median lethal dose
{{Short description|Measurement of lethal dose of substance}}
{{redirect|LD50}}
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In toxicology, the median lethal dose, LD50 (abbreviation for "lethal dose, 50%"), LC50 (lethal concentration, 50%) or LCt50 is a toxic unit that measures the lethal dose of a given substance.{{Cite web|url=https://goldbook.iupac.org/html/A/A00025.html|work=IUPAC Gold Book|title=Absolute lethal dose (LD100)|publisher=International Union of Pure and Applied Chemistry|language=en|access-date=2019-07-01|archive-url=https://web.archive.org/web/20190701134347/https://goldbook.iupac.org/html/A/A00025.html|archive-date=2019-07-01|url-status=dead}} The value of LD50 for a substance is the dose required to kill half the members of a tested population after a specified test duration. LD50 figures are frequently used as a general indicator of a substance's acute toxicity. A lower LD50 is indicative of higher toxicity.
The term LD50 is generally attributed to John William Trevan.{{cite journal | title=John William Trevan, 1887-1956 | journal=Biographical Memoirs of Fellows of the Royal Society | volume=3 | date=1957 | issn=0080-4606 | doi=10.1098/rsbm.1957.0019 | pages=273–288 | url=https://royalsocietypublishing.org/doi/pdf/10.1098/rsbm.1957.0019 | access-date=2024-03-31 | archive-date=2020-03-28 | archive-url=https://web.archive.org/web/20200328170611/https://royalsocietypublishing.org/doi/pdf/10.1098/rsbm.1957.0019 | url-status=live | url-access=subscription }} The test was created by J. W. Trevan in 1927.{{cite web|url=http://www.ccohs.ca/oshanswers/chemicals/ld50.html|title=What is a LD50 and LC50?|work=OSH Answers Fact Sheets|date=5 October 2021|publisher=Canadian Centre for Occupational Health and Safety|access-date=15 July 2006|archive-date=26 June 2015|archive-url=https://web.archive.org/web/20150626013647/http://www.ccohs.ca/oshanswers/chemicals/ld50.html|url-status=live}} The term semilethal dose is occasionally used in the same sense, in particular with translations of foreign language text, but can also refer to a sublethal dose. LD50 is usually determined by tests on animals such as laboratory mice. In 2011, the U.S. Food and Drug Administration approved alternative methods to LD50 for testing the cosmetic drug botox without animal tests.{{cite web
|date=24 June 2011
|title=Allergan Receives FDA Approval for First-of-Its-Kind, Fully in vitro, Cell-Based Assay for BOTOX and BOTOX Cosmetic (onabotulinumtoxinA)
|publisher=Allergan Web site
|url=http://agn.client.shareholder.com/releasedetail.cfm?ReleaseID=587234
|access-date=2012-08-15
|url-status=dead
|archive-url=https://web.archive.org/web/20110626185759/http://agn.client.shareholder.com/releasedetail.cfm?ReleaseID=587234
|archive-date=26 June 2011
}}{{cite news | vauthors = Gaul GM | date = 12 April 2008 | title = In U.S., Few Alternatives To Testing On Animals | newspaper = Washington Post | url = https://www.washingtonpost.com/wp-dyn/content/article/2008/04/11/AR2008041103733.html | access-date = 2011-06-26 | archive-date = 2012-11-12 | archive-url = https://web.archive.org/web/20121112163835/http://www.washingtonpost.com/wp-dyn/content/article/2008/04/11/AR2008041103733.html | url-status = live }}
Conventions
The LD50 is usually expressed as the mass of substance administered per unit mass of test subject, typically as milligrams of substance per kilogram of body mass, sometimes also stated as nanograms (suitable for botulinum toxin), micrograms, or grams (suitable for paracetamol) per kilogram. Stating it this way allows the relative toxicity of different substances to be compared and normalizes for the variation in the size of the animals exposed (although toxicity does not always scale simply with body mass). For substances in the environment, such as poisonous vapors or substances in water that are toxic to fish, the concentration in the environment (per cubic metre or per litre) is used, giving a value of LC50. But in this case, the exposure time is important (see below).
The choice of 50% lethality as a benchmark avoids the potential for ambiguity of making measurements in the extremes and reduces the amount of testing required. However, this also means that LD50 is not the lethal dose for all subjects; some may be killed by much less, while others survive doses far higher than the LD50. Measures such as "LD1" and "LD99" (dosage required to kill 1% or 99%, respectively, of the test population) are occasionally used for specific purposes.{{cite web|editor=Doris V. Sweet|date=July 1997|url=https://www.cdc.gov/niosh/pdfs/97-119-a.pdf|title=Registry of Toxic Effects of Chemical Substances (RTECS) / Comprehensive Guide to the RTECS|publisher=U.S. Department of Health and Human Services|url-status=dead|archive-url=https://web.archive.org/web/20130516165953/http://www.cdc.gov/niosh/pdfs/97-119-a.pdf|archive-date=2013-05-16 |id=DHHS (NIOSH) Publication No. 97-119}}
Lethal dosage often varies depending on the method of administration; for instance, many substances are less toxic when administered orally than when intravenously administered. For this reason, LD50 figures are often qualified with the mode of administration, e.g., "LD50 i.v."
The related quantities LD50/30 or LD50/60 are used to refer to a dose that without treatment will be lethal to 50% of the population within (respectively) 30 or 60 days. These measures are used more commonly within radiation health physics, for ionizing radiation, as survival beyond 60 days usually results in recovery.
A comparable measurement is LCt50, which relates to lethal dosage from exposure, where C is concentration and t is time. It is often expressed in terms of mg-min/m3. ICt50 is the dose that will cause incapacitation rather than death. These measures are commonly used to indicate the comparative efficacy of chemical warfare agents, and dosages are typically qualified by rates of breathing (e.g., resting = 10 L/min) for inhalation, or degree of clothing for skin penetration. The concept of Ct was first proposed by Fritz Haber and is sometimes referred to as Haber's law, which assumes that exposure to 1 minute of 100 mg/m3 is equivalent to 10 minutes of 10 mg/m3 (1 × 100 = 100, as does 10 × 10 = 100).
Some chemicals, such as hydrogen cyanide, are rapidly detoxified by the human body, and do not follow Haber's law. In these cases, the lethal concentration may be given simply as LC50 and qualified by a duration of exposure (e.g., 10 minutes). The material safety data sheets for toxic substances frequently use this form of the term even if the substance does follow Haber's law.
For disease-causing organisms, there is also a measure known as the median infective dose and dosage. The median infective dose (ID50) is the number of organisms received by a person or test animal qualified by the route of administration (e.g., 1,200 org/man per oral). Because of the difficulties in counting actual organisms in a dose, infective doses may be expressed in terms of biological assay, such as the number of LD50s to some test animal. In biological warfare infective dosage is the number of infective doses per cubic metre of air times the number of minutes of exposure (e.g., ICt50 is 100 medium doses - min/m3).
Limitation
As a measure of toxicity, LD50 is somewhat unreliable and results may vary greatly between testing facilities due to factors such as the genetic characteristics of the sample population, animal species tested, environmental factors and mode of administration.Ernest Hodgson (2004). A Textbook of Modern Toxicology. Wiley-Interscience (3rd ed.).{{page needed|date=January 2014}}
There can be wide variability between species as well; what is relatively safe for rats may very well be extremely toxic for humans (cf. paracetamol toxicity), and vice versa. For example, chocolate, comparatively harmless to humans, is known to be toxic to many animals. When used to test venom from venomous creatures, such as snakes, LD50 results may be misleading due to the physiological differences between mice, rats, and humans. Many venomous snakes are specialized predators on mice, and their venom may be adapted specifically to incapacitate mice; and mongooses may be exceptionally resistant. While most mammals have a very similar physiology, LD50 results may or may not have equal bearing upon every mammal species, such as humans, etc.
Examples
Note: Comparing substances (especially drugs) to each other by LD50 can be misleading in many cases due (in part) to differences in effective dose (ED50). Therefore, it is more useful to compare such substances by therapeutic index, which is simply the ratio of LD50 to ED50.{{Cite web |date=2011-01-26 |title=Therapeutic index {{!}} CME at Pharmacology Corner |url=https://pharmacologycorner.com/therapeutic-index/ |access-date=2024-07-15 |website=pharmacologycorner.com |language=en-US}}
The following examples are listed in reference to LD50 values, in descending order, and accompanied by LC50 values, {bracketed}, when appropriate.
| class="wikitable sortable" |
| wa
! Substance ! Animal, route ! class=unsortable| LD50 ! data-sort-type="number"| LD50 : g/kg ! class=unsortable| Reference |
| Water ({{chem2|H2O}})
| rat, oral | >{{ntsh|90000}}90,000 mg/kg | >90 |
| Sucrose (table sugar)
| rat, oral | {{ntsh|29700}}29,700 mg/kg | 29.7 |
| Corn syrup
| rat, oral | {{ntsh|25800}}25,800 mg/kg | 25.8 |
| Glucose (blood sugar)
| rat, oral | {{ntsh|25800}}25,800 mg/kg | 25.8 |
| Monosodium glutamate (MSG)
| rat, oral | {{ntsh|16600}}16,600 mg/kg | 16.6 |
| Stevioside (from stevia)
| mice and rats, oral | {{ntsh|15000}}15,000 mg/kg | 15 |
| Gasoline (petrol)
| rat | {{ntsh|14063}}14,063 mg/kg | 14.0 |
| Vitamin C (ascorbic acid)
| rat, oral | {{ntsh|11900}}11,900 mg/kg | 11.9 | {{cite web|url=http://physchem.ox.ac.uk/MSDS/AS/ascorbic_acid.html |archive-url=https://archive.today/20070209221915/http://physchem.ox.ac.uk/MSDS/AS/ascorbic_acid.html |url-status=dead |archive-date=2007-02-09 |title=Safety (MSDS) data for ascorbic acid |access-date=2007-02-21 |date=2005-10-09 |publisher=Oxford University }} |
| Glyphosate (isopropylamine salt)
| rat, oral | {{ntsh|10537}}10,537 mg/kg | 10.537 |
| Lactose (milk sugar)
| rat, oral | {{ntsh|10000}}10,000 mg/kg | 10 |
| Aspartame
| mice, oral | {{ntsh|10000}}10,000 mg/kg | 10 |
| Urea ({{chem2|OC(NH2)2}})
| rat, oral | {{ntsh|8471}}8,471 mg/kg | 8.471 |
| Cyanuric acid
| rat, oral | {{ntsh|7700}}7,700 mg/kg | 7.7 |
| Cadmium sulfide (CdS)
| rat, oral | {{ntsh|7080}}7,080 mg/kg | 7.08 |
| Ethanol ({{chem2|CH3CH2OH}})
| rat, oral | {{ntsh|7060}}7,060 mg/kg | 7.06 |
| Sodium isopropyl methylphosphonic acid (IMPA, metabolite of sarin)
| rat, oral | {{ntsh|6860}}6,860 mg/kg | 6.86 |
| Melamine
| rat, oral | {{ntsh|6000}}6,000 mg/kg | 6 |
| Taurine
| rat, oral | {{ntsh|5000}}5,000 mg/kg | 5 |
| Melamine cyanurate
| rat, oral | {{ntsh|4100}}4,100 mg/kg | 4.1 |
| Fructose (fruit sugar)
| rat, oral | 4,000 mg/kg | 4 |
| Sodium molybdate ({{chem2|Na2MoO4}})
| rat, oral | 4,000 mg/kg | 4 |
| Sodium chloride (table salt)
| rat, oral | 3,000 mg/kg | 3 |
| Paracetamol (acetaminophen)
| rat, oral | 2000 mg/kg | 2 |
| Aspirin (acetylsalicylic acid)
| rat, oral | 1,600 mg/kg | 1.6 |
| Delta-9-tetrahydrocannabinol (THC)
| rat, oral | 1,270 mg/kg | 1.27 |
| Cannabidiol (CBD)
| rat, oral | 980 mg/kg | 0.98 |
| Methanol ({{chem2|CH3OH}})
| human, oral | {{ntsh|5628}}810 mg/kg | 0.81 |
| Trinitrotoluene (TNT)
|rat, oral |790 mg/kg |0.790 | |
| Arsenic (As)
| rat, oral | 763 mg/kg | 0.763 |
| Ibuprofen
| rat, oral | 636 mg/kg | 0.636 |
| Formaldehyde ({{chem2|CH2O}})
| rat, oral | 600–800 mg/kg | 0.6 |
| Solanine (main alkaloid in the several plants in Solanaceae amongst them Solanum tuberosum)
| rat, oral (2.8 mg/kg human, oral) | {{ntsh|590}}590 mg/kg | 0.590 |
| Alkyl dimethyl benzalkonium chloride (ADBAC)
| rat, oral | 304.5 mg/kg | 0.3045 |title=Reregistration Eligibility Decision for Alkyl Dimethyl Benzyl Ammonium Chloride (ADBAC) |publisher=U.S. Environmental Protection Agency Office of Prevention, Pesticides, and Toxic Substances |editor=Frank T. Sanders |date=August 2006 |url=http://www.epa.gov/oppsrrd1/REDs/adbac_red.pdf |pages=114 |access-date=2009-03-31 |url-status=dead |archive-url=https://web.archive.org/web/20091024165642/http://www.epa.gov/oppsrrd1/REDs/adbac_red.pdf |archive-date=2009-10-24 }} |
| Coumarin (benzopyrone, from Cinnamomum aromaticum and other plants)
| rat, oral | 293 mg/kg | 0.293 |
| Psilocybin (from psilocybin mushrooms)
| mouse, oral | 280 mg/kg | 0.280 |
| Hydrochloric acid (HCl)
| rat, oral | 238–277 mg/kg | 0.238 |
| Ketamine
| rat, intraperitoneal | 229 mg/kg | 0.229 |
| Caffeine
| rat, oral | 192 mg/kg | 0.192 |
| Arsenic trisulfide ({{chem2|As2S3}})
| rat, oral | 185–6,400 mg/kg | 0.185–6.4 |
| Sodium nitrite ({{chem2|NaNO2}})
| rat, oral | 180 mg/kg | 0.18 |
| Methylenedioxymethamphetamine (MDMA)
| rat, oral | 160 mg/kg | 0.18 |
| Uranyl acetate dihydrate ({{chem2|UO2(CH3COO)2}})
| mouse, oral | 136 mg/kg | 0.136 |
| Dichlorodiphenyltrichloroethane (DDT)
| mouse, oral | 135 mg/kg | 0.135 |
| Uranium (U)
| mice, oral | {{ntsh|114}}114 mg/kg (estimated) | 0.114 |
| Bisoprolol
| mouse, oral | 100 mg/kg | 0.1 |
| Cocaine
| mouse, oral | 96 mg/kg | 0.096 |
| Cobalt(II) chloride ({{chem2|CoCl2}})
| rat, oral | 80 mg/kg | 0.08 |
| Cadmium oxide (CdO)
| rat, oral | 72 mg/kg | 0.072 |
| Thiopental sodium (used in lethal injection)
| rat, oral | 64 mg/kg | 0.064 |
| Demeton-S-methyl
| rat, oral | 60 mg/kg | 0.060 |
| Methamphetamine
| rat, intraperitoneal | 57 mg/kg | 0.057 |
| Sodium fluoride (NaF)
| rat, oral | 52 mg/kg | 0.052 |
| Nicotine
| mouse and rat, oral human, smoking | 50 mg/kg | 0.05 |
| Pentaborane
| human, oral | 50 mg/kg | 0.05 |
| Capsaicin
| mouse, oral | 47.2 mg/kg | 0.0472 |
| Vitamin D3 (cholecalciferol)
| rat, oral | 37 mg/kg | 0.037 |
| Piperidine (from black pepper)
| rat, oral | 30 mg/kg | 0.030 |
| Heroin (diamorphine)
| mouse, intravenous | 21.8 mg/kg | 0.0218 |
| Lysergic acid diethylamide (LSD)
| rat, intravenous | 16.5 mg/kg | 0.0165 |
| Arsenic trioxide ({{chem2|As2O3}})
| rat, oral | 14 mg/kg | 0.014 |
| Metallic arsenic (As)
| rat, intraperitoneal | 13 mg/kg | 0.013 |
| Sodium cyanide (NaCN)
| rat, oral | 6.4 mg/kg | 0.0064 |
| Chlorotoxin (CTX, from scorpions)
| mice | 4.3 mg/kg | 0.0043 |
| Hydrogen cyanide (HCN)
| mouse, oral | 3.7 mg/kg | 0.0037 |
| Carfentanil
| rat, intravenous | 3.39 mg/kg | 0.00339 |
| Nicotine (from various Solanaceae genera)
| mice, oral | 3.3 mg/kg | 0.0033 |
| White phosphorus (P)
| rat, oral | 3.03 mg/kg | 0.00303 |
| Strychnine (from Strychnos nux-vomica)
| human, oral | 1–2 mg/kg (estimated) | 0.001–0.002 |
| Aconitine (from Aconitum napellus and related species)
| human, oral | {{ntsh|.080}}1–2 mg/kg | 0.001–0.002 |
| Mercury(II) chloride ({{chem2|HgCl2}})
| rat, oral | 1 mg/kg | 0.001 |
| Cantharidin (from blister beetles)
| human, oral | 500 μg/kg | 0.0005 |
| Aflatoxin B1 (from Aspergillus flavus mold)
| rat, oral | 480 μg/kg | 0.00048 |
| Plutonium (Pu)
| dog, intravenous | 320 μg/kg | 0.00032 | {{cite journal|url=https://fas.org/sgp/othergov/doe/lanl/pubs/00818013.pdf|journal=Los Alamos Science|title=Plutonium and Health — How great is the risk?|vauthors=Voelz GL, Buican IG|issue=26|pages=74–89|date=2000|access-date=2016-12-26|archive-date=2021-01-18|archive-url=https://web.archive.org/web/20210118020351/https://fas.org/sgp/othergov/doe/lanl/pubs/00818013.pdf|url-status=live}} |
| Bufotoxin (from Bufo toads)
| cat, intravenous | {{ntsh|.300}}300 μg/kg | 0.0003 |
| Brodifacoum
| rat, oral | 270 μg/kg | 0.00027 |
| Caesium-137 ({{chem|137|Cs}})
| mouse, parenteral | {{ntsh|.215}}21.5 μCi/g | 0.000245 |
| Sodium fluoroacetate ({{chem2|CH2FCOONa}})
|rat, oral |220 μg/kg |0.00022 |
| Chlorine trifluoride (ClF3)
|mouse, absorption through skin |178 μg/kg |0.000178 |
| Sarin
| mouse, subcutaneous injection | {{ntsh|.172}}172 μg/kg | 0.000172 |
| Robustoxin (from Sydney funnel-web spider)
| mice | {{ntsh|.150}}150 μg/kg | 0.000150 |
| VX
| human, oral, inhalation, absorption through skin/eyes | {{ntsh|.14}}140 μg/kg (estimated) | 0.00014 |
| Venom of the Brazilian wandering spider
| rat, subcutaneous | {{ntsh|.134}}134 μg/kg | 0.000134 | Venomous Animals and their Venoms, vol. III, ed. Wolfgang Bücherl and Eleanor Buckley |
| Amatoxin (from Amanita phalloides mushrooms)
| human, oral | 100 μg/kg | 0.0001 | {{cite journal | vauthors = Hallen HE, Luo H, Scott-Craig JS, Walton JD | title = Gene family encoding the major toxins of lethal Amanita mushrooms | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 104 | issue = 48 | pages = 19097–19101 | date = November 2007 | pmid = 18025465 | pmc = 2141914 | doi = 10.1073/pnas.0707340104 | doi-access = free }}{{cite book | vauthors = Madore F, Bouchard J | chapter = Plasmapheresis in Acute Intoxication and Poisoning |date=2019 | title = Critical Care Nephrology |pages=595–600.e3 |publisher=Elsevier |language=en |doi=10.1016/b978-0-323-44942-7.00100-x |isbn=978-0-323-44942-7 }} |
| Dimethylmercury ({{chem2|Hg(CH3)2}})
|human, transdermal |{{ntsh|.080}}50 μg/kg |0.000050 |
| TBPO (t-Butyl-bicyclophosphate)
|mouse, intravenous |36 μg/kg |0.000036 |
| Fentanyl
| monkey | 30 μg/kg | 0.00003 |
| Venom of the inland taipan
| rat, subcutaneous | {{ntsh|.025}}25 μg/kg | 0.000025 |
| Ricin (from castor oil plant)
| rat, intraperitoneal | {{ntsh|.022}}22 μg/kg | 0.000022 |
| 2,3,7,8-Tetrachlorodibenzodioxin (TCDD, in Agent Orange)
| rat, oral | {{ntsh|.02}}20 μg/kg | 0.00002 | |
| Tetrodotoxin from the blue-ringed octopus
| intravenous | {{ntsh|.0082}}8.2 μg/kg | 0.0000082 |
| CrTX-A (from Carybdea rastonii box jellyfish venom)
| crayfish, intraperitoneal | {{ntsh|.005}}5 μg/kg | 0.000005 |
| Latrotoxin (from widow spider venom)
| mice | {{ntsh|.0043}}4.3 μg/kg | 0.0000043 |
| Epibatidine (from Epipedobates anthonyi poison dart frog)
|mouse, intravenous |1.46-13.98 μg/kg |0.00000146 |
| Batrachotoxin (from poison dart frog)
| human, sub-cutaneous injection | {{ntsh|.002}}2–7 μg/kg (estimated) | 0.000002 |
| Abrin (from rosary pea)
|mice, intravenously |0.7 μg/kg |0.0000007 |{{Citation needed|date=June 2024}} |
| Saxitoxin (from certain marine dinoflagellates)
|human, intravenously |0.6 μg/kg |0.0000006 |
| Pacific ciguatoxin-1 (from ciguateric fish)
| mice, intraperitoneal | 250 ng{{ntsh|.00025}}/kg | 0.00000025 |
| Palytoxin (from Palythoa coral)
|mouse, intravenous |45 ng/kg |0.000000045 |
| Maitotoxin (from ciguateric fish)
| mouse, intraperitoneal | 50 ng{{ntsh|.00005}}/kg | 0.00000005 |{{cite web | url=https://pubchem.ncbi.nlm.nih.gov/compound/maitotoxin | publisher=National Center for Biotechnology Information | title=PubChem Compound Summary for CID 71460273, Maitotoxin | work=PubChem | access-date=2020-12-25 | archive-date=2020-11-01 | archive-url=https://web.archive.org/web/20201101135722/https://pubchem.ncbi.nlm.nih.gov/compound/Maitotoxin | url-status=live }} |
| Polonium-210 ({{chem|210|Po}})
| human, inhalation | {{ntsh|.00001}}10 ng/kg (estimated) | 0.00000001 |
| Diphtheria toxin (from Corynebacterium)
| mice | {{ntsh|.00001}}10 ng/kg | 0.00000001 |
| Shiga toxin (from Shigella bacteria)
| mice | {{ntsh|.000002}}2 ng/kg | 0.000000002 |
| Tetanospasmin (from Clostridium tetani)
| mice | {{ntsh|.000002}}2 ng/kg | 0.000000002 |
| Botulinum toxin (from Clostridium botulinum)
| human, oral, injection, inhalation | {{ntsh|.000001}}1 ng/kg (estimated) | 0.000000001 |
| Ionizing radiation
| human, irradiation | 3–5 Gy (Gray) | — |{{cite journal | vauthors = Ryan JL | title = Ionizing radiation: the good, the bad, and the ugly | journal = The Journal of Investigative Dermatology | volume = 132 | issue = 3 Pt 2 | pages = 985–993 | date = March 2012 | pmid = 22217743 | pmc = 3779131 | doi = 10.1038/jid.2011.411 }}{{cite web |date=2013 |title=Lethal dose |url=https://www.euronuclear.org/info/encyclopedia/l/lethal-dose.htm |url-status=dead |archive-url=https://web.archive.org/web/20180804014252/https://www.euronuclear.org/info/encyclopedia/l/lethal-dose.htm |archive-date=2018-08-04 |access-date=2018-09-15 |website=www.euronuclear.org |vauthors=Winfried K}}{{Cite web |date=2022-12-13 |title=Radiation Exposure - Dose and Dose Rate (the Gray & Sievert) |url=https://ionactive.co.uk/resource-hub/guidance/radiation-exposure-dose-and-dose-rate-the-gray-sievert |access-date=2024-07-27 |website=Ionactive}} |
Poison scale
File:Poison-Scale-long.jpg of the median lethal dose LD50 ({{math|−log10(LD50)}}) on a linearized toxicity scale encompassing 11 orders of magnitude. Water occupies the lowest toxicity position (1) while the toxicity scale is dominated by the botulinum toxin (12).{{cite journal | vauthors= Strey, Karsten | title = Die Gifte-Skala | journal = Chemie in unserer Zeit | volume=53 | issue = 6 | pages = 386–399 | date = December 2019 | doi = 10.1002/ciuz.201900828 | s2cid = 199067092 }}]]
The LD50 values have a very wide range. The botulinum toxin as the most toxic substance known has an LD50 value of 1 ng/kg, while the most non-toxic substance water has an LD50 value of more than 90 g/kg; a difference of about 1 in 100 billion, or 11 orders of magnitude. As with all measured values that differ by many orders of magnitude, a logarithmic view is advisable. Well-known examples are the indication of the earthquake strength using the Richter scale, the pH value, as a measure for the acidic or basic character of an aqueous solution or of loudness in decibels.
In this case, the negative decimal logarithm of the LD50 values, which is standardized in kg per kg body weight, is considered {{math|−log10(LD50)}}.
The dimensionless value found can be entered in a toxin scale. Water as the baseline substance is nearly 1 in the negative logarithmic toxin scale.
Procedures
A number of procedures have been defined to derive the LD50. The earliest was the 1927 "conventional" procedure by Trevan, which requires 40 or more animals. The fixed-dose procedure, proposed in 1984, estimates a level of toxicity by feeding at defined doses and looking for signs of toxicity (without requiring death).{{cite journal | vauthors = van den Heuvel MJ, Clark DG, Fielder RJ, Koundakjian PP, Oliver GJ, Pelling D, Tomlinson NJ, Walker AP | title = The international validation of a fixed-dose procedure as an alternative to the classical LD50 test | journal = Food and Chemical Toxicology | volume = 28 | issue = 7 | pages = 469–482 | date = July 1990 | pmid = 2210519 | doi = 10.1016/0278-6915(90)90117-6 }} The up-and-down procedure, proposed in 1985, yields an LD50 value while dosing only one animal at a time.{{cite journal | vauthors = Lipnick RL, Cotruvo JA, Hill RN, Bruce RD, Stitzel KA, Walker AP, Chu I, Goddard M, Segal L, Springer JA | title = Comparison of the up-and-down, conventional LD50, and fixed-dose acute toxicity procedures | journal = Food and Chemical Toxicology | volume = 33 | issue = 3 | pages = 223–231 | date = March 1995 | pmid = 7896233 | doi = 10.1016/0278-6915(94)00136-c }}{{cite journal | vauthors = Lichtman AH | title = The up-and-down method substantially reduces the number of animals required to determine antinociceptive ED50 values | journal = Journal of Pharmacological and Toxicological Methods | volume = 40 | issue = 2 | pages = 81–85 | date = August 1998 | pmid = 10100496 | doi = 10.1016/s1056-8719(98)00041-0 }}
See also
- Animal testing
- Reed-Muench method
- The dose makes the poison – the toxicology adage that high quantities of any substance is lethal
= Other measures of toxicity =
{{div col}}
- IDLH
- Certain safety factor
- Therapeutic index
- Protective index
- Median toxic dose (TD50)
- Lowest published lethal dose (LDLo)
- EC50 (half maximal effective concentration)
- IC50 (half maximal inhibitory concentration)
- Draize test
- Indicative limit value
- No-observed-adverse-effect level (NOAEL)
- Lowest-observed-adverse-effect level (LOAEL)
{{div col end}}
= Related measures =
- TCID50 Tissue Culture Infective Dosage
- Plaque forming units (pfu)
References
{{reflist|30em}}
Further reading
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- {{cite journal | vauthors = Lipnick RL, Cotruvo JA, Hill RN, Bruce RD, Stitzel KA, Walker AP, Chu I, Goddard M, Segal L, Springer JA | title = Comparison of the up-and-down, conventional LD50, and fixed-dose acute toxicity procedures | journal = Food and Chemical Toxicology | volume = 33 | issue = 3 | pages = 223–231 | date = March 1995 | pmid = 7896233 | doi = 10.1016/0278-6915(94)00136-C }}
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External links
- [http://www.ccohs.ca/oshanswers/chemicals/ld50.html Canadian Centre for Occupational Health and Safety] {{Webarchive|url=https://web.archive.org/web/20150626013647/http://www.ccohs.ca/oshanswers/chemicals/ld50.html |date=2015-06-26 }}
{{Pharmacology}}
{{Toxicology}}
{{DEFAULTSORT:Median Lethal Dose}}
Category:Concentration indicators