Lethal dose
The lethal dose ( LD ) is in the toxicology the dose of a certain substance or a certain radiation , which for a particular living beings fatal ( lethal effect). In contrast, refers to a force acting from the environment of the living organism molar concentration with the same effect as the lethal concentration ( LC of English lethal concentration ). Both are statistical values, i.e. they are obtained as mean values for the acute toxicity within a representative sample and should therefore not be regarded as definitive for an individual. A fatal effect can therefore only occur at significantly higher or even lower doses / concentrations, for example if the dose is weakened by illness.
properties
In addition to species-specific values, age- or weight-specific information can also be important, for example in the simplest case the distinction between adults and children for humans. For example, the lethal dose of potassium cyanide ( potassium cyanide) in an adult is around 140 milligrams, but it is much lower in children. Numerical values for lethal doses that relate to “kg body weight” (in this case “human”) are therefore more suitable. The type of ingestion of the toxin ( oral , subcutaneous , intravenous, etc.), the solvent used in the test substance, the duration of exposure and the observation period are also important.
The measure has been used since 1927 and is based on an idea by pharmacologist John William Trevan .
For specifying the lethal dose or the lethal concentration, there are various measured variables with regard to the dose-dependency of the lethality of a toxin or pathogen , which represent a measure of the toxicity of the substance or the radiation used . Since toxicity determinations are subject to many different factors, such as the general health and nutritional status of the test animal, a sigmoid dose-effect curve is often shown . That is why the dose is usually given whose lethal effect relates to 50 percent of the observed population: the mean lethal dose LD 50 or the mean lethal concentration LC 50 . The mean dose or concentration is a popular measure because in a series of experiments the dose at which all or no individuals die is very large or very small.
Other quantities are LD 75 (lethal dose), LD 99 (sure lethal dose) and LD 100 (absolutely lethal dose). Values such as LD 0 , LD 1 , LD 99 or LD 100 are hardly meaningful, as they only depend on the most sensitive or most resistant individual within the test series.
The dose is given in grams or milligrams of substance per kilogram of body weight , whereas the concentration is given, for example, in grams of substance per kilogram of liquid (mostly water) or cubic meters of gas (mostly air).
In radiology , the time delay of the fatal effect is also given in the notation: LD quota / delay
LD 50 / 30d describes a dose at which 50% of those affected die after 30 days.
In addition, in the scientific literature - sometimes fatal - (poisonous) accidents involving humans are documented if the data situation is beyond doubt. Various abbreviations are used:
- LD Lo ( English lethal dose low ) - the lowest (known) lethal dose
- TD - the toxic dose
- TD Lo - the lowest known toxic dose at which any negative (toxic) effects occurred
Determination and validity
The values are determined in animal experiments by administering the agent once to the animals (dose) or the medium in which the animals are (concentration). Since the route of administration plays a role in determining the toxicity, this must also be stated (e.g. oral , subcutaneous or intravenous ). The determination of the lethal dose in animals is controversial for reasons of animal ethics .
Since the toxic effect of substances can differ greatly between different animal species as well as between animals and humans, the values determined in animals can only be transferred to humans to a very limited extent and only serve as a rough guide. However, the quality of the approximation for humans also differs greatly depending on the animal species tested.
use
With the help of the lethal dose, substances can be classified in a hazard class (or toxicity class ).
Classification according to GHS :
| GHS category | criteria | |||
|---|---|---|---|---|
| orally | dermal | |||
| LD 50 (mg / kg) | H-phrase | LD 50 (mg / kg) | H-phrase | |
| Category I. | < 5 | Danger to life if swallowed. | < 50 | Danger to life in contact with skin. |
| Category II | 5- 50 | Danger to life if swallowed. | 50- 200 | Danger to life in contact with skin. |
| Category III | 50- 300 | Toxic if swallowed. | 200-1000 | Toxic in contact with skin. |
| Category IV | 300-2000 | Harmful if swallowed. | 1000-2000 | Harmful to skin contact. |
| Category V | 2000-5000 | 2000-5000 | ||
Classification of the WHO :
| class | LD 50 (mg / kg), rat | |||
|---|---|---|---|---|
| orally | dermal | |||
| Solids | liquids | Solids | liquids | |
| Yes | < 5 | < 20 | < 10 | < 40 |
| Ib | 5- 50 | 20- 200 | 10- 100 | 40- 400 |
| II | 50- 500 | 200-2000 | 100-1000 | 400-4000 |
| III | > 500 | > 2000 | > 1000 | > 4000 |
LD 50 table
See also
literature
- Aktories, Klaus ; Förstermann, Ulrich; Hofmann, Franz; Starke, Klaus (Ed.): General and special pharmacology and toxicology. Urban & Fischer, Munich, Jena, 9th edition 2005, ISBN 3-437-42521-8 (founded by W. Forth, D.Hentschler and W. Rummel)
- Hunnius, Curt ; Ammon, HPT : Hunnius - Pharmaceutical Dictionary . de Gruyter, Berlin 2004, ISBN 978-3-11-017475-5
Individual evidence
- ↑ a b Entry on LD. In: Römpp Online . Georg Thieme Verlag, accessed on February 27, 2013.
- ↑ JW Trevan: The Error of Determination of Toxicity . In: Proceedings of the Royal Society of London . Series B, Containing Papers of a Biological Character . tape 101 , no. 712 , July 1927, p. 483-514 , doi : 10.1098 / rspb.1927.0030 .
