Legislative and technical aspects of mutagenicity testing

Abstract

A brief account is given of the history of the legislative acts that give responsibility to the U.S. Food and Drug Administration (FDA) for ensuring the safety of foods, drugs, and cosmetics. Withing the present legislative framework the FDA has the authority to impose regulations which are designed to ensure the safety of all foods, drugs, and cosmetics. The existing legislative authority is adequate for this purpose; however, the difficulty lies instead with technology and the inadequacy of scientific perspective in the emerging area of mutagenicity testing. Earlier efforts in development of mutagenicity screening systems culminated only a few years ago in the proposal to use the host-mediated assay, somatic cell cytogenetics, and dominant lethal tests collectively. Subsequent research effects indicated that there were serious practical and scientific deficiencies in using this approach. More recently a new proposal, the tier system, has been suggested as an alternative measure. The proposed tier system at FDA consists of three testing levels of increasing complexity. The first tier is an initial screening effort using techniques having maximum sensitivity that are also useful for large-scale, rapid testing. The second tier is designed to identify and confirm that the presumptie mutaggens detected in the first tier are truly mutagenic for higher organisms, most especialy, for mammals. The third tier would be devoted to explicit genetic tests in mammals designed to ascertain the imposed risk to man by the introduction of a mutagen in our environment. The FDA is currently involved in a number of research activities in the area of mutagenicity safety screening which will explore the adequacies and possible deficiencies of the tier system approach. These efforts are described for our in-house activities, our contract activities, and our cooperative and collaborative activities with other government agencies and institutions.