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How Do You Know How Much Medicine Will Kill 50 Percent of People

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Measure out of the lethal dose of a toxin, radiation, or pathogen required to kill one-half of a tested population

In toxicology, the median lethal dose, LD50 (abbreviation for "lethal dose, l%"), LC50 (lethal concentration, 50%) or LCt50 is a mensurate of the lethal dose of a toxin, radiation, or pathogen.[1] The value of LD50 for a substance is the dose required to kill one-half the members of a tested population later on a specified test duration. LD50 figures are oft used equally a general indicator of a substance's astute toxicity. A lower LD50 is indicative of increased toxicity.

The test was created by J.W. Trevan in 1927.[2] The term semilethal dose is occasionally used in the aforementioned sense, in particular with translations of foreign language text, but tin can also refer to a sublethal dose. LD50 is usually adamant by tests on animals such as laboratory mice. In 2011, the U.S. Food and Drug Assistants approved alternative methods to LD50 for testing the cosmetic drug Botox without beast tests.[iii] [4]

Conventions [edit]

The LD50 is usually expressed as the mass of substance administered per unit mass of test subject area, typically as milligrams of substance per kilogram of body mass, sometimes also stated every bit nanograms (suitable for botulinum), micrograms, or grams (suitable for paracetamol) per kilogram. Stating information technology this style 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 ever scale simply with body mass). For substances in the environment, such every bit 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 LCfifty. Simply in this case, the exposure time is important (run into below).

The choice of l% lethality as a benchmark avoids the potential for ambiguity of making measurements in the extremes and reduces the amount of testing required. However, this as well 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 LDfifty. Measures such as "LDane" and "LD99" (dosage required to kill 1% or 99%, respectively, of the exam population) are occasionally used for specific purposes.[five]

Lethal dosage oft varies depending on the method of assistants; 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.k., "LD50 i.five."

The related quantities LD50/30 or LDl/sixty are used to refer to a dose that without handling will be lethal to 50% of the population within (respectively) 30 or sixty days. These measures are used more normally within radiation health physics, every bit 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 fourth dimension. It is frequently expressed in terms of mg-min/kthree. ICt fifty 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 past rates of breathing (east.chiliad., resting = 10 50/min) for inhalation, or caste of clothing for skin penetration. The concept of Ct was first proposed by Fritz Haber and is sometimes referred to equally Haber'southward police force, which assumes that exposure to 1 infinitesimal of 100 mg/yardthree is equivalent to 10 minutes of x mg/m3 (1 × 100 = 100, as does 10 × 10 = 100).

Some chemicals, such equally hydrogen cyanide, are rapidly detoxified past the human torso, and do non follow Haber's police. And then, in these cases, the lethal concentration may exist given but as LC50 and qualified past a duration of exposure (e.g., 10 minutes). The Material Rubber Data Sheets for toxic substances often use this class of the term fifty-fifty if the substance does follow Haber'south law.

For disease-causing organisms, at that place is besides a measure out 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 past the route of assistants (e.thousand., 1,200 org/man per oral). Considering 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 LDfifty'south 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.thou., ICtfifty is 100 medium doses - min/mthree).

Limitation [edit]

As a measure of toxicity, LD50 is somewhat unreliable and results may vary greatly betwixt testing facilities due to factors such as the genetic characteristics of the sample population, animal species tested, environmental factors and mode of administration.[6]

There can be wide variability betwixt species as well; what is relatively safe for rats may very well exist extremely toxic for humans (cf. paracetamol toxicity), and vice versa. For example, chocolate, insufficiently harmless to humans, is known to be toxic to many animals. When used to examination venom from venomous creatures, such as snakes, LD50 results may exist misleading due to the physiological differences between mice, rats, and humans. Many venomous snakes are specialized predators on mice, and their venom may exist adapted specifically to incapacitate mice; and mongooses may exist exceptionally resistant. While almost mammals take a very similar physiology, LDfifty results may or may not have equal bearing upon every mammal species, such every bit humans, etc.

Examples [edit]

Note: Comparing substances (especially drugs) to each other by LD50 can be misleading in many cases due (in function) to differences in effective dose (EDfifty). Therefore, it is more useful to compare such substances by therapeutic index, which is simply the ratio of LDl to ED50.[ citation needed ]

The following examples are listed in reference to LD50 values, in descending lodge, and accompanied by LC50 values, {bracketed}, when appropriate.

Substance Brute, route LD50
{LCfifty}
LDl : g/kg
{LC50 : k/50}
standardised 		Reference
Water (H2O) rat, oral 90,000 mg/kg 90 [seven]
Sucrose (table sugar) rat, oral 29,700 mg/kg 29.vii [8]
Glucose (blood sugar) rat, oral 25,800 mg/kg 25.8 [9]
Monosodium glutamate (MSG) rat, oral 16,600 mg/kg sixteen.six [10]
Stevioside (from stevia) mice and rats, oral 15,000 mg/kg xv [xi]
Gasoline (petrol) rat 14,063 mg/kg 14.0 [12]
Vitamin C (ascorbic acrid) rat, oral xi,900 mg/kg 11.nine [13]
Glyphosate (isopropylamine salt of) rat, oral 10,537 mg/kg 10.537 [xiv]
Lactose (milk carbohydrate) rat, oral 10,000 mg/kg 10 [15]
Aspartame mice, oral 10,000 mg/kg 10 [16]
Urea (OC(NH2)two ) rat, oral 8,471 mg/kg 8.471 [17]
Cyanuric acid rat, oral 7,700 mg/kg seven.7 [18]
Cadmium sulfide (CdS) rat, oral 7,080 mg/kg vii.08 [19]
Ethanol (CHthreeCH2OH) rat, oral 7,060 mg/kg 7.06 [20]
Sodium isopropyl methylphosphonic acid (IMPA, metabolite of sarin) rat, oral 6,860 mg/kg half dozen.86 [21]
Melamine rat, oral 6,000 mg/kg 6 [18]
Taurine rat, oral 5,000 mg/kg 5 [22]
Melamine cyanurate rat, oral 4,100 mg/kg 4.1 [eighteen]
Fructose (fruit saccharide) rat, oral four,000 mg/kg 4 [23]
Sodium molybdate (Na2MoOiv ) rat, oral 4,000 mg/kg 4 [24]
Sodium chloride (common salt) rat, oral three,000 mg/kg 3 [25]
Paracetamol (acetaminophen) rat, oral ane,944 mg/kg 1.944 [26]
Delta-9-tetrahydrocannabinol (THC) rat, oral 1,270 mg/kg 1.27 [27]
Cannabidiol (CBD) rat, oral 980 mg/kg 0.98 [28]
Methanol (CHiiiOH) human, oral 810 mg/kg 0.81 [29]
Arsenic (Equally) rat, oral 763 mg/kg 0.763 [30]
Ibuprofen rat, oral 636 mg/kg 0.636 [31]
Formaldehyde (CH2O) rat, oral 600–800 mg/kg 0.half dozen [32]
Solanine (main alkaloid in the several plants in Solanaceae among them Solanum tuberosum) rat, oral (ii.8 mg/kg human being, oral) 590 mg/kg 0.590 [33]
Alkyl dimethyl benzalkonium chloride (ADBAC) rat, oral
fish, immersion
aquatic invertebrates, immersion 		304.five mg/kg
{0.28 mg/50}
{0.059 mg/Fifty} 		0.3045
{0.00028}
{0.000059} 		[34]
Coumarin (benzopyrone, from Cinnamomum aromaticum and other plants) rat, oral 293 mg/kg 0.293 [35]
Psilocybin (from magic mushrooms) mouse, oral 280 mg/kg 0.280 [36]
Muriatic acid (HCl) rat, oral 238–277 mg/kg 0.238 [37]
Ketamine rat, intraperitoneal 229 mg/kg 0.229 [38]
Aspirin (acetylsalicylic acid) rat, oral 200 mg/kg 0.ii [39]
Caffeine rat, oral 192 mg/kg 0.192 [twoscore]
Arsenic trisulfide (Assthree ) rat, oral 185–vi,400 mg/kg 0.185–6.iv [41]
Sodium nitrite (NaNO2 ) rat, oral 180 mg/kg 0.eighteen [42]
Methylenedioxymethamphetamine (MDMA, ecstasy) rat, oral 160 mg/kg 0.eighteen [43]
Uranyl acetate dihydrate (UOii(CH3COO)2 ) mouse, oral 136 mg/kg 0.136 [44]
Dichlorodiphenyltrichloroethane (DDT) mouse, oral 135 mg/kg 0.135 [45]
Uranium (U) mice, oral 114 mg/kg (estimated) 0.114 [44]
Bisoprolol mouse, oral 100 mg/kg 0.ane [46]
Cocaine mouse, oral 96 mg/kg 0.096 [47]
Cobalt(II) chloride (CoCl2 ) rat, oral eighty mg/kg 0.08 [48]
Cadmium oxide (CdO) rat, oral 72 mg/kg 0.072 [49]
Thiopental sodium (used in lethal injection) rat, oral 64 mg/kg 0.064 [50]
Demeton-S-methyl rat, oral 60 mg/kg 0.060 [51]
Methamphetamine rat, intraperitoneal 57 mg/kg 0.057 [52]
Sodium fluoride (NaF) rat, oral 52 mg/kg 0.052 [53]
Nicotine mouse and rat, oral

human, smoking

50 mg/kg 0.05 [54]
Pentaborane human, oral l mg/kg 0.05 [55]
Capsaicin mouse, oral 47.2 mg/kg 0.0472 [56]
Vitamin D3 (cholecalciferol) rat, oral 37 mg/kg 0.037 [57]
Piperidine (from black pepper) rat, oral 30 mg/kg 0.030 [58]
Heroin (diamorphine) mouse, intravenous 21.8 mg/kg 0.0218 [59]
Lysergic acid diethylamide (LSD) rat, intravenous 16.5 mg/kg 0.0165 [lx]
Arsenic trioxide (As2O3 ) rat, oral xiv mg/kg 0.014 [61]
Metallic arsenic (Every bit) rat, intraperitoneal 13 mg/kg 0.013 [62]
Sodium cyanide (NaCN) rat, oral 6.4 mg/kg 0.0064 [63]
Chlorotoxin (CTX, from scorpions) mice 4.3 mg/kg 0.0043 [64]
Hydrogen cyanide (HCN) mouse, oral 3.seven mg/kg 0.0037 [65]
Carfentanil rat, intravenous three.39 mg/kg 0.00339 [66]
Nicotine (from various Solanaceae genera) mice, oral 3.iii mg/kg 0.0033 [54]
White phosphorus (P) rat, oral 3.03 mg/kg 0.00303 [67]
Strychnine (from Strychnos nux-vomica) human, oral 1–2 mg/kg (estimated) 0.001–0.002 [68]
Mercury(2) chloride (HgCl2 ) rat, oral ane mg/kg 0.001 [69]
Nicotine homo, oral 0.8 mg/kg (estimated) 0.0008 [54]
Cantharidin (from blister beetles) human, oral 500 μg/kg 0.0005 [70]
Aflatoxin B1 (from Aspergillus flavus mold) rat, oral 480 μg/kg 0.00048 [71]
Plutonium (Pu) dog, intravenous 320 μg/kg 0.00032 [72]
Amatoxin (from Amanita phalloides mushrooms) rat 300-700 μg/kg 0.0007 [73]
Bufotoxin (from Bufo toads) cat, intravenous 300 μg/kg 0.0003 [74]
Caesium-137 ( 137
Cs) 		mouse, parenteral 21.5 μCi/grand 0.000245 [75]
Sodium fluoroacetate (CH2FCOONa) rat, oral 220 μg/kg 0.00022 [76]
Sarin mouse, subcutaneous injection 172 μg/kg 0.000172 [77]
Robustoxin (from Sydney funnel-web spider) mice 150 μg/kg 0.000150 [78]
VX man, oral, inhalation, absorption through pare/eyes 140 μg/kg (estimated) 0.00014 [79]
Venom of the Brazilian wandering spider rat, subcutaneous 134 μg/kg 0.000134 [80]
Aconitine (from Aconitum napellus and related species) rat, intraveneous eighty μg/kg 0.000080 [81]
Dimethylmercury (Hg(CH3)ii ) human, transdermal l μg/kg 0.000050 [82]
TBPO (t-Butyl-bicyclophosphate) mouse, intravenous 36 μg/kg 0.000036 [83]
Fentanyl monkey 30 μg/kg 0.00003 [84]
Venom of the Inland Taipan (Australian snake) rat, subcutaneous 25 μg/kg 0.000025 [85]
Ricin (from castor oil plant) rat, intraperitoneal
rat, oral 		22 μg/kg
xx–30 mg/kg 		0.000022
0.02 		[86]
2,3,7,8-Tetrachlorodibenzodioxin (TCDD, in Agent Orange) rat, oral 20 μg/kg 0.00002
Tetrodotoxin from the blue-ringed octopus intravenous 8.ii μg/kg 0.0000082 [87]
CrTX-A (from Carybdea rastonii box jellyfish venom) crayfish, intraperitoneal 5 μg/kg 0.000005 [88]
Latrotoxin (from widow spider venom) mice 4.iii μg/kg 0.0000043 [89] [ cocky-published source? ]
Epibatidine (from Epipedobates anthonyi poison sprint frog) mouse, intravenous 1.46-thirteen.98 μg/kg 0.00000146 [90]
Batrachotoxin (from poisonous substance dart frog) homo, sub-cutaneous injection 2–7 μg/kg (estimated) 0.000002 [91]
Abrin (from rosary pea) mice, intravenously

human, inhalation

human, oral

0.vii μg/kg

three.3 μg/kg

10–1000 μg/kg

0.0000007

0.0000033

0.00001–0.001

Saxitoxin (from certain marine dinoflagellates) human, intravenously

human being, oral

0.vi μg/kg

5.7 μg/kg

0.0000006

0.0000057

[91]
Pacific Ciguatoxin-1 (from ciguateric fish) mice, intraperitoneal 250 ng/kg 0.00000025 [92]
Palytoxin (from Palythoa coral) mouse, intravenous 45 ng/kg

2.3–31.5 μg/kg

0.000000045

0.0000023

[93]
Maitotoxin (from ciguateric fish) mouse, intraperitoneal fifty ng/kg 0.00000005 [94]
Polonium-210 ( 210
Po) 		human, inhalation 10 ng/kg (estimated) 0.00000001 [95]
Diphtheria toxin (from Corynebacterium) mice 10 ng/kg 0.00000001 [96]
Shiga toxin (from Shigella leaner) mice two ng/kg 0.000000002 [96]
Tetanospasmin (from Clostridium tetani) mice 2 ng/kg 0.000000002 [96]
Botulinum toxin (from Clostridium botulinum) human, oral, injection, inhalation i ng/kg (estimated) 0.000000001 [97]
Ionizing radiation human, irradiation v Gy (Grey) — [98]

Poison scale [edit]

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 (i) while the toxicity scale is dominated by the botulinum toxin (12).[99]

The LD50 values have a very wide range. The botulinum toxin as the most toxic substance known has an LDfifty value of 1 ng/kg, while the virtually non-toxic substance water has an LD50 value of more than 90 one thousand/kg. That's a divergence of about one in 100 billion or 11 orders of magnitude. As with all measured values that differ past 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, every bit a measure for the acidic or basic graphic symbol of an aqueous solution or of loudness in decibels . In this case, the negative decimal logarithm of the LDl values, which is standardized in kg per kg body weight, is considered −logx(LD50).

The dimensionless value found can be entered in a toxin calibration. Water as the baseline substance is neatly one in the negative logarithmic toxin scale.

Animate being rights concerns [edit]

Creature-rights and brute-welfare groups, such every bit Creature Rights International,[100] have campaigned against LD50 testing on animals. Several countries, including the UK, have taken steps to ban the oral LD50, and the Organisation for Economical Co-operation and Development (OECD) abolished the requirement for the oral exam in 2001 (see Test Guideline 401, Trends in Pharmacological Sciences Vol 22, February 22, 2001).

Run across besides [edit]

  • Animal testing
  • Reed-Muench method
  • The dose makes the poisonous substance – the toxicology adage that high quantities of any substance is lethal

Other measures of toxicity [edit]

  • IDLH
  • Certain safety gene
  • Therapeutic alphabetize
  • Protective index
  • Stock-still Dose Process to estimate LD50
  • Median toxic dose (TD50)
  • Everyman published toxic concentration (TCLo)
  • Everyman published lethal dose (LDLo)
  • ECfifty (one-half maximal effective concentration)
  • IC50 (one-half maximal inhibitory concentration)
  • Draize examination
  • Indicative limit value
  • No-observed-adverse-issue level (NOAEL)
  • Everyman-observed-adverse-effect level (LOAEL)
  • Up-and-down procedure

[edit]

  • TCID50 Tissue Culture Infective Dosage
  • EIDl Egg Infective Dosage
  • ELDfifty Egg Lethal Dosage
  • Plaque forming units (pfu)

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External links [edit]

  • Canadian Middle for Occupational Health and Safety
  • Lipnick RL, Cotruvo JA, Hill RN, Bruce RD, Stitzel KA, Walker AP, et al. (March 1995). "Comparison of the upwards-and-downwardly, conventional LD50, and fixed-dose acute toxicity procedures". Nutrient and Chemic Toxicology. 33 (iii): 223–31. doi:x.1016/0278-6915(94)00136-C. PMID 7896233.

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Source: https://en.wikipedia.org/wiki/Median_lethal_dose

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