The evaluation of chemical mutagenicity data in relation to population risk: impact of various types of genetic damage and risk assessment.

I should like to review very briefly the various kinds of genetic damage that might be expected to occur from chemical mutagens, the time delay before such effects might be manifest, and something of the kind of impact that these might be expected to have on human well-being. I hardly need to add that this is an area where we know very little; we know enough to be apprehensive, but not enough to be at all certain. My remarks will draw heavily from two recent reports on radiation effects, the National Academy of Sciences Report (1) and the United Nations Report (2). In the area of radiation protection there are standards which are agreed to internationally and which form the basis of radiation protection policy. I suggest that in the area of chemical mutagenesis we can obtain considerable guidance from the older field of radiation muta-genesis. I shall have a specific suggestion later as to how radiation standards can be used as a starting point in setting limits for chemical mutagens. For assessment of the genetic risk to the population, it is convenient to classify genetic damage to man under four very general headings. Mendelian With increasing knowledge we will be able to distinguish between the various kinds of molecular changes in the gene and minute chromosome aberrations, but for most human traits we must now be content to group together all those that are inherited as men-delian units. Within this class we can divide them meaningfully into autosomal dominant, autosomal recessive, and X-linked recessive. Of course, there are X-linked dominants and perhaps a few Y-linked traits, but these are numerically insignificant. In his recent compedium, McKusick (3) lists 415 dominantly inherited traits and an additional 528 if less well-established conditions are included. In most cases the homo-zygous phenotype of these genes is unknown; they are called dominant because the heter-ozygous expression is sufficient to cause a recognizable abnormality or disease. There are 86 X-linked traits listed plus 64 more if less certain types are included. Most of these are recessive, and therefore the abnormality is mainly in males. He lists 365 well-established autosomal recessive traits and 418 more that are probably inherited this way. In well studied organisms such as Droso-phila and mouse, the ratio of recessive to dominant mutants is much higher than it is in man. Undoubtedly this means that many, probably the great majority, of recessive …