An up-and-down procedure for acute XXXX testing.

@entity35 @entity137 @entity204
An up-and down method for acute @entity137 (LD50) testing has been developed and statistically evaluated. Compared with the "classical" procedure, this method permits a major reduction in the number of animals used. In the up-and-down procedure, animals are dosed one at a time. If an animal survives, the dose for the next animal is increased; if it dies, the dose is decreased. A survey of 48 acute @entity137 tests in @entity35 showed that the great majority of the animals that ultimately died did so within 1 or 2 days. Because of this, it suffices to observe each animal for 1 or 2 days before dosing the next animal. It is recommended, however, that surviving animals be monitored for delayed @entity204 for a total of 7 days. The procedure for estimating the LD50 takes into account all @entity204 , and may be performed using widely available computer program packages. Testing in females alone is recommended, based on the observation that they were generally more sensitive in the survey of 48 studies; selective follow-up in males may sometimes be indicated. The procedure has been tested, by simulation, on 10 of the survey studies. It produced excellent agreement with the original studies. The 95% confidence interval for the LD50 averaged +/- 32% by the up-and-down method, compared with +/- 15% for conventional studies using 40 to 50 animals. The up-and-down procedure will require only 6 to 10 animals, provided that the initial estimate of the LD50 is within a factor of 2 of the true LD50. The method cannot be recommended for testing materials where @entity204 beyond 2 days postdosing are the rule.
