Testing is done as a check on the safety of new drugs or substances for human or animal use, and to check whether new batches of drugs and other agents like vaccines work. There is a legal requirement to test how safe and effective chemicals, drugs and other therapeutic agents are before they can be sold. Well-known tests that cause suffering when the test substance is poisonous, corrosive or otherwise harmful are the LD50 Test and the Draize Eye Irritancy Test. All three of the Three Rs have been successfully applied to testing and scientists are working hard to find more and better ways of applying them. For instance, replacement of animals with tissue cultures (cells kept alive in a test tube) is now used extensively, especially in the early stages of testing when whole animals were once used. Also, employing careful statistical analysis and substitutes for animals (replacements) have markedly reduced the number of animals required in testing procedures, and using earlier more humane endpoints thereby ending a noxious testing procedure much sooner than used to be the case is a form of refinement.