Up-and-down procedure[1] (or method) for toxicology tests inmedicine is an alternative to theLD50 test, in which animals are used for acutetoxicity testing.[2][3] It requires fewer animals to achieve similar accuracy as the LD50 test because animals are dosed one at a time.[4] 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.[5] The US EPA provides a statistical program to calculate the oral LD50 and 95% Confidence Limits called AOT425StatPgm.[6] This program will notify the user when a stopping criteria has been met, while being able to generate statistically valid LD50, using fewer animals.[1] The U.S. Food and Drug Administration has begun to approve non-animal alternatives.[7][8]
^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.PMID7896233.
^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.PMID10100496.
^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.PMID3987991.
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.JSTOR2281287.
