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    • v.39 no.1
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    • pp.9-18
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    • 2017
  • Arsenic (As) has been considered as the most toxic one among various hazardous materials and As contamination can be caused naturally and anthropogenically. Major forms of arsenic in groundwater are arsenite [(As(III)] and/or arsenate [(As(V)], depending on redox condition: arsenite and arsenate are predominant in reduced and oxidized environments, respectively. Because arsenite is much more toxic and mobile than arsenate, there have been a number of studies on the reduction of its toxicity through oxidation of As(III) to As(V). This study was initiated to develop photocatalytic oxidation process for treatment of groundwater contaminated with arsenite. The performance of two types of light sources (UV lamp and UV LED) was compared and the feasibility of goethite as a photocatalyst was evaluated. The highest removal efficiency of the process was achieved at a goethite dose of 0.05 g/L. Based on the comparison of oxidation efficiencies of arsenite between two light sources, the apparent performance of UV LED was inferior to that of UV lamp. However, when the results were appraised on the basis of their emitting UV irradiation, the higher performance was achieved by UV LED than by UV lamp. This study demonstrates that environmentally friendly process of goethite-catalytic photo-oxidation without any addition of foreign catalyst is feasible for the reduction of arsenite in groundwater containing naturally-occurring goethite. In addition, this study confirms that UV LED can be used in the photo-oxidation of arsenite as an alternative light source of UV lamp to remedy the drawbacks of UV lamp, such as long stabilization time, high electrical power consumption, short lifespan, and high heat output requiring large cooling facilities.

Comparison of Liver, Kidney, Bone Metal Concentration in OhJeokSan-Treated Rats (오적산(五積散)을 투여한 흰쥐의 간장, 신장, 골중 금속농도 비교에 관한 연구)

  • Park Chul-Soo;Lee Sun-Dong;Park Hae-Mo;Park Yeong-Chul
    • Journal of Society of Preventive Korean Medicine
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    • v.6 no.2
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    • pp.66-85
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    • 2002
  • Traditional herbal medicine is used extensively among the Korean populations, and other Asian countries employ similar therapies as well In recent years, extensive focus was laid on adulteration of the herbal medicine with heavy metals. This may be mainly due to a soil contamination by an environmental pollution. The objective of this study is to identify the contents of various heavy metals in the blood from OhJeokSan-Decoction (OD) treated-rats. For this study, 13 kinds of metals including essential and heavy metals, i.e. Al, As, Cd, Co, Cr, Cu, Fe, Hg, Mn, Ni, Pb, Se and Zn were analyzed by a slight modification of EPA methods and the following results are obtained. ; 1. There is no significant difference between the OD-treated groups and control group in liver, kidney, bone, brain, weight, food intake. 2. The amount of each metal analyzed in the liver are as follows; Al ; $0.235{\sim}4.215mg/kg$, As ; $0.103{\sim}0.461mg/kg$, Cd ; $0.005{\sim}0.010mg/kg$, Co ; $0.017{\sim}0.046mg/kg$, Cr ; $0.137{\sim}0.403mg/kg$, Cu ; $1.736{\sim}4.827mg/kg$, Fe ; $54.472{\sim}381.447mg/kg$, Hg ; not detected, Mn ; $1.159{\sim}2.803mg/kg$, Ni ; $0.007{\sim}0.095mg/kg$, Pb ; not detected, Se ; $0.682{\sim}1.887mg/kg$, Zn ; $10.213{\sim}26.119mg/kg$, by groups, respectively. In control and other experimental group, several metal (Co, Cu, Mn, Zn, As, Cr) has a significant difference, but in experimental I and other experimental II, III, IV, V groups, there are no significant difference. 3. The amount of each metal analyzed in the kidney are as follows; Al ; $1.712{\sim}31.230mg/kg$, As ; $0.062{\sim}0.439mg/kg$, Cd ; $0.010{\sim}0.062mg/kg$, Co ; $0.000{\sim}0.101mg/kg$, Cr ; $0.125{\sim}0.636mg/kg$, Cu ; $3.385{\sim}12.502mg/kg$, Fe ; $41.148{\sim}99.709mg/kg$, Hg ; $0.000{\sim}0.270mg/kg$, Mn ; $0.433{\sim}2.301mg/kg$, Ni ; $0.000{\sim}0.221mg/kg$, Pb ; $0.000{\sim}0.584mg/kg$, Se ; $0.540{\sim}1.600mg/kg$, Zn ; $8.775{\sim}17.060mg/kg$, by groups, respectively. The concentration of Cu, Se, Cr, and Hg are variated significantly in control and other experimental group, and Cu, Se, Cd, Cr are variated significantly in experimental I and other experimental II, III, IV, V groups. 4. The amount of each metal analyzed in the bone(tibia and fibula) are as follows; Al ; $9.557{\sim}119.464mg/kg$, As ; $0.139{\sim}12.250mg/kg$, Cd ; $0.000{\sim}0.295mg/kg$, Co ; $0.022{\sim}0.243mg/kg$, Cr ; $0.239{\sim}1.999mg/kg$, Cu ; $0.000{\sim}2.291mg/kg$, Fe ; $240.249{\sim}841.956mg/kg$, Hg ; $0.000{\sim}0.983mg/kg$, Mn ; $0.214{\sim}7.353mg/kg$, Ni ; $5.473{\sim}11.453mg/kg$, Pb ; $0.000{\sim}8.502mg/kg$, Se ; $0.000{\sim}3.005mg/kg$, Zn ; $61.158{\sim}195.038mg/kg$, by groups, respectively. The concentration of Se, Cd are variated significantly in control and other experimental groups, and Se is variated significantly in experimental I and other experimental II, III, IV, V groups. 5. Exceptionally several metal concentration is increased or decreased. but there is no significant harmful difference of metal concentration in the liver, kidney and bone, from the OD-treated-rats compared to those of the control group even if higher dosage($1{\sim}8$ times dosage of person) of OD was administered. Thus, it is expected that the herbal decoction in the traditional herbal medicine would not lay any burden on the body and the heavy metal toxins would not affect our physiological system. However, other kinds of herbal treatment, such as i.v. and i.p. should be considered in terms of metal toxicity in the body since the level of certain metal.

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Ecological Risk Assessment of Pesticide Residues in Agricultural Lake : Risk Quotients and Probabilistic Approach (농업용수를 공급하는 호소 수역 내 잔류 농약의 생태위해성평가 : 위해지수방법과 확률론적 방법)

  • Lee, Ji-Ho;Park, Byung-Jun;Park, Sang-Won;Kim, Won-Il;Hong, Su-Myung;Im, Geon-Jae;Hong, Moo-Ki
    • Korean Journal of Environmental Agriculture
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    • v.30 no.3
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    • pp.316-322
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    • 2011
  • BACKGROUND: Pesticides concentration was monitored in 50 agricultural lakes, and ecological risk for aquatic organism was assessed using risk quotient (RQ) and probabilistic methods. METHODS AND RESULTS: Pesticides concentrations detected in 50 agricultural lakes during peak season (June and September) were in the range of $0.17{\sim}0.99{\mu}g/L$. The RQ for algae and the other species was estimated to be 0.25 and below 0.01, indicating medium risk and no risk. Oxadiazon predominantly contributed to RQ value of 99% for algae, fishes, and amphibians. In terms of hazardous concentration at 5% of species ($HC_5$), ecological risk quotients (ERQ) for oxadiazon ranged from 0.18~0.33, showing a medium risk level. Overall, the concentrations of pesticides were much lower than $HC_5$), value. Probability of combined ecological risk for pesticides ranged from 1.82% to 2.41%. CONCLUSION(s): Combined ecological risk probability did not exceed the acceptable level of 5%, indicating no ecological risk for selected aquatic species. This study suggests that regular ecological risk assessment (ERA) will be required to protect and manage an agricultural lake. Not only ERA at screening level by comparing exposure with toxic effects for aquatic species also advanced ERA technique considering species in indigenous to Korea, chronic toxicity, pulse dose, fate, and environmental factors should be required.

Effects of Recombinant Human Epidermal Growth Factor (rhEGF) on Experimental Radiation-Induced Oral Mucositis in Rats (Rat의 방사선 조사성 구내염에 대한 Recombinant Human Epidermal Growth Factor (rhEGF)의 효과)

  • Jung Kwon-Il;Kim Sun-Hee;Moon Soo-Young;Kim Yeon-Wha;Hong Joon-Pio;Kim Hyun-Sook;Lee Sang-Wook
    • Radiation Oncology Journal
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    • v.24 no.1
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    • pp.67-76
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    • 2006
  • Purpose: Oral mucositis is a common toxicity of radiation or chemotherapy, which is used a treatment for head and neck cancer. We investigated effects of recombinant human epidermal growth factor (rhEGF) on radiation-induced oral mucositis in rat model. Materials and Methods: Spraque-Dawley rats (7 per group) exposed to a single dose of 25 Gy (day 0) on their head, except for one group, were randomly divided into un-treated, vehicle-treated, and two rhEGF-treated groups. Rats were topically applied with rhEGF (15 or $30{\mu}g/oral$ cavity/day) or vehicle to their oral mucosa. Survival rate of rats, weight changes, and food intakes were examined from day 0 to 18 after radiation. Histology study was performed from oral mucosa of rats at day 7 and 18 after radiation. Results: rhEGF-treated groups (15 or $30{\mu}g/oral$) showed all survival rate 33%, whereas un-treated and vehicle-treated groups showed all survival rate 0% at the end of experiment. rhEGF-treated groups statistically had less weight loss compared to vehicle-treated group from day 2 to 7 after radiation. Food intake of rats with rhEGF treatment turned to increase at day 14 after radiation. At 7 day after radiation, un-treated and vehicle-treated groups showed severe pseudomembraneous or ulcerative oral mucositis. On the other hand, rhEGF-treated groups had no more than cellular swelling and degeneration of epidermal cells in oral mucosa of rats. Conclusion: These results suggest that rhEGF has significantly positive effects on radiation-induced oral mucositis in rats. rhEGF display a therapeutic potential on a clinical level.

Risk Assessment of As, Cd, Cu and Pb in Different Rice Varieties Grown on the Contaminated Paddy Soil (중금속 오염 논토양에서 재배된 벼 품종간 위해성평가 비교)

  • Kim, Won-Il;Kim, Jin-Kyoung;Yoo, Ji-Hyock;Paik, Min-Kyoung;Park, Sang-Won;Kwon, Oh-Kyung;Hong, Moo-Ki;Yang, Jay-E;Kim, Jeong-Gyu
    • Korean Journal of Soil Science and Fertilizer
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    • v.42 no.1
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    • pp.53-57
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    • 2009
  • Heavy metal pollution may be one of the most serious challenges confront crop production and human health. Therefore, the selection of heavy metal tolerance cultivars which adapted to the contaminated fields will introduced a suitable solution for management this critical environmental risk. The objectives of this research is to assess human health risk using geochemical analyses and exposure assessment of heavy metals in rice cultivars. Risk for inhabitants in the closed mine area was comparatively assessed for As, Cd, Cu and Pb in 10 rice varieties as a major exposure pathway. The average daily dose (ADD) of each heavy metal was estimated by analyzing the exposure pathways to rice and soil. For the non-carcinogenic risk characterization, Hazard Quotient (HQ) and Hazard Index (HI) were calculated using toxicity indices provided by US-EPA IRIS. The different rice varieties revealed a wide range of HI values from 23.6 to 34.3, indicating that all rice varieties have a high potential toxic risk. The DA rice variety showed the lowest HI value while the TB rice variety the highest. The probabilities of cancer risk for As via rice consumption were varied with rice varieties ranging from 2.0E-03 to 3.5E-03 which exceeded the regulatory acceptable risk of 1 in 10,000 set by US-EPA. The DA rice variety also showed the lowest value while the TB rice variety gave the highest value. Our results indicate that risk assessment can be contribute to screen the pollution safe rice cultivars in paddy fields affected by the mining activity.