Up-and-down procedure

Up-and-down procedure^[1] (or method) for toxicology tests in medicine is an alternative to the LD₅₀ test, in which animals are used for acute toxicity 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]