a derived from Drosophila and lower vertebrates are applied to human radiation exposure (a tenuous but not illogical assumption), the increased risk of visible mutational defects in the progeny can be calculated. On the basis of administration to the entire population of sufficient 131-I to deliver to the gonads 2 rads or 2% of the doubling dose (assumed to be the same as in the mouse), the increase in the rate of mutational defects would ultimately be about 0.04%, although only one-tenth would be seen in the first generation. Obviously only a minute fraction of the population will ever receive therapeutic 131-I. The incidence of thyrotoxicosis is perhaps 0.03% per year, or 1.4% for the normal life span. At least one-half of these persons will have their disease after the childbearing age has passed. Although most of them will be women, this fact does not affect the calculations after a lapse of a few generations. Assuming that the entire exposed population receives 131-I therapy in an average amount of 5 mCi, the increase in congenital genetic damage would be on the order of 0.02 (present congenital defect rate) x 0.04 ( 131-I radiation to the gonads as a fraction of the doubling dose) x 0.014 (the fraction of the population ever at risk) x 0.5 (the fraction of patients of childbearing age) = 0.0000056. This crude estimate, developed from several sources, also implies that, if all patients with thyrotoxicosis were treated with 131-I, the number of birth defects might ultimately increase from 4 to 4.0006%. This increase may seem startlingly small or large, depending on one’s point of view, but it is a change that would be essentially impossible to confirm from clinical experience. Unfortunately, it is more difficult to provide a reliable estimate of the increased risk of genetic damage in the offspring of any given treated patient. Calculations such as the above simply state the problem for the whole population. Since most of the mutations are recessive, they appear in the children only when paired with another recessive gene derived from the normal complement carried by all persons.
Assuming that only one parent received radiation from 131-I therapy amounting to 2% of the doubling dose, the risk of apparent birth defects in the patient’s children might increase from the present 4.0% to 4.008%. 0.02 (present genetic defect rate) x 0.04 (fraction of the doubling dose) x 0.1 (fraction of defects appearing in the first generation) = 0.00008, or an increase from 4.0% to 4.008%. Similar estimates can be derived by considering the number of visible mutations derived from experimental radiation in lower species.[ 92, 93] 6 x 10-8 (mutations produced per genetic locus per rad of exposure) x 104 (an estimate of the number of genetic loci in humans) x 2 (gonadal radiation in rads as estimated above) x 0.1 (fraction of mutations appearing in the first generation) = 0.00012 or 0.012% On this basis, the increase in the birth defect rate would be from 4.0% to 4.012%.
One important observation stemming from these calculations is that large numbers of children born to irradiated parents must be surveyed if evidence of genetic damage is ever to be found. Reports of “no problems” among 30 to 100 such children are essentially irrelevant when one is seeking an increase in the defect rate of about 4.0% to about 4.008%. These statistics are presented in an attempt to give some quantitation to the genetic risk involved in 131-I therapy, and should not be interpreted as in any sense exact or final. The point we wish to stress is that radiation delivered to future parents probably will result in an increased incidence of genetic damage, but an increase so slight that it is difficult to measure. Nonetheless, the use of 131-I for large numbers of women who subsequently become pregnant will inevitably introduce change in the gene pool. In considering the significance of these risks, one must remember that the radiation exposure to the gonads from the usual therapeutic dose of 131-I may be only one or two times that produced during a procedure such 