• Title/Summary/Keyword: dose-response model

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Estimating Permissible Intake Level for Endosulfan Using Benchmark Dose based on Reproductive Tonicity (생식독성과 Benchmark Dose를 활용한 Endosulfan의 노출허용수준 산출)

  • 이효민;윤은경;염영나;황명실;양기화;신효선
    • Toxicological Research
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    • v.18 no.1
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    • pp.65-71
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    • 2002
  • A benchmark dose (BMD) approach has been evaluated us a replacement for the traditional NOAEL methodology currently being wed to assess the noncancer effects of toxicants. The endocrine disrupt-ing effect of endosulfan which showed decrement of sperm count and testicular testosterone level in animals, was currently reported. The amount of endosulfan used as pesticide in the country has been continuously increased. The aim of this study was to suggest the permissible intake level (PIL), corresponding to Accept-able Daily Intake (ADI), based on endocrine disrupting effect wing BMD. Various animal data were collected by consideration of critical effect showing endocrine disruption and an animal data for reproductive toxicity was selected. The Power model from BMD software for induction of $BMD_10$ having meaning which is the dose at the 95% lower confidence limit on a 10% response was used due to that the form of selected dose-response animal data was continuous data. The $BMD_10$ was estimated to be 0.393 mg/kg/day based on reproductive toxicity showing decrement of sperm count. The permissible intake level (PIL) was calculated by dividing the $BMD_10$ by the uncertainty factors of 100 with consideration of from animal to human and human variability. The PIL as 0.004 mg/kg/day was compared with traditional ADI as 0.006 mg/kg/day based on the incidence of marked progressive glomerulonephrosis and blood vessel aneurysm in males.

Individual-Based Models Applied to Species Abundance Patterns in Benthic Macroinvertebrate Communities in Streams in Response to Pollution

  • Cho, Woon-Seok;Nguyen, Tuyen Van;Chon, Tae-Soo
    • Korean Journal of Ecology and Environment
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    • v.45 no.4
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    • pp.420-443
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    • 2012
  • An Individual-Based Model (IBM) was developed by employing natural and toxic survival rates of individuals to elucidate the community responses of benthic macroin-vertebrates to anthropogenic disturbance in the streams. Experimental models (dose-response and relative sensitivity) and mathematical models (power law and negative exponential distribution) were applied to determinate the individual survival rates due to acute toxicity in stressful conditions. A power law was additionally used to present the natural survival rate. Life events, covering movement, exposure to contaminants, death and reproduction, were simulated in the IBM at the individual level in small (1 m) and short (1 week) scales to produce species abundance distributions (SADs) at the community level in large (5 km) and long (1~2 years) scales. Consequently, the SADs, such as geometric series, log-series, and log-normal distribution, were accordingly observed at severely (Biological Monitoring Working Party (BMWP<10), intermediately (BMWP<40) and weakly (BMWP${\geq}50$) polluted sites. The results from a power law and negative exponential distribution were suitably fitted to the field data across the different levels of pollution, according to the Kolmogorov-Smirnov test. The IBMs incorporating natural and toxic survival rates in individuals were useful for presenting community responses to disturbances and could be utilized as an integrative tool to elucidate community establishment processes in benthic macroin-vertebrates in the streams.

Gaussian process approach for dose mapping in radiation fields

  • Khuwaileh, Bassam A.;Metwally, Walid A.
    • Nuclear Engineering and Technology
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    • v.52 no.8
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    • pp.1807-1816
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    • 2020
  • In this work, a Gaussian Process (Kriging) approach is proposed to provide efficient dose mapping for complex radiation fields using limited number of responses. Given a few response measurements (or simulation data points), the proposed approach can help the analyst in completing a map of the radiation dose field with a 95% confidence interval, efficiently. Two case studies are used to validate the proposed approach. The First case study is based on experimental dose measurements to build the dose map in a radiation field induced by a D-D neutron generator. The second, is a simulation case study where the proposed approach is used to mimic Monte Carlo dose predictions in the radiation field using a limited number of MCNP simulations. Given the low computational cost of constructing Gaussian Process (GP) models, results indicate that the GP model can reasonably map the dose in the radiation field given a limited number of data measurements. Both case studies are performed on the nuclear engineering radiation laboratories at the University of Sharjah.

A Rapid Dose Assessment and Display System Applicable to PWR Accident (선량평가 및 Display시스템)

  • Moon, Kwang-Nam;Yook, Chong-Chul
    • Journal of Radiation Protection and Research
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    • v.13 no.2
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    • pp.67-77
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    • 1988
  • The necessity of developing a rapid dose assessment system has been emphasized for an effective emergency response of mitigation of off-site radiological consequences. A microcomputer program based on a rapid dose assessment model of the off-site radiological consequences is developed for various accdident sinarios for the Nuclear Power Plants in Korea. This model, which is consists of the user answering-question input format as a menu driven method and the output format of table and graphic types, is helpful to decision-making on Emergency Preparedness by being more rapidly able to implement the off-site dose assessment and to interpret the result.

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The Confidence Band of $ED_{100p}$ for the Simple Logistic Regression Model

  • Cho, Tae Kyoung;Shin, Mi Young
    • Communications for Statistical Applications and Methods
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    • v.8 no.3
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    • pp.581-588
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    • 2001
  • The $ED_{100p}$ is that value of the dose associated with 100p% response rate in the analysis of quantal response data. Brand, Pinnock, and Jackson (1973) studied the confidence bands of $ED_{100p}$ obtained by solving extremal values algebraically on the ellipsoid confidence region of the parameters in the simple logistic regression model. In this paper, we develope and illustrate a simpler method for obtaining confidence bands for $ED_{100p}$ based on the rectangular confidence region of parameters.

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Mouse model system based on apoptosis induction to crypt cells after exposure to ionizing radiation (방사선에 전신 조사된 마우스 음와 세포의 아포토시스 유도를 이용한 생물학적 선량 측정 모델 개발 연구)

  • Kim, Tae-Hwan
    • Korean Journal of Veterinary Research
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    • v.41 no.4
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    • pp.571-578
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    • 2001
  • To evaluate if the apoptotic fragment assay could be used to estimate the dose prediction after radiation exposure, we examined apoptotic mouse crypt cells per 1,000 cells after whole body $^{60}Co$ $\gamma$-rays and 50MeV ($p{\rightarrow}Be^+$) cyclotron fast neutron irradiation in the range of 0.25 to 1 Gy, respectively. The incidence of apoptotic cell death rose steeply at very low doses up to 1 Gy, and radiation at all doses tigger rapid changes in crypt cells in stem cell region. These data suggest that apoptosis may play an important role in homeostasis of damaged radiosensitive target organ by removing damaged cells. The curve of dose-effect relationship for the data of apoptotic fragments was obtained by the linear-quadratic model $y=0.18+(9.728{\pm}0.887)D+(-4.727{\pm}1.033)D^2$ ($r^2=0.984$) after $\gamma$-rays irradiation, while $y=0.18+(5.125{\pm}0.601)D+(-2.652{\pm}0.7000)D^2$ ($r^2=0.970$) after neutrons in mice. The dose-response curves were linear-quadratic, and a significant dose-response relationship was found between the frequency of apoptotic cell and dose. These data show a trend towards increase of the numbers of apoptotic crypt cells with increasing dose. Both the time course and the radiation dose-response curve for high and low linear energy transfer (LET) radiation modalities were similar. The relative biological effectiveness (RBE) value for crypt cells was 2.072. In addition, there were significant peaks on apoptosis induction at 4 and 6h after irradiation, and the morpholoigcal findings of the irradiated groups were typical apoptotic fragments in crypt cells that were hardly observed in the control group. Thus, apoptosis in crypt cells could be a useful in vivo model for studying radio-protective drug sensitivity or screening test, microdosimetric indicator and radiation-induced target organ injury. Since the apoptotic fragment assay is simple, rapid and reproducible in the range of 0.25 to 1 Gy, it will also be a good tool for evaluating the dose response of radiation-induced organ damage in vivo and provide a potentially valuable biodosimetry for the early dose prediction after accidental exposure.

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Dose Assessment for Workers in Accidents (사고 대응 작업자 피폭선량 평가)

  • Jun Hyeok Kim;Sun Hong Yoon;Gil Yong Cha;Jin Hyoung Bai
    • Journal of Radiation Industry
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    • v.17 no.3
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    • pp.265-273
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    • 2023
  • To effectively and safely manage the radiation exposure to nuclear power plant (NPP) workers in accidents, major overseas NPP operators such as the United States, Germany, and France have developed and applied realistic 3D model radiation dose assessment software for workers. Continuous research and development have recently been conducted, such as performing NPP accident management using 3D-VR based on As Low As Reasonably Achievable (ALARA) planning tool. In line with this global trend, it is also required to secure technology to manage radiation exposure of workers in Korea efficiently. Therefore, in this paper, it is described the application method and assessment results of radiation exposure scenarios for workers in response to accidents assessment technology, which is one of the fundamental technologies for constructing a realistic platform to be utilized for radiation exposure prediction, diagnosis, management, and training simulations following accidents. First, the post-accident sampling after the Loss of Coolant Accident(LOCA) was selected as the accident and response scenario, and the assessment area related to this work was established. Subsequently, the structures within the assessment area were modeled using MCNP, and the radiation source of the equipment was inputted. Based on this, the radiation dose distribution in the assessment area was assessed. Afterward, considering the three principles of external radiation protection (time, distance, and shielding) detailed work scenarios were developed by varying the number of workers, the presence or absence of a shield, and the location of the shield. The radiation exposure doses received by workers were compared and analyzed for each scenario, and based on the results, the optimal accident response scenario was derived. The results of this study plan to be utilized as a fundamental technology to ensure the safety of workers through simulations targeting various reactor types and accident response scenarios in the future. Furthermore, it is expected to secure the possibility of developing a data-based ALARA decision support system for predicting radiation exposure dose at NPP sites.

Exploitation of the Dose/Time-Response Relationship for a New Measure of DNA Repari in the Single-Cell Gel Electrophoresis (Comet) Assay

  • Kim, Byung-Soo;Edler, Lutz;Park, Jin-Joo;Fournier, Dietrich Von;Haase, Wulf;Sautter-Bihl, Mare-Luise;Hagmuller, Egbert;Gotzes, Florian;Thielmann, Heinz Walter
    • Toxicological Research
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    • v.20 no.2
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    • pp.89-100
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    • 2004
  • The comet assay (also called the single-cell gel electrophoresis assay) has been widely used for detecting DNA damage and repair in individual cells. Since the conventional methods of evaluating comet assay data using frequency statistics are unsatisfactory we developed a new quantitative measure of DNA damage/repair that is based on all information residing in the dose/time-response curves of a comet experiment. Blood samples were taken from 25 breast cancer patients before undergoing radiotherapy. The comet assay was performed under alkaline conditions using isolated lymphocytes. Tail DNA, tail length, tail moment and tail inertia of the comet were measured for each patient at four doses of $\gamma$-rays (0, 2, 4 and 8 Gy) and at four time points after irradiation (0, 10, 20 and 30 min) using 100 cells each. The resulting three-dimensional dose-time response surface was modeled by multiple regression, and the second derivative, termed 2D, on dose and time was determined. A software module was programmed in SAS/AF to compute 2D values. We applied the new method successfully to data obtained from cancer patients to be assessed for their radiation sensitivity. We computed the 2D values for the four damage measures, i.e., tail moment, tail length, tail DNA and tail inertia, and examined the pairwise correlation coefficients of 2D both on the log scale and the unlogged scale. 2D values based on tail moment and tail DNA showed a high correlation and, therefore, these two damage measures can be used interchangeably as far as DNA repair is concerned. 2D values based on tail inertia have a correlation profile different from the other 2D values which may reflect different facets of DNA damage/repair. Using the dose-time response surface, other statistical models, e.g., the proportional hazards model, become applicable for data analysis. The 2D approach can be applied to all DNA repair measures, Le., tail moment, tail length, tail DNA and tail inertia, and appears to be superior to conventional evaluation methods as it integrates all data of the dose/time-response curves of a comet assay.

Linear Energy Transfer Dependence Correction of Spread-Out Bragg Peak Measured by EBT3 Film for Dynamically Scanned Proton Beams

  • Lee, Moonhee;Ahn, Sunghwan;Cheon, Wonjoong;Han, Youngyih
    • Progress in Medical Physics
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    • v.31 no.4
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    • pp.135-144
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    • 2020
  • Purpose: Gafchromic films for proton dosimetry are dependent on linear energy transfers (LETs), resulting in dose underestimation for high LETs. Despite efforts to resolve this problem for single-energy beams, there remains a need to do so for multi-energy beams. Here, a bimolecular reaction model was applied to correct the under-response of spread-out Bragg peaks (SOBPs). Methods: For depth-dose measurements, a Gafchromic EBT3 film was positioned in water perpendicular to the ground. The gantry was rotated at 15° to avoid disturbances in the beam path. A set of films was exposed to a uniformly scanned 112-MeV pristine proton beam with six different dose intensities, ranging from 0.373 to 4.865 Gy, at a 2-cm depth. Another set of films was irradiated with SOBPs with maximum energies of 110, 150, and 190 MeV having modulation widths of 5.39, 4.27, and 5.34 cm, respectively. The correction function was obtained using 150.8-MeV SOBP data. The LET of the SOBP was then analytically calculated. Finally, the model was validated for a uniform cubic dose distribution and compared with multilayered ionization chamber data. Results: The dose error in the plateau region was within 4% when normalized with the maximum dose. The discrepancy of the range was <1 mm for all measured energies. The highest errors occurred at 70 MeV owing to the steep gradient with the narrowest Bragg peak. Conclusions: With bimolecular model-based correction, an EBT3 film can be used to accurately verify the depth dose of scanned proton beams and could potentially be used to evaluate the depth-dose distribution for patient plans.

Intra-tracheal Administration of the Disinfectant Chloromethylisothiazolinone/methylisothiazolinone (CMIT/MIT) in a Mouse Model to Evaluate a Causal Association with Death (마우스의 기도 내 점적을 통한 가습기살균제 CMIT/MIT와 사망 간의 원인적 연관성에 관한 연구)

  • Kim, Hayoung;Chung, Yonghyun;Park, Yeongchul
    • Journal of Environmental Health Sciences
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    • v.43 no.4
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    • pp.247-256
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    • 2017
  • Objectives: The deaths of Korean victims exposed to the disinfectant CMIT/MIT have remained unresolved. This is mainly due to a lack of concordance between the few available toxicity tests and the abundant epidemiological data, making it difficult to establish a cause-and-effect relationship. Therefore, this study was carried out to investigate any potential associations between CMIT/MIT exposure and death. Methods: Groups of experimental and control C57BL/6 mice were instilled (in the trachea) with chloromethylisothiazolinone/methylisothiazolinone (CMIT/MIT) using a visual instillobot. CMIT/MIT was instilled over a period of three days and eight weeks, respectively, to achieve acute and chronic exposures. A threshold dose-response model was applied for estimating the threshold level as one line of evidence for a causal association between CMIT/MIT and death. Results: An acute exposure of 1.2 mg ai/kg/day of CMIT/MIT was estimated to reflect the threshold for death. The dose-response curve with this threshold showed a very steep slope and a narrow range of CMIT/MIT exposures. The narrow range of CMIT/MIT exposures, in particular, indicated an evident boundary between survival and death, thus implicating a strong causal association. A similar threshold dose-response relationship observed following acute exposure was also seen following chronic exposure to CMIT/MIT. Airborne disinfectant exposure was visible as minimal or mild lung damage with no fibrosis, as shown by histopathological tests. However, many observations are considered to be functional respiratory tract or lung failure due to death, as observed in necropsies of the mice that died due to CMIT/MIT exposures. Conclusions: There are two strong lines of evidence for a causal association between death and CMIT/MIT exposure: 1) The threshold dose-response curve, with a very steep slope and a narrow range of CMIT/MIT exposures showing a visible boundary between survival and death; and 2) many cases of functional respiratory or lung failure.