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In toxicology, the (abbreviation for "Lethal Dose, 50%") or median lethal dose of a poison or radiation is the dose required to kill half the members of a tested population. figures are frequently used as a general indicator of a substance's toxicity. The test was created by J.W. Trevan in 1927.*
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 should generally be avoided.
MeSH (ID D007928) defines as:
The dose amount of poisonous or toxic substance or dose of ionizing radiation required to kill 50% of the tested population. Year introduced: 1976(1971).
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Controversy
Animal-rights and animal-welfare groups, such as Animal Rights International, have campaigned against 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 , 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).*
Conventions
The usual terms for expressing the are in units of mass of substance per mass of body mass, such as grams of substance per kilogram of body mass. Stating it this way allows the relative toxicity of different substances to be compared, and allows one to scale for the different size of the animals exposed (although toxicity does not always scale simply with body mass). Typically, the of a substance is measured in milligrams.
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 is not the lethal dose for all subjects; some may be killed by much less, while others survive doses far higher than the . 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 taken by mouth than when intravenously administered. For this reason, figures are often qualified with the mode of administration, e.g. " i.v."
The related quantities /30 or an /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 which will cause incapacitation rather than death. These measures are commonly used to indicate the comparative efficacy of chemical warfare agents. These 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 x 100 = 100, as does 10 x 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 dosage is qualified by a duration of exposure (e.g., 10 minutes). In environmental studies, LCt can also refer to the concentration in water instead of air.
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).
Substances of extreme toxicity (µg/kg)
In the case of neurotoxins, such as batrachotoxin - a poison found in the skins of certain species of Central American and South American frogs and one of the most deadly venoms known - the LD50 is properly and best expressed in terms of micrograms per kilogram (µg/kg) (or billionths) of body mass. The LD50 of batrachotoxin in humans is estimated to be 1 to 2 µg/kg. (This could be more awkwardly expressed as 0.001 to 0.002 mg/kg, but the simpler form of µg/kg is preferred.) It means that merely 0.1 mg of this substance - equivalent to the mass of a couple of grains of ordinary fine table salt - would quickly lead to paralysis, cardiac arrest and death in a 68 kg person.
Examples
- Oral of alcohol: 8.83g/kg on average, 10.6g/kg in young rats, 7.06g/kg in aged rats.*
- Oral of nicotine: 50mg/kg on average in rats.*
See also
Other measures of toxicity
- Lowest published toxic concentration (TCLo)
- Lowest published lethal dose (LDLo)
- IC50 (50% inhibitory concentration)
- Draize test
Related measures
- TCID50 Tissue Culture Infective Dosage
- EID50 Egg Infective Dosage
- E Egg Lethal Dosage
- Plaque forming units (pfu)
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"LD50"