Up-and-down procedure
Open-knowledge reference entry
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. It requires fewer animals to achieve similar accuracy as the LD50 test because animals are dosed one at a time. 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. The US EPA provides a statistical program to calculate the oral LD50 and 95% Confidence Limits called AOT425StatPgm. This program will notify the user when a stopping criteria has been met, while being able to generate statistically valid LD50, using fewer animals. The U.S. Food and Drug Administration has begun to approve non-animal alternatives.
References
Further reading
Dixon, W. J. (1965). "The Up-and-Down Method for Small Samples".
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