• 대한예방의학회:학술대회논문집
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• 1994.02b
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• pp.270-284
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• 1994

Interim analyses of randomized trials enable investigators to make more efficient use of limited research resources and to satisfy ethical requirements that a regimen be discontinued as soon as it has been established to have an inferior efficacy/toxicity profile. Unfortunately. the integrity and credibility of these trials can be compromised if inappropriate procedures are used in monitoring interim data. 'In this paper we discuss how group sequential designs provide useful guidelines that enable one to satisfy the valid objectives of interim monitoring while avoiding undesirable consequences, and we consider how flexible one can be in the way such designs are implemented. We also provide motivation for the role of data-monitoring committees in preserving study integrity and credibility in either government- or industry-sponsored trials. In our view. these committees should have multidisciplinary representation and membership limited to individuals free of apparent significant conflict of interest, and ideally should be the only individuals to whom the data analysis center provides interim results on relative efficacy of treatment regimens. Finally. we discuss some important practical issues such as estimation following group sequential testing, anal ysis of secondary outcomes after using a group sequential design applied to a primary outcome, early stopping of negative trials. and the role of administrative analyses.

• Journal of the Korean Society of Tobacco Science
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• v.36 no.1
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• pp.20-25
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• 2014

As part of a balanced testing battery, subchronic inhalation studies on rats are performed to ensure that proposed cigarette modifications do not increase the toxicity of smoke and to demonstrate any instances where a modification may actually contribute to harm reduction. For subchronic inhalation studies with aerosols, the OECD suggests an exposure regimen of 6 hours/day (OECD Guideline 413, 1981), but alternative regimens have also been published: 1 hour/day and $2{\times}1$ hour/day. The aim of this study was to validate a rodent nose-only exposure system for the assessment of inhalation toxicity of cigarette smoke. In this study, cigarette smoke exposure system is consisted of cigarette smoke generator, smoke concentration adjusting system, and 20-port nose-only exposure system. Male SD rats were exposed for 35 days ($2{\times}1$ hour/day) to 3R4F Reference cigarette smoke and analysed major monitoring items of OECD Gudeline 413. WTPM, was measured in the test atmosphere, respiratory function (Buxco Biosystems) during exposure, postexposure urinary exposure biomarkers and alveolar neutrophiles in BAL fluid (Day 35) were evaluated. Validation demonstrated steady WTPM ($257{\pm}20ug/L$, $502{\pm}27ug/L$) and spatial uniformity (<10%). Nose port temperature ($22{\sim}26^{\circ}C$ and RH (45~75%) were acceptable over 35 days. Reductions in respiratory rate and minute volume and increase in the neutrophiles in BALF and the urinary exposure biomarkers were observed cigarette smoke dose dependently. This validation and 35-day inhalation study has shown that the rodent nose-only exposure system may be useful in the inhalation toxicity assessment of cigarette smoke.

• Korean Journal of Agricultural Science
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• v.48 no.4
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• pp.1003-1013
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• 2021

Thioredoxin (TRX) protein is an antioxidant responsible for reducing other proteins by exchanging cysteine thiol-disulfide and is also known for its anti-allergic and anti-aging properties. On the other hand, epidermal growth factor (EGF) is an important material used in the cosmetics industry and an essential protein necessary for dermal wound healing facilitated by the proliferation and migration of keratinocytes. EGF also assists in the formation of granulation tissues and stimulates the motility of fibroblasts. Hence, genetically modified soybeans were developed to overexpress these industrially important proteins for mass production. A single-dose oral-toxicity-based study was conducted to evaluate the potential toxic effects of TRX and EGF proteins, as safety assessments are necessary for the commercial use of seed-specific protein-expressing transgenic soybeans. To achieve this rationale, TRX and EGF proteins were mass purified from recombinant E. coli. The single-dose oral-toxicity tests of the TRX and EGF proteins were carried out in six-week old male and female Institute of Cancer Research (ICR) mice. The initial evaluation of the single-dose TRF and EGF treatments was based on monitoring the toxicity signatures and mortality rates among the mice, and the resultant mortality rates did not show any specific clinical symptoms related to the proteins. Furthermore, no significant differences were observed in the weights between the treatment and control groups of male and female ICR mice. After 14 days of treatment, no differences were observed in the autopsy reports between the various treatment and control groups. These results suggest that the minimum lethal dose of TRX and EGF proteins is higher than the allowed 2,000 mg·kg^-1 limit.

• Toxicological Research
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• v.31 no.3
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• pp.241-253
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• 2015

Furan ($C_4H_4O$) is a volatile compound formed mostly during the thermal processing of foods. The toxicity of furan has been well documented previously, and it was classified as "possible human carcinogen (Group 2B)" by the International Agency for Research on Cancer. Various pathways have been reported for the formation of furan, that is, thermal degradation and/or thermal rearrangement of carbohydrates in the presence of amino acids, thermal degradation of certain amino acids, including aspartic acid, threonine, ${\alpha}$-alanine, serine, and cysteine, oxidation of ascorbic acid at higher temperatures, and oxidation of polyunsaturated fatty acids and carotenoids. Owing to the complexity of the formation mechanism, a vast number of studies have been published on monitoring furan in commercial food products and on the potential strategies for reducing furan. Thus, we present a comprehensive review on the current status of commercial food monitoring databases and the possible furan reduction methods. Additionally, we review analytical methods for furan detection and the toxicity of furan.

• Environmental Analysis Health and Toxicology
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• v.20 no.2 s.49
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• pp.109-121
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• 2005

A chemical ranking and scoring (CRS-Korea) system was developed and proposed to use as the first step to prioritize the toxic chemicals for the purpose of monitoring and detailed risk assessment that might follow as necessary. The CRS-Korea system takes a basic concept of risk assessment (both human health risk and ecological risk) in that risk score is determined by the product of toxicity score and exposure score. Included in the toxicity category are acute toxicity, chronic/sub -chronic toxicity, carcinogenicity, and other toxicity. The exposure category consists of quantity released to the environment, bioconcentration, and persistence. A consistent scheme and a comprehensive chemical data base are offered in the CRS-Korea system to calculate a score for the each component in the two categories by using specific physicochemical, fate, and toxic properties and the quantity of the chemical used. The toxicity score is obtained by adding up all the individual scores for the components in the toxicity category. The exposure score is determined by multiplication of the score of the quantity released with the sum of persistent score and bioconcentration score. Equal weight is given to the toxicity score and the exposure score. As the CRS-Korea system was applied to identify 50 national priority chemicals, it was found that significant data gap exists on toxicity and fate properties and that the uncertainty associated with estimating the quantify released to the environment is notably high. The proposed CRS system is only a screening tool in the first step toward the priority setting and should be used with expert judgement and other considerations necessary.

• Safety and Health at Work
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• v.10 no.4
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• pp.409-419
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• 2019

Although the rare earth elements (REEs) recycling industry is expected to increase worldwide in hightech industry, regulations for worker safety have yet to be established. This study was conducted to understand the potential hazard/risk of REE recycling and to support the establishment of regulations or standards. We review the extensive literature on the toxicology, occupational safety, and health issues, and epidemiological surveys related to the REEs, and propose suitable management measures. REE recycling has four key steps such as collection, dismantling, separation, and processing. In these processes, hazardous substances, such as REEs-containing dust, metals, and chemicals, were used or occurred, including the risk of ignition and explosion, and the workers can be easily exposed to them. In addition, skin irritation and toxicities for respiratory, nervous, and cardiovascular systems with the liver toxicity were reported; however, more supplementary data are needed, owing to incompleteness. Therefore, monitoring systems concerning health, environmental impacts, and safety need to be established, based on additional research studies. It is also necessary to develop innovative and environment-friendly recycling technologies, analytical methods, and biomarkers with government support. Through these efforts, the occupational safety and health status will be improved, along with the establishment of advanced REE recycling industry.

• Journal of Microbiology and Biotechnology
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• v.23 no.7
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• pp.1015-1022
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• 2013

We recently showed that polylysine, the polymer of lysines, retains anti-prion activity. Although the effectiveness of prion inhibition by polylysine was demonstrated with the regimen tolerated in mice, a determination of quantitative polylysine toxicity is necessary to precisely address the in vivo toxicity level of polylysine. In this communication, we report the results of body weight monitoring and hematologic tests performed in CD-1 mice that received two different tolerable dosages of polylysine for an either 5-day or 4-week period. We found that there was no significant alteration in overall serum chemistry, blood cell count, and body weight gain compared with controls. The only notable quantitative change with statistical significance was the decrease of platelet numbers in mice subchronically administered with polylysine. Our results suggest that polylysine is harmless in mice if administered for a short period, but administrations of polylysine in mice may require considerate attention for safety in future investigations as mice chronically receive tolerable doses of polylysine.

• Journal of Soil and Groundwater Environment
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• v.19 no.3
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• pp.82-93
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• 2014

A starch ball was devised to conveniently supply carbon source to indigenous microorganisms and to enhance biotransformation of explosive compounds(TNT and RDX) in the sediments of settling basins installed in military shooting ranges. To identify optimum dose/sediment ratio for degradation of explosives in the basin, a series of bench scale settling basin experiments were performed for 30 days while monitoring supernatant pH, DO, concentrations of nitrite, nitrate, sulfate, explosive compounds, and acute toxicity measured by bacterial luminescence. Addition of starch ball induced changes in oxidation conditions from oxic to anoxic in the benthic zone of the basin, which resulted in subsequent reductive degradation of both TNT and RDX in the liquid and solid phase of basin. However, fermentation products of excess starch, acetic acid and formic acid, caused acute toxicity in the liquid phase. The optimum ratio of starch ball/sediment for explosive compounds degradation by inducing changes in bio-geochemical environments without increase in acute toxicity, was found to be 0.009~0.017.

• Proceedings of the Korea Society of Environmental Toocicology Conference
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• 2003.05a
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• pp.158-159
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• 2003

Fluoranthene, a common polycyclicaromatic hydrocarbon (PAH), exhibits phototoxicity which may affect aquatic organisms. The eventual goal of this study is to develop a biomarker used in monitoring abnormal behaviors of Japanese medaka (Oryzias latipes) as a model organism caused by hazardous chemicals that are toxic and persistent in the ecosystem. In this study, we investigated neural toxicity of fluoranthene in Japanese medaka (Oryzias latipes) which was correlated with its behaviors.

• Environmental Analysis Health and Toxicology
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• v.23 no.1
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• pp.47-51
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• 2008

The toxicity of environmental pollutants was measured between a image of the surface topography in HeLa cells using atomic force microscopy for the possibility of toxic effect measurement and environmental monitoring. A image of the surface topography by AFM were estimated as toxic endpoints. The surface topography by AFM was observed a change of the cell surface in the environmental pollutants, but the standard of the measurement requires for the dose-effect degree. The overall results indicate that the possibility of measurement using AFM were confirmed a dose-effect degree related toxic effects, but it requres correlation between more various biomarker and AFM's measurements if the possibility of the toxic effect measurement was established.