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, R.L.; Cotruvo, J.A.; Hill, R.N.; Bruce, R.D.; Stitzel, K.A.; Walker, A.P.; Chu, I.; Goddard, M.; Segal, L.; Springer, J.A.; Myers, R.C. (March 1995). "Comparison of the up-and-down, conventional LD50, and fixed-dose acute toxicity procedures". Food and Chemical Toxicology. 33 (3): 223–231. doi:10.1016/0278-6915(94)00136-c. PMID 7896233.
  2. Lichtman, Aron H (August 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): 81–85. doi:10.1016/s1056-8719(98)00041-0. PMID 10100496.
  3. "Acute Oral Toxicity Up-And-Down-Procedure". US EPA. 2 June 2015.
  4. Bruce, R (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. PMID 3987991.
  5. "Allergan Receives FDA Approval for First-of-Its-Kind, Fully in vitro, Cell-Based Assay for BOTOX® and BOTOX® Cosmetic (onabotulinumtoxinA)" (Press release). Allergan. June 24, 2011. Retrieved May 19, 2020.
  6. Gaul, Gilbert M. (12 April 2008). "In U.S., Few Alternatives To Testing On Animals". The Washington Post.

Further reading
  • Dixon, W. J. (1965). "The Up-and-Down Method for Small Samples". Journal of the American Statistical Association. 60 (312): 967–978. doi:10.1080/01621459.1965.10480843. JSTOR 2283398.
  • Brownlee, K. A.; Hodges, J. L.; Rosenblatt, Murray (1953). "The Up-and-Down Method with Small Samples". Journal of the American Statistical Association. 48 (262): 262–277. doi:10.1080/01621459.1953.10483472. JSTOR 2281287.
  • Dixon, W.J. (March 1991). "Staircase bioassay: The up-and-down method". Neuroscience & Biobehavioral Reviews. 15 (1): 47–50. doi:10.1016/s0149-7634(05)80090-9. PMID 2052197.


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