• Journal of Korean Society for Quality Management
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• v.39 no.2
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• pp.329-336
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• 2011

The purpose of Phase I clinical trial is to identify the maximum tolerated dose with specific toxicity rate. The standard TER design does not guarantee the pre-specified toxicity rate. It depends on the dose-toxicity curves. Therefore it is necessary to check the expected toxicity rate of various dose-toxicity curves before we conduct clinical trials. We developed TERAplusB library to help this situation, especially in cancer research. This package will help design the cancer clinical trial. We can compare the expected toxicity rates, the expected number of patients, and the expected times calculated with various dose-toxicity curves. This process will help find the best clinical trial design of the proposed drug.

• Communications for Statistical Applications and Methods
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• v.16 no.1
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• pp.51-65
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• 2009

The purpose of a phase I clinical trial is to determine the maximum tolerated dose(MTD) of a new drug. This paper investigates the performance of standard method, continual reassessment method and accelerated titration designs in phase I clinical trials. Especially we study the precision and safety at the MTD of these methods. We utilize hyperbolic tangent function and power function to define dose-toxicity model. For each method, expected toxicity rate at MTD is computed and compared with target toxicity probability. We also suggest some modifications of these methods and show some improvements in performance.

• Journal of the Korean Applied Science and Technology
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• v.40 no.3
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• pp.570-578
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• 2023

Experiments on zebrafish embryo toxicity and whitening efficacy, which is an alternative experimental animal model, were conducted using coffee by-products. As a result of the embryo toxicity test treated with the coffee residue extract, the coagulation rate was 3, 3, and 5% at 24, 48, and 72 hpf and concentration of 125 ppm, respectively. The hatching rate of embryos was 73% at the highest concentration of 125 ppm. In the heart beat rate experiment of zebrafish larva, the heart beat rate after 72 hpf was confirmed to be 153 times/60 s' at a concentration of 125 ppm. The negative control group showed no significant change in heart rate compared to the control group at 148 times/60s', and showed low toxicity. In addition, as a result of evaluating the whitening effect in zebrafish, melanin formation was inhibited as the concentration of the coffee residue extract increased. The results of this study suggest the possibility that naturally derived by-product materials can be used as raw materials for cosmetics, and are expected to be used in the cosmetics industry as an example of research that increases the added value of natural product residue.

• The Korean Journal of Applied Statistics
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• v.15 no.2
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• pp.323-336
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• 2002

In this paper we consider the modified continual reassessment method in which a cohort consists of three patients. Simulation has been a main research tool in the investigation of CRM. In this paper we propose complete enumeration as an alternative of simulation. Using new method we show that the expected toxicity rate at the MTD converges to the target toxicity rate well as the sample size increases.

• Journal of Radiation Protection and Research
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• v.40 no.3
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• pp.187-193
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• 2015

Deleterious effects of high dose radiation exposure with high-dose-rate are unarguable, but they are still controversial in low-dose-rate. The regulator of G-protein signaling (RGS) is a negative regulator of G protein-coupled receptor (GPCR) signaling. In addition, it is reported that irradiation stress led to GPCR-mediated mitogen-activated protein kinase (MAPK) and phosphotidylinositol 3-kinase (PI3-k) signaling. The RGS mRNA expression profiles by whole body radiation with low-dose-rate has not yet been explored. In the present study, we, therefore, examined which RGS was modulated by the whole body radiation with low-dose-rate ($3.49mGy{\cdot}h^{-1}$). Among 16 RGS expression tested, RGS6, RGS13 and RGS16 mRNA were down-regulated by low-dose-rate irradiation. This is the first report that whole body radiation with low-dose-rate can modulate the different RGS expression levels. These results are expected to reveal the potential target and/or the biomarker proteins associated with male testis toxicity induced by low-dose-rate irradiation, which might contribute to understanding the mechanism beyond the testis toxicity.

• Journal of the Korean Wood Science and Technology
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• v.45 no.2
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• pp.159-167
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• 2017

Historical wooden buildings in Korea are being damaged by Reticulitermes speratus kyushuensis Morimoto, a type of subterranean termite, and the scale of this damage is increasing gradually because of global warming. This study evaluated the ingestion toxicity of the phenylpyrazole insecticide fipronil to R. s. kyushuensis and its applicability as termite bait with the aim of controlling termite colonies more efficiently. An ingestion toxicity assessment was conducted and the $LT_{50}$ was determined to be 4.43 day at concentrations of 10 ppm, indicating a slow-acting effect; therefore, 10 ppm was selected as an appropriate dose. A field applicability assessment was conducted in which the number of foraging workers and the rate at which the termites fed decreased 2 weeks after baiting, and termite colony activity was no longer apparent after 4 weeks demonstrating the efficacy of fipronil at eliminating colonies. Taken together, these results, indicate that low-dose fipronil eliminated R. s. kyushuensis colonies faster than insect growth regulators; therefore, it is expected to be useful when trying to conserve historical wooden buildings.

• Journal of Korean Society of Water and Wastewater
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• v.8 no.3
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• pp.9-18
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• 1994

Activated sludge pilot plant testing was conducted to determine the ability of a well-designed activated sludge treatment system to remove chromic toxicity from the bleached kraft pulp mill effluent. Removals of conventional(BOD and SS) and nonconventional(resin and fatty acids, color, AOX) pollutants were estimated. The pilot plant was operated at steady state for about 10 weeks at an F/M of 0.28 and a sludge age of 8.4 days. The average MLSS concentration was 4,309mg/l, of which volatile fraction was 57%. During the operation period, the BOD removal reaction rate(k) was determined to be 8.2/day at $30^{\circ}C$. The BOD removal was 84 percent, which was 3 to 6 percent lower than expected for full-scale treatment. The chronic toxicity of the activated sludge effluent was tested by employing both Dinnel and the BML protocols. It was found that the pilot plant could achieve in excess of 90 percent reduction in chronic echinoderm toxicity. The data show slight reduction of color and AOX across the activated sludge system. The pilot system, however, demonstrated on excellent removal of resin and fatty acids.

• Journal of Pharmacopuncture
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• v.22 no.3
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• pp.147-153
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• 2019

Objectives: Many studies have been reported the efficacy of intravenous lipid emulsion (ILE) as an antidote on acute lipophilic drug toxicity. Clozapine, highly lipophilic dibenzodiazepine neuroleptics, is an important medication in the schizophrenia therapy regimen. Acute intoxication with antipsychotics is one of the main reasons for the referral of poisoned patients to the hospital. We expected that ILE could be used for the therapy of acute clozapine intoxicated patients. Methods: We used two groups of consisting of six male rats. Both groups received a toxic dose of clozapine (40 mg/kg) intravenously, via the tail vein. After 15 minutes, they were treated with intravenous infusion of 18.6 mg/kg normal saline (NS group), or 18.6 mg/kg ILE 20% (ILE group). We evaluated blood pressure (BP) and heart rate by power lab apparatus through the tail artery, ataxia by a rat rotary circle, seizure scores and death in multiple times after starting clozapine administration. For biochemical and pathological evaluations the samples of tissue and blood were taken. Results: Our results demonstrated that ILE 20% could return hypotension-induced clozapine better than normal saline. Furthermore, ataxia and seizure have rectified more rapidly and deaths reduced. Clozapine administration causes pancreatitis and lung injury but fat emulsion did not show an optimal effect on tissue damages caused by clozapine toxicity. Conclusion: In conclusion, ILE can remove toxic signs of clozapine same as other lipophilic medicines, however, clinical uses of ILE for this intention requires more appraisement to determine the precise implication and safety.

• Toxicological Research
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• v.18 no.1
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• pp.13-22
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• 2002

In Korea, 2,320 tonnes of acetanilide were mostly wed as intermediates for synthesis in phar-maceuticals or additives in synthesizing hydrogen peroxide, varnishes, polymers and rubber. Only small amount of 120 kg were wed as a stabilizer for hydrogen peroxide solution for hair colouring agents in 1998. Readily available environmental or human exposure data do not exist in Korea at the present time. However, potential human exposures from drinking water, food, ambient water and in work places are expected to be negligible because this chemical is produced in the closed system in only one company in Korea and the processing factory is equipped with local ventilation and air filtering system. Acetanilide could be distributed mainly to water based on EQC model. This substance is readily biodegradable and its bioaccumulation is low. Acute toxicity of acetanilide is low since the L $D_{50}$ of oral exposure in rats is 1,959 mg/kg bw. The chemical is not irritating to skin, but slightly irritating to the eyes of rabbits. horn repeated dose toxicity, the adverse effects in rats were red pulp hyperplasia of spleen, bone marrow hyperplasia of femur and decreased hemoglobin, hematocrit and mean corpuscular hemoglobin concentration. The LOAEL for repeated dose toxicity in rats was 22 mg/kg/day for both sexes. Acetanilide is not considered to be genotoxic. In a reproductive/developmental toxicity study, no treatment-related changes in precoital time and rate of copulation, impregnation, pregnancy were shown in all treated groups. The NOAELs for reproduction and developmental toxicity (off-spring toxicity) are considered to be 200 mg/kg bw/day and 67 mg/kg bw/day, respectively. Ecotoxicity data has been generated in a limited number of aquatic species of algae (72 hr- $E_{b}$ $C_{50}$; 13.5 mg/l), daphnid (48hr-E $C_{50}$ > 100 mg/l) and fish (Oryzias latipes, 96hr-L $C_{50}$; 100 mg/l). Form the acute toxicity values, the predicted no effect concentration (PNEC) of 0.135 mg/1 was derived win an assessment factor of 100. On the basis of these data, acetanilide was suggested as currently of low priority for further post-SIDS work in OECD.in OECD.D.

• Environmental Analysis Health and Toxicology
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• v.19 no.1
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• pp.33-40
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• 2004

Benzoyl peroxide is a High Production Volume Chemical, which is produced about 1,371 tons/year in Korea as of 2001 survey. The substance is mainly used as initiators in polymerization, catalysts in the plastics industry, bleaching agents for flour and medication for acne vulgaris. In this study, Quantitative Structure-Activity Relationships (QSAR) are used for getting adequate information on the physical -chemical properties of this chemical. And hydrolysis in water, acute toxicity to aquatic and terrestrial organisms for benzoyl peroxide were studied. The physical -chemical properties of benzoyl peroxide were estimated as followed; vapor pressure=0.00929 Pa, Log $K_{ow}$ = 3.43, Henry's Law constant=3.54${\times}$10$^{-6}$ atm-㎥/mole at $25^{\circ}C$, the half-life of photodegradation=3 days and bioconcentration factor (BCF)=92. Hydrolysis half-life of benzoyl peroxide in water was 5.2 hr at pH 7 at $25^{\circ}C$ and according to the structure of this substance hydrolysis product was expected to benzoic acid. Benzoyl peroxide has toxic effects on the aquatic organisms. 72 hr-Er $C_{50}$ (growth rate) for algae was 0.44 mg/1.,48 hr-E $C_{50}$ for daphnia was 0.07mg/L and the 96hr-L $C_{50}$ of acute toxicity to fish was 0.24mg/L. Acute toxicity to terrestrial organisms (earth worm) of benzoyl peroxide was low (14 day-L $C_{50}$ = > 1,000 mg/kg). Although benzoyl peroxide is high toxic to aquatic organisms, the substance if not bioaccumulated because of the rapid removal by hydrolysis (half-life=5.2 hr at pH 7 at $25^{\circ}C$) and biodegradation (83% by BOD after 21 days). The toxicity observed is assumed to be due to benzoyl peroxide rather than benzoic acid, which shows much lower toxicity to aquatic organisms. One can assume that effects occur before hydrolysis takes place. From the acute toxicity value of algae, daphnia and fish, an assessment factor of 100 was used to determine the predicted no effect concentration (PNEC). The PNEC was calculated to be 0.7$\mu\textrm{g}$/L based on the 48 hr-E $C_{50}$ daphnia (0.07 mg/L). The substance shows high acute toxicity to aquatic organisms and some information indicates wide-dispersive ore of this substance. So this substance is, a candidate for further work, even if it hydrolysis rapidly and has a low bioaccumulation potential. This could lead to local concern for the aquatic environment and therefore environmental exposure assessment is recommended.