• Title/Summary/Keyword: relative toxicity

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Caenorhabditis elegans as a Biological Model for Multilevel Biomarker Analysis in Environmental Toxicology and Risk Assessment

  • Choi, Jin-Hee
    • Toxicological Research
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    • v.24 no.4
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    • pp.235-243
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    • 2008
  • While in some instances, loss of diversity results from acute toxicity (e.g. major pollution incidents), in most cases it results from long-term sub-lethal effects that alter the relative competitive ability and fitness of certain organisms. In such cases the sub-lethal effects will cause a physiological response in the organism that ultimately leads to community level changes. Very sensitive tools are now available to study sub-lethal responses at the molecular level. However, relating such laboratory measurements to ecological effects represents a substantial challenge that can only be met by investigation at all scales (molecular, individual organism and community level) with an appropriate group of organisms. Among the various in vertebrates which can be used as model organisms in such a way, the soil nematode, Caenorhabditis elegans appear to be a promising biological model to diagnose environmental quality. This paper reviews the current status of multilevel biomarkers in environmental toxicology, and C. elegans as promising organisms for this approach.

Mathematical and Statistical Characterization of LD50 Estimation (LD50 산출방법에 있어서 수리 · 통계학적 특성)

  • Kim Se Ki;Kim Keun-Chong;Lee Byung Mu
    • Toxicological Research
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    • v.20 no.4
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    • pp.321-324
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    • 2004
  • Lethal dose 50% ($LD_{50}$) has been commonly used as a parameter for the estimation of acute toxicity not only in animal experiment, but also in human study. Several methods to estimate $LD_{50}$ had been introduced, but Spearman-Karber and Berens-Karber method have been widely used due to their relative convenience and accuracy. However, $LD_{50}$ values estimated from the two methods showed inconsistency and variation depending on the characteristics of mortality data. In this study, the two methods were comparatively investigated in terms of accuracy and stability for the estimation of $LD_{50}$.

Antiviral Activity of Papaverine and Nucleoside Analogs on the Human Cytomegalovirus Infection (Human Cytomegalovirus 감염에 대한 파파베린과 뉴클레오사이드 유사체의 항바이러스 효과)

  • ;Albrecht, T.
    • Korean Journal of Microbiology
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    • v.29 no.1
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    • pp.25-33
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    • 1991
  • Antiviral activities of papaverine and nucleoside analogs, 9-[(1,3-dihydroxy-2-propoxy)methyl]guanine (DHPG) and acyclovir, against human cytomegalovirus (HCMV) infection were compared in vitro. Papaverine and DHPG were effective in reducing infectious HCMV yields with $ED_{50}{\s}$ (effective dose 50: the concentraion at which 50% of virus yields was obtained) of approximately 1.02 and $0.45{\mu}{\M}$, respectively; while acyclovir was less effective with an $ED_{50}$ of about $10.4{\mu}{\M}$The relative cytotoxicity of these drugs was evaluated under the same conditions used to measure infectious HCMV yields. Papaverine and DHPG demonstrated little cellular toxicity as measured by their effect on the viability of confluent cells at concentrations in the range of those demonstrating potent inhibition of HCMV replication. Similarly, protein synthesis was largely unaffected by these drugs in stationary mock-infected cells as measured by the incorporation of isotopically labelled amino acids. In contrast, cellular DNA synthesis was invariably reduced in the presence of either drug. HCMV-specific DNA synthesis was also strongly inhibited by papaverine and DHPG.

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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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A Study of Environmental Conditions of Survival Rate and Relative Growth Rate in Female Gametophyte of Undaria pinnatifida for Toxicity Assessment (생태독성평가를 위한 미역(Undaria pinnatifida) 암배우체 생존율 및 상대성장률의 환경조건 연구)

  • Ju-Wook, Lee;Yun-Ho, Park;Bo-Ram, Sim;Hyong-Joo, Jeon;Seung, Heo;Un-Ki, Hwang
    • Journal of Marine Life Science
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    • v.7 no.2
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    • pp.86-93
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    • 2022
  • The ecotoxicity test method using Undaria pinnatifida spore is challenging to use throughout the year. Since U. pinnatifida female gametophytes can be cultured in the laboratory, they can be used for ecotoxicity testing at any time. Changes in female gametophyte survival rate and relative growth rate in U. pinnatifida exposed to various environmental conditions were analyzed. The female gametophyte of U. pinnatifida was exposed to salinity (5~40 psu), temperature (5~30℃), pH (4~10), and light intensity (0~120 μmol photon m-2 s-1). Based on the highest average value, the survival rate of female gametophyte was highest at a temperature of 20℃, salinity 27.5 psu, pH 8, and light intensity 30 μmol photon m-2 s-1. And the relative growth rate was highest at a temperature of 15℃, salinity 35 psu, pH 9, and light intensity of 60 μmol photon m-2 s-1. As a result of this study, the method using the optimal conditions for the survival rate and relative growth rate is expected to be a practical test method that can complement the current method.

Study on the Acute and Sub-Acute Inhalation Toxicity of 1-Bromopropane in SD Rats (Rat를 이용 1-Bromopropane의 급성 및 아급성 흡입독성 연구)

  • Kim, Hyeon-Yeong;Jeong, Jae-Hwang;Chung, Yong-Hyun;Lee, Yong-Muk;Sur, Gil-Soo
    • Journal of Korean Society of Occupational and Environmental Hygiene
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    • v.8 no.2
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    • pp.272-288
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    • 1998
  • The purpose of this study was to investigate the acute(4 hrs) and repeated-dose(6 hrs a day, 5 days a week, 8 weeks) toxic effects of 1-bromopropane(1-BP) on Sprague-Dawley (SD) rats which were treated by inhalation. The results were as follows ; 1. The median lethal concentration($LC_{50}$) was estimated 14,374 ppm(confidence limit 95% ; 13,624~15,596 ppm) in acute inhalation. Abnormal clinical signs related to the 1-BP were not observed with the acute inhalation dose. Gross findings of necropsy revealed no evidence of specific toxicity related to the 1-BP. 2. By sub-acute inhalation the body weights of male and female were significantly reduced(p<0.001) by the dose of 1,800 ppm compared with control group, while the relative weights of liver were significantly increased(p<0.001) in both sexes. However there were no significant variation in food consumption, urine biochemistry, hematology and blood biochemistry for the exposed rats compared with the control rats. Abnormal clinical signs and gross findings of necropsy related to the 1-BP were not shown. No toxicologic lesions were observed by the histopathological test.

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Thirteen Weeks Repeated Oral Dose Toxicity Study of Oplopanax elatus (Nakai) Nakai Hydrothermal Extract Powder in Sprague-Dawley Rats (Sprague-Dawley 랫드를 이용한 땃두릅나무 열수추출물 분말의 13주 반복 경구투여 독성에 관한 연구)

  • Yoo, Nam Ho;Kwon, Yongsoo;Chun, Hyeon Soo;An, Kyu Sup;Kim, Hye Jin;Ryu, Hyeon Yeol;Lee, So Min;Song, Kyung Seuk;Park, Byung Jun;Kim, Myong Jo
    • Korean Journal of Pharmacognosy
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    • v.50 no.4
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    • pp.260-271
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    • 2019
  • This study aimed to evaluate the safety of Oplopanax elatus (Nakai) Nakai hydrothermal extract powder. It was conducted using male and female Sprague-Dawley (SD) rats. The test group was established with dose of 500 (low-dosage group), 1,000 (medium- dosage group), and 2,000 (high- dosage group) mg/day. These are investigated that number of dead animals, general symptoms, weight changes, food consumption, ophthalmological examination, urinalysis, urine volume, hematological values, plasma coagulation time values, serum biochemical values, absolute organ weight, relative organ weight and histopathological finding during the experiment. As a result of the above, toxicological changes were not observed. Therefore, the non-toxic content of Oplopanax elatus (Nakai) Nakai hydrothermal extract powder is determined to be 2,000 mg/kg/day, and target organ was not observed.

Pharmacodynamic Modeling of Vincristine in Lymphoma Patients (림프종 환자에서 회귀모형을 이용한 vincristine의 약물 용량 예측 인자 및 부작용 모델 연구)

  • Seo, Jeong-Won;Kim, Dong-Hyun;Yun, Jin-Sang;Kim, Seon-Hwa;Choi, Bo-Yoon;Oh, Jung-Mi;Kwon, Kwang-Il
    • Korean Journal of Clinical Pharmacy
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    • v.21 no.2
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    • pp.145-155
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    • 2011
  • The objective of this study was to determine whether any pretreatment parameters were associated with pharmacological effect or toxicity parameters after vincristine administration and to describe a mathematical model, which explains the interpatient pharmacodynamic variability. The relationship between patient characteristics and vincristine dose and hematological toxicity were evaluated. 68 pediatric and adolescence patients and 107 adults with acute lymphoblastic leukemia were treated with vincristine $1.5mg/m^2/day$ IV and other anticancer drugs as scheduled. Complete blood counts and other blood test results were obtained. The input variables were age, gender, weight, lean body weight (LBW), height, body surface area, vincristine dose and total vincristine dose. The outcome measures were nadir values (white blood cells, absolute neutrophil counts, hemoglobin, and platelets); the absolute decrease, relative decrease, and survival fraction of blood cells. Polynomial regression analysis was carried out to determine the other significant covariates. The variability of $WBC_{nadir}$ was modeled with good precision and accuracy with a two-covariate model. This model should be validated and improved on with further clinical data. We believe that such pharmacodynamic modeling should be explored further to determine its performance and clinical relevance compared with modeling using pharmacokinetic parameter.

Chromosomal Aberration Assay of Taxol and 10-deacetyI baccatin III in Chinese Hamster Lung Cells In Vilro

  • Ryu, Jae-Chun;Kim, Kyung-Ran;Ryu, Eun-Kyung;Kim, Hyun-Joo;Kwon, Oh-Seung;Song, Choong-Eui;Mar, Woong-Chon;Chang, Il-Moo
    • Environmental Mutagens and Carcinogens
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    • v.16 no.1
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    • pp.6-12
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    • 1996
  • To investigate the clastogenicity of taxol and its precursor, 10-aleacetyl baccatin III, we performed chromosomal aberration assay with chinese hamster lung cells in vitro. The IC$_{50}$ values of taxol and 10-deacetyl baccatin III were determined as $1/16 \times 10^{-4}$ M (5.34 $\mu$g/ml) and $1 \times 10^{-2}$ M (560 $\mu$g/ml) in MTT assay, respectively. It means that the cytotoxicity of taxol revealed 100 times more cytotoxic than 10-deacetyl baccatin III in chinese hamster lung cell line. Nevertheless the strong positive genetic toxicity of taxol in the bone marrow micronucleus assay in vivo which was recently reported, we observed weak positive clastogenicity of taxoi only in the absence of metabolic activation system in the concentration ranges used in this experiment. Moreover, to clarify the involvement of metabolic fate of taxol because of its strong positive result in vivo, 10-deacetyl baccatin III which is a precursor in taxol synthesis, also subjected in chromosomal aberration assay in vitro. However, we observed no clastogenicity of 10-deacetyl baccatin III in this experiment. From above results, it was suggested that the esterification at C-13 appears to be relative for its genetic toxicity in chromosome aberration using chinese hamster lung cell in vitro.

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131I-Labeled-Metuximab Plus Transarterial Chemoembolization in Combination Therapy for Unresectable Hepatocellular Carcinoma: Results from a Multicenter Phase IV Clinical Study

  • Ma, Jun;Wang, Jian-Hua
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.17
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    • pp.7441-7447
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    • 2015
  • Objective: This study evaluated the safety and objective response of combining $^{131}I$-labeled-metuximab (Licartin) with transarterial chemoembolization (TACE) in the treatment of unresectable hepatocellular carcinoma (HCC). Materials and Methods: In a multicenter open-label clinical trial, 341 enrolled patients with stage III/IV HCC according to TNM criteria were nonrandomly assigned to a trial group (n=167) and a control group (n=174), undergoing TACE following hepatic intra-arterial injection of licartin or TACE alone from July 2007 to July 2009. Radiopharmaceutical distribution was evaluated. The primary endpoint was overall survival; secondary endpoints included time-to-progression (TTP), toxicity and adverse events (AEs). Results: The radiobiological distribution demonstrated better localization of licartin in liver tumors than other tissues (P<0.01). The organ absorbed doses to liver and red marrow were $3.19{\pm}1.01Gy$ and $0.55{\pm}0.22Gy$, respectively. The 1-year survival rate was significantly higher [79.47% vs. 65.59%, hazard ratio (HR), 0.598, P=0.041] and TTP significantly improved ($6.82{\pm}1.28$ vs. $4.7{\pm}1.14months$, P=0.037) compared with the control group. Patients at stage III achieved more benefit of one year survival than stage IV in the trial group (86.9% vs. 53.8%, P<0.001). There were significant different toxicities in leukocytopenia, thrombocytopenia and increased total bilirubin level [P<0.001, P=0.013, P<0.01, relative risk (RR) 1.63, 1.33, 1.43], but no differences in severe AEs of upper GI hemorrhage and severe liver dysfunction between the groups (5.39% vs. 2.3%, P=0.136). Conclusions: Owing to excellent tumor-targeting, promised efficacy and favourable toxicity profile, the novel combination therapy of licartin and TACE could be applied in patients with unresectable HCC.