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MeSH Review

Lethal Dose 50

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Disease relevance of Lethal Dose 50


Psychiatry related information on Lethal Dose 50

  • Mice intravenously injected with concentrated infectious influenza B/Lee/40 virus (LD50 = 6400 hemagglutinin units) developed lethargy, seizures, coma, and death 1 to 3 days later [5].
  • Conversely, if levels of cerebral prostaglandins were enhanced by a preceding electroshock, the toxicity of pentylenetetrazole was significantly reduced (increase in LD50), and the time of onset of clonic seizures was markedly prolonged [6].
  • The induction of MN was significantly higher in foetal than adult cells for 0.75 LD50 monocrotaline and benzidine after 21 h (p < 0.0005), and for one LD50 heliotrine at 12, 24 and 30 h after injection in a time-response study (p < 0.02) [7].
  • Pathogen-free OF1 male and female mice of six different ages (between 31 and 387 days), grouped by 10, sex-separated and synchronized by a light (100 lux)-dark 12:12 alternation, were submitted to an acute LD50 carbon monoxide intoxication during the light period during which respiratory and motor activities are at a minimum [8].
  • Soman (less than or equal to 3% LD50), physostigmine (less than or equal to 4.5% LD50), and pyridostigmine (less than or equal to 10% LD50) interfered with two-way shuttlebox avoidance learning, open field behavior, and complex coordinated movements ( hurdle -stepping task) [9].

High impact information on Lethal Dose 50

  • Injected PON1 protects against OP poisoning in rodent model systems and interspecies differences in PON1 activity correlate well with observed median lethal dose (LD50) values [10].
  • To determine whether alcohol enhances acetaminophen hepatotoxicity, a lethal dose for 50% survival of a test group (LD50) was performed for mice fed 10% alcohol in their water supply for three weeks and for mice receiving a normal diet only [11].
  • The same hydrazine sulfate pretreatment has now been found to protect mice against endotoxin in the D-galactosamine model with an increase in the endotoxin LD50 of approximately four orders of magnitude [12].
  • In adult HA/ICR mice pretreated with ferric chloride, the LD50 for S-plus strain 84-32 was 43.3 times lower than its spontaneous S-minus mutant 84-54 [13].
  • Incubation of cells with 200 microM zinc acetate before exposure to copper, raised the LD50 for confluent cells to 1,250 microM copper chloride, improved protein synthesis, and increased synthesis of a 10-kD protein, apparently metallothionein [14].

Chemical compound and disease context of Lethal Dose 50

  • Nimodipine, an antagonist of voltage-sensitive calcium channels, protected cells against cadmium toxicity by increasing the LD50 for CdCl2 from 15 to 45 microM, whereas the calcium channel agonist BAY K8644 decreased the LD50 [15].
  • Toxicity assays in vivo established that sP05-NH2, like native P05, is a potent and lethal neurotoxic agent in mice (LD50 of 20 ng per mouse) [16].
  • Liposome-encapsulated MTP-PE (L-MTP-PE) was superior to free MTP-PE in activating alveolar macrophages and in protecting mice against intranasal challenge with 10 LD50 (50% lethal dose) of herpes simplex virus type 1 (HSV-1) [17].
  • Six additional serotypes (K12, K24, K32, K55, K62, and K67) were examined, and all showed a positive correlation between the ability of the Klebsiella serotype to interact with a human mannose receptor, as expressed by Cos I cell recombinants, and the LD50 of the serotype [18].
  • Groups of mice were injected for 8 weeks with formalin-killed bacteria and subsequently challenged with 10 x LD50 of viable E. coli [19].

Biological context of Lethal Dose 50

  • At the same time, cell viability was determined by trypan blue exclusion and revealed median lethal doses (LD50) of 3.5 micrograms/ml (HL60), 15 micrograms/ml (Raji), 24 micrograms/ml (L1210), and 38 micrograms/ml (K562) [20].
  • Median lethal doses (LD50) for PMB-decaprenylamine and SDB-ethylenediamine administered ip were 123 and 350 mg/kg against mice, whereas the LD50 for verapamil, another modifier of cellular drug resistance, was about 7.6 mg/kg [21].
  • Exposure of septohippocampal cultures to 1.0, 2.0, and 4.0 mmol/L glutamate induced a dose-dependent cell death with an LD50 of 2.0 mmol/L glutamate after 24 hours of incubation [22].
  • Virulence plasmids, which are found in a small number of Salmonella serotypes, greatly enhance the extraintestinal growth of salmonellae and lower the LD50 by 2-5 logs in experimental murine infections [23].
  • In contrast, an S. typhimurium strain carrying mutations in all four fimbrial operons (quadruple mutant) had a 26-fold increased oral LD50 [24].

Anatomical context of Lethal Dose 50


Associations of Lethal Dose 50 with chemical compounds

  • The lucanthone hydrochloride effect was reversible in that control values of LD50/7 were attained by 40 hours post inoculation [25].
  • The median lethal dose for 7-day survival (LD50/7), indicative of death from gastrointestinal epithelial denudation, was reduced from 1,235 rads to minimum values of 995 rads or 985 rads by lucanthone hydrochloride inoculation 10 hours before irradiation or 7.5 hours post irradiation, respectively [25].
  • Heat fractionation with gentamicin increased the LD50/7 (total time at 45 degrees C) to 23.0 and 12.5 minutes at 45 degrees C for 1- and 3-day intervals, respectively [30].
  • The results showed that the LD50 was the same as that for 1-ethyl-1-nitrosourea (ENU) and that its was slightly more potent than ENU as a carcinogen in this system [1].
  • Animals were divided into 3 groups: Group I received ip injections of freshly prepared senkirkine at a dose of 10% of the median lethal dose (LD50) twice weekly for 4 weeks and then once a week for 52 weeks [31].

Gene context of Lethal Dose 50

  • In vivo studies revealed that Mut2 was more effective than TNF or LT against MethA (a mouse tumor line) as judged by the therapeutic ratio [calculated as LD50 (dose that kills 50% of the animals)/ED50 (dose that reduces the tumor size by 50%)] [32].
  • First, deletion of the gene encoding the calcineurin regulatory B subunit, CNB1, from a wild-type strain decreases the LD50 of alpha-factor but has no further effect on a cmd1-6 strain [33].
  • Deletion of the CMK1 and CMK2 genes, which encode CaMK, decreases the LD50 of pheromone compared with that for a wild-type strain but again has no effect in a cmd1-6 strain [33].
  • The LD50 for the mouse of the yscH mutant was 10-fold higher than that of the parental strain indicating that YopR is involved in pathogenesis [34].
  • The LD50 was not affected by rhIL-11 but was 10-fold lower in the anti-TNF MAb group (P<.001) [35].

Analytical, diagnostic and therapeutic context of Lethal Dose 50


  1. Synthesis of 1-(2-hydroxyethyl)-1-nitrosourea and comparison of its carcinogenicity with that of 1-ethyl-1-nitrosourea. Swenson, D.H., Frei, J.V., Lawley, P.D. J. Natl. Cancer Inst. (1979) [Pubmed]
  2. 16, 16 Dimethyl prostaglandin E2 prevents the development of fulminant hepatitis and blocks the induction of monocyte/macrophage procoagulant activity after murine hepatitis virus strain 3 infection. Abecassis, M., Falk, J.A., Makowka, L., Dindzans, V.J., Falk, R.E., Levy, G.A. J. Clin. Invest. (1987) [Pubmed]
  3. Dihydrofluorouracil, a fluorouracil catabolite with antitumor activity in murine and human cells. Diasio, R.B., Schuetz, J.D., Wallace, H.J., Sommadossi, J.P. Cancer Res. (1985) [Pubmed]
  4. 5'-Deoxy-5-fluorouridine selective toxicity for human tumor cells compared to human bone marrow. Armstrong, R.D., Cadman, E. Cancer Res. (1983) [Pubmed]
  5. Experimental influenza B virus toxicity in mice. A possible model for Reye's syndrome. Davis, L.E., Cole, L.L., Lockwood, S.J., Kornfeld, M. Lab. Invest. (1983) [Pubmed]
  6. Potential anticonvulsive properties of endogenous prostaglandins formed in mouse brain. Förstermann, U., Heldt, R., Knappen, F., Hertting, G. Brain Res. (1982) [Pubmed]
  7. Micronuclei in adult and foetal mice exposed in vivo to heliotrine, urethane, monocrotaline and benzidine. Sanderson, B.J., Clark, A.M. Mutat. Res. (1993) [Pubmed]
  8. Age and survival of an acute carbon monoxide intoxication: an animal model. Demaria Pesce, V.H., Stupfel, M., Gourlet, V., Lemercerre, C. Sci. Total Environ. (1987) [Pubmed]
  9. Behavioral changes in the rat after low doses of cholinesterase inhibitors. Wolthuis, O.L., Vanwersch, R.A. Fundamental and applied toxicology : official journal of the Society of Toxicology. (1984) [Pubmed]
  10. The effect of the human serum paraoxonase polymorphism is reversed with diazoxon, soman and sarin. Davies, H.G., Richter, R.J., Keifer, M., Broomfield, C.A., Sowalla, J., Furlong, C.E. Nat. Genet. (1996) [Pubmed]
  11. Potentiation of acetaminophen hepatotoxicity by alcohol. McClain, C.J., Kromhout, J.P., Peterson, F.J., Holtzman, J.L. JAMA (1980) [Pubmed]
  12. Hydrazine sulfate protects D-galactosamine-sensitized mice against endotoxin and tumor necrosis factor/cachectin lethality: evidence of a role for the pituitary. Silverstein, R., Turley, B.R., Christoffersen, C.A., Johnson, D.C., Morrison, D.C. J. Exp. Med. (1991) [Pubmed]
  13. Pathogenesis of Campylobacter fetus infections. Role of surface array proteins in virulence in a mouse model. Pei, Z., Blaser, M.J. J. Clin. Invest. (1990) [Pubmed]
  14. Hepatocellular copper toxicity and its attenuation by zinc. Schilsky, M.L., Blank, R.R., Czaja, M.J., Zern, M.A., Scheinberg, I.H., Stockert, R.J., Sternlieb, I. J. Clin. Invest. (1989) [Pubmed]
  15. Cadmium uptake and toxicity via voltage-sensitive calcium channels. Hinkle, P.M., Kinsella, P.A., Osterhoudt, K.C. J. Biol. Chem. (1987) [Pubmed]
  16. P05, a new leiurotoxin I-like scorpion toxin: synthesis and structure-activity relationships of the alpha-amidated analog, a ligand of Ca(2+)-activated K+ channels with increased affinity. Sabatier, J.M., Zerrouk, H., Darbon, H., Mabrouk, K., Benslimane, A., Rochat, H., Martin-Eauclaire, M.F., Van Rietschoten, J. Biochemistry (1993) [Pubmed]
  17. Therapeutic efficacy of liposome-encapsulated ribavirin and muramyl tripeptide in experimental infection with influenza or herpes simplex virus. Gangemi, J.D., Nachtigal, M., Barnhart, D., Krech, L., Jani, P. J. Infect. Dis. (1987) [Pubmed]
  18. Relationships among capsular structure, phagocytosis, and mouse virulence in Klebsiella pneumoniae. Kabha, K., Nissimov, L., Athamna, A., Keisari, Y., Parolis, H., Parolis, L.A., Grue, R.M., Schlepper-Schafer, J., Ezekowitz, A.R., Ohman, D.E. Infect. Immun. (1995) [Pubmed]
  19. Immunization of mice with antibiotic-treated Escherichia coli results in enhanced protection against challenge with homologous and heterologous bacteria. Raponi, G., Keller, N., Overbeek, B.P., Rozenberg-Arska, M., Torensma, R., Verhoef, J. J. Infect. Dis. (1991) [Pubmed]
  20. Sensitivity of leukemia cell lines to cytotoxic alkyl-lysophospholipids in relation to O-alkyl cleavage enzyme activities. Unger, C., Eibl, H., Kim, D.J., Fleer, E.A., Kötting, J., Bartsch, H.H., Nagel, G.A., Pfizenmaier, K. J. Natl. Cancer Inst. (1987) [Pubmed]
  21. Overcoming drug resistance in cancer cells with synthetic isoprenoids. Yamaguchi, T., Nakagawa, M., Shiraishi, N., Yoshida, T., Kiyosue, T., Arita, M., Akiyama, S., Kuwano, M. J. Natl. Cancer Inst. (1986) [Pubmed]
  22. Novel characteristics of glutamate-induced cell death in primary septohippocampal cultures: relationship to calpain and caspase-3 protease activation. Zhao, X., Newcomb, J.K., Pike, B.R., Wang, K.K., d'Avella, D., Hayes, R.L. J. Cereb. Blood Flow Metab. (2000) [Pubmed]
  23. Salmonella typhimurium bacteremia: association with the virulence plasmid. Fierer, J., Krause, M., Tauxe, R., Guiney, D. J. Infect. Dis. (1992) [Pubmed]
  24. Multiple fimbrial adhesins are required for full virulence of Salmonella typhimurium in mice. van der Velden, A.W., Bäumler, A.J., Tsolis, R.M., Heffron, F. Infect. Immun. (1998) [Pubmed]
  25. Effect of lucanthone hydrochloride on the radiation response of intestine and bone marrow of the Chinese hamster. Milligan, A.J., Katz, H.R., Leeper, D.B. J. Natl. Cancer Inst. (1978) [Pubmed]
  26. Relationship of resistance to oxygen free radicals to CuZn-superoxide dismutase activity in transgenic, transfected, and trisomic cells. Huang, T.T., Carlson, E.J., Leadon, S.A., Epstein, C.J. FASEB J. (1992) [Pubmed]
  27. Toxicity of an antitumor ribonuclease to Purkinje neurons. Newton, D.L., Walbridge, S., Mikulski, S.M., Ardelt, W., Shogen, K., Ackerman, S.J., Rybak, S.M., Youle, R.J. J. Neurosci. (1994) [Pubmed]
  28. Flavopiridol sensitivity of cancer cells isolated from ascites and pleural fluids. Richard, C., Matthews, D., Duivenvoorden, W., Yau, J., Wright, P.S., Th'ng, J.P. Clin. Cancer Res. (2005) [Pubmed]
  29. Chlorambucil induction of HsRad51 in B-cell chronic lymphocytic leukemia. Christodoulopoulos, G., Malapetsa, A., Schipper, H., Golub, E., Radding, C., Panasci, L.C. Clin. Cancer Res. (1999) [Pubmed]
  30. Thermotolerance in the murine jejunum. Henle, K.J. J. Natl. Cancer Inst. (1982) [Pubmed]
  31. Induction of hepatic tumors in rats by senkirkine and symphytine. Hirono, I., Haga, M., Fujii, M., Matsuura, S., Matsubara, N., Nakayama, M., Furuya, T., Hikichi, M., Takanashi, H., Uchida, E., Hosaka, S., Ueno, I. J. Natl. Cancer Inst. (1979) [Pubmed]
  32. Human lymphotoxin mutein lacks hypotensive activity but has higher in vivo antitumor activity than lymphotoxin or tumor necrosis factor. Taniyama, M., Morita, T., Yamagishi, Y., Kato, A., Bando, C., Okawa, N., Kaji, A. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  33. Ca2+-calmodulin promotes survival of pheromone-induced growth arrest by activation of calcineurin and Ca2+-calmodulin-dependent protein kinase. Moser, M.J., Geiser, J.R., Davis, T.N. Mol. Cell. Biol. (1996) [Pubmed]
  34. Mutational analysis of the Yersinia enterocolitica virC operon: characterization of yscE, F, G, I, J, K required for Yop secretion and yscH encoding YopR. Allaoui, A., Schulte, R., Cornelis, G.R. Mol. Microbiol. (1995) [Pubmed]
  35. Recombinant human interleukin-11 has anti-inflammatory actions yet does not exacerbate systemic Listeria infection. Opal, S.M., Keith, J.C., Palardy, J.E., Parejo, N. J. Infect. Dis. (2000) [Pubmed]
  36. Effect of intraventricular administration of anti-somatostatin gamma-globulin on the lethal dose-50 of strychnine and pentobarbital in rats. Chihara, K., Arimura, A., Chihara, M., Schally, A.V. Endocrinology (1978) [Pubmed]
  37. Effect of endotoxin on rat liver. Analysis of acid phosphatase isozymes in the liver of normal and endotoxin-treated rats. Hirata, K., Kaneko, A., Ogawa, K., Hayasaka, H., Onoé, T. Lab. Invest. (1980) [Pubmed]
  38. Teratogenicity/fetotoxicity of DEHP in mice. Tomita, I., Nakamura, Y., Yagi, Y., Tutikawa, K. Environ. Health Perspect. (1982) [Pubmed]
  39. Differential effect of cimetidine on drug oxidation (antipyrine and diazepam) vs. conjugation (acetaminophen and lorazepam): prevention of acetaminophen toxicity by cimetidine. Abernethy, D.R., Greenblatt, D.J., Divoll, M., Ameer, B., Shader, R.I. J. Pharmacol. Exp. Ther. (1983) [Pubmed]
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