• Title/Summary/Keyword: $LD_{50}$values

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

  • Park, Yeong-Chul;Lee, Sundong
    • Journal of Society of Preventive Korean Medicine
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    • v.17 no.3
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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.

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

  • 조대현;황세진;이원용;이주영;윤형중;문병우
    • Biomolecules & Therapeutics
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    • v.1 no.2
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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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Studies on Infectivity of Cordyceps, Paecillomyces japonica, on the Domestic Silkworm, Bombyx mori. (눈꽃 동충하초균의 누에감염에 관한 연구)

  • Yun, Jae-Su
    • The Korean Journal of Pesticide Science
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    • v.4 no.4
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    • pp.77-80
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    • 2000
  • This study was carried out to investigate infection process, symptoms and $LD_{50}$ values of the entomopathogenic fungus cordyceps, Paecillomyces japonica, on the domestic silkworm, Bombyx mori. Susceptibility of infection in the silkworms by cordyceps, Paecillomyces japonica, was 100% in $10^{7}$ block, 96% in $10^{6}$ block, 76% in $10^{5}$ block, 44% in $10^{4}$ block, 28% in $10^{3}$ block and 8% in $10^{2}$ block. Cordyceps, Paecillomyces japonica, was highly infectious to the silkworms. A pathogenicities of cordyceps, Paecillomyces japonica, may be highly virulent because of the low resistance or high susceptibility of the silkworms. Dosage of the pathogen of $LD_{50}$ was $3.78{\times}10^{3}\;spores/mm^{3}$.

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Biochemical, Hematological Effects and Complications of Pseudosynanceia Melanostigma Envenoming

  • Babaie, Mahdi;Zolfagharian, Hossein;Zolfaghari, Mohammad;Jamili, Shahla
    • Journal of Pharmacopuncture
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    • v.22 no.3
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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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    • v.58 no.3
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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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    • v.9 no.1
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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.

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

  • Jeong, Mi-Hye;You, Are-Sun;Park, Kyung-Hun;Kim, Byung-Seok;Lee, Hee-Dong;Lee, Jae-Bong;Kwon, Oh-Kyung
    • The Korean Journal of Pesticide Science
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    • v.12 no.2
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    • pp.141-147
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    • 2008
  • Globally Harmonized System (GHS) for classification and labelling will provide an internationally agreed hazard classification system of chemical products and for communication of those hazards. This study aimed for establishment of the oral acute toxic class (ATC) method and application of GHS on pesticides. The ATC method was developed for determining $LD_{50}$ estimates of chemical substances with significantly fewer animals than needed when applying conventional $LD_{50}$ tests. We carried out $LD_{50}$ test and ATC test on 13 pesticides, Although methidathion EC and parathion-ethyl EC showed significantly different in $LD_{50}$ values between $LD_{50}$ test and ATC method, there are no difference in toxicity class by GHS. Both tests on the other pesticides showed almost equal results and toxicity class by GHS. Therefore, this study indicated high possibility of application of ATC method and GHS on pesticides.

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

  • 김재현;박창원;강진석;유영효;박정식
    • Toxicological Research
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    • v.11 no.1
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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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Study on Acute Toxicity of Fermented Ohyaksungi-san (Wuyaoshunqi-san) Extracts (오약순기산 발효물의 급성 독성에 관한 연구)

  • Lee, Ji-Hye;Kwak, Dong-Hoon;Kim, Tae-Soo;Ma, Jin-Yeul
    • Journal of Korean Medicine for Obesity Research
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    • v.11 no.2
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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

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

  • 구성회;김창환
    • Journal of Environmental Health Sciences
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    • v.6 no.1
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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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