• Title/Summary/Keyword: No-observed effect level

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Single and 13-week Repeated Dose Toxicity Study of DA-3002, An Authentic Recombinant Human Growth Hormone (천연형 인성장호르몬 DA-3002의 단회 및 13주 반복투여독성연구)

  • 김옥진;강경구;안병옥;백남기;이순복;김원배;양중익
    • Biomolecules & Therapeutics
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    • v.2 no.2
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    • pp.161-172
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    • 1994
  • This study was conducted to examine DA-3002, a biosynthetic human growth hormone, for its acute and subacute toxicities in mice and rats. The drug was administered subcutaneously and orally at a dose level of 1.0, 3.0, 8.9, 26.7 or 80.0 lU/kg once for single dose toxicity and given subcutaneously at a dose level of 0.34, 1.7 or 8.4 lU/kg daily for 13 weeks to investigate repeated dose toxicity. In the acute toxicity study, doses up to 80 lU/kg had no adverse effect on the behavior or body weight gain. Pathological examinations revealed no abnormal changes which could be attributed to toxic effect of DA-3002. In the subacute toxicity study, the growth hormone was tolerated well in broth mice and rats. No drug related deaths occurred and all animals appeared to be normal throughout the dosing period. Increases in body weight gain, food utilisation and absolute organ weights were observed in the rats in the high dose group. Mild changes in the blood chemical parameters were also seen in the treated groups. Histopathologically, however, no abnormal changes were observed in any organ. The changes noted during the treatment periods presumably represent exaggerated pharmacological effects of the growth hormone, and no observed adverse effect level (NOAEL) was considered to be more than 8.4 lu/kg/day.

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Repeated Dose 90-Day Oral Toxicity Study of Modified Samjung-Hwan in Sprague-Dawley Rats (삼정환의 랫드를 이용한 90일 반복 경구투여 독성시험)

  • Kim, Min-Jee;Lee, Myeong-Jong;Kim, Hojun
    • Journal of Korean Medicine for Obesity Research
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    • v.18 no.1
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    • pp.36-49
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    • 2018
  • Objectives: The study is aimed at evaluating the possible toxicity in 90-day repeated oral administration of modified Samjung-hwan (mSJH) in Sprague-Dawley (SD) rats. This study was conducted to detect the no-observed adverse effect level (NOAEL). Methods: Modified SJH extract was administered orally in male and female SD rats at dose of 0, 1,000, 2,000, 4,000 mg/kg. Each group consisted of 10 rats of each gender. The modified SJH extract was given once a day for 90 days. We monitored the changes of mortalities, clinical signs, body weight changes, food consumption, ophthalmologic findings, urine analysis, hematology, serum biochemistry, necropsy findings, organ weights, histological markers of all animals treated with modified SJH extract during the study period. Results: There were no toxicologically significant changes in mortalities, clinical signs, body weight gains, food consumption, ophthalmologic findings, urine analysis, hematology, serum biochemistry, necropsy findings, organ weights, histological markers in any of rats tested. Conclusions: The NOAEL of the modified SJH extract in male rats and no observed effect level (NOEL) in female rats are considered 4,000 mg/kg.

Toxicity Study of Red Ginseng Acidic Polysaccharide (RGAP) : Single and 2-week Repeated Oral Dose Toxicity Study in Rats

  • Park, Jong-Dae;Song, Yong-Bum;Kwak, Yi-Seong;Kim, Jong-Choon;Im, Doo-Hyun;Junghee Han
    • Toxicological Research
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    • v.19 no.3
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    • pp.173-180
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    • 2003
  • The present study was conducted to investigate the single and 2-week repeated dose toxicity of red ginseng acidic polysaccharide (RGAP) in Sprague-Dawley rats. The test article was administered orally to rats at dose levels of 0, and 2000 mg/kg/day for single dose toxicity study and at dose levels of 0, 250, 500, and 1000 mg/kg/day for repeated dose toxicity study. In both studies, there were no treatment-related effects on mortality, clinical signs, food and water consumption, ophthalmoscopy, urinalysis, hematology, serum biochemistry, necropsy findings and organ weights of all animals treated RGAP. Based on these results, it was concluded that the 2-week repeated oral dose of RGAP may have no toxic effect in rats at a dose level of 1000 mg/kg/day. In the condition of this study, the no-observed-adverse-effect level (NOAEL) was considered to be 1000 mg/kg/day for both sexes.

Single and Two-Week Repeated] Oral Dose Toxicity Study of DHP2, a Hydrophobic Drug Delivery Vehicle in Mice

  • Han, Jung-Hee;Chung, He-Sson;Lee, Jong-Hwa;Suh, Jeong-Eun;Lee, Gab-Soo;Kim, Jong-Choon;Kang, Boo-Hyon
    • Toxicological Research
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    • v.20 no.2
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    • pp.123-129
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    • 2004
  • The present study was conducted to investigate the single and 2-week repeated dose toxicity of DHP2, a hydrophobic drug delivery vehicle, in ICR mice. The test article was administered orally to mice at the dose levels of 2.5, 12.5 and 37.5 g/kg for single dose toxicity study and at the dose levels of 0, 2.5, 5, and 10 g/kg for repeated dose toxicity study. In both studies, there were no treatment-related effects on mortality, clinical signs, food and water consumption, ophthalmoscopy, urinalysis, hematology, serum biochemistry, necropsy findings and organ weights of all animals treated DHP2. Based on these results, it was concluded that the 2-week repeated oral dose of DHP2 may have no toxic effect in mice at a dose level of 10 g/kg. In the condition of this study, the no-observed-adverse-effect level (NOAEL) was considered to be 10 g/kg/day for both sexes.

Nitrate Metabolism Affected by Osmotic Stress and Nitrate Supply Level in Relation to Osmoregulation

  • Kim, Tae-Hwan
    • Journal of The Korean Society of Grassland and Forage Science
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    • v.20 no.2
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    • pp.77-84
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    • 2000
  • Eight-week old perennial ryegrass (Lolium perenne L. cv. Reveille) plants were exposed to different NO3-concentrations or osmotic stress with NaCI. Previously labeled "N was chased during 14 days of non-labeled'NO3 feeding in order to investigate NO3 metabolism in relation to osmoregulation. The short termmeasurement of osmotic potential showed that the extemal concentration of Nos- had not great effect on theosmotic potential, but that osmotic adjustment was observed in NaCl-treated plants. Total uptake of NO 3 - waslargely increased by increasing supply level of NO3 while it was depressed by exposing to osmotic stress.Nitrate reduction increased to more than 29% by increasing extemal NO,- concentration from 1 mM to 10mM. When osmotically stressed with NaCI, nitrate reduction was depressed to about 37% as compared to thecontrol. The decrease in translocation of reduced N into leaves was also observed in NaCl exposed plants. Inthe medium exposed to 10 mM NO,., osmotic contribution of nitrate to cumulative osmotic potential wasdecreased, and it was osmotically compensated with soluble carbohydrate. When osmotically stressed withNaC1, the contribution of chloride was much higher than that of nitrate. The present data indicate that N03-in plant tissues, factually affected by the assimilation of this ion, plays an active role in osmotic regulation incorrelation with other osmotica such carbohydrate and chloride.(Key words : Nitrate metabolism, Osmotic stress, Nitrate supply level, Osmoregulation)ate supply level, Osmoregulation)

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Subcutaneous Toxicity Study of Saposhnikovia divaricata (Turcz.) Schischk in Rats (랫드에서 방풍, Saposhnikovia divaricata (Turcz.) Schischk의 피하투여 독성에 대한 연구)

  • 이영순;조성대;안남식;정지원;양세란;박준석;박기수;홍인선;서민수
    • Toxicological Research
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    • v.19 no.1
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    • pp.73-82
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    • 2003
  • To evaluate influence of Saposhnikovia divaricata (Turcz.) Schischk extract on rat, Saposhnikovia divaricata (Turcz.) Schischk extract was diluted with 0.9% saline (100 mg/ml/kg, 10 mg/ml/kg, and 1 mg/ml/kg, respectively), and each of diluted test material extract was daily treated subcutaneously for 4 weeks and single-treated subcutaneously for 2 weeks. There were no significances in body weight analysis, urinary analysis, and ophthalmological test. However, in serum biochemical analysis and hematological analysis, we found some significances in high and middle dose group compared with control group. These significances in serum biochemical analysis and hematological analysis may be not induced by test material, because it was not found to be significant from control group in histopathological examination. Therefore, it was concluded that NOEL (No Observed Effect Level) of test material extract may be higher than all treatment doses used in this study, and Saposhnikovia divaricata (Turcz.) Schischk extract may be a non-toxic material.

Single and Four-Week Subcutaneous Toxicity Studies of a Bee Venom Extracts (F1, F3) In Rats (봉독 추출물(Fl, F3)의 랫드에 대한 단회 및 4주 반복 피하 투여 독성시험)

  • 박기수;조성대;안남식;정지원;양세란;박준석;홍인선;서민수;조은혜
    • Toxicological Research
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    • v.19 no.1
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    • pp.51-66
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    • 2003
  • This study was performed to evaluate single and repeated-dose toxicities of Bee Venom Extracts (F1, F3) in Spraque-Dawley. F1 was injected subcutaneously to rat at dose levels of 0, 0.0002, 0.002, 0.02 mg/kg/day for single-dose toxicity study and repeated-dose toxicity study. F3 was injected subcutaneously to rat at dose level of 0, 0.003, 0.03, 0.3 mg/kg/day for single-dose toxicity study and repeated-dose toxicity study. In both studies, there were no dose related changes in mortality, clinical sign, body weight change, food and water consumption, opthalmoscopy, organ weights, urine analysis, biochemical examination, and hematological findings of all animals treated with Bee Venom (F1, F3). Gross and histopathological findings revealed no evidence of specific toxicity related to Bee Venom (F1, F3). These results suggest that the subcutaneous NOEL (No Observed Effect Level) of Bee Venom (F1, F3) may be over F1 -0.02 mg/kg, F3-0.3 mg/kg.

Effect of Dietary Fat and Marginal Tocopherol Supplement on Plasma Lipid, Tocopherol Contet and Fatty acid Composition of Rat Tissues (식이지방과 Tocopherol 첨가가 혈액의 지질 및 조직의 Tocopherol 함량과 지방산조성에 미치는 영향)

  • 남정혜
    • Journal of Nutrition and Health
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    • v.19 no.5
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    • pp.304-314
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    • 1986
  • To observe the effect of the different level of PUFA and marginal tocopherol supplement on HDL-chol, tissue tocopherol content and fatty acid composition, the rats were supplied either safflower oil or conconut oil with or without tocopherol supplement to the experimental diet. Plasma tocopherol level was not greatly influenced by the different dietary fat and similar effect was observed in the liver but not in the adipose tissue. HDL-chol level was reduced in the high PUFA diet regardless of tocopherol content. No effect by tocopherol supplement was observed in the fatty acid composition of liver and adipose tissue lipid in both dietary PUFA levels . There was also no increase in the content of tissue polyenoid acid by tocopherol in the high PUFA diet . Fatty acid composition of tissue lipid was rather more influenced by dietary fat. Lauric and myristic acid contents were higher in the low PUFA diet and linoleic acd and total polynoic acid content were higher in the high PUFA diet. With tocopherol supplement tocopherol /PUFA ratio of tissue was increased but the ratio of high PUFA diet was significantly lower than that of low PUFA diet. Marginal tocopherol supplement could not reduce the peroxidizability index of high PUFA diet.

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Switching and sensing molecular spins by chemical reactions on metal surfaces

  • Kahng, Se-Jong
    • Proceedings of the Korean Vacuum Society Conference
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    • 2015.08a
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    • pp.63.2-63.2
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    • 2015
  • Controlling and sensing spin states of magnetic molecules such as metallo-porphyrins at the single molecule level is essential for spintronic molecular device applications. Axial coordinations of diatomic molecules to metallo-porphyrins also play key roles in dynamic processes of biological functions such as blood pressure control and immune response. However, probing such reactions at the single molecule level to understand their physical mechanisms has been rarely performed. Here we present on our single molecule association and dissociation experiments between diatomic and metallo-porphyrin molecules on Au(111) describing its adsorption structures, spin states, and dissociation mechanisms. We observed bright ring shapes in NO adsorbed metallo-porphyrin compelxes and explained them by considering tilted binding and precession motion of NO. Before NO exposure, Co-porphryin showed a clear zero-bias peak in scanning tunneling spectroscopy, a signature of Kondo effect in STS, whereas after NO exposures it formed a molecular complex, NO-Co-porphyrin, that did not show any zero-bias feature implying that the Kondo effect was switched off by binding of NO. Under tunneling junctions of scanning tunneling microscope, both positive and negative energy pulses. From the observed power law relations between dissociation rate and tunneling current, we argue that the dissociations were inelastically induced with molecular orbital resonances. Our study shows that single molecule association and dissociation can be used to probe spin states and reaction mechanisms in a variety of axial coordination between small molecules and metallo-porphyrins.

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Effects of Dietary Levels of Glycine, Threonine and Protein on Threonine Efficiency and Threonine Dehydrogenase Activity in Hepatic Mitochondria of Chicks

  • Lee, C.W.;Cho, I.J.;Lee, Y.J.;Son, Y.S.;Kwak, I.;Ahn, Y.T.;Kim, S.C.;An, W.G.
    • Asian-Australasian Journal of Animal Sciences
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    • v.27 no.1
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    • pp.69-76
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    • 2014
  • This study was carried out to evaluate the relationship between threonine (Thr) efficiency and Thr dehydrogenase (TDG) activity as an indicator of Thr oxidation on chicks fed with levels of diets (CP [17.5% and 21.5%] and Thr [3.8 and 4.7 g/100 g CP]; glycine [Gly][0.64% and 0.98%] and true digestible Thr [dThr] [0.45% and 0.60%]). Calculation of the Thr efficiency was based on N-balance data and an exponential N-utilization model, and TDG activity was determined as accumulation of aminoacetone and Gly during incubation of hepatic mitochondria. This study found that in the liver of chicks who received a diet containing up to 0.79% Thr (4.7 g Thr/100 g of CP) in the 17.5% CP diet, no significant (p>0.05) effect on TDG activity was observed. However, significantly (p = 0.014) increased TDG activity was observed with a diet containing 21.5% CP (4.7 g Thr/100 g of CP) and the efficiency of Thr utilization showed a significant (p = 0.001) decrease, indicating the end of the Thr limiting range. No significant (p>0.05) effect on the total TDG activity and accumulation of Gly was observed with addition of Gly to a diet containing 0.45% dThr. In addition, addition of Gly to a diet containing 0.60% dThr also did not result in a change in accumulation of Gly. Due to an increase in accumulation of aminoacetone, an elevated effect on total TDG activity was also observed. No significant (p>0.05) reduction in the efficiency of Thr utilization was observed after addition of Gly at the level of 0.45% dThr. However, significantly (p<0.001) reduced efficiency of Thr utilization was observed after addition of Gly at the level of 0.60% dThr. Collectively, we found that TDG was stimulated not only by addition of Thr and protein to the diet, but also by addition of Gly, and efficiency of Thr utilization was favorably affected by addition of Gly at the level near to the optimal Thr concentration. In addition, no metabolic requirement of Gly through the TDG pathway was observed with almost the same accumulation of Gly and a slight increase in TDG activity by addition of Gly. Thus, our findings suggest that determination of TDG activity and parameter of efficiency of Thr utilization may be useful for evaluation of dietary Thr level.