• The Korean Journal of Applied Statistics
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• v.27 no.7
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• pp.1115-1123
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• 2014

The main purpose of phase I clinical trials is to estimate the Maximum Tolerated Dose (MTD), which minimizes side effect and assures safety of a new drug by evaluating the toxicity at each dose-level. The conventional MTD estimation methods is Standard method (Storer, 1989; Korn et al., 1994), Accelerated Titration Designs (Simon et al., 1997) and DM method (Dixon and Mood, 1948) etc. In this paper, MTD estimation method with de-escalation is suggested phase I clinical trials. The proposed MTD estimation method is compared to Accelerated Titration Designs, SM3 without de-escalation method and SM3 with de-escalation method using a Monte Carlo simulation.

• Journal of Korean Society of Environmental Engineers
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• v.39 no.3
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• pp.132-139
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• 2017

Endocrine disrupting chemicals (EDCs) interfere with endocrine system in organisms, and have different mode of actions compared to conventional chemicals. Therefore, EDCs specific ecotoxicity tests and assessments have been globally developed by some organizations such as OECD, ASTM, and USEPA. In Korea, researches on EDCs and monitoring of EDCs in domestic environments were also continued. However, Korean ecotoxicity test guidelines for EDCs are not suggested till date. The purpose of this study is to review and analyze international ecotoxicity test guidelines for EDCs and the compare ecotoxicity methods and toxicity endpoints among standard test guidelines. We found that there are very limited EDCs specific soil ecotoxicity test guidelines (only in ASTM) compared to aquatic ecotoxicity test guidelines. Currently, fish, amphibian, waterflea, copepoda, earthworm, white worm, springtail, nematode, mite, and midge are suggested as standard ecotoxicity test species for EDCs. Reproduction, hormones, growth, vitellogenin, sex retio and development were proposed as endpoints for EDCs ecotoxicity. This study provided the comparison of EDCs specific ecotoxicity methods and endpoints between standard test guidelines, and suggested the further research to develop the method for assesseing ecotoxicity of EDCs.

• Journal of Dairy Science and Biotechnology
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• v.34 no.2
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• pp.117-135
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• 2016

The present study was performed to develop a functional raw food material from hydrolyzed whey protein powder (23%-GNANA) medication containing sialic acid as a marker compound that is naturally occurring at 7% concentration in GMP (glycomacropeptide). GMP is used worldwide in foodstuffs for babies and infants and is obtained from the milk protein as safe food. While the purpose of our detailed evaluation was aimed to assess preliminary NOAEL values for and above 2,000 mg/kg/day, a clinical dose allowance for 23%-GNANA (as per characteristic of a functional health product, a highly refined test substance of 23% (v/v) sialic acid combined in GMP), at the same time we also wanted to assess the safety of GMP hydrolyzate lacking sialic acid but with identical properties as GMP. Animal safety evaluation was conducted using 23%-GNANA as the test substance, produced from hydrolyzed whey protein powder (product name: HELICOBACTROL-23; provided by Medinutrol Inc. [Korea]; composed of 23% sialic acid and GMP protein) after isolating the sialic acid using enzymes approved as food additives, with GMP as a raw material, and subsequently increasing the content of xx up to 23% through 80% (v/v) ethanol soaking and concentrating, in accordance with GLP Guideline. The animal safety evaluation mentioned above was made on the basis of toxicity in SPF Sprague-Dawley female and male rats dosed with 10 mL of the test substance diluted to 0, 1,250, 2,500, and 5,000 mg/kg directly into their stomachs for 90 d. This was determined in terms of the general symptoms and animal viability, weight and amount of feed intake, eye examination, uracrasia tests, hematological and blood biochemical disorder tests, blood coagulation test, abnormal intestine weight, abnormalities during postmortem and histopathological examinations. Statistical significance was set at P<0.05. Based on the toxicity determination, a certain minor effect associated with the test substance was observed in male rats with no major effects of the tested substance, in comparison with the control group dosed with sterilized water. Nevertheless, the NOAEL value, evaluated as per toxicity criteria, was verified as 5,000 mg/kg/day (P<0.05). Similarly, for female rats, a certain minor effect associated with the test substance was observed in 5,000 mg/kg/day dosed group, with no major effect, yet the NOAEL value (as assessed as per toxicity criteria) was determined to be 5,000 mg/kg/day (P<0.05), which was the same as for male rats. Accordingly, the NOAEL values of the test substances for all female and male rats were finally verified as 5,000 mg/kg/day (P<0.05). In conclusion, it was determined that the 23%-GNANA test substance exceeds 2,000 mg/kg/day, the clinical allowance characteristic for functional health food, and was finally evaluated to cause no safety concerns when used as a raw material in functional health food production, which was the ultimate goal of the present study.

• The Sea:JOURNAL OF THE KOREAN SOCIETY OF OCEANOGRAPHY
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• v.13 no.2
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• pp.121-128
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• 2008

As an aquatic ecotoxicity test method, a bioassay using the inhibition of sporualtion of the green macroalga, Ulva pertusa, has been developed. Optimal test conditions determined for photon irradiance, pH, salinity and temperature were $100\;{\mu}mol{\cdot}m^{-2}{\cdot}s^{-1}$, $7{\sim}9$, $25{\sim}35\;psu$ and $15{\sim}20^{\circ}C$, respectively. The validity of the test endpoint was evaluated by assessing the toxicity of four metals (Cd, Cu, Pb, Zn) and elutriates of sewage or waste sludge collected from 9 different locations. When the metals were assayed, the $EC_{50}$ values indicated the following toxicity rankings: Cu ($0.062\;mg{\cdot}L^{-1}$) > Cd ($0.208\;mg{\cdot}L^{-1}$) > Pb ($0.718\;mg{\cdot}L^{-1}$) > Zn ($0.776\;mg{\cdot}L^{-1}$). When compared with other commonly used bioassays of metal pollution listed on US ECOTOX database, the sporualtion test proved to be the most sensitive. Ulva sporulation was significantly inhibited in all elutriates with the greatest and least effects observed in elutriates of sludge from industrial waste ($EC_{50}=6.78%$) and filtration bed ($EC_{50}=15.0%$), respectively. The results of the Spearman rank correlation analysis for $EC_{50}$ data versus the concentrations of toxicants in the sludge presented a significant correlation between toxicity and four heavy metals(Cd, Cu, Pb, Zn). The method described here is sensitive to toxicants, simple to use, easy to interpret and economical. It is also easy to procure samples and maintain cultures. The present method would therefore probably make a useful assessment of aquatic toxicity of a wide range of toxicants. In addition, the genus Ulva has a wide geographical distribution and species have similar reproductive processes, so the test method would have a potential application worldwide.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.24 no.1
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• pp.96-110
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• 2011

목적 : 본 임상시험을 통하여 혈열(血熱)형으로 변증된 아토피피부염의 한약 치료 후 임상 효능과 안전성을 관찰함으로써 아토피피부염에 대한 한약치료의 유용성을 평가하고자 한다. 방법 : 본 임상시험은 무작위배정, 이중맹검, 양성대조군, 평행 설계로 진행되었다. 자의에 의해 임상시험 동의서에 서명한 대상자 중 선정기준 및 제외기준에 부합된 36명의 대상자들에게 시험약과 양성대조약 과립제를 1일 3회(5.0g* 3회/ 1일) 4주간 복용하도록 하였다. 36명 중 31명의 환자가 4주간의 치료를 종료하였다(시호청간산 복용군: n = 16, 소풍산 복용군: n =15). 아토피피부염 증상을 평가하기 위해 Scoring atopic dermatitis (SCORAD) index와 Eczemaarea and severity index (EASI) 를 사용하여 시험 시작 전과 4주 후 시험 종료일에 환자들의 피부소견을 평가하였다. 아토피 피부염에 대한 한약치료의 안정성을 평가하기 위하여 치료 전후 혈중 AST, ALT, BUN, creatinine 변화를 검토하여 한약치료의 간/신독성 여부에 대해 조사하였다. 결과 및 결론: 두 군 모두에서 유의하게 SCORAD 점수와 EASI 점수가 감소하였으나 두 군 간의 차이는 유의하지 않았다. 부종/구진, 찰상 항목의 점수에는 두 군 간에 유의한 차이가 관찰되었다. 31명의 환자에게서 한약 치료 후 간장과 신장에 미치는 독성이 발견되지 않았으며 한약투여와 관련된 이상반응은 보고되지 않았다. 위의 결과로부터 시호청간산과 소풍산이 혈열형 아토피피부염에 대한 효과적이고 안전한 치료 방법이 될 수 있을 것으로 생각된다.

• Fire Science and Engineering
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• v.25 no.6
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• pp.27-31
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• 2011

In this study, combustion toxicity evaluation for building interior materials and study for toxicity as using FT-IR analysis. this experiment for the calculation of toxicity index, it using a cone calorimeter model in KS F ISO/TR 9122-4 as a fire model. It is following ISO 19702 procedure for assessing fire toxic gas using FT-IR. This experiment used calculation method for toxicity index (FED) among the international standards. $LC_{50}$ is a concentration that it can cause death to 50 % of experimental animal in 30 minutes - exposure gas test. comparison with the three kinds of toxicity fire gas of construction materials using toxicity index.

• The Korean Journal of Applied Statistics
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• v.35 no.2
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• pp.251-263
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• 2022

Phase I clinical trial is called 'Dose finding study'. It is first step of experimenting on humans with new drugs developed through animal experiments or vitro experiments. The important area of interest in designing Phase I clinical trial is determining the dose that acceptable level to the patients and provides the greatest efficacy. In this paper, we explain about methods to determine the maximum tolerated dose using various stopping rules. The SM3, NM, Rim, J3, BSM methods are compared through simulation. And we consider how the methods might be reformed. As a result of the simulation, BSM estimated the MTD closest to the target toxicity probability. J3 method required the least number of subjects. These results are due to the feature of the stopping rules of both methods. The BSM adds 2 or 1 subject at the same dose level when there is a toxic reaction. In addition, the J3 method has a smaller number of subjects than the other methods. If the methods are improved by combining these features, MTD can be estimated more efficiently. If the total number of subjects can be reduced while using the stopping rule of the BSM, accurate estimation is possible for a small number of subjects.

• Journal of Food Hygiene and Safety
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• v.31 no.5
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• pp.356-364
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• 2016

In vivo genotoxic potential of isoquercetin, a plant common flavonoid, in comparison with quercetin was investigated for the DNA breakage and the clastogenicity endpoints. Male ICR mice were administered by oral gavage for 3 days with $3{\times}0.5%$ carboxymethyl cellulose (CMC), 3 ${\times}$ isoquercetin (250, 500 mg/kg/day), 3 ${\times}$ quercetin (250, 500 mg/kg/day) and 2 ${\times}$ ethyl methanesulfonate (EMS, 200 mg/kg/day). Tissues were collected 48 hours after the first treatment and within 3 hours after the last treatment. The DNA damages were evaluated using Comet assay in liver and stomach, while the clastogenicities were determined using micronucleus test in bone marrow of same animals. The treatment of isoquercetin as well as quercetin did not cause the DNA damages in liver and stomach, and not induce the frequencies of micronucleus polychromatic erythrocytes in bone marrow. In conclusion, isoquercetin as well as quercetin did not cause the DNA breakages and the chromosomal damages in vivo system in these study conditions.

• Proceedings of the KAIS Fall Conference
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• 2012.05a
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• pp.36-38
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• 2012

본 연구는 석탄계 핏치를 원료로 하여 구형 활성탄소를 제조하여 독성 물질인 Dimethyl Methlphosphonate, Hydrogen Chloride에 대한 흡착과파 특성을 연구하였다. 본 연구에서 적용된 구형활성탄 제조방법은 피치를 이용하여 제조하였다. 제조방법은 원료 핏치의 연화점을 상승시키는 전처리 과정, 상기 전처리된 원료 핏치 용융물을 수용액에 현탁시켜 구형입자로 성장시키는 구형화 과정, 구형입자를 산화, 탄화 및 활성화하는 과정으로 구성되며 첨착 활성탄소에 첨착되는 첨착물질의 성분 및 첨착방법의 변화에 따른 독성가스의 흡착성능을 관찰하기 위하여 Dimethyl Methlphosphonate와 Hydrogen Chloride 가스를 대상으로 열중량반응기를 이용하여 흡착실험을 수행하였다. 최적의 담지체 선정을 위하여 담지금속에 따른 흡착능을 시험하여 최적 금속과 함침량을 도출하였다.

• The Korean Journal of Pesticide Science
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• v.7 no.4
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• pp.271-279
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• 2003

To investigate the toxicological effects of technical of IAP-3006, we performed subchronic oral toxicity study in Sprague-Dawley (SD) rats. In the subchronic dietary study, rats of both sexes were fed diets containing technical of IAP-3006 at concentrations of 0, 1000, 10,000, or 15,000 ppm for 90 days. No clinical signs and mortality were observed in animals treated with technical of IAP-3006 throughout the experimental period. There were also no significant changes in body weights, feed consumption, and any gross or histopathological lesions. Although there were statistically significant differences between the control and treated groups in some relative and absolute organ weights, and hematological and biochemical analyses, the data were in biologically normal ranges and did not show a dose-dependent manner. From these results, it is suggested that subchronic oral toxicity NOEL of technical of IAP-3006 in rats may be over 15,000 ppm.