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Description

In toxicology, the LD50 or colloquially semilethal dose of a particular substance is a measure of how much constitutes a lethal dose. The test was created by J.W. Trevan in 1927. In animal testing studies, and those of other organisms, the dose administered that kills half the test population is referred to as the LD50, for "Lethal Dose, 50%".

Animal-rights and animal-welfare groups have campaigned against LD50 testing on animals in particular, citing it as cruel and unnecessary, and 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 (1).

Background

The usual terms for expressing the LD50 are in units of mass of substance per mass of body mass, eg 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. The choice of the 50% mark avoids the potential for ambiguity of making measurements in the extremes.

The related units of an 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/m�. 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 (microgram/kilogram)

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 (microg/kg) (or billionths) of body mass. The LD50 of batrachotoxin in humans is estimated to be 1 to 2 microg/kg. (This could be more awkwardly expressed as 0.001 to 0.002 mg/kg, but the simpler form of microg/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 man.

Attribution

References


1. Test Guideline 401, Trends in Pharmacological Sciences Vol 22, February 22, 2001

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