Toxicology then and now.

A review of the history of the evolution of the science of toxicology from the original concepts of Paracelsus through the early development of analytical chemistry and its contributions to the detection of toxic substances in foods and drugs as these have led to modern regulatory rules for public protection is presented. The legal actions taken to protect against adulteration of food prior to the early steps by the U.S. Department of Agriculture that concluded with the passage of the 1906 Food and Drug Act are systematically documented. The history is reviewed of the Food and Drug Administration's role in the use of animal toxicity studies to develop reasonable criteria for safety of foods and drugs for man. Modern concepts of molecular distribution, metabolism, and excretion of substances in the animal body are discussed as these impinge on the so-called "protection index." The legal and often litigious controversies over the claimed carcinogenicity of chemical substances is documented with comments on the Delaney dilemma and the role of in vitro tests in toxicology. The review concludes with a discussion of the hazards of use of stochastic mathematical models to assess carcinogenicity and suggests that the criteria employed in the report of the Scientific Committee of the Food Safety Council are properly structured to give a contemporary evaluation of all the currently available data. References give documentation of events over the past 200 years that explain the present state of toxicology as a discipline.