median lethal dose median lethal dose 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 toxin, radiation, or pathogen. 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 increased toxicity. the test was created by j.w. trevan in 1927. 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. 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), 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. 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, 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. so, 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. 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. the following examples are listed in reference to ld50 values, in descending order, and accompanied by lc50 values, , when appropriate. substance animal, route ld50 ld50 : g/kg standardised reference water (h2o) rat, oral >90,000 mg/kg >90 sucrose (table sugar) rat, oral 29,700 mg/kg 29.7 corn syrup rat, oral 25,800 mg/kg 25.8 glucose (blood sugar) rat, oral 25,800 mg/kg 25.8 monosodium glutamate (msg) rat, oral 16,600 mg/kg 16.6 stevioside (from stevia) mice and rats, oral 15,000 mg/kg 15 gasoline (petrol) rat 14,063 mg/kg 14.0 vitamin c (ascorbic acid) rat, oral 11,900 mg/kg 11.9 glyphosate (isopropylamine salt of) rat, oral 10,537 mg/kg 10.537 lactose (milk sugar) rat, oral 10,000 mg/kg 10 aspartame mice, oral 10,000 mg/kg 10 urea (oc(nh2)2) rat, oral 8,471 mg/kg 8.471 cyanuric acid rat, oral 7,700 mg/kg 7.7 cadmium sulfide (cds) rat, oral 7,080 mg/kg 7.08 ethanol (ch3ch2oh) rat, oral 7,060 mg/kg 7.06 sodium isopropyl methylphosphonic acid (impa, metabolite of sarin) rat, oral 6,860 mg/kg 6.86 melamine rat, oral 6,000 mg/kg 6 taurine rat, oral 5,000 mg/kg 5 melamine cyanurate rat, oral 4,100 mg/kg 4.1 fructose (fruit sugar) rat, oral 4,000 mg/kg 4 sodium molybdate (na2moo4) rat, oral 4,000 mg/kg 4 sodium chloride (table salt) rat, oral 3,000 mg/kg 3 paracetamol (acetaminophen) rat, oral 1,944 mg/kg 1.944 delta-9-tetrahydrocannabinol (thc) rat, oral 1,270 mg/kg 1.27 cannabidiol (cbd) rat, oral 980 mg/kg 0.98 methanol (ch3oh) human, oral 810 mg/kg 0.81 arsenic (as) rat, oral 763 mg/kg 0.763 ibuprofen rat, oral 636 mg/kg 0.636 formaldehyde (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) 590 mg/kg 0.590 alkyl dimethyl benzalkonium chloride (adbac) rat, oral fish, immersion aquatic invertebrates, immersion 304.5 mg/kg 0.3045 coumarin (benzopyrone, from cinnamomum aromaticum and other plants) rat, oral 293 mg/kg 0.293 psilocybin (from magic 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 aspirin (acetylsalicylic acid) rat, oral 200 mg/kg 0.2 caffeine rat, oral 192 mg/kg 0.192 arsenic trisulfide (ass3) rat, oral 185–6,400 mg/kg 0.185–6.4 sodium nitrite (nano2) rat, oral 180 mg/kg 0.18 methylenedioxymethamphetamine (mdma, ecstasy) rat, oral 160 mg/kg 0.18 uranyl acetate dihydrate (uo2(ch3coo)2) mouse, oral 136 mg/kg 0.136 dichlorodiphenyltrichloroethane (ddt) mouse, oral 135 mg/kg 0.135 uranium (u) mice, oral 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 (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 (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 mercury(ii) chloride (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 amatoxin (from amanita phalloides mushrooms) rat 300-700 μg/kg 0.0007 bufotoxin (from bufo toads) cat, intravenous 300 μg/kg 0.0003 caesium-137 (137cs) mouse, parenteral 21.5 μci/g 0.000245 sodium fluoroacetate (ch2fcoona) rat, oral 220 μg/kg 0.00022 chlorine trifluoride (clf3) mouse, absorption through skin 178 μg/kg 0.000178 sarin mouse, subcutaneous injection 172 μg/kg 0.000172 robustoxin (from sydney funnel-web spider) mice 150 μg/kg 0.000150 vx human, oral, inhalation, absorption through skin/eyes 140 μg/kg (estimated) 0.00014 venom of the brazilian wandering spider rat, subcutaneous 134 μg/kg 0.000134 aconitine (from aconitum napellus and related species) rat, intraveneous 80 μg/kg 0.000080 dimethylmercury (hg(ch3)2) human, transdermal 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 (australian snake) rat, subcutaneous 25 μg/kg 0.000025 ricin (from castor oil plant) rat, intraperitoneal rat, oral 22 μg/kg 20–30 mg/kg 0.000022 0.02 2,3,7,8-tetrachlorodibenzodioxin (tcdd, in agent orange) rat, oral 20 μg/kg 0.00002 tetrodotoxin from the blue-ringed octopus intravenous 8.2 μg/kg 0.0000082 crtx-a (from carybdea rastonii box jellyfish venom) crayfish, intraperitoneal 5 μg/kg 0.000005 latrotoxin (from widow spider venom) mice 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 2–7 μg/kg (estimated) 0.000002 abrin (from rosary pea) mice, intravenously human, inhalation human, oral 0.7 μg/kg 3.3 μg/kg 10–1000 μg/kg 0.0000007 0.0000033 0.00001–0.001 saxitoxin (from certain marine dinoflagellates) human, intravenously human, oral 0.6 μg/kg 5.7 μg/kg 0.0000006 0.0000057 pacific ciguatoxin-1 (from ciguateric fish) mice, intraperitoneal 250 ng/kg 0.00000025 palytoxin (from palythoa coral) mouse, intravenous 45 ng/kg 2.3–31.5 μg/kg 0.000000045 0.0000023 maitotoxin (from ciguateric fish) mouse, intraperitoneal 50 ng/kg 0.00000005 polonium-210 (210po) human, inhalation 10 ng/kg (estimated) 0.00000001 diphtheria toxin (from corynebacterium) mice 10 ng/kg 0.00000001 shiga toxin (from shigella bacteria) mice 2 ng/kg 0.000000002 tetanospasmin (from clostridium tetani) mice 2 ng/kg 0.000000002 botulinum toxin (from clostridium botulinum) human, oral, injection, inhalation 1 ng/kg (estimated) 0.000000001 ionizing radiation human, irradiation 5 gy (gray) — poison scale negative values of the decimal logarithm of the median lethal dose ld50 (−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). 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. that's 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