Some general principles of mutagenicity screening and a possible framework for testing procedures.

It is likely that the assessment of chemicals for mutagenicity will soon become a widespread practice, and a large number of different screening procedures have been proposed. The subjection of every new chemical to be released into the environment to every available test is clearly an impossible task, and it is necessary for an understanding of priorities in terms of risk and benefit to be built into any approach. The present paper represents an attempt to frame a protocol for the assessment of new compounds that is concerned not with the details of individual tests but rather with the questions these tests should be designed to answer and to the evaluation of the answers obtained. It is obviously inherent in such an approach that a similar assessment must be made of chemicals already in the environment, but that is not the purpose of the present article. Genetic hazards (with the exception of nondisjunction and some other chromo-somal abnormalities) are very different from toxic hazards, in that there is little or no likelihood of any feedback from human epidemiological data. Toxicologists have stressed (1) that, despite all the animal testing of the past two decades and before, most of what we know about toxic hazards for man has been derived from clinical or epidemiological studies on man himself. Unfortunately , even the overall mutagenic effect of chemicals already in the environment is unlikely to be detectable in man for many generations unless special monitoring procedures are instituted such as electrophore-tic analysis of proteins from umbilical blood. Laboratory experiments are therefore even more important in the evaluation of genetic risk than in the evaluation of toxic hazards. General Principles In drawing up a framework for the testing and evaluation of chemicals I have been guided by three general principles. The first is that no generally mutagenic chemical should be released into the environment or be permitted to be used if there exists a satisfactory nonmutagenic substitute. Tests are thus required to detect the mutagenic activity of substances and most of the procedures so far proposed have had this object. The phrase, "general mutagenic chemical," is used specifically to exclude those substances whose mutagenic action is confined to a rather special situation such as formaldehyde when fed to fruit flies. There is likely to be a hazy line between such special mutagens and general muta-gens and some knowledge of the mechanism December 1973 …