• Environmental Analysis Health and Toxicology
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• 제8권1_2호
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• pp.37-58
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• 1993

In order to investigate the toxicities of S-bioallethrin (5-biol) and its combination treatment with N-octyl bicycloheptene dicarboximide (MGK-264), the acute and subacute toxicity, and enzyme activity test were performed. $LD_{50}$ levels of S-biol and MGK-264 in rats are 640 mg/kg and 3, 280 mg/kg respectively. However, when rats were treated with the mixture of S-biol and MGK-264 (1 : 5 ratio), the $LD_{50}$ was decreased to 545 mg/kg. In serological analysis, ALT and LDH were increased in animals treated with the mixture. Also glucose level was significantly increased after 5 weeks in animals treated with both S-biol and the mixture. Other biochemical parameters such as cytochrome P-450 and NADPH-cytochrome c reductase in the liver and kidney were shown to be not significantly changed. Levels of total ATPase and $mg^{2+}$ ATPase were significantly decreased in the liver of animals treated with the mixture after 4-5 weeks. In addition, S-biol can alone decrease total ATPase activity. Total ATPase activity was also significantly decreased in the kidney after 5 week treatment with the mixture. Similarily, glucose-6-phosphatase activity was significantly decreased in animals treated with the mixture. When either S-biol or MGK-264 was administered, cholinesterase and carboxyesterase activities were slightly decreased but they were significantly decreased when the mixture was administered.

• 대한환경공학회지
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• 제27권1호
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• pp.67-74
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• 2005

기존의 방류수 모니터링에서는 개별 오염물질들의 농도를 기준으로 독성을 평가하였다. 그러나 많은 연구자들에 의해서 오염물질들이 공존하는 상황에서 나타나는 독성은 그들 간의 상호작용을 통해서 혼합독성의 형태로 나타난다고 보고되고 있다. 본 연구에서는 GC/MS 분석을 통해 방류수 중에 존재하는 주요 독성 기여 오염 물질들을 분석하고, Independent Action(IA), Concentration Addition(CA), Effect Summation(ES) 모델을 사용하여 방류수의 혼합독성을 상호 비교 평가하였다. GC/MS로 분석된 오염물질을 대상으로 D. magna 기준 독성 평가를 실시하였고, 10가지의 주요 독성 기여 오염물질을 선별하였다. Chloroneb, butylbenzylphthalate, pendimethaline, di-n-butylphthalate, di-iso-butylphthalate, diazinon, isofenphos, 2-chlorophenol, 2,4,6-trichlorophenol 과 p-octylphenol을 주요 오염물질로 선정하여 혼합독성 평가를 실시하였다. 혼합독성 평가 결과는 IA 예측모델과 매우 높은 상관성($r^2\;=\;0.8475$)을 나타내었다. ES와 CA 모델은 IA 모델과 비교하여 혼합독성 결과와 매우 낮은 상관성을 나타내었으며, 특히 ES는 실측값을 5배나 과도하게 예측하였다. 이러한 결과를 통해서 전남지역 방류수에 존재하는 주요 오염물질들의 혼합독성은 IA 모델을 통해 예측이 가능할 것으로 판단된다.

• 한국자원식물학회:학술대회논문집
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• 한국자원식물학회 2021년도 춘계학술대회
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• pp.59-59
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• 2021

Stachys sieboldii Miq. (SSM) and Acorus gramineus Soland. (AGS) have been used as traditional medicines for thousands of years in parts of Asia, including Korea, China, and Japan. Recent researches on SSM and AGS have documented a wide spectrum of therapeutic properties, including anti-inflammatory, anti-oxidative, neurodegenerative disease effects. However, the toxicity and safety of SSM and AGS, and their mixture (medicinal herber mixture, MHMIX) were not confirmed. Therefore, this study was performed to evaluate the acute toxicity and safety of SSM, AGS and MHMIX. SSM, AGS and MHMIX were orally administered at a dose of 5,000 mg/kg in ICR mice. Animals were monitored for the mortality and changes in the body weight, clinical signs and gross observation during the 14 days after dosing, upon necropsy. We also measured parameters of organ weight, clinical chemistry, and hematology. No dead and no clinical signs were found during the experiment period after administration of a single oral dose of SSM, AGS and MHMIX. There were no adverse effects on clinical signs, body weight, or organ weight and no gross pathological findings in any treatment group. Therefore, LD50 value of SSM, AGS and MHMIX may be over 5,000 mg/kg and it may have no side toxic effect to ICR mice. The results on the single-dose toxicity of SSM, AGS and MHMIX indicate that it is not possible to reach oral dose levels related to death or dose levels with any harmful side effects.

• Toxicological Research
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• 제20권3호
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• pp.281-292
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• 2004

The purpose of this study was to assess the single and 5 week oral dose toxicity of calcitriol and alendronate combination (1 : 10,000) treatment for osteoporosis or Paget's disease in male and female rats. In single dose oral toxicity study, the values of $LD_{50}$ of calcitriol and alendronate mixture were 750.075 mg/kg in male rats and 775.0775 mg/kg in female rats, respectively. Body weight and food consumption were continuously increased after adminstration of calcitriol and alendronate mixtures, and there was no significant changes in body weight and food consumption in all groups. In five-week oral toxicity study of calcitriol and alendronate mixture at a dose of 0.2 $\mu\textrm{g}$ + 2 mg, 1 $\mu\textrm{g}$ + 10 mg, 5 $\mu\textrm{g}$ + 50 mg and 25 $\mu\textrm{g}$ + 250 mg, respectively, there was no mortality, abnormal behavior and appearance in all groups throughout the administration period (5 weeks) and recovery period (2 weeks). Dose-dependent changes in parameters of urinalysis and hematological analysis were not observed in male and female rats treated with calcitriol and alendronate mixtures. All the values of the parameters appeared to be in the normal range. These data indicate that both calcitriol and alendronate are drugs having low toxicity in rats. NOAEL of calcitriol and alendronate mixtures were 50.005 mg/kg in 5-week oral toxicity.

• 한국환경보건학회:학술대회논문집
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• 한국환경보건학회 2003년도 Challenges and Achievements in Environmental Health
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• pp.158-161
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• 2003

Toxicity evaluations of 3-tert-butyl-, 2-isopropyl-, 3-isopropyl- and 4-propyl-phenol and their binary mixtures were performed with the Microtox$\^$(R) / assay and compared to invertebrates and fish. The single chemical, 4-isopropylphenol, exhibited the greatest relative toxicity to the Microtox organism (Vibrio fischeri). The relative electrophilicity (LUMO) of the phenols, in contrast to the lipophilicity (Log P), was strongly correlated with toxicity to V fischeri (r$^2$=0.96, p<0.01). In contrast, relative electrophilicity alone could not explain variances in toxicity of the phenols to Ceriodaphnia dubia. Results suggest that electrophilicity in conjunction with lipophilicity provide better correlation with toxicity to C. dubia and Pimephales promelas. Microtox results from the binary mixture toxicity tests of selected phenolics indicate a mechanism of interaction governed by suppression/antagonism.

• Toxicological Research
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• 제12권2호
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• pp.231-236
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• 1996

The toxicity of the mixture of diazinon, toxaphene(TOX) and/or endrin was studied in ICR male mice(18-22 g) by oral intubation, in corn oil, daily for up to 14 days. On day 15, the exposure was discontinued and animals were monitored for an additional period of 7 days for the possible reversibility of the toxicity. The body weight gain decreased with the mixtures, as well as with the individual pesticides, during the 14-day period. TOX and TOX containing mixtures significantly increased the liver/body weight ratio. The serum glutamic pyruvic transaminase level increased at 23~374% in diazinon, TOX, and endrin or their mixture group. The cholinesterase(ChE) activity in the serum and brain was inhibited in the animals of the group of diazinon(5, 10 mg/kg) and diazinon(5 mg/kg) containing mixtures. TOX(40, 80 mg/kg) caused initial inhibitory effects on the serum ChE Day 1. but there is little effects on the brain ChE levels. endrin(5,10 mg/kg) results in significantly elevated levels of the serum ChE, with substantial decreases in the brain ChE activity. TOX and TOX containing mixtures decreased the pentobarbital(60 mg /kg, ip., in saline) induced sleep. The effects produced by this pesticides singly, as well as by their mixtures, appeared to be reversible in nature. The toxic effects exhibited by the mixtures of diazinon(5 mf/kg), TOX(40 mg/kg), and /or endrin(5 mg/kg) were found to be the resultant of the effect showed by their components individually.

• 한국버섯학회지
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• 제8권3호
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• pp.91-95
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• 2010

본 연구에서는 혈당강하 소재로서 가능성이 확인된 GFPC와 잎새버섯 및 흰목이 추출 혼합물의 안전성을 평가하기 위하여 수행되었었다. 마우스에 대한 급성경구독성을 평가하기 위해 체중 kg 당 최고 5g의 각 시험물질을 마우스 위에 직접 투여하여 48시간 동안 관찰 한 결과 모든 실험군에서 사망예가 관찰되지 않아 LD50 은 5g/kg B.W. 이상으로 계산되었으며, 임상 증상이나 체중에서도 유의할만한 소견이 관찰되지 않았다. 따라서 본 실험의 GFPC와 잎새버섯 및 흰목이 추출 혼합물은 마우스에 있어서 단기 급성 경구독성이나 부작용을 유발하지 않는 안전한 식품소재로 평가되었다. 결론적으로 GFPC와 잎새버섯 및 흰목이 추출 혼합물은 급성 독성이나 부작용을 유발하지 않아 임상사용의 가능성을 제시하여 주었다.

• Toxicological Research
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• 제35권3호
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• pp.215-224
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• 2019

As various populations are rapidly becoming an aging society worldwide and interest in health issues has increased, demand for functional foods including herbal products has increased markedly to maintain a healthy state which has led to safety issues about their intake as an inevitable result. The objective of this study was to identify the safety profile of a Korean red ginseng and Salvia plebeia R. Br. extract mixture (KGC-03-PS) which is a valuable ingredient that can be used as a functional food. In the present study, the subacute oral toxicity and bacterial reverse mutagenicity of KGC-03-PS were evaluated. Sprague Dawley rats were administered KGC-03-PS orally for 28 days by gavage. Daily KGC-03-PS dose concentrations were 0, 500, 1,000, or 2,000 mg/kg body weight (bw) per day. Bacterial reverse mutation test with KGC-03-PS dose levels ranging from 312.5 to $5,000{\mu}g/plate$ was carried out by OECD test guideline No. 471. Five bacterial strains (Salmonella typhimurium TA98, TA100, TA1535, TA1537, and Escherichia coli WP2) were tested in the presence or absence of metabolic activation by plate incorporation method. There were no toxicological effects related with test substance in the clinical evaluation of subacute oral toxicity test including clinical signs, body weight, and food consumption. Moreover, no toxicological changes related to KGC-03-PS were observed in the hematological and serum biochemical characteristics as well as in the pathological examinations, which included organ weight measurements and in the gross- or histopathological findings. KGC-03-PS did not induce an increase in the number of revertant colonies in all bacterial strains of the bacterial reverse mutation test. The no-observed-adverse-effect level of KGC-03-PS is greater than 2,000 mg/kg bw/day, and KGC-03-PS did not induce genotoxicity related to bacterial reverse mutations under the conditions used in this study.

• Bulletin of the Korean Chemical Society
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• 제35권12호
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• pp.3637-3641
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• 2014

In this study, we analyzed the toxicity of mixtures of dimethylformamide (DMF) and methyl ethyl ketone (MEK) or DMF and toluene (TOL) and predicted their toxicity using quantitative structure-activity relationships (QSAR). A QSAR model for single substances and mixtures was analyzed using multiple linear regression (MLR) by taking into account the statistical parameters between the observed and predicted $EC_{50}$. After preprocessing, the best subsets of descriptors in the learning methods were determined using a 5-fold cross-validation method. Significant differences in physico-chemical properties such as boiling point (BP), specific gravity (SG), Reid vapor pressure (rVP), flash point (FP), low explosion limit (LEL), and octanol/water partition coefficient (Pow) were observed between the single substances and the mixtures. The $EC_{50}$ of the mixture of DMF and TOL was significantly lower than that of DMF. The mixture toxicity was directly related to the mixing ratio of TOL and MEK (MLR $EC_{50}$ equation = $1.76997-1.12249{\times}TOL+1.21045{\times}MEK$), as well as to SG, VP, and LEL (MLR equation $EC_{50}=15.44388-19.84549{\times}SG+0.05091{\times}VP+1.85846{\times}LEL$). These results show that QSAR-based models can be used to quantitatively predict the toxicity of mixtures used in manufacturing industries.

• 한국지하수토양환경학회:학술대회논문집
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• 한국지하수토양환경학회 2001년도 총회 및 춘계학술발표회
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• pp.11-14
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• 2001

In this study, the relationship between metals (Cu, Cr, Cd, Zn. Pb, and Fe) 5 fractions and toxicity of soil samples from various contaminated sites in Korea were investigated. Metal toxicity of soils was tested using MetPLATE$^{TM}$ test kit, which is known as metal sensitive and organic insensitive. Significant amount of Fe was found in soils, and metal contents were in the order of Fe>Zn>Pb>Cu>Cr>Cd. Metal levels in organic fraction were rather high for all metals except Fe, and quite high percentages (35~79%) for residual fraction were observed for all metals. There were no significant relationships between the content of each metal fraction and toxicity which showed regression $R^2$in the range of 0.0003~0.414. However, correlation between toxicity and total metal contents showed regression coefficient $R^2$= 0.72. These results showed that the risk evaluation of metals in contaminated sites should be difficult to assess only by the contents of metal distribution because of the complexity of mixture of various metals.s.