What does LD50 mean?

LD50 is a term used to represent Median Lethal Dose, which is defined as the amount of a chemical required to kill 50% of a particular test population. It represents an objective way of measuring the acute toxicity of any substance against a specific organism. The LD of LD50 is of Anglo-Saxon origin and comes from the English term for lethal dose , while 50 comes from the 50% of the population of a specific organism that, on average, will die when exposed to the dose of the substance in question.

Despite the fact that this term is commonly used in all languages, in the toxicology literature in Spanish, LD50 is often used instead (which comes directly from lethal dose).

Units of the median lethal dose or LD50

The LD50 of a substance is generally reported as the amount of that substance expressed in mass units, per unit body weight of the test organism.

The mass of the substance is usually expressed in different units of mass as appropriate. For many substances of moderate toxicity it is sufficient to measure this amount in milligrams, while for more dangerous substances it may be necessary to use smaller units of mass such as micrograms.

On the other hand, the body mass unit of the organism is standardized in most countries of the world and corresponds to either 1 kg or 1 pound, depending on the system of units commonly used in the country. The reason why the lethal dose is expressed in terms of the body mass of the organism is because the greater the body mass, the more the substance is diluted in the tissues. By dividing the lethal dose by the mass of the organism, it is possible to normalize the concentration in order to be able to objectively compare the lethality or toxicity of a substance.

Interpretation of the value of the median lethal dose or LD50

To begin, we must understand that the LD50 value is a statistical measure related to the probability that an organism exposed to said dose of the substance will die. The formal statistical interpretation would be that if we give the LD50 dose to one individual and then to another and then to another, and continue to do so until the entire population is covered, on average 1 in 2 will die.

From the point of view of toxicity, if we compare the LD50 values ​​of two substances for the same species or organism, the lower the LD50, the more toxic the substance will be in said organism. This is because a smaller amount of the substance is required to kill the same number of individuals. In other words, if A has an LD50 of 10 mg/kg and B has an LD50 of 5 mg/kg, then B is twice as toxic as A, since half the amount of B is required to kill the same number of individuals. that of a

On the other hand, we must also correctly interpret the units of the LD50. It may seem strange to say that the median lethal dose of a substance for a small organism such as a mouse or an insect is 10 mg per kilogram of body weight, since neither weigh as much as 1 kg. However, we must remember that these values ​​should not be taken literally, but rather are relative amounts that are independent of the actual size of the animal or organism.

To determine the lethal dose for a particular individual, we must consider their actual body weight. For example, suppose we have a mouse that weighs 100 g and we know that substance A has an LD50 of 10 mg/kg body weight. Since 10 mg is required for every 1 kg (which is 1000 g), then the mean lethal dose for that individual corresponds to 1 mg of substance A (given that his actual body mass is one-tenth of 1 kg).

Seen even more simply, to determine the actual mass of the substance that we must supply to an individual to achieve the median lethal dose, we simply must multiply the LD50 value by the individual’s body mass expressed in the same units in which it is reported. the LD50. In our mouse example, its mass in kilograms is 0.100 kg, so the mass of substance A would be (10 mg A/kg body mass) x (0.100 kg body mass) = 1 mg A.

How is the LD50 determined?

The median lethal dose is determined experimentally by exposing a sample of individuals of a certain organism to various doses of a substance and then recording the number of individuals who die from the effects of this substance. The substance is administered by force in different ways, including the oral, respiratory, parenteral, intramuscular or intravenous routes, among others.

The animals or organisms commonly used in this type of test are usually mice, rats, rabbits and guinea pigs, but they can also be smaller organisms such as certain insects, or larger organisms such as dogs or even horses. It all depends on the intention with which this measure of toxicity is determined.

For example, when what is desired is to estimate toxicity in humans, given that, for obvious reasons, experiments cannot be carried out on living people, animal models that closely replicate the functioning of some physiological system are often used. human. Mice frequently serve this purpose, but in other cases chimpanzees or other evolutionarily closely related species are used.

On the other hand, you may want to estimate the effectiveness of a certain new formulation of a pesticide. In this case, the tests are almost always carried out on the organism for which the product is intended to be used (the pest). This may be some insect or other organism.

Interpretation of experimental data

Once the data from the experiment is available, we proceed to its analysis for the calculation of the LD50. Since the median lethal dose of a substance for a given organism is not known in advance, several tests must be carried out with increasing doses of the substance. Lower doses may not kill any individual, while high doses may kill the vast majority. However, the dose that kills just half of the individuals will hardly be achieved during the experiment.

For this reason, the actual value of the LD50 (or, more appropriately, an estimate thereof) must be determined by interpolation or by other graphical or statistical methods from the data obtained during the experiment. The dose-response curve is usually in the shape of the letter S (sigmoid curve), which means that direct interpolation of the data may present a high interpolation error in some cases. In view of this, data are often linearized prior to interpolation, which is accomplished by plotting the response against the log dose rather than the dose itself. This almost always results in a straight-line plot that can be fitted for least squares, thus making it easier to accurately determine the point at which 50% of individuals show the expected response (i.e.,

Origin of LD50

The median lethal dose or LD50 test is nothing new. In fact, it is almost 100 years old, having been developed in 1927. In the original experiments, a total of 200 animals were used, of which half died from the effects of the test substance, while half that survived were sacrificed. to study other non-lethal effects.

However, this classic procedure for determining the median lethal dose has been discontinued in most countries of the world, in favor of other more appropriate and less inhumane methods.

Other lethal dose values

The LD50 (or LD50) has become a world standard for comparing the toxicity of a substance against a certain animal species or organism. However, it is not the only one that exists. In the same way that the LD50 is defined and determined, other doses that cause death at different proportions of a population can also be defined. Thus, we can define a lethal dose LD90 as the dose of a substance that kills 90% of a population or LD10 which indicates the dose of a substance that kills only 10% of the population. Each one has its particular uses and its challenges when measuring them.

Examples of LD50 values ​​for common harmless substances

The following table shows some median lethal dose or LD50 values ​​for common substances, such as some foods:

Examples of LD50 values ​​for common poisonous substances

The following table presents some values ​​of the median lethal dose or LD50 for common toxic substances, as well as some of the most dangerous poisons or toxins that are known:

References

AnimaNaturalis. (2015, September 12). Lethal Dose 50 (LD50) . https://www.animanaturalis.org/p/1361/dosis_letal_50_dl50

Canadian Center for Occupational Health and Safety. (2018, November 12). What is a LD50 and LC50? :OSH Answers . https://www.ccohs.ca/oshanswers/chemicals/ld50.html

Department of Legal Medicine and Toxicology. (nd). Topic 1. Concept, History and scope of Toxicology. University of Granada. https://www.ugr.es/%7Eajerez/proyecto/t2-13.htm

Food and Drug Administration (FDA). (nd). Chapter IV. Guidelines for Toxicity Tests – Acute Oral Toxicity . https://www.fda.gov/media/72257/download

National Human Genome Research Institute. (2022, July 25). Animal model . genome.gov. https://www.genome.gov/es/genetics-glossary/Animal-model

Nelson, R. (2019, September 3). Most Venomous Snakes in the World . Untamed Science. https://untamedscience.com/blog/most-venomous-snakes-in-the-world/

Chemistry.is. (nd). Lethal_dose_50% . https://www.quimica.es/enciclopedia/Dosis_mortal_50%25.html