Prospects for reduction and replacement alternatives in regulatory toxicology.

There is a considerable impetus to developing alternative methods in regulatory toxicity testing from the introduction of legislation requiring alternative methods to be used whenever possible. Some progress has been made in the search for and validation of alternative methods in regulatory toxicology. When replacement and reduction alternatives are considered, the absolute reduction in the number of animals used in testing is a good indicator of the progress that is being made. Attempts at replacing existing animal methods have focused on acute studies where the endpoints are simple and the mechanism of toxic action understood. The majority of animal studies rely on non-specific endpoints from chronic studies and where there is little understanding of the mechanism of toxic action; these studies are much more difficult to replace. The conclusion is that the methods that are currently under validation to replace regulatory toxicology studies will only reduce the number of animals used to test a chemical (such as a pesticide) by about 3%. The process of validation is likened to technology, where additional resources can improve and hasten the process; however, the rate-limiting step in the overall objective of reducing animal use is the development of suitable tests for validation, a scientific process which draws on the full range of biomedical research and hence will be slow to reveal the necessary data for test development.