• 품질경영학회지
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• 제39권2호
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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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• 제16권1호
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• pp.51-65
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• 2009

제 1상 임상시험은 사람을 대상으로 처음 실시되므로 약물 투여의 안전성과 정확성이 신중히 고려되어야 한다. 따라서 제 1상 임상시험에서는 적은 수의 피험자를 통해 최대허용용량(maximum tolerated dose)을 정확하게 찾아야 한다. 제 1상 임상시험에서 최대허용용량을 결정하는 방법에는 표준방법(standard method), 연속재평가방법(continual reassessment method) 그리고 가속적정계획(accelerated titration designs) 방법이 있다. 본 연구에서는 동일한 모형에서 세 방법을 동시에 고려하여 최대허용용량의 안전성과 정확성을 살펴보았다. 또한 세 방법에 대해 최대허용용량에서 기대독성확률을 구하여 비교하였다. 그리고 ATD와 CRM의 단점을 보완한 수정된 ATD와 수정된 CRM을 포함하여 여러 방법들을 동일한 모형에서 동시에 그 성능을 비교하였다.

• 한국응용과학기술학회지
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• 제40권3호
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• pp.570-578
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• 2023

커피 부산물을 이용하여 대체실험동물 모델인 제브라피쉬 배아 독성 및 미백 효능에 대한 실험을 진행하였다. 커피 부산물 추출물을 처리한 배아 독성 실험의 결과 24, 48, 72hpf에서 125ppm 농도에서는 각각 3, 3, 5%로 응고율을 나타냈다. 배아의 부화율은 최고 농도인 125ppm에서 73%를 나타냈다. 제브라피쉬 치어의 심장 박동수 실험에서 72hpf 후 심박수가 125ppm 농도에서 153회/60s'로 확인되었다. 음성대조군은 148회/60s'으로 대조군의 비해 심박수의 변화가 크지 않았으며, 낮은 독성을 나타냈다. 또한 미백효능을 평가한 결과 커피 부산물 추출물의 농도가 증가할수록 멜라닌 형성이 저해되는 것으로 나타났다. 본 연구 결과를 통해 천연 유래 부산물 소재가 화장품 원료로 활용할 수 있다는 가능성을 제안하며, 천연 부산물의 부가가치를 높이는 연구 예시로서 화장품 산업에 활용되기를 기대한다.

• 응용통계연구
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• 제15권2호
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• pp.323-336
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• 2002

최근에 1상 임상실험 에서 사용되는 continual reassessment method (CRM)에 대한 연구가 활발히 이루어지고 있다. 본 논문에서는 세 명의 환자를 하나의 환자 군으로 삼아 동일한 용량을 투여하는 수정된 CRM에 대한 연구를 실행하였다. 지금까지 CRM에 대한연구는 대부분 시뮬레이션에 의존하여 왔지만, 본 논문에서는 모든 가능한 경우를 고려하는 방법(complete enumeration)을 사용하였다. 이 새로운 방법은 시뮬레이션을 대체할 유용한 방법이라 사료된다. 이 새로운 방법을 이용하여, 용량독성곡선이 logistic함수, hyperbolic tangent 함수, power 함수일 때, 수정된 CRM에서 결정한 최대허용용량에서의 독성 확률이 목표 독성 확률로 잘 수렴함을 보였다. 하지만, 실험 전에 용량들을 적절히 선택하지 못하면, 최대허용용량에서의 독성 확률이 목표 독성 확률과 상당한 차이를 낼 수도 있음을 발견하였다.

• Journal of Radiation Protection and Research
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• 제40권3호
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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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• 제45권2호
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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.

• 상하수도학회지
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• 제8권3호
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• pp.9-18
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• 1994

활성슬러지 공정을 이용하여 Kraft 펄프공장에서 배출되는 유출수에 잔류하는 만성독성의 제거가능성을 평가하기 위하여 pilot plant를 운전하였다. 독성 이외에도 폐수내의 BOD, SS, resin과 fatty acids, 색도, 그리고 AOX와 같은 오염물질의 제거효과도 측정되었다. Pilot plant는 정상상태에서 약 10주 동안 운전되었으며 운전기간 동안의 평균 F/M 비율은 0.28, 그리고 sludge age는 8.4일로 계산되었다. 평균 MLSS 농도는 4,309mg/l이었으며 이중 휘발성 물질은 57%이었다. 운전기간 동안, BOD 제거계수(k)는 $30^{\circ}C$에서 8.2/일 이었으며 BOD 제거율은 full-scale 운전시보다 3~6% 정도 낮은 84%로 나타났다. 활성슬러지 유출수의 만성독성 시험은 Dinnel 방법과 BML 방법이 활용되었으며, 시험결과 pilot plant 활성슬러지 시스템에서도 효율적인 운전을 통하여 90% 이상의 독성제거가 가능함을 알 수 있었다. Pilot plant의 진 공정을 통해서 색도와 AOX의 제거는 매우 미미하였으나 resin과 fatty acids는 뛰어난 제거율을 나타내었다.

• 대한약침학회지
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• 제22권3호
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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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• 제18권1호
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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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• 제19권1호
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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.