Lethal dose
In toxicology, the lethal dose (LD) is an indication of the lethal toxicity of a given substance or type of radiation. Because resistance varies from one individual to another, the "lethal dose" represents a dose (usually recorded as dose per kilogram of subject body weight) at which a given percentage of subjects will die. The lethal concentration is a lethal dose measurement used for gases or particulates. The LD may be based on the standard person concept, a theoretical individual that has perfectly "normal" characteristics, and thus not apply to all sub-populations.
Median lethal dose (LD50)
The median lethal dose, LD50 (abbreviation for "lethal dose, 50%"), LC50 (lethal concentration, 50%) or LCt50 (lethal concentration and time) of a
History
The test was created by J.W. Trevan in 1927.
Units and measurement
The LD50 is usually expressed as the mass of substance administered per unit mass of test subject, typically as
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 LD50 is not the lethal dose for all subjects; some may be killed by much less, while others survive doses far higher than the LD50. Measures such as "LD1" and "LD99" (dosage required to kill 1% or 99%, respectively, of the test population) are occasionally used for specific purposes.[4]
Lethal dosage often varies depending on the method of
The related quantities LD50/30 or 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 with radiation, as survival beyond 60 days usually results in recovery.
Estimation using model organisms
LD values for humans are best estimated by extrapolating results from human cell cultures. One form of measuring LD is to use model organisms, particularly animals like mice or rats, converting to dosage per kilogram of biomass, and extrapolating to human norms. The degree of error from animal-extrapolated LD values is large. The biology of test animals differs in important aspects to that of humans. For instance, mouse tissue is approximately fifty times less responsive than human tissue to the venom of the Sydney funnel-web spider[citation needed]. The square–cube law also complicates the scaling relationships involved. Researchers are shifting away from animal-based LD measurements in some instances. The U.S. Food and Drug Administration has begun to approve more non-animal methods in response to animal welfare concerns.[5]
Median infective dose
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).)
Lowest lethal dose
The lowest lethal dose (LDLo) is the least amount of drug that can produce death in a given animal species under controlled conditions.
Median lethal concentration
For gases and aerosols, lethal concentration (given in mg/m3 or ppm, parts per million) is the analogous concept, although this also depends on the duration of exposure, which has to be included in the definition. The term incipient lethal level is used to describe a LC50 value that is independent of time.[8]
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. LCt50 is the dose that will cause incapacitation rather than death. These measures are commonly used to indicate the comparative efficacy of
Some chemicals, such as
Lowest lethal concentration
The LCLo is the lowest concentration of a chemical, given over a period of time, that results in the fatality of an individual animal. LCLo is typically for an acute (<24 hour) exposure.[9][10] It is related to the LC50, the median lethal concentration. The LCLo is used for gases and aerosolized material.[11]
Limitations
As a measure of toxicity, lethal dose is somewhat unreliable and results may vary greatly between testing facilities due to factors such as the genetic characteristics of the sample population, animal species tested, environmental factors and mode of administration.[12]
There can be wide variability between species as well; what is relatively safe for rats may very well be extremely toxic for humans (cf.
Animal rights concerns
See also
- IDLH
- Certain safety factor
- Therapeutic index
- Protective index
- Fixed-dose procedure to estimate LD50
- Median lethal dose, LD50
- Median toxic dose (TD50)
- Lowest published toxic concentration(TCLo)
- EC50 (half maximal effective concentration)
- IC50 (half maximal inhibitory concentration)
- Draize test
- Indicative limit value
- No-observed-adverse-effect level (NOAEL)
- Lowest-observed-adverse-effect level (LOAEL)
- Up-and-down procedure
- TCID50Tissue Culture Infective Dosage
- EID50 Egg Infective Dosage
- ELD50 Egg Lethal Dosage
- Plaque forming units(pfu)
References
- S2CID 255473013.
- ^ What is an LD50 and LC50 Archived 2015-06-26 at the Wayback Machine
- ^ "In U.S., Few Alternatives To Testing On Animals". Washington Post. 12 April 2008. Archived from the original on 12 November 2012. Retrieved 2011-06-26.
- ^ REGISTRY OF TOXIC EFFECTS OF CHEMICAL SUBSTANCES (RTECS)
COMPREHENSIVE GUIDE TO THE RTECS Archived 2013-05-16 at the Wayback Machine - ^ "Vision and Roadmap for the 21st Century". National Toxicology Program. Archived from the original on 2008-10-12. Retrieved 2011-10-29.
- ^ What is an LD50 and LC50 Archived 2015-06-26 at the Wayback Machine
- ^ "Allergan Receives FDA Approval for First-of-Its-Kind, Fully in vitro, Cell-Based Assay for BOTOX® and BOTOX® Cosmetic (onabotulinumtoxinA)". Allergan Web site. 24 June 2011. Archived from the original on 26 June 2011. Retrieved 2012-08-15.
- ISBN 978-0-12-396951-4.
- ISBN 978-1-4020-6754-9.
- ^ "MSDS Glossary". Archived from the original on 2015-06-21. Retrieved 2015-05-31.
- ^ "The MSDS HyperGlossary: LC-Lo, Lowest Lethal Concentration". Archived from the original on 2015-06-19. Retrieved 2015-05-31.
- ^ Ernest Hodgson (2004). A Textbook of Modern Toxicology. Wiley-Interscience (3rd ed.).[page needed]
- ^ Thirty-Two Years of Measurable Change Archived 2007-02-11 at the Wayback Machine
- .