As in the BEIR V report (NRC 1990), estimates of the risks of adverse heritable effects of radiation exposure are made indirectly through extrapolation from mouse data on rates of radiation-induced germ cell mutations using population genetic theory and a set of plausible assumptions (see Chapter 4). These estimates are expressed as increases in the frequencies of genetic diseases relative to their baseline frequencies in the population. The method that is used for this purpose is referred to as the “doubling dose method.” Equation (10-1) below summarizes the method:


where P is the baseline frequency of the disease class under consideration, DD is the doubling dose (i.e., the dose of radiation required to double the rate of spontaneous mutation in a generation, estimated as a ratio of rates of spontaneous and induced mutations in defined genes), MC is the mutation component (a measure of the responsiveness of the disease class to an increase in mutation rate), and PRCF is the potential recoverability correction factor (the fraction of induced mutations that are compatible with live births and cause disease).

This report incorporates several important advances that have been made since the publication of BEIR V (NRC 1990), among which are those that relate to the four quantities mentioned above. It suffices to note that the estimates for P, MC, and PRCF are different for Mendelian and multifactorial diseases; however, the DD estimate of 1 Gy (for low-dose or chronic low-LET exposure) is common to both classes of disease.

The risk estimates provided in Chapter 4 are about 3000 to 4700 cases of excess genetic disease per million first-generation progeny per gray of radiation to the parental generation. Compared to the natural (i.e., baseline) risk of genetic diseases of 738,000 per million live births in the population, the radiation risk (per gray) is very low (about 0.4 to 0.6% of the baseline).

As mentioned earlier, the results of the extensive genetic epidemiologic studies of A-bomb survivors in Japan have shown no adverse effects in the progeny that could be attributed to the radiation exposures (of the order of 0.4 Sv) sustained by most survivors. The indicators of adverse effects used in these studies were untoward pregnancy outcomes (UPOs), mortality of live born children through a period of about 26 years (exclusive of those resulting from malignant tumors), malignancies in the F1 children, frequency of balanced structural rearrangements of chromosomes, frequency of sex chromosomal aneuploids, frequency of mutations affecting protein charge or function, sex ratio shift among children of exposed mothers, and growth and development of F1 children. The important point here is that these indicators of adverse effects cannot be compared readily to what are formally called genetic diseases.

The total numbers of children included in the analyses to ascertain radiation effects were about 41,000 in the “unexposed” and 31,000 in the “exposed” groups, although the numbers were different for different indicators (e.g., ~8000 children each in the exposed and control groups for balanced structural chromosomal rearrangements and sex chromosomal aneuploidy; ~41,000 in the exposed and ~31,000 in the exposed groups for malignancies in F1).

Although no statistically significant effects of parental radiation exposures were found, Neel and colleagues (1990) estimated doubling doses on the basis of data for five of the indicators (i.e., UPO, F1 mortality, F1 cancers, sex chromosomal aneuploids, mutations) that would be consistent with the findings. In order to do this, several assumptions had to be made (discussed in Annex 4G). The oft-quoted DD estimated from these data, corrected for low-dose or chronic, low-LET radiation conditions is 3.4 to 4.5 Sv.

The perception remains that the above estimate of the DD is indicative of far lower heritable risk than that implied by the DD of 1 Gy used by the present BEIR committee and UNSCEAR (2001; since 1/DD, the relative mutation risk per unit dose, is a smaller fraction with the Japanese DD). It should be stressed that comparison of the DDs alone does not present the correct picture of risks for the following reasons: (1) the Japanese DDs are estimated retrospectively from empirical observations using measures of genetic ill health that are totally different from those used by this committee; besides, these measures have not shown any significant differences between the control and radiated groups; and (2) the DD of 1 Gy used by the present committee (and by UNSCEAR 2001) is based on data on mutations in defined genes and is used prospectively as one of the four factors in predicting the risk of genetic diseases. Nonetheless, the principal message that emerges from the Japanese epidemiologic studies and the present risk estimates projected from mouse data on radiation-induced mutations is the same—namely, that at low or chronic doses of low-LET irradiation, the genetic risks are very small compared to the baseline risk in the population.


The principal objective of this chapter is to highlight the ways in which cellular, molecular, and animal data considered in this report may be integrated with epidemiologic findings in order to develop coherent judgments on the health effects of low-LET radiation. Emphasis is placed on data integration for the purposes of modeling these health risks.

The principal conclusions from this work can be summarized as follows:

  • Current knowledge of the cellular or molecular mechanisms of radiation tumorigenesis tends to support the appli-

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