bined, the resultant figure is about 26 × 10−4 per gamete per gray and this has been rounded upwards to 30 × 10−4 per gamete per gray. This estimate summarizes the overall risk of congenital abnormalities for acute X-irradiation of males. With a dose-rate reduction factor of 3, the rate applicable for chronic or low-dose irradiation conditions is about 10 × 10−4 per gamete per gray. Under the assumption that the rate in females will be the same, the rate applicable for irradiation of both sexes is about 20 × 10−4 per gamete per gray.

Current Risk Estimates

Estimates of risk for all classes of disease except congenital abnormalities have been obtained using the equation: Risk = P × 1/DD × MC × PRCF. The values used for estimating the first-generation risk are the following:

Autosomal Dominant + X-Linked
Chronic Diseases

For the second postradiation generation, the MC value is 0.51 for autosomal dominant and X-linked diseases; the values for all others remain the same. Estimates for congenital abnormalities have been obtained using mouse data on developmental abnormalities (see Table 4-3D); the DD method was not used.

Table 4-6 (top part) presents the current estimates of genetic risks of radiation and compares them with those in BEIR V (NRC 1990; bottom part). All estimates are per million progeny per gray.

Risk to Progeny of the First Postradiation Generation

As can be seen, the risk is of the order of about 750 to 1500 cases for autosomal dominant and X-linked diseases (versus 16,500 cases of naturally occurring ones) and zero for autosomal recessive diseases (versus 7500 cases of naturally occurring ones). For congenital abnormalities, the estimate is about 2000 cases (versus 60,000 cases of naturally occurring ones), and for chronic diseases, it is about 250 to 1200 cases (versus 650,000 cases of naturally occurring ones). Overall, the predicted risks per gray represent 0.4 to 0.6% of the baseline frequency (738,000 per million).

Risk to Second Postradiation Generation Progeny

Under conditions of continuous radiation exposure in every generation, the risk to the second postradiation genera

TABLE 4-3D Mouse Database Used for Estimating the Rate of Induction of Dominant Heritable Developmental Effects Listed as Congenital Abnormalities in Table 4-6

End Point

Dose (Gy)

Frequency of Affected Progeny

Rate per Gray (× 104)a

References: Ehling (1965, 1966); Selby and Selby (1977)

1. Skeletal abnormalities

6.0

5/754

 

11

2. Skeletal abnormalities

1+ 5

5/277

(30)a

15

3. Skeletal abnormalities

1+ 5

37/2646

(23)a

12

Overall average induction rate

 

~13

Rate applicable to humans

~6.5

Reference: Favor (1989)

4. Cataractsb

1.5

2/23,157

 

0.28

 

3.0

3/22,712

0.29

5.3

3/10,212

0.47

6.0

3/11,095

0.38

6.0

3/17,599

0.21

Overall average induction rate

 

0.33

Reference: Nomura (1988)

5. Congenital anomalies (detected in utero; ICR strain)

0.36

1/163c

 

56d

1.08

3/234c

83

2.16

9/496c

65

Reference: Kirk and Lyon (1984)

6. Congenital anomalies (detected in utero; [(C3H/HeH) × (101/H) strain]

5.00

22/1014c

 

30e

Unweighted average induction rate

48

Corrected for viability in human live births

19f

Overall rate for developmental abnormalities

30g

NOTE: All these studies involved spermatogonial irradiation.

aEstimates in parentheses: observed rate per gray for fractionated radiation conditions (24 h interval between fractions); estimates without parentheses are standardized to acute radiation conditions by dividing the above by 2, the factor by which specific locus mutation frequencies are known to be enhanced under fractionated radiation conditions.

bRates have been corrected for controls in which the frequency was 1/22,594.

cDenominator refers to the number of live fetuses screened.

dRates corrected for controls (8/1967).

eRate corrected for controls (5/720).

fUnder the assumption that about 40% of the abnormalities may be compatible with live births in humans (see Nomura 1988).

g(6.5 + 0.3 + 19)10−4 = 26 × 10−4 rounded to 30 × 10−4.

tion progeny is slightly higher for autosomal dominant and X-linked diseases and for congenital abnormalities. The overall increase in risk (all classes of disease) relative to the baseline is small (0.53%–0.91% of 738,000 per million progeny).



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