In toxicology, the LD₅₀ or colloquially semilethal dose of a particular substance is a measure of how much constitutes a lethal dose. In toxicological studies of substances, one test is to administer varying doses of the substance to populations of test animals; that dose administered which kills half the test population is referred to as the LD₅₀, for "Lethal Dose, 50%".

This concept was created by J.W. Trevan in 1927

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.

Some animal welfare groups (particularly those influenced by the animal rights and animal liberation movement) object to the studies needed to calculate this figure. This is particularly the case where the substance is not particularly toxic and a large quantity of the material is ingested by the animals over a long period, in some cases causing slow, painful deaths.

Another criticism of LD₅₀ testing is that lethality in test animals does not always give an accurate indication of lethality in humans, because resistance varies from one species to another.

As concern grows for the welfare for animals, and as alternatives become more sophisticated, the test is administered less frequently, though the collection of data already obtained make it useful. Estimated LD₅₀ numbers can be compared to those older numbers obtained more traditionally.

A comparable measurement is LCt₅₀ which relates to lethal dose by inhalation, where C is concentration and t is time. It is usually 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 nerve agents.

Limits of this test

• This test does not reliably hint at the long-term effects of chronic accumulation in humans if rats and other short-lived; multiplicating the dosage the animal gets by an arbitrary large number to get the same exposure per kilo of animal than a human would get may lead to innacuracies both too restrictive and too permissive.

• When an organisation decides the "maximum legal level" of a substance based on animal studies, it is determined and tested one substance at a time (as systematically testing the substance's interaction with hundreds of other toxins is too expensive). This may lead to the separate approval of substances that are relatively harmless at their legal level when only one exposure is present, but cause significant disease or death rates someone is exposed to both. [1]

• Animals may react in completely different ways to substances than humans. Many substances are harmless in one species and very toxic in another. [2]

Those flaws, common to almost all animal studies, mean that human toxicity levels are not known until significant human follow-up studies are completed or a major accident exposes hundred of individuals so a death statistic can be made. Neverthenless, it is claimed that LD50 studies do prove useful in identifying very toxic substances rapidly and providing a legal framework for the use of a useful substance whose toxicity is not fully known.

Countries which have abolished the LD50 test

• The UK government claimed to have stopped issuing LD50 licenses after lobbying by the British Union for the Abolition of Vivisection - however, an illegal laboratory raid in 2004 exposed evidence that the LD50 test is still used on every batch of botox "anti-wrinkle" preparations [3].
• The OECD has also recently abolished use of the LD50 known as Test Guideline 401 (Source: TRENDS in Pharmacological Sciences Vol22 No.2 February 2001)

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
• ELD50 Egg Lethal Dosage
• Plaque forming units pfu