LD50
Encyclopedia
In toxicology
, the median lethal dose, LD50 (abbreviation for “Lethal Dose, 50%”), LC50 (Lethal Concentration, 50%) or LCt50 (Lethal Concentration & Time) of a toxin
, radiation
, or pathogen
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
. The test was created by J.W. Trevan in 1927. It is being phased out in some jurisdictions in favor of tests such as the Fixed Dose Procedure
; however the concept, and calculation of the median lethal dose for comparison purposes, is still widely used.
The term semilethal dose is occasionally used with the same meaning, particularly in translations from non-English-language texts, but can also refer to a sublethal dose; because of this ambiguity, it is usually avoided.
The U.S. Food and Drug Administration has begun to approve alternative methods to LD50 in response to research cruelty concerns and the lack of validity/sensitivity of the test as it relates to humans.
s of substance per kilogram
of body mass. 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). Typically, the LD50 of a substance is given in milligrams per kilogram of body weight. In the case of some neurotoxin
s such as batrachotoxin
, one of the most deadly toxins known, the LD50 may be more conveniently expressed as micrograms per kilogram (µg/kg) or nanograms per kilogram (ng/kg) of body mass.
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 an 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 Sheet
s 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 LD50's to some test animal. In biological warfare
infective dosage is the number of infective doses per minute for a cubic meter (e.g., ICt50 is 100 medium doses - min/m³).
at lower doses), and does not take into account toxic effects that do not result in death but are nonetheless serious (e.g., brain damage
). There can be wide variability between species as well; what is relatively safe for rats may very well be extremely toxic for humans, and vice versa. In other words, a relatively high LD50 does not necessarily mean a substance is harmless, since its relative harmfulness depends on its usual dose, but a very low one is always a cause for concern.
When used to test venom
from venomous creatures, such as snakes, LD50 results may be misleading due to the physiological differences between mice and humans. Many venomous snakes are specialized predators on mice, their venom may be adapted specifically to incapacitate mice. While most mammals have a very similar physiology, LD50 results may or may not be directly relevant to humans.
(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, {bracketed}, when appropriate.
and animal-welfare
groups, such as Animal Rights International, have campaigned against LD50 testing on animals in particular as, in the case of some substances, causing the animals to die slow, painful deaths. Several countries, including the UK
, have taken steps to ban the oral LD50, and the Organization for Economic Co-operation and Development (OECD) abolished the requirement for the oral test in 2001 (see Test Guideline 401, Trends in Pharmacological Sciences Vol 22, February 22, 2001).
Toxicology
Toxicology is a branch of biology, chemistry, and medicine concerned with the study of the adverse effects of chemicals on living organisms...
, the median lethal dose, LD50 (abbreviation for “Lethal Dose, 50%”), LC50 (Lethal Concentration, 50%) or LCt50 (Lethal Concentration & Time) of a toxin
Toxin
A toxin is a poisonous substance produced within living cells or organisms; man-made substances created by artificial processes are thus excluded...
, radiation
Radiation
In physics, radiation is a process in which energetic particles or energetic waves travel through a medium or space. There are two distinct types of radiation; ionizing and non-ionizing...
, or pathogen
Pathogen
A pathogen gignomai "I give birth to") or infectious agent — colloquially, a germ — is a microbe or microorganism such as a virus, bacterium, prion, or fungus that causes disease in its animal or plant host...
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
Acute toxicity
Acute toxicity describes the adverse effects of a substance that result either from a single exposure or from multiple exposures in a short space of time...
. The test was created by J.W. Trevan in 1927. It is being phased out in some jurisdictions in favor of tests such as the Fixed Dose Procedure
Fixed Dose Procedure
The Fixed Dose Procedure , proposed in 1984 by the British Toxicology Society, is a method to assess a substance's acute oral toxicity. In this procedure the test substance is given at one of the four fixed-dose levels The Fixed Dose Procedure (FDP), proposed in 1984 by the British Toxicology...
; however the concept, and calculation of the median lethal dose for comparison purposes, is still widely used.
The term semilethal dose is occasionally used with the same meaning, particularly in translations from non-English-language texts, but can also refer to a sublethal dose; because of this ambiguity, it is usually avoided.
The U.S. Food and Drug Administration has begun to approve alternative methods to LD50 in response to research cruelty concerns and the lack of validity/sensitivity of the test as it relates to humans.
Conventions
The LD50 is usually expressed as the mass of substance administered per unit mass of test subject, such as gramGram
The gram is a metric system unit of mass....
s of substance per kilogram
Kilogram
The kilogram or kilogramme , also known as the kilo, is the base unit of mass in the International System of Units and is defined as being equal to the mass of the International Prototype Kilogram , which is almost exactly equal to the mass of one liter of water...
of body mass. 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). Typically, the LD50 of a substance is given in milligrams per kilogram of body weight. In the case of some neurotoxin
Neurotoxin
A neurotoxin is a toxin that acts specifically on nerve cells , usually by interacting with membrane proteins such as ion channels. Some sources are more general, and define the effect of neurotoxins as occurring at nerve tissue...
s such as batrachotoxin
Batrachotoxin
Batrachotoxins are extremely potent cardiotoxic and neurotoxic steroidal alkaloids found in certain species of frogs , melyrid beetles, and birds...
, one of the most deadly toxins known, the LD50 may be more conveniently expressed as micrograms per kilogram (µg/kg) or nanograms per kilogram (ng/kg) of body mass.
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
Intravenous therapy
Intravenous therapy or IV therapy is the infusion of liquid substances directly into a vein. The word intravenous simply means "within a vein". Therapies administered intravenously are often called specialty pharmaceuticals...
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 an 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
Chemical warfare
Chemical warfare involves using the toxic properties of chemical substances as weapons. This type of warfare is distinct from Nuclear warfare and Biological warfare, which together make up NBC, the military acronym for Nuclear, Biological, and Chemical...
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
Fritz Haber
Fritz Haber was a German chemist, who received the Nobel Prize in Chemistry in 1918 for his development for synthesizing ammonia, important for fertilizers and explosives. Haber, along with Max Born, proposed the Born–Haber cycle as a method for evaluating the lattice energy of an ionic solid...
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 Sheet
Material safety data sheet
A Material Safety Data Sheet is a form with data regarding the properties of a particular substance....
s 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 LD50's to some test animal. In biological warfare
Biological warfare
Biological warfare is the use of biological toxins or infectious agents such as bacteria, viruses, and fungi with intent to kill or incapacitate humans, animals or plants as an act of war...
infective dosage is the number of infective doses per minute for a cubic meter (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. Another weakness is that it measures acute toxicity only (as opposed to chronic toxicityChronic toxicity
Chronic toxicity is a property of a substance that has toxic effects on a living organism, when that organism is exposed to the substance continuously or repeatedly. Compared with acute toxicity.Two distinct situations need to be considered:...
at lower doses), and does not take into account toxic effects that do not result in death but are nonetheless serious (e.g., brain damage
Brain damage
"Brain damage" or "brain injury" is the destruction or degeneration of brain cells. Brain injuries occur due to a wide range of internal and external factors...
). There can be wide variability between species as well; what is relatively safe for rats may very well be extremely toxic for humans, and vice versa. In other words, a relatively high LD50 does not necessarily mean a substance is harmless, since its relative harmfulness depends on its usual dose, but a very low one is always a cause for concern.
When used to test venom
Venom
Venom is the general term referring to any variety of toxins used by certain types of animals that inject it into their victims by the means of a bite or a sting...
from venomous creatures, such as snakes, LD50 results may be misleading due to the physiological differences between mice and humans. Many venomous snakes are specialized predators on mice, their venom may be adapted specifically to incapacitate mice. While most mammals have a very similar physiology, LD50 results may or may not be directly relevant to humans.
Examples
NOTE: Comparing substances (especially drugs) to each other by LD50 can be misleading in many cases due (in part) to differences in effective doseEffective dose
Effective dose may refer to:*Effective dose the dose of pharmacologic agent which will have a therapeutic effect in some fraction of the population receiving the drug...
(ED50). Therefore, it is more useful to compare such substances by therapeutic index
Therapeutic index
The therapeutic index is a comparison of the amount of a therapeutic agent that causes the therapeutic effect to the amount that causes death or toxicity ....
, 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, {bracketed}, when appropriate.
| Substance | Animal, Route | LD50 {LC50} |
LD50 : g/kg {LC50 : g/L} standardized |
Reference |
|---|---|---|---|---|
| Sucrose Sucrose Sucrose is the organic compound commonly known as table sugar and sometimes called saccharose. A white, odorless, crystalline powder with a sweet taste, it is best known for its role in human nutrition. The molecule is a disaccharide composed of glucose and fructose with the molecular formula... (table sugar) |
rat, oral | 29,700 mg/kg | 29.7 | |
| Vitamin C Vitamin C Vitamin C or L-ascorbic acid or L-ascorbate is an essential nutrient for humans and certain other animal species. In living organisms ascorbate acts as an antioxidant by protecting the body against oxidative stress... (ascorbic acid) |
rat, oral | 11,900 mg/kg | 11.9 | |
| Cyanuric acid Cyanuric acid Cyanuric acid or 1,3,5-triazine-2,4,6-triol is a chemical compound with the formula 3. Like many industrially useful chemicals, this triazine has many synonyms. This white, odorless solid finds use as a precursor or a component of bleaches, disinfectants, and herbicides... |
rat, oral | 7,700 mg/kg | 7.7 | |
| cadmium sulfide Cadmium sulfide Cadmium sulfide is the inorganic compound with the formula CdS. Cadmium sulfide is a yellow solid. It occurs in nature with two different crystal structures as the rare minerals greenockite and hawleyite, but is more prevalent as an impurity substituent in the similarly structured zinc ores... |
rat, oral | 7,080 mg/kg | 7.08 | |
| Grain alcohol Ethanol Ethanol, also called ethyl alcohol, pure alcohol, grain alcohol, or drinking alcohol, is a volatile, flammable, colorless liquid. It is a psychoactive drug and one of the oldest recreational drugs. Best known as the type of alcohol found in alcoholic beverages, it is also used in thermometers, as a... (ethanol) |
rat, oral | 7,060 mg/kg | 7.06 | |
| Melamine Melamine Melamine is an organic base and a trimer of cyanamide, with a 1,3,5-triazine skeleton. Like cyanamide, it contains 66% nitrogen by mass and, if mixed with resins, has fire retardant properties due to its release of nitrogen gas when burned or charred, and has several other industrial uses.... |
rat, oral | 6,000 mg/kg | 6 | |
| Melamine cyanurate Melamine cyanurate Melamine cyanurate, also known as melamine-cyanuric acid adduct or melamine-cyanuric acid complex, is a crystalline complex formed from a 1:1 mixture of melamine and cyanuric acid. The substance is not a salt despite its non-systematic name melamine cyanurate... |
rat, oral | 4,100 mg/kg | 4.1 | |
| Sodium molybdate Sodium molybdate Sodium molybdate, Na2MoO4, is useful as a source of molybdenum. It is often found as the dihydrate, Na2MoO4·2H2O.The molybdate anion is tetrahedral. Two sodium cations coordinate with every one anion.-History:... |
rat, oral | 4,000 mg/kg | 4 | |
| Table Salt Sodium chloride Sodium chloride, also known as salt, common salt, table salt or halite, is an inorganic compound with the formula NaCl. Sodium chloride is the salt most responsible for the salinity of the ocean and of the extracellular fluid of many multicellular organisms... |
rat, oral | 3,000 mg/kg | 3 | |
| Paracetamol Paracetamol Paracetamol INN , or acetaminophen USAN , is a widely used over-the-counter analgesic and antipyretic . It is commonly used for the relief of headaches and other minor aches and pains and is a major ingredient in numerous cold and flu remedies... (acetaminophen) |
rat, oral | 1,944 mg/kg | 1.944 | |
| Delta-9-tetrahydrocannabinol (THC) | rat, oral | 1,270 mg/kg | 1.270 | |
| Metallic Arsenic Arsenic Arsenic is a chemical element with the symbol As, atomic number 33 and relative atomic mass 74.92. Arsenic occurs in many minerals, usually in conjunction with sulfur and metals, and also as a pure elemental crystal. It was first documented by Albertus Magnus in 1250.Arsenic is a metalloid... |
rat, oral | 763 mg/kg | 0.763 | |
| Alkyl dimethyl benzalkonium chloride (ADBAC) | rat, oral fish, immersion aq. invertebrates, imm. |
304.5 mg/kg {0.28 mg/L} {0.059 mg/L} |
0.3045 {0.00028} {0.000059} |
|
| Coumarin Coumarin Coumarin is a fragrant chemical compound in the benzopyrone chemical class, found in many plants, notably in high concentration in the tonka bean , vanilla grass , sweet woodruff , mullein , sweet grass , cassia cinnamon and sweet clover... (benzopyrone Benzopyrone Benzopyrone may refer to either of two ketone derivatives of benzopyran which constitute the core skeleton of many flavonoid compounds:*Chromone *Coumarin... , from Cinnamomum aromaticum and other plants) |
rat, oral | 293 mg/kg | 0.293 | |
| Aspirin Aspirin Aspirin , also known as acetylsalicylic acid , is a salicylate drug, often used as an analgesic to relieve minor aches and pains, as an antipyretic to reduce fever, and as an anti-inflammatory medication. It was discovered by Arthur Eichengrun, a chemist with the German company Bayer... (acetylsalicylic acid) |
rat, oral | 200 mg/kg | 0.2 | |
| Caffeine Caffeine Caffeine is a bitter, white crystalline xanthine alkaloid that acts as a stimulant drug. Caffeine is found in varying quantities in the seeds, leaves, and fruit of some plants, where it acts as a natural pesticide that paralyzes and kills certain insects feeding on the plants... |
rat, oral | 192 mg/kg | 0.192 | |
| Arsenic trisulfide Arsenic trisulfide Arsenic trisulfide is the inorganic compound with the formula As2S3. This bright yellow solid is a well known mineral orpiment , has been used as a pigment, and has played a role in the analysis of arsenic compounds. This chalcogenide material is a group V/VI, intrinsic p-type semiconductor and... |
rat, oral | 185–6,400 mg/kg | 0.185 | |
| Sodium nitrite Sodium nitrite Sodium nitrite is the inorganic compound with the chemical formula NaNO2. It is a white to slight yellowish crystalline powder that is very soluble in water and is hygroscopic... |
rat, oral | 180 mg/kg | 0.18 | |
| Cobalt(II) chloride Cobalt(II) chloride Cobalt chloride is an inorganic compound of cobalt and chloride, with the formula CoCl2. It is usually supplied as the hexahydrate CoCl2·6H2O, which is one of the most commonly used cobalt compounds in the laboratory. The hexahydrate is deep purple in color, whereas the anhydrous form is sky blue... |
rat, oral | 80 mg/kg | 0.08 | |
| Cadmium oxide Cadmium oxide Cadmium oxide is an inorganic compound with the formula CdO. It is one of the main precursors to other cadmium compounds. It crystallizes in a cubic rocksalt lattice like sodium chloride, with octahedral cation and anion centers. It occurs naturally as the rare mineral monteponite. Cadmium oxide... |
rat, oral | 72 mg/kg | 0.072 | |
| Sodium fluoride Sodium fluoride Sodium fluoride is an inorganic chemical compound with the formula NaF. A colorless solid, it is a source of the fluoride ion in diverse applications. Sodium fluoride is less expensive and less hygroscopic than the related salt potassium fluoride.... |
rat, oral | 52 mg/kg | 0.052 | |
| Nicotine Nicotine Nicotine is an alkaloid found in the nightshade family of plants that constitutes approximately 0.6–3.0% of the dry weight of tobacco, with biosynthesis taking place in the roots and accumulation occurring in the leaves... |
rat, oral | 50 mg/kg | 0.05 | |
| Pentaborane Pentaborane Pentaborane, also called pentaborane to distinguish it from B5H11, is an inorganic compound with the formula B5H9. It is one of the most common boron hydride clusters, although it is a highly reactive compound. Because of its high reactivity toward oxygen, it was once evaluated as rocket or jet fuel... |
human, oral | <50 mg/kg | <0.05 | |
| Lysergic acid diethylamide (LSD) | rat, intravenous | 16.5 mg/kg | 0.0165 | |
| Arsenic trioxide Arsenic trioxide Arsenic trioxide is the inorganic compound with the formula As2O3. This commercially important oxide of arsenic is the main precursor to other arsenic compounds, including organoarsenic compounds. Approximately 50,000 tonnes are produced annually... |
rat, oral | 14 mg/kg | 0.014 | |
| Metallic Arsenic Arsenic Arsenic is a chemical element with the symbol As, atomic number 33 and relative atomic mass 74.92. Arsenic occurs in many minerals, usually in conjunction with sulfur and metals, and also as a pure elemental crystal. It was first documented by Albertus Magnus in 1250.Arsenic is a metalloid... |
rat, intraperitoneal | 13 mg/kg | 0.013 | |
| Sodium cyanide Sodium cyanide Sodium cyanide is an inorganic compound with the formula NaCN. This highly toxic colorless salt is used mainly in gold mining but has other niche applications... |
rat, oral | 6.4 mg/kg | 0.0064 | |
| White phosphorus | rat, oral | 3.03 mg/kg | 0.00303 | |
| Strychnine Strychnine Strychnine is a highly toxic , colorless crystalline alkaloid used as a pesticide, particularly for killing small vertebrates such as birds and rodents. Strychnine causes muscular convulsions and eventually death through asphyxia or sheer exhaustion... |
human, oral | 1–2 mg/kg(estimated) | 0.001 | |
| Mercury(II) chloride Mercury(II) chloride Mercury chloride or mercuric chloride , is the chemical compound with the formula HgCl2. This white crystalline solid is a laboratory reagent and a molecular compound. It is no longer used for medicinal purposes Mercury(II) chloride or mercuric chloride (formerly corrosive sublimate), is the... |
rat, dermal | 41 mg/kg | 0.041 | |
| Beryllium oxide Beryllium oxide Beryllium oxide , also known as beryllia, is an inorganic compound with the formula BeO. This colourless solid is a notable electrical insulator with a higher thermal conductivity than any other non-metal except diamond, and actually exceeds that of some metals. As an amorphous solid, beryllium... |
rat, oral | 0.5 mg/kg | 0.0005 | |
| Aflatoxin B1 Aflatoxin Aflatoxins are naturally occurring mycotoxins that are produced by many species of Aspergillus, a fungus, the most notable ones being Aspergillus flavus and Aspergillus parasiticus. Aflatoxins are toxic and among the most carcinogenic substances known... (from Aspergillus flavus) |
rat, oral | 0.48 mg/kg | 0.00048 | |
| Venom of the Inland taipan (Australian snake) | rat, subcutaneous | 25 µg/kg | 0.000025 | |
| Dioxin (TCDD) | rat, oral | 20 µg/kg | 0.00002 | |
| VX (nerve agent) VX (nerve agent) VX, IUPAC name O-ethyl S-[2-ethyl] methylphosphonothioate, is an extremely toxic substance whose only application is in chemical warfare as a nerve agent. As a chemical weapon, it is classified as a weapon of mass destruction by the United Nations in UN Resolution 687... |
human, oral, inhalation, absorption through skin/eyes | 2.3 µg/kg (estimated) | 0.0000023 | |
| Batrachotoxin Batrachotoxin Batrachotoxins are extremely potent cardiotoxic and neurotoxic steroidal alkaloids found in certain species of frogs , melyrid beetles, and birds... (from poison dart frog) |
human, sub-cutaneous injection | 2-7 µg/kg (estimated) | 0.000002 | |
| Venom of Hydrophis belcheri Hydrophis belcheri The Faint-banded Sea snake is a species of elapid sea snake. It has a friendly temperament and would normally have to be subjected to severe mistreatment before biting... (Belcher's Sea Snake) |
mouse, intraperitoneal | 0.25 µg/kg | 0.00000025 | |
| Maitotoxin Maitotoxin Maitotoxin is an extremely potent toxin produced by Gambierdiscus toxicus, a dinoflagellate species. Maitotoxin is so potent that it has been demonstrated that an intraperitoneal injection of 0.13 µg/kg was lethal in mice... |
mouse, intraperitoneal | 0.13 µg/kg | 0.00000013 | |
| Polonium Polonium Polonium is a chemical element with the symbol Po and atomic number 84, discovered in 1898 by Marie Skłodowska-Curie and Pierre Curie. A rare and highly radioactive element, polonium is chemically similar to bismuth and tellurium, and it occurs in uranium ores. Polonium has been studied for... -210 |
human, inhalation | 10 ng/kg (estimated) | 0.00000001 | |
| Botulinum toxin Botulinum toxin Botulinum toxin is a protein produced by the bacterium Clostridium botulinum, and is considered the most powerful neurotoxin ever discovered. Botulinum toxin causes Botulism poisoning, a serious and life-threatening illness in humans and animals... (Botox) |
human, oral, injection, inhalation | 1 ng/kg (estimated) | 0.000000001 | |
| Ionizing radiation Ionizing radiation Ionizing radiation is radiation composed of particles that individually have sufficient energy to remove an electron from an atom or molecule. This ionization produces free radicals, which are atoms or molecules containing unpaired electrons... |
human, irradiation | 3-6 Gy Gray (unit) The gray is the SI unit of absorbed radiation dose of ionizing radiation , and is defined as the absorption of one joule of ionizing radiation by one kilogram of matter .... |
Animal rights concerns
Animal-rightsAnimal rights
Animal rights, also known as animal liberation, is the idea that the most basic interests of non-human animals should be afforded the same consideration as the similar interests of human beings...
and animal-welfare
Animal welfare
Animal welfare is the physical and psychological well-being of animals.The term animal welfare can also mean human concern for animal welfare or a position in a debate on animal ethics and animal rights...
groups, such as Animal Rights International, have campaigned against LD50 testing on animals in particular as, in the case of some substances, causing the animals to die slow, painful deaths. Several countries, including the UK
United Kingdom
The United Kingdom of Great Britain and Northern IrelandIn the United Kingdom and Dependencies, other languages have been officially recognised as legitimate autochthonous languages under the European Charter for Regional or Minority Languages...
, have taken steps to ban the oral LD50, and the Organization for Economic Co-operation and Development (OECD) abolished the requirement for the oral test in 2001 (see Test Guideline 401, Trends in Pharmacological Sciences Vol 22, February 22, 2001).
Other measures of toxicity
- Certain safety factorCertain safety factorThe Certain Safety Factor is the ratio of the lethal dose to 1% of population to the effective dose to 99% of the population . This is a better safety index than the LD50 for materials that have both desirable and undesirable effects, because it factors in the ends of the spectrum where doses may...
- Therapeutic indexTherapeutic indexThe therapeutic index is a comparison of the amount of a therapeutic agent that causes the therapeutic effect to the amount that causes death or toxicity ....
- Protective indexProtective indexThe protective index is a comparison of the amount of a therapeutic agent that causes the therapeutic effect to the amount that causes toxicity. Quantitatively, it is the ratio given by the toxic dose divided by the therapeutic dose. A protective index is the toxic dose of a drug for 50% of the...
- Fixed Dose ProcedureFixed Dose ProcedureThe Fixed Dose Procedure , proposed in 1984 by the British Toxicology Society, is a method to assess a substance's acute oral toxicity. In this procedure the test substance is given at one of the four fixed-dose levels The Fixed Dose Procedure (FDP), proposed in 1984 by the British Toxicology...
to estimate LD50 - Median toxic doseMedian toxic doseIn toxicology, the median toxic dose of a drug or toxin is the dose at which toxicity occurs in 50% of cases. The type of toxicity should be specified for this value to have meaning for practical purposes. Since toxicity need not be lethal, the TD50 is generally lower than the median lethal dose...
(TD50) - Lowest published toxic concentration (TCLo)
- Lowest published lethal doseLowest published lethal doseIn toxicology, the LDLo is the lowest dosage per unit of bodyweight of a substance known to have resulted in fatality in a particular animal species...
(LDLo) - IC50IC50The half maximal inhibitory concentration is a measure of the effectiveness of a compound in inhibiting biological or biochemical function. This quantitative measure indicates how much of a particular drug or other substance is needed to inhibit a given biological process by half...
(50% inhibitory concentration) - Draize testDraize testThe Draize Test is an acute toxicity test devised in 1944 by Food and Drug Administration toxicologists John H. Draize and Jacob M. Spines...
- Indicative limit valueIndicative limit valueIn the law of the European Union, indicative limit values, more exactly indicative occupational exposure limit values , are human exposure limits to hazardous substances specified by the Council of the European Union based on expert research and advice.They are not binding on member states but must...
- No Observable Adverse Effect Level (NOAEL)
- Lowest Observable Adverse Effect Level (LOAEL)
- Up-and-down procedureUp-and-down procedureUp-and-down procedure is an alternative to the acute toxicity test.It requires fewer animals to achieve similar accuracy as the LD50 test. However, the U.S. Food and Drug Administration has begun to approve non-animal alternatives, in response to research cruelty concerns and the lack of...
Related measures
- TCID50 Tissue Culture Infective Dosage
- EID50 Egg Infective Dosage
- ELD50 Egg Lethal Dosage
- Plaque forming units (pfu)