status, we have reported that the parents who were not exposed because they came to Hiroshima and Nagasaki following the bombings as released service men, repatriates, spouses, or immigrants were slightly younger and had a little more education and somewhat higher occupational ratings than the exposed parents (14). In principle, this might result in a higher indicator frequency in the children of exposed parents and also lead to an overestimate of radiation effects.

It is important to note that the estimate of genetic damage following exposure to ionizing radiation derived here rests on mutational events manifesting themselves as an untoward pregnancy outcome recognizable between 20 weeks after fertilization and 14 days following birth. Clearly this does not represent all of the mutational damage that could be expressed throughout life or even all of that from fertilization to 14 days postpartum. Pregnancies terminating prior to the 20th week were not ascertained in this study, and to the extent that such occurrences were dose-related, reflecting mutational damage, our data would underestimate the risk. The magnitude of this possible underestimation is uncertain, indeed impossible to estimate, since pregnancies terminating within 4 weeks of fertilization, before a menses is missed or other symptoms of pregnancy become apparent, are often unrecognized by the prospective mother. Although the proportion of pregnancies terminating this early in gestation is not precisely known, it appears relatively large. However, from the societal standpoint, these early losses are much less traumatic than the untoward pregnancy outcomes of this study.

Since radiation has caused genetic damage in every species properly studied in an experimental setting, we assume that some genetic damage resulted from the Hiroshima-Nagasaki experience. We must then also accept that the data from these children, despite their limitations, provide the best available basis for estimating the confidence limits to be placed on the computed genetic risk involved in exposure to ionizing radiation. Briefly, under a linear dose-response function, the excess relative risk for genetic effects can be defined as the ratio of the slope to the intercept. When concomitant sources of variability are taken into account (Tables VII and IX), this ratio at an RBE of 20 is 0.0986, based on the restricted sample. The 95% lower confidence limit on this doubling dose estimate is approximately 0.15 Sv. The comparable values for the extended sample are 0.0685, and 0.19 Sv, respectively. To utilize these estimates to derive a doubling dose applicable to the genetic component, however, it is necessary to postulate what fraction of the indicator may be attributed to spontaneous mutation in the preceding generation. We shall provide an estimate of this fraction based upon current information and combine the findings of this study with other genetic endpoints that have been measured in the children of survivors to derive estimates of both the minimal and most likely doubling dose in a future paper. 2

ACKNOWLEDGMENTS

This research was conducted at the Radiation Effects Research Foundation, Hiroshima, Japan. The Radiation Effects Research Foundation (formerly ABCC) was established in April 1975 as a private non-profit-making Japanese foundation, supported equally by the Government of Japan through the Ministry of Health and Welfare, and the Government of the United States through the National Academy of Sciences under contract with the Department of Energy.

RECEIVED: June 7, 1989; ACCEPTED: October 30, 1989

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