Design of Carcinogenicity Studies: A Backward Glance

Abstract

Despite extensive research carried out over many years, a completely satisfactory method of testing drugs and chemicals for carcinogenicity continues to elude toxicologists. In the past, numerous scientific groups, regulatory agencies, and regional bodies have discussed and published specific recommendations and guidelines regarding the testing requirements for carcinogenicity studies. The Food, Drug and Cosmetic Act became law in 1938, but it was not until after the Second World War that serious concerns regarding chemicals became prevalent. Testing guidelines were nonexistent until 1949 when the FDA published “Procedures for the Appraisal of the Toxicity of Chemicals in Foods.” This key publication was the forerunner of the famous “Gray Book” (1959) in which were outlined many of the specific carcinogenicity testing procedures still used today. Guidelines and regulations became the watchwords during the 60's and 1970's. Formation of the EPA, more stringent testing requirements, Toxic Substances legislation, and Environmental Control Acts followed one another in short order. NCI's Technical Report #1 (1976) entitled, “Guidelines for Carcinogen Bioassay in Small Rodents” probably had the greatest impact of any publication on carcinogenicity testing. Many later guidelines and recommendations were based on this publication.

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