Potency and safety analysis of hemp-derived delta-9 products: The hemp vs. cannabis demarcation problem

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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.[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]


  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.

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