Editing Median lethal dose (section)

== Procedures ==
A number of procedures have been defined to derive the LD<sub>50</sub>. The earliest was the 1927 "conventional" procedure by Trevan, which requires 40 or more animals. The [[fixed-dose procedure]], proposed in 1984, estimates a level of toxicity by feeding at defined doses and looking for signs of toxicity (without requiring death).<ref>{{cite journal | vauthors = van den Heuvel MJ, Clark DG, Fielder RJ, Koundakjian PP, Oliver GJ, Pelling D, Tomlinson NJ, Walker AP | title = The international validation of a fixed-dose procedure as an alternative to the classical LD50 test | journal = Food and Chemical Toxicology | volume = 28 | issue = 7 | pages = 469–482 | date = July 1990 | pmid = 2210519 | doi = 10.1016/0278-6915(90)90117-6 }}</ref> The [[up-and-down procedure]], proposed in 1985, yields an LD<sub>50</sub> value while dosing only one animal at a time.<ref>{{cite journal | vauthors = Lipnick RL, Cotruvo JA, Hill RN, Bruce RD, Stitzel KA, Walker AP, Chu I, Goddard M, Segal L, Springer JA | title = Comparison of the up-and-down, conventional LD<sub>50</sub>, and fixed-dose acute toxicity procedures | journal = Food and Chemical Toxicology | volume = 33 | issue = 3 | pages = 223–231 | date = March 1995 | pmid = 7896233 | doi = 10.1016/0278-6915(94)00136-c }}</ref><ref>{{cite journal | vauthors = Lichtman AH | title = The up-and-down method substantially reduces the number of animals required to determine antinociceptive ED50 values | journal = Journal of Pharmacological and Toxicological Methods | volume = 40 | issue = 2 | pages = 81–85 | date = August 1998 | pmid = 10100496 | doi = 10.1016/s1056-8719(98)00041-0 }}</ref>