Health Risks of Radon and Other Internally Deposited Alpha-Emitters BEIR IV (1988) / Chapter Skim
Currently Skimming:
8 Genetic, Teratogenic, and Fetal Effects
8 Genetic, Teratogenic, and Fetal Effects
Pages 367-396
The Chapter Skim interface presents what we've algorithmically identified as the most significant single chunk of text within every page in the chapter.
Select key terms on the right to highlight them within pages of the chapter.
From page 367... ...
.4i The BEIR }~6 committees estimates of the risks due to genetic damage were recently updated in a study for the U.S. Nuclear Regulatory Comrnission.6 That study incorporated several modifications to the BEIR ITI estimates, including the adoption of equivalent induced mutation rates for the two sexes, the development of an X-linked mutation rate for humans, and the development of an estimate for induced numerical chromosomal abnormalities of nondisjunctional origin.
|
From page 368... ...
report.26 We have, however, noted the influence that the adoption of the HEM6 would have on the estimates of genetic risk in the BEIR IlI report. We have also adopted the demographic projection techniques developed for the HEM as a logical extension of the tabulations in the BEIR ITI report, so that we could project genetic effects into future generations.
|
From page 369... ...
Many mutations induced by ionizing radiation, in both man and experimental animals (such as the laboratory mouse) , are now recognized as chromosomal aberrations.
|
From page 370... ...
The most recent edition of McKusick's catalog of human mutations 23 lists 588 definite plus 710 probable recessives, 934 definite plus 893 probable dominants, and 115 definite plus 128 probable X-linked mutations, as wed as many chromosomal abnormalities. In addition to these relatively simply inherited conditions, however, much human ill health has some heritable component, even though such conditions are not inherited in any clear-cut simple pattern.
|
From page 371... ...
The degree, if any, of mutational sensitivity difference between males and females has been controversial. The authors of the 1985 HEM6 decided to adopt equal mutation rates, although the BEIR ITI report26
|
From page 372... ...
The doubling-dose estimate of 50-250 rem translates into estimates, at genetic equilibrium, of 40-200 autosomal dominant and X-~mked effects and 2~900 irregularly inherited effectsmnillion liveborn offspring for a dose of 1 rem/generation unfit equilibrium is reached. For recessively inherited effects, the BEIR Ill Subcommittee on Genetic Effects made no numerical estimate, noting only that there would be a very slow increase in such effects.
|
From page 373... ...
No separate estimate was made for irregularly inherited or recessive effects, as the effects in heterozygotes were expected to be included in the 5~5 autosomal dominant and X-linked effects. The numerical estimate for first-generation chromosomal aberrations, also a direct estimate, was based on direct cytogenetic observation of aberrations; fewer than 10 were estimated to result from a 1-rem parental exposure among a million liveborn offspring.
|
From page 374... ...
such linearity is reasonable to assume in the case of high-LET radiation. But many geneticists believe that, for mutation induction and the induction of some kinds of chromosomal aberrations, the linear assumption is not a valid interpretation of the experimental high-dose-rate, low-LET results.
|
From page 375... ...
Russell and Lindenbaum35 used the specific-Iocus method to determine mutation rates in male mice into which 239Pu was injected. They used what appeared to be an appropriate factor to describe the location of the plutonium and derived an RBE for alpha particles of only about 2.5, compared with low-dose-rate, low-LET radiation.
|
From page 376... ...
One small experiment in which male mice were given 239Pu failed to yield mutations; thus, it provided some assurance, at least, that the rate of induction of such effects by an internally deposited alpha-emitter is not very large. Chromosomal Aberrations Abundant evidence from experiments with alpha-emitters en c} with neutrons indicate that RBEs for the induction of chromosomal aberrations in plant material or in somatic cells of mammals can be high.
|
From page 377... ...
The lack of any substantive information on these effects in females is unfortunate; nevertheless, since the major contributions to the numbers of genetic health effects estimated by the BEIR ITI Genetic Effects Subcommittee comes from the male, application of the male-derived plutonium-239 RBEs stated above does not seem inappropriate. There is no direct information on any of the other radionuclides of interest, so there seems little choice but simply to adopt for their alpha particles the same RBE values as those for 239Pu.
|
From page 378... ...
NUMERICAL ESTIMATES Table 8-1 shows the numerical estimates of genetic effects of an average population exposure of the gonads to 1 red of alpha particles per 3~yr generation. Table 8-1 is derived from the BEIR Ill report26 using RBEs of 2.5 for gene mutations (dominant, X-linked, and recessive)
|
From page 379... ...
BEIR ITI did not give separate estimates for autosomal dominant and X-~mked conditions. The estimates contained in the HEM6 review allotted roughly one-fourth of the total for the two classes to the X-~nked conditions, and we have similarly apportioned the combined BEIR ITI estimates In preparing Table ~1.
|
From page 380... ...
380 .o at U)
|
From page 381... ...
FETAL EFFECTS, TERATOGENESIS, AND NEONATAL EFFECTS OF IN UTERO EXPOSURE By definition, teratogenic effects can be produced only by injury received after conception. Although alpha-emitting radionuclides can be transmitted across a placenta and incorporated into the body of a developing fetus, only the alpha decays that occur during ~ntrauterine life can cause teratogenesis.
|
From page 382... ...
382 HEALTH RISKS OF RADON AND OTHER ALPHA-EMITTERS TABLE 8-4 Genetic Effects of Population Exposure to 1 red of Alpha Particles to the Gonads per 30-yr Generation over Five Generations Cumulative Absolute No./ ~ 1,000,000 Population Generation Years Dominants X-Linked Translocations 1 5 0 0 0 10 2 1 2 15 2 1 2 20 2 2 4 25 4 3 4 30 6 4 6 2 35 6 6 8 40 8 7 10 45 10 9 12 50 10 12 14 55 12 14 16 60 14 17 19 3 65 15 19 21 70 16 22 24 75 18 25 26 80 19 28 29 85 20 31 31 90 21 35 34 4 95 23 38 37 100 24 41 39 105 25 45 43 110 27 48 45 115 28 52 47 120 29 55 50 5 125 31 58 53 130 33 61 57 135 34 63 61 140 35 66 64 145 37 68 68 150 39 70 69 NOTE: Values are cumulative totals by 5-yr intervals to an approximately stable population of 1,000,000 persons.
|
From page 383... ...
Because the gestation periods of experimental animals differ so widely and are so much shorter than that of humans, estimates are based on the times at which comparable developmental events occur in the different species. EFFECT OF EMBRYoNIc DEvELoPMENT STAGE The teratogenic effects of radiation exposure tend to be closely related to the stage in embryonic development at which the radiation dose is received.
|
From page 384... ...
PLACENTAL TRANSFER AND FETAL ACCRETION OF RADIONUCLIDES The inherent mechanisms involved in the production of developmental effects by exposure of a conceptus or neonate to radiation from internally deposited radioactive materials do not differ from those associated with exposure to photons from external sources. The several factors to be discussed in detail as pertaining to exposure of adults also lead to differences between the developmental effects produced by internal and external exposures and affect the quantitative relationships between administered dose (or maternal body burden)
|
From page 385... ...
The resulting exposures occur at low and varying dose rates, and that makes it difficult to establish reliable quality factors. Many of the deleterious ejects of internal emitters are displayed as postnatal deficits, and it is necessary to separate the effects produced by prenatal exposure from those produced by postnatal exposure to remaining radioisotope and to material transferred in mother's milk.
|
From page 386... ...
unit, and the absorbed radiation is protracted at varying dose rates. As a result, most experiments have been directed either at measurement of placental transfer and fetal content or at determination of effect relative to administered dose, but rarely at both.
|
From page 387... ...
Studies have shown that inhaled 85Kr freely crosses the placenta and that its concentration is the same in maternal and fetal blood; it can be inferred that radon would behave in a similar manner. Because of the consistent involvement of the placenta in the effect, the presence of edema and/or hemorrhage, and the mechanical effects In malformation production, it is not clear to what extent the effects were directly on the conceptus or were secondary to placental and/or yolk sac changes.
|
From page 388... ...
concentrations and partition, measured in other rats, were affected by dosage evaluated late in gestation, but not at earlier times, and there was less selective localization in the yolk sac than was the case with many actinides. The resulting radiation doses throughout the fetoplacental unit were calculated from the distribution data.
|
From page 389... ...
Kelman and Sikov~8 directly examined placental transfer using a system in which the vesseb of the fetal side of the near-term guinea pig placenta were cannulated and perfused to el~rninate the role of the fetus. Graded dosages of citrated 239 Pu and a trace dose of tritiated water were injected into the maternal circulation, and placental transfer was calculated in terms of clearance.
|
From page 390... ...
The primitive cells that ultimately give rise to the gametes and the hematopoietic system are formed in the early yolk sac and migrate into the embryo proper. It can be hypothesized that alpha particles emitted by radionuclides deposited in the yolk sac of the early embryo could produce persistent adverse effects on these primitive cell lines.
|
From page 391... ...
The effects are smaller if based on intravenous dosages administered to pregnant rats, but there is better correspondence between the effects when they are considered relative to radiation doses to particular components of the fetoplacental unit, especially the yolk sac. Measurable amounts of 253 Es cross the placenta, but, according to the limited data available, the fraction of maternal dose that is deposited in the conceptus is low, approximating that of 24,Am.
|
From page 392... ...
Virtually all other teratogenic effects of radiation are believed to be due to multiple cell killing, and one can simply translate the accepted tetrad threshold for singI - dose low-I`ET radiation exposures by applying the RBE commonly observed for alpha particles in in vitro cell-killing experiments. RBEs for cell killing by alpha particles are around 10, but could be higher for the very low dose rates expected from internal emitters.
|
From page 393... ...
· ~ · ~ ~ · . ~ s- ~ ~ Interpretation of cy~ogener~c damage induced In the germ fine ot male mice exposed for over 1 year to 239 Pu alpha particles, fission neutrons, or 60Co gamma rays.
|
From page 394... ...
1976. Cytogenetic effects of protracted exposures to alpha-particles from plutonium239 and to gamma rays from cobalt-60 compared in male mice.
|
From page 395... ...
1982. Dominant lethal and ovarian effects of plutonium-239 in female mice.
|
Key Terms
This material may be derived from roughly machine-read images, and so is provided only to facilitate research.
More
information on Chapter Skim is available.