Up-and-down procedure

Up-and-down procedure (or method) is an alternative to the LD50 test, in which animals are used for acute toxicity testing.[1][2] It requires fewer animals to achieve similar accuracy as the LD50 test because animals are dosed one at a time.[3] 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.[4] The U.S. Food and Drug Administration has begun to approve non-animal alternatives.[5][6]

References
  1. Lipnick, RL; Cotruvo, JA; Hill, RN; Bruce, RD; Stitzel, KA; Walker, AP; Chu, I; Goddard, M; et al. (1995). "Comparison of the up-and-down, conventional LD50, and fixed-dose acute toxicity procedures". Food and Chemical Toxicology. 33 (3): 223–31. doi:10.1016/0278-6915(94)00136-C. PMID 7896233.
  2. Lichtman, A (1998). "The up-and-down method substantially reduces the number of animals required to determine antinociceptive ED50 values". Journal of Pharmacological and Toxicological Methods. 40 (2): 81–5. doi:10.1016/S1056-8719(98)00041-0. PMID 10100496.
  3. Acute Oral Toxicity (AOT) Up-And-Down-Procedure
  4. Bruce, R. D. (February 1985). "An up-and-down procedure for acute toxicity testing". Fundamental and Applied Toxicology. 5 (1): 151–157. doi:10.1016/0272-0590(85)90059-4. ISSN 0272-0590. PMID 3987991.
  5. "Allergan Receives FDA Approval for First-of-Its-Kind, Fully in vitro, Cell-Based Assay for BOTOX® and BOTOX® Cosmetic (onabotulinumtoxinA)". Source: Allergan, Inc. News Provided by Acquire Media. 24 June 2011. Archived from the original on 26 June 2011. Retrieved 26 June 2011.
  6. "In U.S., Few Alternatives To Testing On Animals". Washington Post. 12 April 2008. Retrieved 2011-06-26.


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