• Title/Summary/Keyword: repeated dose

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Single- and Repeated-Dose Oral Toxicity in Rats and Bacterial Reverse Mutation Test of Morus alba L. Extracts (상지추출물의 단회/반복투여 독성 및 복귀돌연변이능 평가)

  • Han, Taewon;Um, Min Young;Lim, Young Hee;Kim, Jeong-Keun;Kim, In-Ho
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.45 no.10
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    • pp.1406-1413
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    • 2016
  • This study was carried out to evaluate the toxicity of ethanolic extracts of Morus alba L. branch (ME). In the reverse mutation test, Salmonella Typhimurium TA98, TA100, TA1535, TA1357, and Escherichia coli WP2uvrA were used to estimate the mutagenic potential of ME. Sprague-Dawley rats were orally administered ME at levels of 1,250, 2,500, and 5,000 mg/kg for the single-dose toxicity test and 500, 1,000, and 2,000 mg/kg/d for the repeated-dose toxicity test for 28 consecutive days. As expected, reverse mutation was not detected at any concentration of ME, regardless of application of the metabolic activation system with or without S9 mix. In the single-dose toxicity test, ME caused neither significant visible signs of toxicity nor mortality in rats, and $LD_{50}$ was estimated to be over 5,000 mg/kg. In the repeated-dose toxicity test, ME administration at 500, 1,000, and 2,000 mg/kg for 28 days to male or female rats did not result in mortality. Similarly, no toxicologically significant treatment-related changes in body weight, food intake, or organ weights were noted. Several hematological and biochemical parameters in both genders showed significant differences, but these were within normal ranges. These results support the safe use of ME.

Epidural Hematoma Related with Low-Dose Aspirin : Complete Recovery without Surgical Treatment

  • Kim, Kyoung-Tae;Cho, Dae-Chul;Ahn, Suk-Won;Kang, Suk-Hyung
    • Journal of Korean Neurosurgical Society
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    • v.51 no.5
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    • pp.308-311
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    • 2012
  • Hemorrhagic complications associated with aspirin use occur primarily at skin or gastrointestinal sites but can occasionally occur in the central nervous system. In particular, spontaneous spinal epidural hemorrhage (SSEH) associated with aspirin is very rare. We report a case of low-dose (100 mg daily) aspirin-related SSEH that was successfully treated with medical management. Our case indicates that low-dose aspirin could induce SSEH and that conservative treatment with close observation and repeated imaging studies should be considered in cases with neurological improvement or mild deficits.

Single & 14-Day Repeated Oral Toxicity Study and Genotoxicological Safety Estimate of Plantamajoside Isolated from Plantago asiatica (차전초(Plantago asiatica)로부터 분리된 Plantamajoside의 단회와 14일 반복투여 독성시험 및 유전독성학적 안전성 평가)

  • Park, Byung-Gyu;Lee, Hyun-Sun;Jung, Sung-Hoon;Koo, Yun-Chang;Hong, Chung-Qui;Lee, Sun-Joo;Lee, Kwang-Won
    • Toxicological Research
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    • v.23 no.1
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    • pp.79-86
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    • 2007
  • The isolated plantamajoside from Plantago asiatica that is often used as a marker compound in chemotaxonomic studies has various bioactivites such as the inhibitions of cyclic AMP phosphodi-esterase and 5-lipoxygenase, microbial growth and inflammation, and currently demands the generation of toxicity data. The purpose of this study was to examine the toxicities of the single and 14 days repeated dose toxicity in Sprague-Dawley rats orally administrated with plantamajoside at dose levels of 0, 500, 1000, and 2000 mg of dried material/kg body weight/day. The results showed that there was no difference in body weight change, food intake, water consumption, or relative organ weight among different dose groups. Also we observed no death and abnormal clinical signs were observed during the experimental period. Between the groups orally administered Plantago asiatica and the control group, there was no statistical significance in hematological test or serum biochemical values. There were no gross findings at final sacrifice. There was no evidence of histopathological alteration mediated by 14 days treatment with Plantago asiatica. These results suggest that no observed adverse effect level (NOAEL) of the oral application was considered to be more than 2000 mg/kg in rats under the conditions employed in this study. Another observation was performed to investigate the safety of Plantago asiatica in respect of genotoxicity. This substance was examined that Salmonella typhimurium reversion assay (Ames test) in strain TA98, TA100, TA1535. In the reverse mutation test, Plantago asiatica did not induce mutagenicity in Samonella typhimurium with and without metabolic activation. These results indicated that Plantago asiatica had no genotoxicity.

Repeated Dose and Reproductive/Developmental Toxicities of Acetanilide in Rats (랫드를 이용한 Acetanilide의 반복투여 및 생식/발생독성 병행시험)

  • Chung, Moon-Koo;Baek, Sung-Soo;Lee, Sang-Hee;Kim, Hyun-Mi;Choi, Kyung-Hee;Han, Sang-Seop
    • Toxicological Research
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    • v.23 no.4
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    • pp.391-403
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    • 2007
  • The study was conducted to assess the repeated dose and reproduction and developmental toxicities of acetanilide, an intermediate for drug production, as a part of OECD Screening Information Data Set (SIDS) program. The test agent was administered by gavage at dose levels of 0, 22, 67, 200 and 600 mg/kg to Sprague-Dawley rats (12/group/sex) during pre-mating and mating period for males(up to 30 days) and females and pregnancy and early lactation period for females (up to 39-50 days). At 22 mg/kg, decreases in HGB, HCT (males) and MCHC (females), hyperplasia of spleen red pulp, hyperplasia of femur bone marrow (both sexes) were observed. At 67 mg/kg, salivation (males), reduced food consumption (both sexes), decreases in RBC, HGB, HCT and MCHC (males), increases in MCV (males) and spleen weight (males), hyperplasia of spleen red pulp and femur bone marrow (both sexes) were observed. At 200 mg/kg, decreases in locomotor activity and salivation (both sexes), reduced food consumption (both sexes), decreases in RBC, HGB, HCT and increases in MCV, MCH, BUN, T-BIL (males), enlargement of spleen (both sexes), increased weight of spleen (males), hyperplasia of spleen red pulp and femur bone marrow and extramedullary hematopoiesis of liver (both sexes), atrophy of thymus and corpus luteum hyperplasia of ovary (females) were observed. At 600 mg/kg, decreases in locomotor activity, cyanosis (both sexes), reddish tear, and salivation (males), mortality (4 out of 12 females), decreased body weight (females), reduced food consumption (both sexes), decreases in RBC, HGB, HCT and MCHC and increases in WBC, MCV, MCH, reticulocyte, neutrophil, lymphocyte, monocyte, AST, ALT, BUN, T-BIL, ALB, Ca and A/G ratio (males), enlargement of spleen, increased weights of spleen (both sexes), liver (males), kidney and ovary, decreased weights of thymus (females), hyperplasia of spleen red pulp, hyperplasia of femur bone marrow and extramedullary hematopoiesis of liver (both sexes), and atrophy of thymus and corpus luteum hyperplasia of ovary (females) were observed. Regarding the reproduction and development toxicities, there were no treatment-related changes in precoital time, mating index, fertility index and pregnancy index at all doses tested. At 22 and 67 mg/kg, there were no adverse effects on all the parameters observed. At 200 mg/ kg, decreased body weight of pups (day 4 p.p.) were observed. At 600 mg/kg, decreased body weight of pups (day 0 and 4 p.p.) and viability index (day 4 p.p.), increased incidence of newborns dead or with abnormal clinical signs were observed. The results suggest that the NOAELs for general toxicity are < 22 mg/kg, LOAELs are 22 mg/kg and the NOAELs for reproductive toxicity are 67 mg/kg.

Evaluating Surface dose of Treatment Immobilization Devices according to their Electron Energy (전자선에너지에 따른 치료보조기구의 표면선량 평가)

  • Park, Chul-Woo;Im, In-Chul
    • The Journal of the Korea Contents Association
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    • v.10 no.6
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    • pp.360-363
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    • 2010
  • This study evaluated surface dose of treatment immobilization devices such as Themo-plastic, Vac-lock, Cotton and Plaster according to their electron energy. Using a linear accelerater, a plane parallel chamber was set up on 6Mev, 9Mev, 12Mev and 15Mev. A distance between a source and a surface was 100cm and a field size was 10cm*10cm. An incident angle was 0 degree and a radiation dose was 100MU. To decrease an error, the measurement repeated 3 times. The analysis reveals that the surface dose of Vac-lock was the highest and Themo-plastic, Plaster and Cotton were high in order.

Acute Hepatotoxicity and Toxicokinetics of Acetaminophen in Mice (마우스에서 아세트아미노펜의 급성간독성과 독물동태학)

  • 서경원;류정상;김효정
    • Toxicological Research
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    • v.13 no.3
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    • pp.237-245
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    • 1997
  • As the development of a pharmaceutical product is a dynamic process which involves continuousfeed-back between non-clinical and clinical studies, the integration of pharmacokinetics into toxicity testing became increasingly important in recent years. Toxicokinetic measurements in the toxicity studies is considered to be an important scientific approach in the interpretation of the toxicology findings and the promotion of rational study design development. Primarily this research project was conducted to determine the systemic exposure achieved in acute toxicity test and its relationship to dose level and the time course of the toxicity study. Acute hepatotoxicity study and its relevant toxicokinetic study in mice were performed using acetarninophen (AA) as a model compound. The correlation between acute hepatotoxicity indices and toxicokinetic parameters following intraperitoneally administration of various dosages of AA in mice was evaluated and discussed minutely in the text. Based on these studies, single-dose toxicity testing of AA including kinetic studies was evaluated in ICR mice for 7 days and interpreted in the text. Our results from the integration of toxicokinetic monitoring into single-dose toxicity study enable to elucidate the relation of the exposure achieved in toxicity study to toxicological findings and assist in the selection of appropriate dose levels for use in repeated-dose toxicity or later studies.

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Toxicity Study of CKD-602, a Camptothecin Anticancer Agent: 5-Day Repeated Intravenous Administration in Rats

  • Han, Jung-Hee;Cha, Shin-Woo;Kim, Choong-Yong;Lee, Gab-Soo;Suh, Jeong-Eun;Kim, Joon-Kyum;Kim, Jong-Choon;Kang, Boo-Hyon
    • Biomolecules & Therapeutics
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    • v.12 no.1
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    • pp.49-54
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    • 2004
  • The present study was conducted to investigate the potential subacute toxicity of CKD-602 by a 5-day repeated intravenous administration in Sprague-Dawley rats. CKD-602 was administered intravenously to male rats at dose levels of 0, 0.08, 0.2, and 0.5 mg/kg for 5 days. Studies included general observation, body weight changes, ophthalmoscopic examination, hematology, se겨m biochemistry, gross findings at necropsy and organ weight measurement. There were no deaths in any treatment group and treatment related clinical sign was depilation in the 0.5 mg/kg groups. The decrease or suppression of body weight was also observed dose-dependently in all treatment groups. Decreased leukocyte in all treatment groups, decreased platelet in the above 0.2 mg/kg groups and increase in the serum levels of total cholesterol in the 0.5 mg/kg group were considered as a treatment related toxic effects. Decreased weight of thymus in all treatment groups anti decreased weight of spleen in the above 0.2 mg/kg group were observed. The intravenous administration of CKD-602 caused depilation and decreased weight and had toxic effect on the leukocyte, platelet, spleen and thymus. In the condition of this study, the target organs were spleen and thymus and the toxic effect level was determined to be 0.2 mg/kg, but no-observed-adverse-effect level (NOAEL) was considered to be lower than 0.08 mg/kg.

The Effect of Three 20 mg Caudal Epidural Injections of Triamcinolon on the Blood Glucose, ACTH and Cortisol Concentrations in the Elderly Women (노인에서 경막외강에 3회 분할 투여된 Triamcinolone 60 mg이 혈중 포도당, ACTH와 Cortisol에 미치는 영향)

  • Goh, Jee Eun;Min, Soon;Jeong, Young Ju;Lee, Heon Keun
    • The Korean Journal of Pain
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    • v.18 no.1
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    • pp.15-18
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    • 2005
  • Background: Epidural steroid injections (ESI) have been used widely for the treatment of back and radiating extremity pain. Although its effects on the metabolic and endocrine system have been studied, the effects following repeated injections remain to be determined. We studied the effects of three repeated caudal epidural injections of low dose triamcinolone. Methods: the subject were 10 elderly women with spinal stenosis. Caudal epidural injections were performed biweekly. Triamcinolone (20 mg), mixed with 15 ml of 0.25% lidocaine, was used as the ESI injectate. The procedures were performed with the patient in the prone position. Blood sampling was performed just before the first injection, and used as the baseline, and then just before each injection on the same day of the 2nd and 4th weeks, with the last samples taken 2 weeks after the third injection. Results: The blood glucose concentrations showed no significant changes. The blood cortisol and ACTH concentrations were significantly decreased after the first injection, but there were no further decreases after each of the subsequent injections. The cortisol concentrations were maintained within the normal range. Conclusion: Caudal epidural injections, with low dose triamcinolone, suppressed the hypothalamus-pituitary-adrenal (HPA) axis, but no further suppression followed the subsequent repeated injections. Three consecutive caudal injections at 2 week intervals seems to be a safe procedure.

Comparison between Old and New Versions of Electron Monte Carlo (eMC) Dose Calculation

  • Seongmoon Jung;Jaeman Son;Hyeongmin Jin;Seonghee Kang;Jong Min Park;Jung-in Kim;Chang Heon Choi
    • Progress in Medical Physics
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    • v.34 no.2
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    • pp.15-22
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    • 2023
  • This study compared the dose calculated using the electron Monte Carlo (eMC) dose calculation algorithm employing the old version (eMC V13.7) of the Varian Eclipse treatment-planning system (TPS) and its newer version (eMC V16.1). The eMC V16.1 was configured using the same beam data as the eMC V13.7. Beam data measured using the VitalBeam linear accelerator were implemented. A box-shaped water phantom (30×30×30 cm3) was generated in the TPS. Consequently, the TPS with eMC V13.7 and eMC V16.1 calculated the dose to the water phantom delivered by electron beams of various energies with a field size of 10×10 cm2. The calculations were repeated while changing the dose-smoothing levels and normalization method. Subsequently, the percentage depth dose and lateral profile of the dose distributions acquired by eMC V13.7 and eMC V16.1 were analyzed. In addition, the dose-volume histogram (DVH) differences between the two versions for the heterogeneous phantom with bone and lung inserted were compared. The doses calculated using eMC V16.1 were similar to those calculated using eMC V13.7 for the homogenous phantoms. However, a DVH difference was observed in the heterogeneous phantom, particularly in the bone material. The dose distribution calculated using eMC V16.1 was comparable to that of eMC V13.7 in the case of homogenous phantoms. The version changes resulted in a different DVH for the heterogeneous phantoms. However, further investigations to assess the DVH differences in patients and experimental validations for eMC V16.1, particularly for heterogeneous geometry, are required.

The Optimization Experience of Occupational Exposure during Unclear Power Plant Outage (원자력발전소 계획예방정비 기간중 피폭최적화 경험)

  • Song, Young-Il;Kim, Hyung-Jin;Park, Hun-Kook;Kim, Hee-Geun
    • Journal of Radiation Protection and Research
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    • v.28 no.2
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    • pp.145-154
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    • 2003
  • By optimizing the radiation protection the collective dose and individual dose could be reduced during YGN #4 $5^{th}$ outage in 2001. The collective doses for the two high radiation jobs decreased to 85% and 65% of expected doses. The proportion of workers with low dose (below 1mSv) exposure increased 4% while the proportion of workers with over 3mSv and 5mSv exposure are decreased to 2%, 1% respectively. But none is exposed over 8mSv for the annual dose. To aid decision of utilizing the robot, cost- benefit analysis was performed and reasonable point was proposed to use the robot. For the first time job, repeated ALARA meeting and mock up training were implemented to set up working procedure by identifying the trouble. To easily set up standard procedure, mockup process was videotaped and reviewed during ALARA meeting. Monitoring is a good approach to chase radiological working condition such as working time, dose rate. behavior of workers, especially for high radiation work. Those data were estimated and adjusted from the stage of work planning to mock up. At the stage of actual work the monitoring data were compared to the estimation and recorded to database. This database will not only be used as a powerful tool for dose optimization at the following outage but also as a guideline to dose constraint set up for optimization for each specific situation.