up-and-down procedure

Up-and-down procedure (or method) for toxicology tests in medicine is an alternative to the {{LD50}} test, in which animals are used for acute toxicity testing.{{cite journal |last1=Lipnick |first1=R.L. |last2=Cotruvo |first2=J.A. |last3=Hill |first3=R.N. |last4=Bruce |first4=R.D. |last5=Stitzel |first5=K.A. |last6=Walker |first6=A.P. |last7=Chu |first7=I. |last8=Goddard |first8=M. |last9=Segal |first9=L. |last10=Springer |first10=J.A. |last11=Myers |first11=R.C. |title=Comparison of the up-and-down, conventional LD50, and fixed-dose acute toxicity procedures |journal=Food and Chemical Toxicology |date=March 1995 |volume=33 |issue=3 |pages=223–231 |doi=10.1016/0278-6915(94)00136-c |pmid=7896233 }}{{cite journal |last1=Lichtman |first1=Aron H |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 |date=August 1998 |volume=40 |issue=2 |pages=81–85 |doi=10.1016/s1056-8719(98)00041-0 |pmid=10100496 }} It requires fewer animals to achieve similar accuracy as the LD₅₀ test because animals are dosed one at a time.{{cite web |title=Acute Oral Toxicity Up-And-Down-Procedure |url=https://www.epa.gov/pesticide-science-and-assessing-pesticide-risks/acute-oral-toxicity-and-down-procedure |website=US EPA |language=en |date=2 June 2015 }} If the first animal survives, the dose for the next animal is increased; if it dies, the dose is decreased. It is usual to observe each animal for 1 or 2 days before dosing the next animal, however, surviving animals should be monitored for 7 days in case of delayed death. The up-and-down method is not recommended where deaths beyond 2 days are the norm.{{cite journal |last1=Bruce |first1=R |title=An up-and-down procedure for acute toxicity testing |journal=Fundamental and Applied Toxicology |date=February 1985 |volume=5 |issue=1 |pages=151–157 |doi=10.1016/0272-0590(85)90059-4 |pmid=3987991 }} The U.S. Food and Drug Administration has begun to approve non-animal alternatives.{{cite press release |title=Allergan Receives FDA Approval for First-of-Its-Kind, Fully in vitro, Cell-Based Assay for BOTOX® and BOTOX® Cosmetic (onabotulinumtoxinA) |publisher=Allergan |date=June 24, 2011 |url=https://www.businesswire.com/news/home/20110624005918/en/Allergan-Receives-FDA-Approval-First-of-Its-Kind-Fully-vitro |access-date=May 19, 2020 }}{{cite news |last1=Gaul |first1=Gilbert M. |title=In U.S., Few Alternatives To Testing On Animals |url=https://www.washingtonpost.com/wp-dyn/content/article/2008/04/11/AR2008041103733.html |newspaper=The Washington Post |date=12 April 2008 }}