• 제목/요약/키워드: $LD_{50}$ values

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한약의 안전성 등급화를 위한 evidence-based approach : Human equivalent dose-based the margin of safety (Evidence-based approach for herbal medicine-safety classification : Human equivalent dose-based the margin of safety)

  • 박영철;이선동
    • 대한예방한의학회지
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    • 제17권3호
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    • pp.19-30
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    • 2013
  • This study was aimed to develop a new formula for herbal medicine-safety classification in terms of evidence-based medicine. Recently, human equivalent dose(HED)-based therapeutic index was developed for herbal medicine-safety classification by transforming $LD_{50}$ to HED. However, the use of the $ED_{50}$ and $LD_{50}$ to derive the therapeutic index may be misleading as to safety, depending on the slope of the dose-response curves for therapeutic and lethal effects. To overcome this deficiency, HED-based MOS(Margin of Safety)was developed and suggested in this study. The HED-based MOS developed by using $LD_1$, changing to ALD(approximate lethal dose), and $ED_{99}$. The HED-based MOS seems to be more useful and safer than HED-based therapeutic index since its values for several herbal medicines are basically two times less than the values from HED-based therapeutic index. Thus, HED-based MOS can be a good example of Evidence-based approach for herbal medicine-safety classification.

경구용 복합제 WHS-1,2의 급성독성시험 연구 (Acute Oral Toxicity Studies of WHS-1 and WHS-2 in Rats)

  • 조대현;황세진;이원용;이주영;윤형중;문병우
    • Biomolecules & Therapeutics
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    • 제1권2호
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    • pp.275-279
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    • 1993
  • Single oral administration to SD rats of both sexes were performed to investigate the acute toxicity of two new cough and cold remedies, WHS-1 and WHS-2. WHS-1 is composed of acetaminophen, chlorpheniramine maleate, cloperastine hydrochloride, dl-methylephedrine hydrochloride, caffein anhydrous, thiamine hydrochloride, riboflavin and serratiopeptidase. WHS-2 is composed of similar formula except that thiamine hydrochloride and riboflavin is not added. The results were as follows. $LD_{50}$ values of WHS-1 were 4295.5 mg/kg for males and 4606.3 mg/kg for females, and $LD_{50}$ values of WHS-2 were 3236.7 mg/kg for males and 4360.5 mg/kg for females. Death occurred within 2~3 hours after administration at doses up to 2900 mg/kg in WHS-1 and 2500 mg/kg in WHS-2, the main cause of deaths seemed to be respiratory disturbance. General symptoms included decreased motor activity, salivation and loss of consciousness which were commonly observed in all dead animals treated with WHS-1 and WHS-2. No significant gross finding and body weight changes were observed at any dose level in the groups treated with WHS-1 and WHS-2.

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눈꽃 동충하초균의 누에감염에 관한 연구 (Studies on Infectivity of Cordyceps, Paecillomyces japonica, on the Domestic Silkworm, Bombyx mori.)

  • 윤재수
    • 농약과학회지
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    • 제4권4호
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    • pp.77-80
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    • 2000
  • 건강식품으로 각광 받고 있는 누에 동충하초균의 누에에 대한 병원성을 알아보기 위하여 동충하초균을 4령기잠에 접종 후 감염잠 발생율을 조사한 결과 $10^{7}/mm^{3}$ 시험구에서는 100%, $10^{6}/mm^{3}$ 시험구에서는 96%, $10^{5}/mm^{3}$ 시험구에서는 76%, $10^{4}/mm^{3}$ 시험구에서는 44%, $10^{3}/mm^{3}$ 시험구에서는 28% $10^{2}/mm^{3}$ 시험구에서는 8%의 감염율을 나타내었다. Probit법에 의한 생물검정 결과 감염효과는 $LD_{50}$ 값이 $3.78{\times}10^{3}\;spores/mm^{3}$ 로서 생물 살충제로 개발 가능성이 높았다.

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Biochemical, Hematological Effects and Complications of Pseudosynanceia Melanostigma Envenoming

  • Babaie, Mahdi;Zolfagharian, Hossein;Zolfaghari, Mohammad;Jamili, Shahla
    • 대한약침학회지
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    • 제22권3호
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    • pp.140-146
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    • 2019
  • Objectives: Venomous fishes have different pharmacological effects and are useful. Among the venomous fish, stonefishes; especially Pseudosynanceia melanostigma has various pharmacological effects on the nervous, muscular and cardiovascular system of humans. In this study, toxicological characteristics, some blood effects, pharmacological and enzymatic properties of Pseudosynanceia melanostigma venom was investigated. Methods: Crude venom purified by using gel filtration chromatography and the molecular weights of the venom and its fractions were estimated. The approximate LD values of this venom were determinedand the effects of LD50 dose on the blood of rabbits were studied. Hemolytic and Hemorrhagic activity of the venom sample was determined. In this case coagulation tests were performed. Results: The LD50 of the Pseudosynanceia melanostigma crude venom was also determined to be $194.54{\mu}g/mouse$. The effect of two doses of LD50 showed a non-significant differences decrease in RBCs and MCV. In other cases, the results showed significant differences in WBC, Plt, Hb, MCH, MCHC and HCT; also it's showed a significant decrease. WBC count showed a significant increase with two doses of LD50 groups. The prothrombin time and partial prothrombin time were increased after venom treatment. As well as bleeding and clotting time were increased. According to the results, a minimum dose for Haemorrhagic effect $40{\mu}g$ was obtained. Conclusion: Venom of Pseudosynanceia melanostigma has inhibitory effect on platelet aggregation that can be used to design and develop of anticoagulant drugs.

Chemical Composition and Acaricidal Effects of Essential Oils Extracted from Ligustrum japonicum against Acaridae and Pyroglyphid Mites

  • Lee, Hoi-Seon
    • Journal of Applied Biological Chemistry
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    • 제58권3호
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    • pp.197-199
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    • 2015
  • The composition of the essential oil of Ligustrum japonicum leaves was determined by GC-MS analysis. The major constituents of L. japonicum leaf oil were germacrene D (40.50%), ${\alpha}$-pinene (13.63%), (-)-${\beta}$-elemene (6.42%), ${\beta}$-caryophyllene (5.73%), and $\delta$-cadinene (5.47%). The acaricidal activities of L. japonicum oil were evaluated against acaridae and pyroglyphid mites. In the fumigant bioassay, the $LD_{50}$ values of L. japonicum oil were 16.48, 12.38, and $15.63{\mu}g/cm^3$ against Tyrophagus putrescentiae, Dermatophagoides farinae, and D. pteronyssinus, respectively. In the contact bioassay, the $LD_{50}$ values of L. japonicum oil were 8.02, 5.02, and $7.67{\mu}g/cm^2$ against T. putrescentiae, D. farinae, and D. pteronyssinus, respectively.

Evaluation of Nigella sativa Seed Constituents for Their in vivo Toxicity in Mice

  • EI-Hadiyah, T.M.;Raza, M.;Mohammed, O.Y.;Abdallah, A.A.
    • Natural Product Sciences
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    • 제9권1호
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    • pp.22-27
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    • 2003
  • This study was designed to investigate the effects of main constituents of Nigella sativa (NS) seed on the survival and CNS responses in experimental animals. The toxicological investigations were conducted for the determination of median lethal doses $(LD_{50})$ of NS seed constituents [i.e. aqueous extract (AE), fixed oil (FO), volatile oil (VO)] and main components of its VO [i.e. thymoquinone (TQ), ${\alpha}-pinene$ (AP) and p-cymene (PC)]. A part of this study includes evaluation NS constituents in the induction of minimal neurological deficit (MND) as a parameter for neurotoxicity using chimney test. In this study, the i.p. $LD_{50}$ values of AE, FO, VO, TQ (suspended In 0.5%CMC), TQ (dissolved in corn oil), AP and PC, were 3020, 3371, 1853, 616.6, 90.3, 1726 and 1523 mg/kg, respectively. All the NS constituents can be considered moderately toxic ($LD_{50}$ ranged from 616.6 to 3371 mg/kg), except the oily solution of TQ, which was very toxic ($LD_{50}$ was 90.3 mg/kg). It appeared that the toxicity of the whole VO is mainly due to its content of TQ and to some extent PC. All the NS constituents induced different degrees of MND at certain dose levels. The median neurotoxic (or sedating) doses $(TD_{50})$ of AE, FO, VO, TQ (suspended in CMC) and AP and PC, were 950, 1403, 306, 88.1, >173 and 368 mg/kg, respectively. TQ was the most potent component in inducing MND, whereas the FO and AE were the least. Neurotoxicity induced by the VO in the chimney test may refer basically to its contents of TQ and to some extent PC and AP.

국내에서 농약에 대한 급성경구독성등급법 적용 및 GHS 체계 도입 제안 (Application of Oral Acute Toxic Class Method and Globally Harmonized Classification System on Pesticide)

  • 정미혜;유아선;박경훈;김병석;이희동;이제봉;권오경
    • 농약과학회지
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    • 제12권2호
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    • pp.141-147
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    • 2008
  • 최근 국제적으로 화학물질에 대하여 분류체계를 단일화하기 위하여 "화학물질의 분류표지 등에 대한 세계 조화시스템(Globally Harmonized classification system, GHS)" 분류체계를 도입하고 있고, 또한 동물보호법에 따라 실험동물수를 축소한 급성경구독성시험법-고정용량법, 급성독성등급법(acute toxic class method, ATC), Up-and Down법을 새롭게 적용하고 있다. 본 시험은 국내 농약 등록시 수행하고 있는 급성경구독성시험인 $LD_{50}$ 시험법과 개정된 시험법 중 급성독성등급법(ATC)을 비교하여 새로운 시험법 적용과 GHS 분류체계 도입여부를 평가하기 위하여 실시하였다. 시험 농약은$LD_{50}$이 GHS 분류기준의 경계부분에 있는 농약 13종을 선발하여 $LD_{50}$ 시험법과 급성독성등급법을 동시에 수행한 결과 Methidathion EC, Parathion-ethyl의 $LD_{50}$$LD_{50}$ 시험법은 각각 57.3, $60\;mg\;kg^{-1}$ 이었고, 급성독성등급법은 $200\;mg\;kg^{-1}$ 으로 $LD_{50}$ 차이가 있었으나, GHS 분류체계의 독성구분 결과 모두 3급으로 동일하게 분류되었고, Carbofuran GR은 $LD_{50}$ 시험법은 $310\;mg\;kg^{-1}$, 급성독성등급법은 $300\;mg\;kg^{-1}$ 으로 비슷하였으나 GHS 분류 3급 기준이 $300\;mgvkg^{-1}$이하이므로 각각 4등급, 3등급으로 분류되었으며, Phosphamidon SL, Endosulfan EC, EPN EC, Dimethoate EC, Phenthoate EC, Zeta-cypermethrin EW, Bifenthrin EC, Fenthion EC, Carbaryl WP, Chlorpyrifos.Diflubenzuron WP의 $LD_{50}$ 은 두 시험 모두 비슷하였고, GHS 독성분류도 동일하였다. 이상의 결과 농약 등록시 급성경구독성시험에 급성독성등급법과 GHS 분류체계에 대한 적용가능성을 제시하고 있다.

랫드 및 마우스에서 DWC-751의 급성정맥 및 경구 독성시험 (Acute Intravenous and Oral Toxicity of DWC-751 in Rats and Mice)

  • 김재현;박창원;강진석;유영효;박정식
    • Toxicological Research
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    • 제11권1호
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    • pp.109-116
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    • 1995
  • Single intravenous and oral administration to SD rats and ICR mice of both sexes were performed to investigate the acute toxicity of DWC-751, a new parenteral cephalosporin. $LD_50$ values for ICR mice and SD rats administered intravenously with DWC-751 were as follows; 1151.1 mg/kg (male SD rat), 1183.5 mg/kg (female SD rat), 2698.1 mg/kg (male ICR mouse), 2833.0 mg/kg (female ICR mouse). It is suggested that $LD_50$ values in rats and mice of both sexes would be 5000 mg/kg in oral route. Major general symptoms induced by injection intravenously with DWC-751 are decreased motor activity, increased respiratory rate, tremor and convulsion. In oral route, piloerection and soft stool are observed to 4 day after administration. No significant body weight changes were observed at any level in the groups administered with DWC-751. The gross finding of rats administered intravenously was observed cecum distension.

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오약순기산 발효물의 급성 독성에 관한 연구 (Study on Acute Toxicity of Fermented Ohyaksungi-san (Wuyaoshunqi-san) Extracts)

  • 이지혜;곽동훈;김태수;마진열
    • 한방비만학회지
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    • 제11권2호
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    • pp.25-32
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    • 2011
  • Objectives: The purpose of this study was to investigate the acute toxicity with oral administration in ICR mice of Ohyaksungi-san fermented with Lactobacillus sp. Methods: In single oral administered toxic test, four groups were administrated different dosages(0, 1250, 2500, 5000 mg/kg) of fermented Ohyaksungi-san. After single oral administration, we observed number of death, clinical signs, body weight changes, hematological values and autopsy. Results: Compared with the control group, we could not find any toxic signs in the mortalities, clinical signs, body weight changes, necropsy findings and hematological values in all treated groups (1250, 2500 and 5000 mg/kg). Conclusions: These results indicate that the $LD_{50}$ value of fermented Ohyaksungi-san extract might be over 5000 mg/kg and it have no side toxic effect to ICR mice

쇠우렁에 대한 살충제의 살패작용에 관한 조사 (A Study on the molluscicidal effect of the insecticides upon Parafossarulus manchouricus)

  • 구성회;김창환
    • 한국환경보건학회지
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    • 제6권1호
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    • pp.10-21
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    • 1979
  • In preventing the infection of Clonorchis sinensis, there is one way in which life cycle of Clonorchis sinensis is cut off by eradicating the first intermediate host viz Parafossarulus manchuoricus, with molluscicides or insecticides. This survey was carried out in order to evaluating the molluscicidal effect of several insecticides upon P. manchauricus. In this survey, diazinon, heptachlor, E.P.N., E.M., and malathion was applied as molluscidies. Those insecticides had been generaly used in farming area. The results are summarized as follows. 1) In molluscicidal effect, E.M. showed the higher molluscicidal effect than any other insecticides in all experiment parts, and the order of insecticides upon molluscicidal effect was that of E.M., E.P.N., heptachlor and malathion. 2) $LD_{50}$ values are varied according to the exposure time in insecticide solution, and the longer the exposure time is, the lower the values of $LD_{50}$ is. 3) To take the exposure time in low concentration of insecticide solution for the long time would obtain the more molluscicidal effect. 4) The mortality rate increases in proportion as the concentration of insecticides increases.

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