The evaluation of chemical mutagenicity data in relation to population risk: the need for better methods of extrapolation.

In the fall of 1966 the Food and Drug Administration established an Advisory Committee on Protocols for Safety Evaluation. The first problem to be reviewed was the requirement for reproduction studies in the safety evaluation of pesticides and food additives, and the adequacy of the current methods involved. Reproduction studies are designed to give information on: (1) effects on male and female fertility, (2) effects during gestation on the mother and the fetus, (3) effects appearing after parturition on the mother (for example, lactation) and the offspring (for example, growth, development, sexual maturation), and (4) mutagenic effects, particularly those which might not appear in the first generation. The report of panel dealing with this problem was written in November 1968 and published later (1). During the time the panel was considering the problem, a report prepared by the Genetic Study Section under the chairmanship of Dr. James F. Crow (2), became available to us (C. C. Cockerham, personal communication). The emphasis in this particular report of the Genetic Study Section was that there is reason to be concerned about chemicals as a mutagenic risk equivalent to radiation, possibly even more serious. The concern, of course, is with the welfare of future generations as well as with the health of contemporary populations. It is useful to emphasize again that