• Title/Summary/Keyword: ACUTE TOXICITY

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TOXICOLOGICAL STUDIES ON RAW AND PROCESSED (PREBREWED) ACONITI TUBERS; ACUTE, SUBACUTE TOXICITY STUDIES AND ASSAY OF ACONITINE ALKALOIDS (生附子와 修治附子에 관한 毒性연구 : 급성 및 아급성 독성과 Aconitine 알칼로이드 함량분석)

  • Park, Han-Soo;Kim, Seung-Hee;Kim, Pu-Young;Chang, Il-Moo
    • Toxicological Research
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    • v.6 no.1
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    • pp.41-49
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    • 1990
  • Aconiti Tuber is the root of Aconitum sp (Ranunclaceae) which has been considered as one of the most important medicinal plant having cordiotonic, diuretic and analgesic effect. On the other hand, it has been known that Aconiti Tuber contained toxic agent, aconitine alkaloids so that only processed Aconiti Tubers have been used as herbal drug traditionally. For the safety evaluation of processed Aconiti Tuber, quantitative determination of aconitine and acute, subacute toxicity test were performed on 5 commercial processed Aconiti Tubers. Arapid and precise method using HPLC has been developed for the separation and determination of aconitine. Samples were extracted with hydrochloric acid (pH3) and hot water decoction. In case of d-HCL extracts, the contents of aconitine were from 0.08 mg/g to trace. But in case of hot water decoction extracts, the contents of aconitine were not detected. For the investigation of Aconiti Tuber toxicity in rats, hot water decoction samples and methanol extracts were tested. 1) Acute toxicity test Hot water decoction sample and methanol extracts from Aconiti Tuber did not show any toxic effects in rats by an oral administration. $LD_50values of 2 extracts were above 10.0 g/kg. 2) Subacute toxicity study In the repeated administration study, hot water decoction samples were given orally to Sprague-Dawlay rats for 2 week at daily doses of 5.0 g/kg. The results are as follows; No toxic manifestation, body weight changes and lethality were observed during wxperimental period. There were no significant changes in serum enzyme activities such as GOT, GPT, LDH, ALP between treated and control groups. However CPK values were decreased in the Subuja-treated group. (P<0.01). In addition, no gross and microscopic changes were noted in Aconiti Tuber-treated groups.

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A Study on the Acute Toxicity of Leejung-tang(Lizhong-tang) and Fermented Leejung-tang(Lizhong-tang) Extract in ICR Mice (ICR 마우스를 이용한 이중탕 및 발효이중탕의 급성독성 연구)

  • Jung, Young-Pil;Hwang, Yun-Hwan;Lee, Ji-Hye;Yim, Nam-Hui;Cho, Won-Kyung;Ma, Jin-Yeul
    • The Korea Journal of Herbology
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    • v.27 no.3
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    • pp.95-100
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    • 2012
  • Objectives : This study was carried out to investigate the acute toxicity and safety of $Leejung$-$tang$($Lizhong$-$tang$) and fermented $Leejung$-$tang$($Lizhong$-$tang$) extract. Methods : To evaluate their acute toxicity and safety, 0(control group), 1250, 2500 and 5000 mg/kg of $Leejung$-$tang$($Lizhong$-$tang$) and fermented $Leejung$-$tang$($Lizhong$-$tang$) extracts were orally administered to 35 male and 35 female ICR mice. After a single administration, we observed survival rates, general toxicity, changes of body weight, and autopsy. Results : Compared with the control group, we could not find any toxic alteration in any of treated groups (1250, 2500 and 5000 mg/kg). Conclusions : $LD_{50}$ of $Leejung$-$tang$($Lizhong$-$tang$) and fermented $Leejung$-$tang$($Lizhong$-$tang$) were over 5000 mg/kg and it is very safe to ICR mice.

Intensity-Modulated Radiotherapy for Nasopharyngeal Carcinoma: Penang General Hospital Experience

  • Phua, Chee Ee;Tan, Boon Seang;Tan, Ai Lian;Eng, Kae Yann;Ng, Bong Seng;Malik, Rozita Abdul;Ishak, Wan Zamaniah Wan
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.7
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    • pp.3287-3292
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    • 2012
  • Purpose: To study the overall treatment time (OTT) and acute toxicity of intensity-modulated radiotherapy (IMRT) treatment for nasopharyngeal carcinoma (NPC). Methods: This retrospective study covered all NPC patients who underwent radical IMRT treatment at the Penang General Hospital from June 2011 to February 2012. Patients of any age and stage of disease with histologically proven diagnosis were included. Information was collected on patient demographics, clinical stage, treatment received, including any neoadjuvant and/or concurrent chemotherapy, acute toxity and completion of IMRT within the OTT. Results: A total of 26 NPC patients were treated with IMRT during the study period; 88.5% had stage III/IV disease. 45.2% received neo-adjuvant chemotherapy while 50.0% were given concurrent chemo-irradiation. All patients completed the treatment and 92.3% within the 7 weeks OTT. Xerostomia was present in all patients with 92.3% having grade 2. Severe grade III/IV acute toxicity occurred in 73.1% of patients, the commonest of which was oral mucositis (57.6%). This was followed by dysphagia which occurred in 53.8%, skin reactions in 42.3% and weight loss in 19.2%. However, haematological toxicity was mild with only one patient having leucopaenia. Conclusion: IMRT treatment for NPC is feasible in our center. More importantly, it can be delivered within the 7 weeks OTT in the majority of patients. Severe grade 3/4 toxicity is very common (73.1%) and thus maximal nutritional and analgesic support is required throughout the treatment.

Acute Toxicity Study on Gumiganghwal-tang and Fermented Gumiganghwal-tang Extracts (구미강활탕 및 발효 구미강활탕 추출물의 급성독성 연구)

  • Park, Hwayong;Hwang, Youn-Hwan;Jang, Doorye;Ha, Jeong-Ho;Jung, Kiyoun;Ma, Jin Yeul
    • Herbal Formula Science
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    • v.20 no.2
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    • pp.93-102
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    • 2012
  • Objectives : Traditional medicine Gumiganghwal-tang (GT) has been used in Asia to treat inflammatory diseases including common cold, pain, fever, and algor. In this study we investigated the acute toxicity and safety of GT and fermented GT (FGT). Methods : Acute toxicity and safety were evaluated in male and female ICR mice orally administered 0 (control) and 2,000 mg/kg of GT and FGT. After the administration of GT and FGT, we observed mortality, body weight, clinical symptoms. After necropsy, organ weights were measured and blood analysis was performed. Results : There was no mortality and clinical symptoms according to the administration of GT and FGT. Comparing with control group, there were no significant alterations on the organ weight, complete blood cell count and biochemical parameters. Conclusions : Median lethal dose of GT and FGT considered to be over 2,000 mg/kg in both male and female mice, and recognized as safe with no toxicity.

Acute Toxicity Study on Socheongryong-Tang and Fermented Socheongryong-Tang extracts in Mice (소청룡탕 및 발효 소청룡탕 추출물의 단회투여 독성에 관한 연구)

  • Lee, Ji-Seon;Hwang, Youn-Hwan;Lee, Ji-Hye;Oh, Su-Young;Kim, Tae-Soo;Ma, Jin-Yeul
    • The Korea Journal of Herbology
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    • v.26 no.4
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    • pp.101-107
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    • 2011
  • Objectives : Socheongryong-Tang (小靑龍湯, SCRT) has been widely used to treat respiratory disease. In this study, we investigate the acute toxicity and safety of fermented Socheongryong-Tang extract. Methods : To evaluate the acute toxicity and safety, 0 (control group), 1250, 2500 and 5000 mg/kg of Socheongryong-Tang and fermented Socheongryong-Tang extracts were orally administered to male and female ICR mice. After single administration, we observed survival rates, general toxicity, changes of body weight for the 14 days and autopsy. Results : Compared with the control group, we could not find any toxic alteration in all treated group (1250, 2500 and 5000 mg/kg). Conclusions : $LD_{50}$ of Socheongryong-Tang and fermented Socheongryong-Tang extracts might be over 5000 mg/kg and it is safe to ICR mice.

Acute Toxicity Assessment of New Algicide, Thiazolidinedione Derivative (TD53) to Marine Ecosystem (신규 살조물질인 Thiazolidinedione 유도체 (TD53)의 해양생태계에 대한 급성독성평가)

  • Yim, Eun-Chae;Shin, Jun-Jae;Park, In-Taek;Han, Hyo-Kyung;Kim, Si-Wouk;Cho, Hoon;Kim, Seong-Jun
    • KSBB Journal
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    • v.26 no.1
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    • pp.7-12
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    • 2011
  • In order to perform an acute toxicity assessment of a new algicide, thiazolidinedione derivative (TD53) with enhanced solubility and lower toxicity to marine ecosystem, representative 3 organisms: plant plankton (Skeletonema costatum), animal plankton (Daphnia magna), fish (Paralichthys olivaceus) related in the food chain of marine ecosystem according to OECD standard methods were employed in the exposure experiment. The exposure assessment showed that $EC_50$ of S. costatum in 96-hour, $EC_50$ of D. magna in 48-hour and $LC_50$ of P. olivaceus in 72-hour for TD53 were $1.53\;{\mu}M$, $0.61\;{\mu}M$ and $2.14\;{\mu}M$ respectively. NOEC (No Observed Effect Concentration) and PNEC (Predicted No Effect Concentration) were calculated to be $0.25\;{\mu}M$ and 6.10 nM, respectively from $EC_50$ of most sensitive strain, D. magna. Comparing with the results of toxicity assessment previously performed by using Ulva pertusa Kjellman accepted as an ISO standard method, the values of PNEC showed 3.7 times lower toxicity in case of this study employing 3 organisms, indicating that if the organisms which are more representative and sensitive in marine ecosystem are further investigated, more accurately and validly predicted toxicity of TD53 could be applied in field.

Radiosurgery for Recurrent Brain Metastases after Whole-Brain Radiotherapy : Factors Affecting Radiation-Induced Neurological Dysfunction

  • Gwak, Ho-Shin;Yoo, Hyung-Jun;Youn, Sang-Min;Lee, Dong-Han;Kim, Mi-Sook;Rhee, Chang-Hun
    • Journal of Korean Neurosurgical Society
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    • v.45 no.5
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    • pp.275-283
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    • 2009
  • Objective : We retrospectively analyzed survival, local control rate, and incidence of radiation toxicities after radiosurgery for recurrent metastatic brain lesions whose initial metastases were treated with whole-brain radiotherapy. Various radiotherapeutical indices were examined to suggest predictors of radiation-related neurological dysfunction. Methods : In 46 patients, total 100 of recurrent metastases (mean 2.2, ranged 1-10) were treated by CyberKnife radiosurgery at average dose of 23.1 Gy in 1 to 3 fractions. The median prior radiation dose was 32.7 Gy, the median time since radiation was 5.0 months, and the mean tumor volume was $12.4cm^3$. Side effects were expressed in terms of radiation therapy oncology group (RTOG) neurotoxicity criteria. Results : Mass reduction was observed in 30 patients (65%) on MRI. After the salvage treatment, one-year progression-free survival rate was 57% and median survival was 10 months. Age(<60 years) and tumor volume affected survival rate(p=0.03, each). Acute (${\leq}$1 month) toxicity was observed in 22% of patients, subacute and chronic (>6 months) toxicity occurred in 21 %, respectively. Less acute toxicity was observed with small tumors (<$10cm^3$. p=0.03), and less chronic toxicity occurred at lower cumulative doses (<100 Gy, p=0.004). "Radiation toxicity factor" (cumulative dose times tumor volume of <1,000 Gy${\times}cm^3$) was a significant predictor of both acute and chronic CNS toxicities. Conclusion: Salvage CyberKnife radiosurgery is effective for recurrent brain metastases in previously irradiated patients, but careful evaluation is advised in patients with large tumors and high cumulative radiation doses to avoid toxicity.

Acute and Subacute Toxicity of DWP305 (Ursodeoxycholic acid : Silymarin : Fursulthiamine : Riboflavin tetrabutyrate) in Rats (DWP305 (Ursodeoxycholic acid : Silymarin : Fursulthiamine : Riboflavin tetrabutyrate)의 경구 투여에 의한 랫드에서의 급성 및 아급성 독성 연구)

  • 남석우;박승희;유세근;서동완;김형식;이병무;심점순;유영효;박명환
    • Biomolecules & Therapeutics
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    • v.2 no.3
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    • pp.213-222
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    • 1994
  • The acute tonicity of DWP305 (Ursodeoxycholic acid : Silymarin : Fursulthiamine : Riboflavin tetrabutyrate=1: 1 : 0.1 : 0.05) was evaluated in both sexes of Sprague-Dawley rats, 6weeks old by the oral route of administration. DWP305 was not considered to induce any toxic effect on the rats in mortalities, clinical findings, body weights and gross findings. It is suggested that LD$_{50}$ value in rats would be above 5 g/kg in the oral administration. Subacute toxicity of DWP305 was examined in Sprague-Dawley rats. Four groups of rats were administered orally at doses of 0, 0.32, 0.8, and 2.0 g/kg/day of DWP305 for one month. Any significant toxic clinical symptom was not observed in the treated rats during the experimental period. Macroscopic examination on the organs of tested animals showed no abnormal findings. On autopsy, no significant changes were found in organs examined. Maximum tolerated dose of DWP305 for the rat was estimated to be above 2 g/kg in this study.y.

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The Effect of Trichosanithes kirilowii Max. Subfractions on the Insulin Activity in Streptozotocin Induced Diabetic Rats and Their Acute Toxicity (하늘타리(Trichosanthes kirilowii Max) 재분획물이 Steptozotocin 유발 당뇨 흰쥐의 인슐린 활성에 미치는 영향 및 급성독성에 관한 연구)

  • 임숙자
    • Journal of Nutrition and Health
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    • v.30 no.1
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    • pp.25-31
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    • 1997
  • The effects of Trichosanthes kirilowii Max. subfractions, which has long been used as a wild vegetable and folk medicine, on insulin activity and acute toxicity were investigated. Diabetes melitus was induced in male Sprague-Dawley rats by the injection of streptozotocin(STZ) into the tail vein at a dose of 45mg/kg. The hexane fraction of the plant was subfractioned by silica gel column chromatography and were administered orally for 14 days and the normal and STZ-control group were orally administered with tween 80. The body weight gain was monitored and plasma levels of glucose, cholesterol, triglyceride, free fatty acid HDL-cholesterol were determined. The plasma activities of aspartate aminotransferase(AST) and alanine aminotransferase (ALT) were analysed. The subjraction A of hexane fraction lowered plasma glucose levels significantly and increased insulin activity compared to that of STZ-control. The activities of AST and ALT were decreased by administration of subfractions A and C of hexane fraction. The intakes of the hexane fraction of Trichosanthes kirilowii Max. did not showed the acute toxicity. It is suggested from the results that the subfraction A of the hexane fraction of Trichosanthes kirilowii Max. showed a hypoglycemic effect on diabetic rats and that the subfraction may be beneficial for insulin secreation.

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Acute Toxicity Study on Samul-tang(Siwu-tang) in Mice (ICR 마우스를 이용하여 사물탕(四物湯)의 급성 독성에 관한 연구)

  • Ma, Jin-Yeul;Yu, Young-Beob;Ha, Hye-Kyung;Huang, Dae-Sun;Ma, Choong-Je;Shin, Hyun-Kyoo
    • Herbal Formula Science
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    • v.15 no.2
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    • pp.113-117
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    • 2007
  • Objectives: Samul-tang(Siwu-tang) has been traditionally prescribed a medicine as a restorative. Methods: In this study, we investigated the acute toxicity about water-extracted Samul-tang(Siwu-tang). Twenty-five mice completed 14 days of oral Samul-tang(Siwu-tang) at the respective doses of 0(control group), 2560, 3200, 4000 and 5000mg/kg. Results: We observed survival rates, general toxicity, change of body weight, and autopsy. Conclusions: Compared with the control group, we could not find any toxic alteration in all treated groups (2560, 3200, 4000 and 5000mg/kg). $LD_{50}$ of Samul-tang(Siwu-tang) was over 5000mg/kg and it is very safe to ICR mice.

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