• Title/Summary/Keyword: repeated dose

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Fourteen-day Repeated-dose Oral Toxicity Study of the Ethanol Extracts Isolated from Oplopanax elatus in Sprague-Dawley Rat (흰쥐에서 땃두릅 에탈올 추출물의 14일 반복경구토여에 의한 독성시험)

  • Kwon, Hyuck-Se;Kim, Dae-Hwan;Shin, Hyun-Kyung;Yu, Chang-Yeon;Kim, Myong-Jo;Lim, Jung-Dae;Park, Jae-Kun;Kim, Jin-Kyung
    • Korean Journal of Food Science and Technology
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    • v.39 no.4
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    • pp.470-475
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    • 2007
  • Oplopanax elatus (O. elatus) is a tall deciduous shrub that has traditionally been used for σ eating a variety of ailments such as diabetes, coughling, rheumatism, gastro-intestinal disorders, and wounds. In order to examine the safety of the ethanol extracts of O. elatus, we performed a 14-day repeated-dose toxicity study with Sprague-Dawley rats. The rats were treated with daily doses of the D. elatus ethanol extracts by gavage at 0, 500, 1000, and 2000 mg/kg/day for 14 consecutive days. We recorded clinical signs of toxicity, body weight, hematology, organ weights, gross and histological changes in target organs, and clinical chemistry analysis data for all rats. There were no significant changes in body and organ weights during the experimental period. The hematological analysis and clinical blood chemistry data revealed no toxic effects from the O. elatus ethanol extracts. Pathologically, neither gross abnormalities nor histopathological changes were observed between the control and treated rats of both sexes. Collectively, these data suggest that the ethanol extracts of O. elatus have a high margin of safety.

Initial Risk Assessment of Acetanilide in OECD High Production Volume Chemical Program

  • Park, Hye-Youn;Park, Yoonho;Sanghwan Song;Kwon, Min-Jeoung;Koo, Hyun-Ju;Jeon, Seong-Hwan;Na, Jin-Gyun;Park, Kwangsik
    • Toxicological Research
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    • v.18 no.1
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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.

Thirteen-week Repeated Oral Dose Toxicity Study of WK-38 in Rats (랫트에서 WK-38에 대한 13주 반복경구투여 독성에 관한 연구)

  • Chang, Bo-Yoon;Kim, Yoon-Chul;Kang, Dae-Gill;Lee, Ho-Sub;Kim, Sung-Yeon
    • Journal of Food Hygiene and Safety
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    • v.23 no.2
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    • pp.169-176
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    • 2008
  • The subcronic toxicity of WK-38, a herbal preparation for the atherosclerosis, was examined in male and female Sprague-Dawley rats. WK-38 is composed of Rhei Rhizoma, Magonoliae Cortx, Moutan Cortex Radicis. Rats were treated with the test substance at a dose of 5 mg/kg, 50 mg/kg and 500 mg/kg intragastrically for 13 weeks. Control rats were treated with vehicle only. No death and abnormal clinical signs were observed throughout the administration period. Also there was no difference in net body weight gain, food and water consumption, organ weight, gross pathological findings, and urine analysis among the groups of rats treated with different doses of the WK-38. Hematological findings and biochemical examination revealed no evidence of specific toxicity related to WK-38. The results suggested that under the condition employed in this study no observation effect level (NOEL) of WK-38 would be 500 mg/kg/day.

Evaluation of 3-week Repeated Dose Oral Toxicity on Amomum tsao-ko Extract in Balb/c Mice (Balb/c 마우스에서 초과 추출물의 3주간 반복 경구투여 독성평가)

  • Park, Ju-Hyeong;Cho, Young-Rak;Ko, Hye-Jin;Jeong, Wonsik;Ahn, Eun-Kyung;Oh, Junho;Oh, Joa Sub
    • Journal of Applied Biological Chemistry
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    • v.58 no.2
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    • pp.139-143
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    • 2015
  • In the present study, we investigated the oral toxicity of Amomum tsao-ko Crevost et Lemaire, (Zingiberaceae) extract in Balb/c mice (BALB, n=60) for 3 weeks. Balb/c mice (10 mice/group, 6 group, $20{\pm}2g$, 6 weeks) were orally administered for 21 days, with dosage of 250, 500, 1000, 2000 mg/kg/day. Ethanol extract of A. tsao-ko did not affect any significant change of mortality, clinical signs, organs and body weights. Also, there were not significantly difference from the naive group (control) in hematological and serum biochemical examination. Consequently, these findings indicate that 3-week treatment with the ethanol extract of A. tsao-ko was not any toxic effects in Balb/c mice and the no-observed adverse effect level (NOAEL) for oral toxicity was determined to be 2000 mg/kg/day under our experimental conditions.

Repeated Intramuscular-dose Toxicity Test of Water-soluble Carthami Flos (WCF) Pharmacopuncture in Sprague-Dawley Rats

  • Choi, Yoo-Min;Jung, Da-Jung;Kim, Seok-Hee;Kim, Jong-Uk;Yook, Tae-Han
    • Journal of Pharmacopuncture
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    • v.18 no.1
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    • pp.36-43
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    • 2015
  • Objectives: Water-soluble carthami flos (WCF) is a new mixture of Carthami flos (CF) pharmacopuncture. We conducted a 4-week toxicity test of repeated intramuscular injections of WCF in Sprague-Dawley rats. Methods: Forty male and 40 female rats were divided into 4 groups of 10 male and 10 female SD rats: The control group received 0.5 mL/animal/day of normal saline whereas the three experimental groups received WCF at doses of 0.125, 0.25, and 0.5 mL/animal/day, respectively. For 4 weeks, the solutions were injected into the femoral muscle of the rats alternating from side to side. Clinical signs, body weights, and food consumption were observed; opthalmological examinations and urinalyses were performed. On day 29, blood samples were taken for hematological and clinical chemistry analyses. Then, necropsy was conducted in all animals to observe weights and external and histopathological changes in the bodily organs. All data were tested using a statistical analysis system (SAS). Results: No deaths were observed. Temporary irregular respiration was observed in male rats of the experimental group for the first 10 days. Body weights, food consumptions, opthalmological examinations, urinalyses, clinical chemistry analyses, organ weights and necropsy produced no findings with toxicological meaning. In the hematological analysis, delay of prothrombin time (PT) was observed in male rats of the 0.25- and the 0.5-mL/animal/day groups. In the histopathological test, a dose-dependent inflammatory cell infiltration into the fascia and panniculitis in perimuscular tissues was observed in all animals of the experimental groups. However, those symptoms were limited to local injection points. No toxicological meanings, except localized changes, were noted. Conclusion: WCF solution has no significant toxicological meaning, but does produce localized symptoms. No observed adverse effect level (NOAEL) of WCF in male and female rats is expected for doses over 0.5 mL/animal/day.

Twenty-Eight-Day Repeated Inhalation Toxicity Study of Aluminum Oxide Nanoparticles in Male Sprague-Dawley Rats

  • Kim, Yong-Soon;Chung, Yong-Hyun;Seo, Dong-Seok;Choi, Hyun-Sung;Lim, Cheol-Hong
    • Toxicological Research
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    • v.34 no.4
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    • pp.343-354
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    • 2018
  • Aluminum oxide nanoparticles ($Al_2O_3$ NPs) are among the most widely used nanomaterials; however, relatively little information about their risk identification and assessment is available. In the present study, we aimed to investigate the potential toxicity of $Al_2O_3$ NPs following repeated inhalation exposure in male Sprague-Dawley rats. Rats were exposed to $Al_2O_3$ NPs for 28 days (5 days/week) at doses of 0, 0.2, 1, and $5mg/m^3$ using a nose-only inhalation system. During the experimental period, we evaluated the clinical signs, body weight change, hematological and serum biochemical parameters, necropsy findings, organ weight, and histopathology findings. Additionally, we analyzed the bronchoalveolar lavage fluid (BALF), including differential leukocyte counts, and aluminum contents in the major organs and blood. Aluminum contents were the highest in lung tissues and showed a dose-dependent relationship in the exposure group. Histopathology showed alveolar macrophage accumulation in the lungs of rats in the $5mg/m^3$ group during exposure and recovery. These changes tended to increase at the end of the recovery period. In the BALF analysis, total cell and neutrophil counts and lactate dehydrogenase, tumor necrosis factor-${\alpha}$, and interleukin-6 levels significantly increased in the 1 and $5mg/m^3$ groups during exposure. Under the present experimental conditions, we suggested that the no-observed-adverse-effect level of $Al_2O_3$ NPs in male rats was $1mg/m^3$, and the target organ was the lung.

Effect of Pain Control with Percutaneous Radiofrequency Rhizotomy in Secondary Trigeminal Neuralgia (이차성 삼차신경통에서 경피적 고주파 삼차신경절제술에 의한 동통조절 효과)

  • Kang, Seong-Buhm;Son, Byung-Chul;Kim, Moon-Chan;Kang, Joon-Ki
    • Journal of Korean Neurosurgical Society
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    • v.29 no.1
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    • pp.66-71
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    • 2000
  • Objective : There are many treatment modalitis in management of idiopathic trigeminal neuralgia. In the secondary trigeminal neuralgia, there has been only sporadic reports of the etiology. Authors report the treatment result of secondary trigeminal neuralgia with percutaneous radiofrequency rhizotomy. Methods : During last ten years, 129 trigeminal neuralgias were treated by percutaneous radiofrequency(RF) rhizotomy by authors. Among them, nine patients were secondary trigeminal neuralgias. These patients refused treatment for the primary cause and only wanted pain control. The offending lesions were three arachnoid cysts, six tumors. The mean age was 47.8 years and the mean duration of follow-up was 6.2 years. The right V2,3 distribution was most prevalent area of pain. Authors used the conventional Hartel's anterior approach and straight electrode for RF lesion generation. Result : The early result was satisfactory. Eight of nine patients became free of pain and one patient needed minimal dose of carbamazepine. The overall pain control was 100%. There was no mortality or morbidity for initial RF rhizotomy. During follow-up, four patients showed recurrence of pain(44%). Among these, two underwent repeated RF rhizotomy and became free of pain. The other two were controlled with medical management. Conclusion : These results indicate that the percutaneous RF rhizotomy is effective means of pain control. Overall recurrence was somewhat higher than that of idiopathic trigeminal neuralgia. Even with recurrence, however, repeated RF rhizotomy seems to be effective method of control of pain in these cases.

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Blockade of ERK Phosphorylation in the Nucleus Accumbens Inhibits the Expression of Cocaine-induced Behavioral Sensitization in Rats

  • Kim, Seung-Woo;Shin, Joong-Keun;Yoon, Hyung-Shin;Kim, Jeong-Hoon
    • The Korean Journal of Physiology and Pharmacology
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    • v.15 no.6
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    • pp.389-395
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    • 2011
  • Repeated administration of psychostimulants such as cocaine leads to the development of behavioral sensitization. Extracellular signal-Regulated Kinase (ERK), an enzyme important for long-term neuronal plasticity, has been implicated in such effects of these drugs. Although the nucleus accumbens (NAcc) is the site mediating the expression of behavioral sensitization by drugs of abuse, the precise role of ERK activation in this site has not been determined. In this study we demonstrate that blockade of ERK phosphorylation in the NAcc by a single bilateral microinjections of PD98059 (0.5 or $2.0{\mu}g/side$), or U0126 (0.1 or $1.0{\mu}g/side$), into this site dose-dependently inhibited the expression of cocaine-induced behavioral sensitization when measured at day 7 following 6 consecutive daily cocaine injections (15 mg/kg, i.p.). Acute microinjection of either vehicle or PD98059 alone produced no different locomotor activity compared to saline control. Further, microinjection of PD98059 ($2.0{\mu}g/side$) in the NAcc specifically lowered cocaine-induced increase of ERK phosphorylation levels in this site, while unaffecting p-38 protein levels. These results indicate that ERK activation in the NAcc is necessary for the expression of cocaine-induced behavioral sensitization, and further suggest that repeated cocaine evokes neuronal plasticity involving ERK pathway in this site leading to long-lasting behavioral changes.

Anneal Characteristics of LiF:Mg,Cu,Na,Si Teflon TLDs (LiF:Mg,Cu,Na,Si Teflon TLD의 열처리 특성)

  • Nam, Young-Mi;Chung, Woon-Hyuk;Lee, Dae-Won;Kim, Hyun-Ja;Kim, Gi-Dong
    • Journal of Radiation Protection and Research
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    • v.22 no.3
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    • pp.135-141
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    • 1997
  • The study of anneal characteristics is important for TL dosimeter to reuse. To obtain the annealing condition of the recently developed, new TL dosimeter, LiF:Mg,Cu,Na,Si Teflon Tills in a disk type (diameter 4.5 mm, thickness about $90mg/cm^2$), we studied for pre-irradiation annealing, readout procedure and post-readout annealing, in order. The gamma irradiations were carried out with a $^{60}Co$, dose of 0.1 Gy. We have used the method that observe the variation of thermoluminescent(TL) intensity of these Teflon TLDs over repeated cycles by changing both anneal temperature and anneal time with the TLD reader and the oven. There is a 5% loss in sensitivity over the ten repeated readouts by the annealing condition:pre-irradiation annealing at $80^{\circ}C$ for one hour, readout to $280^{\circ}C$ and post-readout annealing at $270^{\circ}C$ for 20 seconds.

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Chronic Administration of Catechin Decreases Depression and Anxiety-Like Behaviors in a Rat Model Using Chronic Corticosterone Injections

  • Lee, Bombi;Sur, Bongjun;Kwon, Sunoh;Yeom, Mijung;Shim, Insop;Lee, Hyejung;Hahm, Dae-Hyun
    • Biomolecules & Therapeutics
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    • v.21 no.4
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    • pp.313-322
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    • 2013
  • Previous studies have demonstrated that repeated administration of the exogenous stress hormone corticosterone (CORT) induces dysregulation in the hypothalamic-pituitary-adrenal (HPA) axis and results in depression and anxiety. The current study sought to verify the impact of catechin (CTN) administration on chronic CORT-induced behavioral alterations using the forced swimming test (FST) and the elevated plus maze (EPM) test. Additionally, the effects of CTN on central noradrenergic systems were examined by observing changes in neuronal tyrosine hydroxylase (TH) immunoreactivity in rat brains. Male rats received 10, 20, or 40 mg/kg CTN (i.p.) 1 h prior to a daily injection of CORT for 21 consecutive days. The activation of the HPA axis in response to the repeated CORT injections was confirmed by measuring serum levels of CORT and the expression of corticotrophin-releasing factor (CRF) in the hypothalamus. Daily CTN administration significantly decreased immobility in the FST, increased open-arm exploration in the EPM test, and significantly blocked increases of TH expression in the locus coeruleus (LC). It also significantly enhanced the total number of line crossing in the open-field test (OFT), while individual differences in locomotor activities between experimental groups were not observed in the OFT. Taken together, these findings indicate that the administration of CTN prior to high-dose exogenous CORT significantly improves helpless behaviors, possibly by modulating the central noradrenergic system in rats. Therefore, CTN may be a useful agent for the treatment or alleviation of the complex symptoms associated with depression and anxiety disorders.