Editing Lethal dose (section)

==<span id="LD50"></span>Median lethal dose (LD<sub>50</sub>)==
{{Main article|Median lethal dose}}
The median lethal dose, LD<sub>50</sub> (abbreviation for "lethal dose, 50%"), LC<sub>50</sub> (lethal concentration, 50%) or LCt<sub>50</sub> (lethal concentration and time) of a [[toxin]], [[radiation]], or [[pathogen]] is the [[Dose (pharmacology)|dose]] required to kill half the members of a tested population after a specified test duration. LD<sub>50</sub> figures are frequently used as a general indicator of a substance's [[acute toxicity]].<ref>{{cite journal |vauthors=Gavanji S, Bakhtari A, Famurewa AC, Othman EM |title=Cytotoxic Activity of Herbal Medicines as Assessed in Vitro: A Review |journal=Chemistry & Biodiversity |volume=20 |pages=3–27 |date=January 2023 |issue=2 |pmid=36595710 |doi=10.1002/cbdv.202201098|s2cid=255473013 |doi-access=free }}</ref> A lower LD<sub>50</sub> is indicative of increased toxicity.

=== History ===
The test was created by J.W. Trevan in 1927.<ref>[http://www.ccohs.ca/oshanswers/chemicals/ld50.html What is an LD50 and LC50] {{webarchive|url=https://web.archive.org/web/20150626013647/http://www.ccohs.ca/oshanswers/chemicals/ld50.html |date=2015-06-26 }}</ref> The term "semilethal dose" is occasionally used with the same meaning, in particular in translations from non-English-language texts, but can also refer to a ''sub''lethal dose; because of this ambiguity, it is usually avoided. LD<sub>50</sub> is usually determined by tests on animals such as [[laboratory mice]]. In 2011 the US [[Food and Drug Administration]] approved alternative methods to LD<sub>50</sub> for testing the cosmetic drug [[Botox]] without animal tests.<ref>
{{cite news
 |date        = 12 April 2008
 |title       = In U.S., Few Alternatives To Testing On Animals
 |newspaper   = Washington Post
 |url         = https://www.washingtonpost.com/wp-dyn/content/article/2008/04/11/AR2008041103733.html
 |access-date  = 2011-06-26
 |url-status     = live
 |archive-url  = https://web.archive.org/web/20121112163835/http://www.washingtonpost.com/wp-dyn/content/article/2008/04/11/AR2008041103733.html
 |archive-date = 12 November 2012
}}</ref>

=== Units and measurement ===
The LD<sub>50</sub> is usually expressed as the mass of substance administered per unit mass of test subject, typically as [[milligram]]s of substance per [[kilogram]] of body mass, but stated as nanograms (suitable for [[botulinum]]), micrograms, milligrams, or grams (suitable for [[paracetamol]]) per kilogram. Stating it this way allows the relative toxicity of different substances to be compared, and normalizes for the variation in the size of the animals exposed, although toxicity does not always scale simply with body mass.

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 LD<sub>50</sub> is ''not'' the lethal dose for all subjects; some may be killed by much less, while others survive doses far higher than the LD<sub>50</sub>. Measures such as "LD<sub>1</sub>" and "LD<sub>99</sub>" (dosage required to kill 1% or 99%, respectively, of the test population) are occasionally used for specific purposes.<ref>[https://www.cdc.gov/niosh/pdfs/97-119-a.pdf REGISTRY OF TOXIC EFFECTS OF CHEMICAL SUBSTANCES (RTECS)<br>COMPREHENSIVE GUIDE TO THE RTECS] {{webarchive|url=https://web.archive.org/web/20130516165953/http://www.cdc.gov/niosh/pdfs/97-119-a.pdf |date=2013-05-16 }}</ref>

Lethal dosage often varies depending on the method of [[Drug administration|administration]]; for instance, many substances are less toxic when administered orally than when [[Intravenous therapy|intravenously]] administered. For this reason, LD<sub>50</sub> figures are often qualified with the mode of administration, e.g., "LD<sub>50</sub> i.v."

The related quantities LD<sub>50</sub>/30 or LD<sub>50</sub>/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 culture]]s. One form of measuring LD is to use [[model organism]]s, 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|date=April 2018}}. 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.<ref>{{Cite web
 |title       = Vision and Roadmap for the 21st Century
 |publisher   = [[National Toxicology Program]]
 |url         = http://ntp.niehs.nih.gov/go/vision
 |access-date  = 2011-10-29
 |url-status     = live
 |archive-url  = https://web.archive.org/web/20081012173524/http://ntp.niehs.nih.gov/go/vision
 |archive-date = 2008-10-12
}}</ref>

=== Median infective dose ===
The median infective dose (ID<sub>50</sub>) 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 LD<sub>50</sub>'s to some test animal. In [[biological warfare]] infective dosage is the number of infective doses per minute for a cubic meter (e.g., ICt<sub>50</sub> is 100 medium doses - min/m<sup>3</sup>).)