• 한국환경보건학회지
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• 제43권4호
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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.

• The Korean Journal of Pain
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• 제20권2호
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• pp.92-99
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• 2007

Background: A correlation between a T-type voltage activated calcium channel (VACC) and pain mechanism has not yet been established. The purpose of this study is to find out the effect of ethosuximide and mibefradil, representative selective T-type VACC blockers on postoperative pain using an incisional pain model of rats. Methods: After performing a plantar incision, rats were stabilized on plastic mesh for 2 hours. Then, the rats were injected with ethosuximide or mibefradil, intraperitoneally and intrathecally. The level of withdrawal threshold to the von Frey filament near the incision site was determined and the dose response curves were obtained. Results: After an intraperitoneal ethosuximide or mibefradil injection, the dose-response curve showed a dose-dependent increase of the threshold in a withdrawal reaction. After an intrathecal injection of ethosuximide, the threshold of a withdrawal reaction to mechanical stimulation increased and the increase was dose-dependent. After an intrathecal injection of mibefradil, no change occurred in either the threshold of a withdrawal reaction to mechanical stimulation or a dose-response curve. Conclusions: The T-type VACC blockers in a rat model of postoperative pain showed the antihyperalgesic effect. This effect might be due to blockade of T-type VACC, which was distributed in the peripheral nociceptors or at the supraspinal level. Further studies of the effect of T-type VACC on a pain transmission mechanism at the spinal cord level would be needed.

• Asian Journal of Atmospheric Environment
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• 제12권1호
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• pp.1-16
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• 2018

Ground-level ozone ($O_3$) can be a menace for vegetation, especially in Asia where $O_3$ levels have been dramatically increased over the past decades. To ensure food security and maintain forest ecosystem services, such as nutrient cycling, carbon sequestration and functional diversity of soil biota, in the over-populated Asia, environmental standards are needed. To set proper standards, dose-response relationships should be established from which critical levels are derived. The predictor of the response in the dose-response relationship is an $O_3$ metric that indicates the dose level to which the plant has been exposed. This study aimed to review the relevant scientific literature and summarize the $O_3$ metrics used worldwide to provide insights for Asia. A variety of $O_3$ metrics have been used, for which we discuss their strengths and weaknesses. The most widely used metrics are based only on $O_3$ levels. Such metrics have been adopted by several regulatory agencies in the global. However, they are biologically irrelevant because they ignore the plant physiological capacity. Adopting AOT40 ($O_3$ mixing ratios Accumulated Over the Threshold of $40nmol\;mol^{-1}$) as the default index for setting critical levels in Asia would be a poor policy with severe consequences at national and Pan-Asian level. Asian studies should focus on flux-based $O_3$ metrics to provide relevant bases for developing proper standards. However, given the technical requirements in calculating flux-based $O_3$ metrics, which can be an important limitation in developing countries, no-threshold cumulative exposure indices like AOT0 should always accompany flux-based indices.

• Communications for Statistical Applications and Methods
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• 제29권3호
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• pp.287-299
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• 2022

In radiation epidemiology, the excess relative risk (ERR) model is used to determine the dose-response relationship. In general, the dose-response relationship for the ERR model is assumed to be linear, linear-quadratic, linear-threshold, quadratic, and so on. However, since none of these functions dominate other functions for expressing the dose-response relationship, a Bayesian semiparametric method using splines has recently been proposed. Thus, we improve the Bayesian semiparametric method for the selection of the tuning parameters for splines as the number and location of knots using a Bayesian knot selection method. Equally spaced knots cannot capture the characteristic of radiation exposed dose distribution which is highly skewed in general. Therefore, we propose a nonparametric Bayesian knot selection method based on a Dirichlet process mixture model. Inference of the spline coefficients after obtaining the number and location of knots is performed in the Bayesian framework. We apply this approach to the life span study cohort data from the radiation effects research foundation in Japan, and the results illustrate that the proposed method provides competitive curve estimates for the dose-response curve and relatively stable credible intervals for the curve.

• 한국식품위생안전성학회지
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• 제14권4호
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• pp.319-326
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• 1999

최근 국내에서는 Escherichia coli O157:H7, Listeria monocytogenes등의 미생물에 대한 건강위해성이 강조되면서 미생물 위해성평가에 대한 필요성이 제기되고 있고, U.S.FPA, U.S.DA, FAO/WHO를 비롯한 국제기구 및 외국 유관기관들에서도 미생물 위해성평가 방법을 식품관리에 활용하고자 방법론 연구에 주력하고 있다. 미생물 위험성은 화학물질과 달리 인체건강에 대한 영향이 즉각적이고, 심각하게 나타나 정량적인 위해성평가가 용이하지 않고 유해화학물질과는 다른 평가방법이 요구된다. 식품중 미생물의 위해성평가는 크게 4단계로 구분되는데, 미생물관련질환 추세파악 및 미생물 관련질병에 관한 역학조사 등을 활용하는 위험성확인 단계와 실제 식품원료, 식품가공, 수송, 포장단계 중 식품의 물리적, 화학적 조건에 따른 미생물 변화를 고려하여 식품중 미생물에 대한 노출을 정량화하는 노출평가 단계, 미생물의 용량에 따른 질병발생에 근거하여 용량-반응관계를 규명하는 용량-반응평가 단계, 규명된 모델을 활용하여 모든 평가결과를 통합함으로 위해 도치 예측과 불확실성 분석 등을 수행하는 위해도결정단계로 구성되어 있다. 미생물 용량-반응평가는 크게 비역치(Nonthreshold)와 역치(Threshold) 평가 방법론으로 구분되는데, 비역치 평가방법론은 단일 병원균이 감염을 일으킬 수 있다는 것과 감염을 일으킬 수 있는 확률이 독립적이라는 가정을 전제로 하고, 역치평가방법론은 미생물이 감염을 일으키기 위해서 각기 개별 역치가 존재하는데 어느 정도의 미생물수가 모여 서로 작용해야 독성유발물질을 만들어 낸다는 가정을 전제로 한다. 현재 받아들여지고 있는 비역치 모델로는 Exponential, Beta-poisson, Gompertz, Gamma-weibull 모델 등이 있으며, 역치모델로는 Log-normal, Log-logistic모델 등이 있다. 본 연구에서는 인체 volunteer자료를 활용하여 용량-반응자료를 입력하고 용량-반응자료를 토대로 적합한 수학적 모델을 찾아내어, 선별한 모델의 적합도 검정을 실시하는 방법론 연구를 실시하였으며, 노출평가 자료와 용량-반응평가 결과를 연계하여 위해도를 결정하는 과정에 대해 연구하였다 이 밖에도 모델(Food MicroModel)을 이용하여 식품의 염도, 수분활성도, 온도, pH등의 조건에 따른 미생물의 성장률, 사멸률 등 변화를 예측할 수 있는 방법론 연구를 통해 식품의 최적 보관 조건등을 찾아내는 방법을 습득하였다. 미생물 위해성평가는 외국에서도 아직 초기 연구단계에 있으며 현재로서 사후조사자료인 역학자료보다 건강한 성인남자를 대상으로 한 volunteer 자료를 우선적으로 활용하고 있으나 노약자나 민감그룹에 대한 실험은 현실적으로 불가능하여 동물실험을 이용한 평가방법을 연구중에 있다. 추후 연구방향으로는 국내 volunteer들을 대상으로 한 미생물별 용량-반응결과를 토대로 population sensitivity를 비교할 수 있는 기초자료를 확보함으로써 미생물에 대한 인구집단의 반응 민감성 차이를 비교하고 시료채취 후 즉각적인 실험실적 분석이 가능토록하여 정확한 인체노출평가를 수행함으로써 미생물 위해성평가방법론을 식품미생물관리에 적용하는 것이다.

• 대한방사선기술학회지:방사선기술과학
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• 제25권1호
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• pp.73-76
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• 2002

In order to evaluate the exposure to the radiologic technologists from patients who had been administrated with radiopharmaceuticals, we measured the spatial dose rates at 5 cm, 50 cm, and 100 cm from skin surface of patients using an proportional digital surveymeter, both 5 min after injection and right before the studies. In results, the exposure to the technologists in each procedure was small, compared nth the dose limits of the medical workers. However, the dose-response relationships in cancer and hereditary effects, referred to as the stochastic effects, have been assumed linear and no threshold models ; therefore, the exposure should be minimized. For this purpose, the measurements of spatial dose rate distributions were thought to be useful.

• 약학회지
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• 제48권5호
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• pp.285-290
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• 2004

The purpose of this study is to prove how magnetic field (MF) acts on sympathetic neuro-transmissions using thermal response. Mice were divided into two groups and each one was exposed to MF (20 G, 24 hrs) or sham. Every vehicle or drugs were treated a half hour before the thermal response test. The pain threshold was lowered by MF (20 G, 24 hrs) alone. This reduction of pain threshold by MF was not blocked by a single treatment of $\alpha$-receptor antagonist (prazosin), $\alpha$$_2$-receptor agonist (clonidine, guanabenz), $\beta$$_1$-receptor antagonist (atenolol) or $\beta$$_1$,$\beta$$_2$-receptor antagonist (propranolol). But administration of $\alpha$$_2$-receptor antagonist (yohimbine) completely inhibited the decrease in pain threshold by MF. Moreover, it increased by high dose of yohimbine over normal condition. These results suggest that MF acts on sympathetic nerve terminal to induce hyperalgesia, in which pre-synaptic az receptor might be involved.

• Toxicological Research
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• 제18권1호
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• pp.99-106
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• 2002

The United States Environmental Protection Agency (EPA) characterized the cancer hazard of di(2-ethylhexyl)-phthalate (DEHP) as a B2 group (probable human carcinogen) and proposed "Guide-lines for Carcinogen Risk Assessment". This guidelines proposed alternative methods for analyzing carcinogen dose-response data and for extrapolating the effects of observed at high dose to predict that might occur at lower doses relevant to human exposure. This proposed guidelines state that "If in a particular case, the evidence indicated a threshold, as in the case of carcinogenicity being secondary to another toxicity that has a threshold, the margin of exposure analysis for toxicity is the same as is done for a non-cancer endpoint". DEHP is excellent candidate for reconideration under the new guidelines for carcinogen risk assessment (John Doull et al., 1998). This study is conducted about risk assessment for infant exposure on DEHP in powdered milk wing methodology in EPA's new guideline on carcinogenic risk assessment. Estimated cancer risk of DEHP in powdered milk and cow milk is 2.83$\times$$10^5$ (using cancer potency: 1.4$\times$$10^2$/ (mg/kg/day)) as mean and MOE is 12075 (using selected NOEL 20 mg/kg/day) as mean. mg/kg/day) as mean.

• 한국산업보건학회지
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• 제22권3호
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• pp.175-183
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• 2012

Objectives: This study developed a harmonized method for risk assessment based on the Hazard & Risk Evaluation of Chemicals (HREC) according to the Industrial Safety and Health Act (ISHA). Methods: Three preliminary studies, performed during 2010 and 2011 by the Occupational Safety and Health Research Institute and three academic research groups, were compared. The differences in risk assessment, especially in the dose-response assessment method, were analyzed. A new harmonized method for dose-response assessment was suggested and its applicability for the HREC was examined. Results: Considering the various steps of each dose-response assessment, the equivalent steps in quantitative correction, uncertainty factor 2 (UF2) for intra-species uncertainty, and UF3 for the experimental period in the uncertainty correction were relatively high. Using our new method, the total correction values (quantitative correction plus uncertainty correction) ranged from 72~15,789 to 30~60, and the ratio of the threshold limit value (TLV) to the reference concentration decreased from 12.8~1900 to 5.4~11.8. Furthermore, when we performed risk characterization by our new method, hazard quotient (HQ) values for chloroethylene, epichlorohydrin, and barium sulfate became 3.0, 14.1, and 1.13 respectively, whereas three previous studies reported HQ values of 7.1, 4580, and 87.3 considering reasonable maximum exposure (RME) conditions. HQs of the three chemicals were calculated to be 0.6, 2.4, and 0.1 respectively, when compared to their TLVs. Conclusions: Our new method could be applicable for the HREC because the total correction values and the ratio of TLVs were within reasonable ranges. It is also recommended that additional risk management measures be applied for epichlorohydrin, for which the HQ values were greater than 1 when compared with both reference values and the TLV. Our proposed method could be used to harmonize dose-response assessment methods for the implementation of risk assessment based on the HREC according to ISHA.

• Journal of Radiation Protection and Research
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• 제31권2호
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• pp.69-89
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• 2006

Biological mechanisms for ionizing radiation effects are different at low doses than at high doses. Radiation hormesis involves low-dose-induced protection and high-dose-induced harm. The protective component is associated with a reduction in the incidence of cancer below the spontaneous frequency, brought about by activation of defensive and repair processes. The Linear No-Threshold (LNT) hypothesis advocated by the International Commission on Radiological Protection (ICRP) and the Biological Effects of ionizing Radiation (BEIR) Report VII for cancer risk estimations Ignores hormesis and the presence of a threshold. Cancer incidences significantly less than expected have been found in a large number of epidemiological studies including, airline flight personnel, inhabitants of high radiation backgrounds, shipyard workers, nuclear site workers in scores of locations throughout the world, nuclear power utility workers, plutonium workers, military nuclear test site Participants, Japanese A-bomb survivors, residents contaminated by major nuclear accidents, residents of Taiwan living in $^{60}Co$ contaminated buildings, fluoroscopy and mammography patients, radium dial painters, and those exposed to indoor radon. Significantly increased cancer was not found at doses <200 $mSv^*$. Evidence for radiation hormesis was seen in both sexes for acute or chronic exposures, low or high LET radiations, external whole- or partial body exposures, and for internal radionuclides. The ubiquitous nature of the Healthy Worker Effect (HWE)-like responses in cellular, animal and epidemiological studies negates the HWE as an explanation for radiation hormesis. The LNT hypothesis is wrong and does not represent the true nature of the dose-response relationship, since low doses or dose-rates commonly result in thresholds and reduce cancer incidences below the spontaneous rate. Radiation protection organizations should seriously consider the cost and health implications of radiation hormesis.