National Academies Press: OpenBook

Health Effects of Exposure to Low Levels of Ionizing Radiation: BEIR V (1990)

Chapter: 6 Other Somatic and Fetal Effects

« Previous: 5 Radiogenic Cancer at Specific Sites
Suggested Citation:"6 Other Somatic and Fetal Effects ." National Research Council. 1990. Health Effects of Exposure to Low Levels of Ionizing Radiation: BEIR V. Washington, DC: The National Academies Press. doi: 10.17226/1224.
×
Page 352
Suggested Citation:"6 Other Somatic and Fetal Effects ." National Research Council. 1990. Health Effects of Exposure to Low Levels of Ionizing Radiation: BEIR V. Washington, DC: The National Academies Press. doi: 10.17226/1224.
×
Page 353
Suggested Citation:"6 Other Somatic and Fetal Effects ." National Research Council. 1990. Health Effects of Exposure to Low Levels of Ionizing Radiation: BEIR V. Washington, DC: The National Academies Press. doi: 10.17226/1224.
×
Page 354
Suggested Citation:"6 Other Somatic and Fetal Effects ." National Research Council. 1990. Health Effects of Exposure to Low Levels of Ionizing Radiation: BEIR V. Washington, DC: The National Academies Press. doi: 10.17226/1224.
×
Page 355
Suggested Citation:"6 Other Somatic and Fetal Effects ." National Research Council. 1990. Health Effects of Exposure to Low Levels of Ionizing Radiation: BEIR V. Washington, DC: The National Academies Press. doi: 10.17226/1224.
×
Page 356
Suggested Citation:"6 Other Somatic and Fetal Effects ." National Research Council. 1990. Health Effects of Exposure to Low Levels of Ionizing Radiation: BEIR V. Washington, DC: The National Academies Press. doi: 10.17226/1224.
×
Page 357
Suggested Citation:"6 Other Somatic and Fetal Effects ." National Research Council. 1990. Health Effects of Exposure to Low Levels of Ionizing Radiation: BEIR V. Washington, DC: The National Academies Press. doi: 10.17226/1224.
×
Page 358
Suggested Citation:"6 Other Somatic and Fetal Effects ." National Research Council. 1990. Health Effects of Exposure to Low Levels of Ionizing Radiation: BEIR V. Washington, DC: The National Academies Press. doi: 10.17226/1224.
×
Page 359
Suggested Citation:"6 Other Somatic and Fetal Effects ." National Research Council. 1990. Health Effects of Exposure to Low Levels of Ionizing Radiation: BEIR V. Washington, DC: The National Academies Press. doi: 10.17226/1224.
×
Page 360
Suggested Citation:"6 Other Somatic and Fetal Effects ." National Research Council. 1990. Health Effects of Exposure to Low Levels of Ionizing Radiation: BEIR V. Washington, DC: The National Academies Press. doi: 10.17226/1224.
×
Page 361
Suggested Citation:"6 Other Somatic and Fetal Effects ." National Research Council. 1990. Health Effects of Exposure to Low Levels of Ionizing Radiation: BEIR V. Washington, DC: The National Academies Press. doi: 10.17226/1224.
×
Page 362
Suggested Citation:"6 Other Somatic and Fetal Effects ." National Research Council. 1990. Health Effects of Exposure to Low Levels of Ionizing Radiation: BEIR V. Washington, DC: The National Academies Press. doi: 10.17226/1224.
×
Page 363
Suggested Citation:"6 Other Somatic and Fetal Effects ." National Research Council. 1990. Health Effects of Exposure to Low Levels of Ionizing Radiation: BEIR V. Washington, DC: The National Academies Press. doi: 10.17226/1224.
×
Page 364
Suggested Citation:"6 Other Somatic and Fetal Effects ." National Research Council. 1990. Health Effects of Exposure to Low Levels of Ionizing Radiation: BEIR V. Washington, DC: The National Academies Press. doi: 10.17226/1224.
×
Page 365
Suggested Citation:"6 Other Somatic and Fetal Effects ." National Research Council. 1990. Health Effects of Exposure to Low Levels of Ionizing Radiation: BEIR V. Washington, DC: The National Academies Press. doi: 10.17226/1224.
×
Page 366
Suggested Citation:"6 Other Somatic and Fetal Effects ." National Research Council. 1990. Health Effects of Exposure to Low Levels of Ionizing Radiation: BEIR V. Washington, DC: The National Academies Press. doi: 10.17226/1224.
×
Page 367
Suggested Citation:"6 Other Somatic and Fetal Effects ." National Research Council. 1990. Health Effects of Exposure to Low Levels of Ionizing Radiation: BEIR V. Washington, DC: The National Academies Press. doi: 10.17226/1224.
×
Page 368
Suggested Citation:"6 Other Somatic and Fetal Effects ." National Research Council. 1990. Health Effects of Exposure to Low Levels of Ionizing Radiation: BEIR V. Washington, DC: The National Academies Press. doi: 10.17226/1224.
×
Page 369
Suggested Citation:"6 Other Somatic and Fetal Effects ." National Research Council. 1990. Health Effects of Exposure to Low Levels of Ionizing Radiation: BEIR V. Washington, DC: The National Academies Press. doi: 10.17226/1224.
×
Page 370

Below is the uncorrected machine-read text of this chapter, intended to provide our own search engines and external engines with highly rich, chapter-representative searchable text of each book. Because it is UNCORRECTED material, please consider the following text as a useful but insufficient proxy for the authoritative book pages.

OTHER SOMATIC AND FETAL EFFECTS 352 6 Other Somatic and Fetal Effects CANCER IN CHILDHOOD FOLLOWING EXPOSURE IN UTERO Human Epidemiologic Studies Preliminary results of the Oxford Survey of Childhood Cancers, published over 30 years ago, suggested an association between the risk of cancer, primarily leukemia, in childhood (within 15 years of birth) and prenatal exposure to diagnostic x rays in utero (St56, 58). A subsequent survey of 734,243 children born in New England supported this suggestion (Ma62). The initial results of follow-up of prenatally irradiated atomic-bomb survivors during the first 10 years of life had failed to support the suggestion (Ja70). However, in a more recent, 1950-1984, follow-up based on DS86 dosimetry (Yo88), two cases of childhood cancer have been observed among 1,630 in utero-exposed survivors during the first 14 years of life, both of which occurred in persons who had been heavily exposed (1.39 and 0.56 Gy). The occurrence of these two cases corresponds to an upper bound risk estimate (95% confidence level) of 279 cases/104 PGy, an estimate consistent with Bithell and Stiller's estimate on reanalysis of the Oxford survey data (Bi88). An extension of the New England survey to include cancer deaths in 1,429,400 children born between 1940 and 1960 in 42 hospitals in New England and the mid-Atlantic states (Mo84) also showed an excess of cancers among those exposed to diagnostic x rays in utero. In this study, cases were compared with age-and sex-matched nonirradiated controls. For leukemia and other cancers, the relative risks were 1.52 and 1.27,

OTHER SOMATIC AND FETAL EFFECTS 353 respectively, with no evidence that the excess was attributable to risk factors other than radiation or was limited to a particular subpopulation (Mo84). To explore the possibility that both prenatal x-ray examination and childhood cancer might be attributable to a separate, common risk factor, and since radiographic examination of women who are pregnant with twins has usually been performed because of the twin pregnancy rather than because of other diagnostic concerns, the incidence of cancer has been investigated in irradiated twins. The first such study, conducted in the United Kingdom, found the relative risks of childhood leukemia and other cancers in irradiated twins (versus nonirradiated twins) to be 2.0 and 1.7, respectively. It also found as many excess cases of cancer in irradiated dizygotic and monozygotic twins as in irradiated singleton births (Mo74). The second study, conducted on twins in Connecticut, likewise found the relative risks of childhood leukemia and other cancers in irradiated twins versus those in nonirradiated twins, especially at ages 10-14 years, to be 1.6 (90% C.I. 0.4, 6.8) and 3.2 (0.9, 10.7), respectively (Ha85); however, the excess was restricted largely to children of mothers with a history of previous pregnancy loss, in whom the overall relative risk of cancer was 7.8 (1.2, 50.4), compared with 1.4 (0.5, 4.3) in irradiated twins born to mothers without a history of pregnancy loss (Ha85). Because of the comparatively small magnitude of the average radiation dose to the fetus from diagnostic radiography, which has been estimated as 5-50 mGy, the data imply that susceptibility to radiation carcinogenesis is relatively high during prenatal life (NRC72, NRC80, UN77, Mo84). Such an interpretation is complicated, however, by the fact that little increase in susceptibility has been evident in prenatally x-irradiated experimental animals and there is no known biological basis for such an increase in susceptibility or for the suggested equivalence in magnitude of the leukemia excess with that of other childhood cancers (Mi86). These complications notwithstanding, the concordance of the studies of twins with the studies of prenatally irradiated singleton births prompts the tentative conclusion that susceptibility to the carcinogenic effects of irradiation is high during prenatal life. Although, mortality from cancer now appears to be increased in prenatally exposed atomic-bomb survivors more than four decades after they were irradiated (Yo88), it remains to be established that the risk of cancer in adult life is increased by prenatal irradiation. During the observation period 1950-1984, however, the relative risk of fatal cancer at a dose of 1 Gy to the mother's uterus (DS86 organ dose), among a total of 1,630 in utero-exposed A-bomb survivors has been estimated as 3.77 (90% C.I. 1.14, 13.48), corresponding to an absolute risk of 6.57 (90% C.I. 0.47, 14.49) per 104 PYGy and an attributable risk of 40.9% per Gy (90% C.I. 2.9%,

OTHER SOMATIC AND FETAL EFFECTS 354 90.2%). Thus, these results also suggest that susceptibility to radiation-induced cancer is higher in prenatally exposed survivors than in postnatally exposed survivors (Yo88). Comparable late-occurring carcinogenic effects from prenatal irradiation have been observed in laboratory mice (Co84). Summary Based on the limited epidemiologic data available through the early 1970s, the 1977 UNSCEAR committee (UN77) estimated the risk per unit absorbed dose to be about 200 to 250 excess cancer deaths/104 person Gy in the first 10 years of life, with one-half of these malignancies being leukemias and one- quarter tumors of the nervous system. Bithell and Stiller's (Bi88) recent estimate from the Oxford survey, 217 cases/104 person Gy, falls within this range. The epidemiologic studies also suggest that an association exists between in utero exposure to diagnostic x rays and carcinogenic effects in adult life; however, the magnitude of the risk remains uncertain. EFFECTS ON GROWTH AND DEVELOPMENT Animal Studies The effects of prenatal irradiation on the growth and development of the mammalian embryo and fetus, mediated through direct radiation injury of developing tissues (Br87), include gross structural malformations, growth retardation, embryo lethality, sterility, and central nervous system abnormalities (UN77). Major anatomical malformations have been produced in all mammalian species by irradiation of the embryo during early organogenesis; however, the time of maximal susceptibility is sharply circumscribed, and the evidence suggests that there may be a threshold for many, if not most, major malformations (NRC80). Retardation of postnatal growth also has been observed to be produced over a broad range of mammalian gestational ages in experimental animals and humans (NRC80). The developing central nervous system exhibits a particular sensitivity to ionizing radiation (ICRP87). In experimental animals, the central nervous system malformations most likely to be produced by irradiation during early organogenesis include hydrocephaly, anencephaly, encephalocele, and spina bifida. In rats, mice, and monkeys, radiation has been shown to induce functional and behavioral effects too, including motor defects (Ya62), emotionality (Fu58), impairment of nervous reflexes and hyperactivity (Ma66), and deficits in learning (Le62). In rodents, disturbances of conditional reflexes, impairment of learning ability, and locomotor damage also have

OTHER SOMATIC AND FETAL EFFECTS 355 been reported after doses that were large enough to cause gross structural damage (UN86). Human Studies The most definitive human data concerning the effects of prenatal irradiation are those relating to brain development (UN86). Severe Mental Retardation Injurious effects of ionizing radiation on the developing human brain have been documented in Japanese A-bomb survivors who were exposed in utero (Bl73, Bl75, IC86, Mi76, Ot83, Sc86a, Sc86b, UN86, Wo67), in whom the prevalence of mental retardation and small head size increases with increasing exposure. In recent studies based on a cohort of 1,598 such individuals, all of the 30 children who were found to have severe mental retardation were diagnosed before the age of 17. Nine of the mentally retarded individuals, only 3 of whom had doses greater than 0.5 Gy, also had other health problems, presumably not related to radiation, which might account for their severe mental retardation. Two individuals had conditions unlikely to be casual for mental retardation, neonatal jaundice and, possibly, neurofibromatosis. Three have or have had Down syndrome, one a retarded sibling and another Japanese encephalitis during infancy. Dosimetry: Estimates of the dose received by the children as fetuses are not yet available from the DS86 system, but the intrauterine doses received by their mothers should provide a useful approximation. DS86 organ dose estimates for the uterus have been computed for most of the exposed mothers who were within 1600 m of the hypocenter in Hiroshima and 2000 m in Nagasaki (Ot87, Ro87). Organ doses were modeled individually to take account of house shielding and the orientation and posture of the exposed individuals. For exposed individuals with incomplete shielding histories, the calculated free- in-air (FIA) kerma was adjusted by means of average house and body transmission factors to obtain an average organ dose. Under the DS86 dose system, neutrons are not a significant contributor to most fetal exposures; the DS86 FIA neutron kerma in Hiroshima at 2000 meters was only 0.0004 Gy and in Nagasaki, 0.0003 Gy (Ro87). Gestational Age: Gestational age is an important factor in determining the nature of the radiation injury to the developing brain of the embryo or fetus (Bl73, Bl75, Mi76, Ot83, Ot86, Ot87, Sc86a, Sc86b). Gestational ages have been grouped to reflect the known phases in normal brain development. The four categories measured from the time of conception were 0-7, 8-15, 16-25, and ≥26 weeks. During the first period (0-7 weeks), the precursors of the neurons and neuroglia emerge and are mitotically active (Ma82). During the second period (8-15 weeks), a rapid increase in

OTHER SOMATIC AND FETAL EFFECTS 356 the number of neurons occurs; they migrate to their developmental sites and lose their capacity to divide, (Ra75, Ra78). During the third period (16-25 weeks), differentiation in situ accelerates, synaptogenesis that began at about week 8 increases, and the definitive cytoarchitecture of the brain results. The fourth period (≥26 weeks) is one of continued architectural and cellular differentiation and synaptogenesis of the cerebrum with, at the same time, accelerated growth and development of the cerebellum. FIGURE 6-1 Percentages of severe mental retardation at various fetal doses in the combined Hiroshima and Nagasaki data. The number of cases is given at the top of the histogram (Ot87). Among atomic-bomb survivors exposed in utero, a dose-dependent increase in the incidence of severe mental retardation occurred in the gestational age group 8-15 weeks after conception and, to a lesser extent, in the gestational age group 16-25 weeks after conception (Figure 6-1). No subjects exposed to radiation at less than 8 weeks or ≥26 weeks of gestational age were observed to be mentally retarded. The relative risk for exposure during the 8-15 week period is at least 4 times greater than that for exposure at 16-25 weeks after conception. Dose-Response Models: The dose response for severe mental retardation has been examined in depth by Otake, Yoshimaru, and Schull (Ot87). Their results are shown in Figure 6-2. Within the critical gestational age period of 8-15 weeks, the prevalence of severe mental retardation can be linearly related to the absorbed dose received by the fetus. There is a highly significant increase in the occurrence of severe mental retardation

OTHER SOMATIC AND FETAL EFFECTS 357 with dose in Hiroshima and in the combined data from both cities. This increase is strongest in the children irradiated at 8-15 weeks after conception but a suggestive increase is also seen at 16-25 weeks after conception. In the data for both cities, the variation in frequency of occurrence with dose, when exposure occurred 8-15 weeks after conception, can be accounted for by a linear model, although there is some suggestion of a nonlinear component in the dose- response function for both the 8-15 and 16-25 week periods (Figure 6-2). Maximum likelihood analyses based on a simple linear model were made to estimate a possible threshold dose and its 95% confidence intervals (Ot87). When all cases were considered, the estimated lower bound of the threshold for the most sensitive period of 8-15 weeks after conception was zero. However, exclusion of cases with a possible nonradiation related etiology yields a threshold with a lower bound of 0.12 Gy for ungrouped data and 0.23 Gy when the data is stratified by dose interval. Both of the estimated thresholds, 0.39 and 0.46 Gy, respectively, are significantly different from zero. Further investigation, using an exponential linear model, found an estimated lower bound for a threshold of 0.09 Gy for FIGURE 6-2 The percentage of severe mental retardation among those exposed in utero by dose and gestational age in Hiroshima and Nagasaki. The vertical lines indicate 90% confidence intervals (Ot87).

OTHER SOMATIC AND FETAL EFFECTS 358 the grouped data and 0.15 Gy for the individual data for those exposed in the 8-15 week period. Similarly, a threshold was also indicated for the 16-25 week- period, with a lower bound of 0.21 Gy, based on a linear model with either the individual or the grouped data, and 0.22-0.25 Gy with the exponential linear model. However, the case for a threshold is not clear; linear regressions using a threshold predict a larger response than was actually observed at large doses (W. J. Schull, personal communication). In summary, analysis of the epidemiologic data has identified the maximal sensitivity of the human brain to occur between 8 and 15 weeks of gestational development. During this period, the dose-effect relationship resulting from the new DS86 dosimetry system indicates a frequency of severe mental retardation of 43% at 1 Gy and suggests that a threshold for the effect may exist in the range 0.2 to 0.4 Gy (Ot87, IC88). Uncertainties: A number of uncertainties are associated with these risk estimates. These include the limited number of cases, the appropriateness of the comparison group, errors in the estimation of the absorbed doses and the calculated prenatal ages at exposure, variation in the severity of mental retardation, and other confounding factors in the postbombing period, including malnutrition and disease (Sc86a). Discussion: Significant harmful effects of radiation on the developing brain of children exposed in utero during the atomic bombings of Hiroshima and Nagasaki were observed only for those exposed during the periods 8-15 and 16-25 weeks after conception. During the period at 8-15 weeks, the period of maximum sensitivity, the dose-response relationship appeared to be different from that at subsequent gestational ages, indicating that radiation effects on cerebral growth and development vary with gestational age at exposure. This period of maximum radiation sensitivity is the time of the most rapid cell proliferation and migration of immature neurons from the ventricular and subventricular proliferative layers to the cerebral cortex (Do73, Ra75, Ra78). Radiation exposure during this period may be inferred to induce neuronal abnormalities and misarrangement of neurons, as well as decreasing the number of normal neurons. This inference appears to be supported by nuclear magnetic resonance images of the brains of severely mentally retarded children, in which abnormal collections of neurons in areas of disturbed brain architecture have been demonstrated (W. J. Schull, personal communication). The data for 8-15 weeks after conception, based on the DS86 doses, fit either a linear or linear exponential dose-response relationship without a threshold. Otake et al. have pointed out that estimating a threshold for this effect is difficult and may depend on the clinical criteria for severe mental retardation. If exposure to radiation moves the distribution of intelligence downward in proportion to dose, as described below, the number of individuals with levels of intellectual function below the diagnostic threshold must

OTHER SOMATIC AND FETAL EFFECTS 359 necessarily increase as the dose increases (Ot87). Clinical selection of an arbitrary level for severe mental retardation dichotomizes the distribution of intelligence levels and could lead to an apparent threshold for this effect. At 16-25 weeks after conception, differentiation accelerates, synaptogenesis that begins at about week 8 increases, and the functional cytoarchitecture of the brain takes place. During this period radiation may impair synaptogenesis, producing a functional deficit in brain connections. The response seen among the atomic-bomb survivors, irradiated during the period 16-25 weeks after conception, suggests that the evidence for a threshold is stronger during this period than during the 8-15 week interval. No evidence of a radiation-related increase in mental retardation has been observed in survivors exposed earlier than 8 weeks after conception or later than 26 weeks after conception. The absence of an effect prior to the eighth week suggests that either the cells that were killed or inactivated at this stage of development are more readily replaced than those that were damaged later, or that the embryo fails to develop further. The final weeks of gestation are largely a time of continued cytoarchitectural and cellular differentiation and synaptogenesis, and the basic neuronal structure of the cerebrum is nearing completion at this time. Since differentiated cells are generally less radiosensitive than undifferentiated ones, measurable damage may require much higher doses and, given the small number of atomic-bomb survivors at these doses, may be more difficult to detect (Ot87). Nonradiation-related explanations for the observed effects on the embryonic and fetal central nervous system that could affect these findings include: (1) genetic variation, (2) nutritional deprivation, (3) bacterial and viral infections during pregnancy, and (4) embryonic or fetal hypoxemia. It is possible that one or more of these factors could have confounded the observations. It is commonly presumed that radiation-related damage to the developing brain results largely, if not solely, from neuronal death. This assumption rests in part on the relatively large proportion of the mentally retarded who have small heads. There is a need, therefore, to determine what role, if any, these other possible causes of a relatively small brain may play in the radiation-related risk of mental retardation. Intelligence Test Scores Intelligence test (Koga) scores of individuals of 10-11 years of age who were exposed prenatally to the Hiroshima and Nagasaki atomic bombs have been analyzed, using estimates of the uterine absorbed dose based on the DS86 system of dosimetry (Sc88). As indicated in Figure 6-3, no radiation-related effect on intelligence is evident among survivors who were exposed in utero during the first seven weeks after conception or during week 26 or later. In contrast, children exposed at 8-15 weeks after conception and,

OTHER SOMATIC AND FETAL EFFECTS 360 to a lesser extent, those exposed at 16-25 weeks after conception show a progressive shift downward in individual scores with increasing exposure. Within the group exposed 8-15 weeks after conception, a linear model fits the regression of intelligence scores on dose somewhat better than linear-quadratic models. The diminution in intelligence score under the linear model is 21-29 points at 1 Gy and is somewhat greater (24-33 points) at 1 Gy when controls who received less than 0.01 Gy are excluded from the analysis (Sc88). FIGURE 6-3 Mean IQ scores and 95% confidence limits by gestational age in weeks and fetal dose. The numbers in parentheses are severely retarded cases, IQ £ 64 (Sc86a). School Performance In a study of the school performance of prenatally exposed atomic-bomb survivors, the DS86 sample included 929 children. As judged by a simple regression of school performance as a function of fetal dose, there is a highly significant decrease in school achievement in children exposed 8-15 weeks and 16-25 weeks after conception (Figure 6-4) (Ot88). This trend is strongest in the earlier school years. In the groups exposed within 0-7 weeks, or ≥26 weeks after conception, there is no evidence of a radiation-related effect on scholastic performance. These results parallel those obtained for prenatally exposed atomic-bomb survivors with regard to achievement on standard intelligence tests in childhood as discussed above (Sc88). Summary—Japanese Results: The DS86 in utero sample consisted

OTHER SOMATIC AND FETAL EFFECTS 361 of almost 1,600 atomic-bomb survivors, including 30 individuals who were severely mentally retarded. A variety of dose-response models with and without a threshold have been fitted to the individual, as well as grouped, dose data. The highest risk of radiation damage to the embryonic and fetal brain occurred in individuals irradiated 8-15 weeks after conception. The frequency of severe mental retardation in the 8-15 week-old fetus is described by a simple linear, nonthreshold model. The risk at 1 Gy is about 43% with the DS86 dosimetry systems under a simple linear model, and about 48% when a linear exponential model is used. There is some indication of a threshold for severe mental retardation, but this is difficult to assess because there is a continuous diminution of intelligence with increasing dose. Using a 95% confidence interval, the grouped dose data suggest a lower bound on the threshold dose of about 0.1 Gy, whereas regressions using individual doses yield a lower bound of about 0.2 Gy. However, linear regressions which include thresholds are not consistent with the observations at doses greater than 1 Gy. When individual doses are used, damage to the fetus exposed at 16-25 weeks after conception seems to fit a linear-quadratic or quadratic regression and suggests a lower bound of about 0.2 Gy on a possible threshold dose. FIGURE 6-4 Average school subject score in the first grade with 95% confidence limits by gestational age and fetal dose (Ot88). Within the group exposed 8-15 weeks after conception, the regression of the intelligence test (Koga) score on absorbed dose in linear; the range of the decrease in intelligence test score is between 21 and 29 points at 1

OTHER SOMATIC AND FETAL EFFECTS 362 Gy. Similarly, damage to the fetal brain at 8-15 weeks after conception is linearly related to fetal absorbed dose, as judged by a simple regression of school performance scores on dose. Other Epidemiologic Studies New York Tinea Capitis Study: Albert et al. (Al66) reported that children in New York, treated for tinea capitis by x irradiation, had a higher incidence of treated psychiatric disorders than those treated with chemotherapy. Shore et al. (Sh76) and Omran et al. (Om78) confirmed these observations in this series of 2,215 patients with tinea capitis and demonstrated a higher frequency of mild, nontreated forms of behavioral maladjustment and mental disease in the irradiated population. Israel Tinea Capitis Study: Ron et al. (Ro82) evaluated several measures of mental and brain function in 10,842 Israeli children treated for tinea capitis by x- ray therapy (mean brain dose, 1.3 Gy) and two nonirradiated, tinea capitis-free comparison groups were used. While not all measures were statistically significant, there was a consistent trend for the irradiated children to exhibit subsequent behavioral impairment more often than those in the comparison group. The irradiated children had lower examination scores on scholastic aptitude, intelligence quotient, and psychological tests; completed fewer school grades; had increased admissions to mental hospitals for certain neuropsychiatric diseases; and had a slightly higher frequency of mental retardation. Childhood Leukemia Patients: Meadows et al. (Me81) also reported lower intelligence quotient scores and disturbances in cognitive functions in children with acute lymphocytic leukemia who were treated with radiation to the brain. Summary The consequences of irradiation of the mammalian embryo and fetus during the period of major organogenesis may include teratogenic effects on various organs. In humans, mental retardation is the best documented of the developmental abnormalities following radiation exposure. In the Japanese atomic-bomb survivors who were irradiated in utero, the prevalence of radiation- related mental retardation was highest in those irradiated between 8 and 15 weeks after conception, decreased in those irradiated between 16 and 25 weeks, and was negligible or absent in those irradiated before 8 weeks or later than 25 weeks. In those irradiated between weeks 8 and 15, the prevalence of mental retardation appeared to increase with dose in a manner consistent with a linear, nonthreshold response, although the data do not exclude a threshold in the range of 0.2-0.4 Gy.

OTHER SOMATIC AND FETAL EFFECTS 363 CATARACT OF THE EYE LENS Radiation-induced opacification of the lens of the eye, or cataract formation, has been observed to result from a dose of radiation to the lens in excess of 0.6-1.5 Gy, depending on the dose rate and the linear energy transfer (LET) of the radiation, as well as on the sensitivity of the method used to examine the lens (ICRP84). The threshold for ophthalmologically detectable opacities in atomic-bomb survivors has been estimated to range, using T65 dosimetry, from 0.6 to 1.5 Gy (Ot82), whereas the threshold in persons treated with x rays to the eye has been observed to range from about 2 Gy when the dose was received in a single exposure to more than 5 Gy when the dose was received in multiple exposures over a period of weeks (Me72, ICRP84). The threshold for neutrons appears to be lower; that is, in patients treated with 7.5 MeV neutrons in multiple exposures over a period of 1 month, the threshold for a vision-impairing cataract was estimated to approximate 3-5 Gy (Ro76). By the same token, long-continued occupational exposure to 0.7-1 Gy of mixed neutron-gamma radiation has been observed to cause cataracts (Ha53, Lv74), whereas similar occupational exposure to comparable doses of x rays or gamma rays has not (ICRP84). Although it is clear from the foregoing that detectable injury of the lens can result from a dose of as low as 1 Gy, depending on the dose rate and LET of the radiation, the threshold for a vision-impairing cataract under conditions of highly fractionated or protracted exposure is thought to be no less than 8 Sv (ICRP84). This dose exceeds the amount of radiation that can be accumulated by the lens through occupational exposure to irradiation under normal working conditions and greatly exceeds that which is likely to be accumulated by a member of the general population through other types of exposure. LIFE SHORTENING In laboratory mammals exposed to whole-body radiation, life expectancy decreases with increasing dose. From early experiments with rats and mice, the life-shortening effect of irradiation was interpreted as a manifestation of accelerated aging (Ru39, He44, Br52, Al57, Ca57). When analyzed in relation to the cause of death, however, the effect was not observed to be the same for all age-related diseases (Up60) but to result principally from an accelerated onset of neoplasia (Wa75). Mortality from diseases other than cancer has not been consistently or significantly increased by irradiation in human populations (Be78, UN82), with the possible exception of an early cohort of U.S. radiologists (Wa56, Wa66, Se58, Se65, Ma75a, Ma75b) in whom the confounding influence of

OTHER SOMATIC AND FETAL EFFECTS 364 other risk factors cannot be excluded. The bulk of the epidemiologic data appear to be consistent, therefore, with the data from laboratory animals (UN82). Although the data do not support the view that radiation causes a nonspecific acceleration of the aging process, the life-shortening effects of a given dose in different species are similar when analyzed in terms of the upward displacement of the age-specific death rate for the species (Sa66, Sa70). In the earlier literature, the mean survival time of animals exposed to low- level, whole-body radiation was reported, in a few instances, to exceed that of the controls. This phenomenon has since been interpreted by some observers as evidence for the existence of a beneficial, or hormetic, effect of small doses of radiation (Lu82, Hi83). In each such experiment, however, the survival of the nonirradiated controls was compromised by mortality from intercurrent infection. Even if such an effect of low-level irradiation were reproducible, which is uncertain, its biological significance and its relevance to human populations living under contemporary conditions of nutrition and sanitation are questionable (Sa62, UN82). Relatively low doses of ionizing radiation can produce certain other types of effects which might be interpreted as beneficial (Sa87). For example, experimental studies have demonstrated prolongation of the life span in arthropods and single-celled organisms under certain conditions. Again however, the various types of molecular and cellular changes in biological systems (e.g., alterations in cell proliferation kinetics, changes in cell life cycle, induction of sterility, and other adaptive mechanisms) through which radiation may produce the observed effects are of doubtful relevance to the risks of radiation-induced mutagenic and carcinogenic effects in human populations. FERTILITY AND STERILITY General Considerations Depending on their degree of maturation and differentiation, the germinal cells of the mammalian testis and ovary are highly radiosensitive (Fa72, Ha87). The seminiferous epithelium of the testis maintains a steady state of spermatogenesis throughout reproductive life, which involves the active proliferation and differentiation of spermatogonial stem cells. Through this process, the stem cells sequentially give rise to type A and type B spermatogonia spermatocytes, spermatids, and, ultimately, the functional end cells, spermatozoa. In contrast, the female is born with a full complement of maturing oocytes that no longer undergo cell division. On the contrary,

OTHER SOMATIC AND FETAL EFFECTS 365 the number of oocytes in the ovary decreases throughout adult life through physiological attrition and, to a much lesser extent, ovulation. Radiation damage to the reproductive cells of the mammalian testis or ovary can impair fertility and fecundity. If the dose is high enough, sterility may result; however, impairment of fertility requires a dose large enough to damage or deplete most of the reproductive cells. If the number or proportion of cells that are damaged remains sufficiently small, fertility is not impaired. Thus, the effect is dose-dependent, with a threshold which varies among species and individuals of differing susceptibility (ICRP84, Up87). Testis The germ cells of the human testis may be highly radiosensitive, depending on their degree of maturation (Fa72, Ha87). Type A spermatogonia appear to represent the most sensitive cell stage; later stages of spermatogenesis are highly radioresistant. Sufficient numbers of type A spermatogonia are killed by 0.15 Gy of acute x-radiation to interrupt spermatozoa production, leading to temporary infertility. After an x ray dose in excess of 3-5 Gy, whether delivered acutely or fractionated over a few days or weeks, permanent sterility may result (UN82). An x ray dose of 1.2-1.7 mGy/day has been observed to be tolerated indefinitely by dogs, without detectable effects on their sperm production (Ca68, Fe78, Fe79). Under continuous gamma-radiation exposure to 18 mGy/ day, the testis of the mouse has been observed to maintain spermatogenesis, similarly, albeit at reduced levels, for as long as 16 weeks (Fa72). Ovary In the human ovary, mature oocytes represent the most sensitive germ cell stage, being killed in sufficient numbers by an acute exposure to 0.65-1.5 Gy to impair fertility temporarily. In contrast, a dose of 6-20 Gy may be tolerated by the ovaries if it is fractionated over a period of weeks (Lu72, Lu76). The threshold for permanent sterilization of the human ovary decreases with increasing age (UN82, ICRP84, Up87). Conclusions The estimated threshold dose equivalent for induction of temporary sterility in the adult human testis is 0.15 Sv; for permanent sterility it is 3.5 Sv when received as a single exposure. The corresponding threshold dose equivalent for permanent sterility in the adult ovary is 2.5-6.0 Sv received

OTHER SOMATIC AND FETAL EFFECTS 366 in a single exposure and 6.0 Sv when received in highly fractionated or protracted exposures (ICRP84). REFERENCES Al57 Alexander, P. 1957. Accelerated aging: Long term effect of exposure to ionizing radiations. Gerontologia 1:174-193. Al66 Albert, R. E., A. R. Omran, E. W. Brauer et al. 1966. Follow-up study of patients treated by x- ray for tinea capitas. Am. J. Public Health 56:2114-2120. Be78 Beebe, G. W., C. E. Land, and H. Kato. 1978. The hypothesis of radiation-accelerated aging and the mortality of Japanese A-bomb victims. Pp. 3-37 in Late Effects of Ionizing Radiation. Vienna: International Atomic Energy Agency. Bi88 Bithell, J. F., and C. A. Stiller. 1988. A new calculation of the carcinogenic risk of obstetric x- raying. Stat. Med. 7:857-864. Bl73 Blot, W. J., and R. W. Miller. 1973. Mental retardation following in utero exposure to the atomic bombs of Hiroshima and Nagasaki. Radiology 106:617-619. Bl75 Blot, W. J. 1975. Review of thirty years study of Hiroshima and Nagasaki atomic bomb survivors. II. Biological effect. C. Growth and development following prenatal and children exposure to atomic radiation. J. Radiat. Res. 16(Suppl):82-88. Br52 Brues, A. M., and G. A. Sacher. 1952. Analysis of mammalian radiation injury and lethality. Pp. 441-465 in Symposium on Radiobiology, J. J. Nickson, ed. New York: John Wiley. Br87 Brent, R. L., D. A. Beckman, and R. P. Jensh. 1987. Relative radiosensitivity of fetal tissue. Adv. Radiat. Biol. 12:239-256. Ca57 Casarett, G. W. 1957. Acceleration of Aging by Ionizing Radiation. UR-492. Ca68 Casarett, G. W., and H. A. Eddy. 1968. Fractionation of dose in radiation-induced male sterility. Pp. 14.1-14.10 in Dose Rate in Mammalian Radiation Biology, D. G. Brown, R. G. Cragle, and T. R. Noonon, eds. USAEC CONF-680410. Co84 Covelli, V., V. Di Majo, B. Bassani, S. Rebessi, M. Coppola, and G. Silini. 1984. Influence of age on life shortening and tumor induction after x-ray and neutron irradiation. Radiat. Res. 100:348-364. Do73 Dobbing, J., and J. Sands. 1973. Quantitative growth and development of human brain. Arch. Dis. Child 48:757-767. Fa72 Fabrikant, J. I. 1972. Radiobiology. Chicago: Year Book Medical. Fa72b Fabrikant, J. I. 1920. Cell population kinetics in the eminiferous epithelian under continuous low dose rate radiation. Pp. 805-814 in Advances in Radiation Research, Biology and Medicine, Vol. II, J. F. Duplan and A. Chapiro, eds. New York: Gordon and Breach. Fe78 Fedorova, N. L., and B. A. Markelov. 1978. Functional activity of dog's testicles at chronic and combined gamma radiation in the course of three years. Kosmicheskara Biologua Aviakomicheskaia Meditsina 12:42-46. Fe79 Fedorova, N. L., and B. A. Markelov. 1979. Dog's spermatogenesis after interruption of three year's chronic gamma-irradiation. Radiobiologica 12:42-46. Fu58 Furchtgott, E., and M. Echols. 1958. Activity and emotionality in pre-and neonatally x- irradiated rats. J. Comp. Physiol. Psychol. 51:541-545. Fu75 Furchtgott, E. 1975. Ionizing radiation and the nervous system. In Biology of Brain Dysfunction, G. E. Gaull, ed. New York: Plenum Press.

OTHER SOMATIC AND FETAL EFFECTS 367 Ha53 Ham, W. T., Jr. 1953. Radiation cataract. Arch. Ophthalmol. 50:618-643. Ha85 Harvey, E. B., J. D. Boice, Jr., M. Honeyman, and J. T. Fannery. 1985. Prenatal x-ray exposure and childhood cancer in twins. N. Engl. J. Med. 312:541-545. Ha87 Hall, E. 1987. Radiobiology for the radiologist. New York: Harper & Row. He44 Henshaw, P. S. 1944. Experimental roentgen injury. IV. Effects of repeated small doses of x- rays on the blood picture, tissue morphology and life span in mice. J. Natl. Cancer Inst. 4:513-522. Hi83 Hickey, R. J., E. J. Bowers, and R. C. Clelland. 1983. Radiation hormesis, public health, and public policy: A commentary. Health Phys. 44:207-209. Hs76 Hsu, T. H., and J. I. Fabrikant. 1976. Spermatogonial cell renewal under continuous irradiation at 1.8 and 4.5 rads per day. Pp. 157-168 in Biological and Environmental Effects of Low-Level Irradiation, Vol. 1. Report IAEA-SM-202/214. Vienna: International Atomic Energy Agency. ICRP84 International Commission on Radiological Protection (ICRP). 1984. Nonstochastic Effects of Ionizing Radiation. ICRP Publication 41. Oxford: Pergamon. ICRP86 International Commission of Radiological Protection. 1986. Developmental Effects of Irradiation on the Brain of the Embryo and Fetus. ICRP Publication 49. Oxford: Pergamon. ICRP88 International Commission on Radiological Protection. In press. Statement from the 1987 Como Meeting of the ICRP. Oxford: Pergamon. Ja70 Jablon, S., and H. Kato. 1970. Childhood cancer in relation to prenatal exposure to a-bomb radiation. ABC TR 26-70. Lancet ii:1000-1003. Ka88 Kato, H., Y. Yoshimoto, and W. J. Schull. 1988. Risk of Cancer among in Utero Children Exposed to A-Bomb Radiation . RERF Technical Report. In press. Le62 Levinson, B. 1962. Effects of neonatal irradiation on learning in rats. In Response of the Nervous System to Ionizing Radiation, T. J. Haley and R. S. Snider, eds. New York: Academic Press. Lu72 Lushbaugh, C. C., and R. C. Ricks. 1972. Some cytokinetic and histopathologic considerations of irradiated male and female gonadal tissues. Pp. 228-248 in Frontiers of Radiation Therapy and Oncology, Vol. 6, J. M. Vaeth, ed. Basel: Karger. Lu76 Lushbaugh, C. C., and G. W. Casarett. 1976. The effects of gonadal irradiation in clinical radiation therapy: A review. Cancer 37:1111-1120. Lu82 Luckey, T. D. 1982. Physiological benefits from low levels of ionizing radiation. Health Phys. 43:771-789. Lv74 Lvovskaya, E. N. 1974. The state of eye in persons occupied in roentgen-radiological facilities of Moscow. Proceedings of NIJGT i PZ:209-214. Ma62 MacMahon, B. 1962. Prenatal x-ray exposure and childhood cancer. J. Natl. Cancer Inst. 28:1173-1191. Ma66 Manosevitz, M., and J. R. Rostkowski. 1966. The effects of neonatal irradiation on postnatal activity and elimination. Radiat. Res. 28:701-707. Ma75a Matanoski, G. M., R. Seltser, P. E. Sartwell, et al. 1975. The current mortality rates of radiologists and other physician specialists: Death rate from all causes and from cancer. Am. J. Epidemiol. 101:188-198. Ma75b Matanoski, G. M., R. Seltser, P. E. Sartwell, et al. 1975. The current mortality rates of radiologists and other physician specialists: Specific causes of death. Am. J. Epidemiol. 101:199-210. Ma82 Martinez, P. F. A. 1982. Neuroanatomy. Development and Structure of the Central Nervous System. Philadelphia: W. B. Saunders.

OTHER SOMATIC AND FETAL EFFECTS 368 Me72 Merriam, G. R., A. Schechter, and E. F. Focht. 1972. The effects of ionizing radiation on the eye. Front. Radiat. Ther. Oncol. 6:346-385. Me81 Meadows, A. T., J. Gordan, D. J. Massari, P. Littman, J. Fergusson, and K. Moss. 1981. Declines in IQ scores and cognative dysfunctions in children with acute lymphocytic leukemia treated with cranial irradiation. Lancet ii:1015-1018. Mi76 Miller, R. W., and J. H. Mulvihill. 1976. Small head size after atomic irradiation. Teratology 14:335-338. Mi86 Miller, R. W., and J. D. Boice, Jr. 1986. Radiogenic cancer after prenatal or childhood exposure. In Radiation Carcinogenesis, A. Upton et al., eds. New York: Elsevier. Mo74 Mole, R. H. 1974. Antenatal irradiation and childhood cancer: Causation or coincidence? Br. J. Cancer 30:199-208. Mo84 Monson, R. R., and B. MacMahon. 1984. Prenatal x-ray exposure and cancer in children. In Radiation Carcinogenesis: Epidemiology and Biological Significance, J. D. Boice, Jr., and J. F. Fraumeni. Jr., eds. New York: Raven Press. NRC72 National Research Council Advisory Committee on the Biological Effects of Ionizing Radiations. 1972. The Effects on Populations of Exposure to Low Levels of Ionizing Radiations (BEIR I). Washington, D.C.: National Academy of Sciences. NRC80 National Research Council Committee on the Biological Effects of Ionizing Radiation. 1980. The Effects on Populations of Exposure to Low Levels of Ionizing Radiation (BEIR III). Washington, D.C.: National Academy of Sciences. Om78 Omran, A. R., R. E. Shore, R. A. Markoff et al. 1978. Follow-up study of patients treated by x-ray epilation for tinea capitas: Psychiatric and psychomotor evaluation. Am. J. Public Health 68:561-567. Ot82 Otake, M., and W. J. Schull. 1982. The relationship of gamma and neutron radiation to posterior lenticular opacities among atomic bomb survivors in Hiroshima and Nagasaki. Radiat. Res. 92:574-595. Ot83 Otake, M., and W. J. Schull. 1983. In Utero Exposure to A-Bomb Radiation and Mental Retardation. A Reassessment. RERF Technical Report No. 1-83. Ot86 Otake, M., and W. J. Schull. 1986. Analysis and interpretation on deficits of the central nervous system observed in the in utero exposed survivors of Hiroshima and Nagasaki. Jpn. J. Appl. Stat. 15:163-180. Ot87 Otake, M., H. Yoshimaru, and W. J. Schull. 1987. Severe Mental Retardation among the Prenatally Exposed Survivors of the Atomic Bombing of Hiroshima and Nagasaki: A Comparison of the Old and New Dosimetry Systems. RERF Technical Report 16-87. Ot88 Otake, M., W. J. Schull, Y. Fujikoshi, and H. Yoshimaru. 1988. Effect on School Performance of Prenatal Exposure to Ionizing Radiation in Hiroshima: A Comparison of the T65DR and DS86 Dosimetry Systems. RERF Technical Report 2-88. In press. Pr87 Preston, D. L., and D. A. Pierce. 1987. The Effect of Changes in Dosimetry on Cancer Mortality Risk Estimates in the Atomic Bomb Survivors. RERF Technical Report 9-87. Ra75 Rakic, P. 1975. Cell migration and neuronal ectopias in the brain. Pp. 95-129 in Morphogenesis and Malformation of the Face and Brain, D. Bergsma, ed. New York: Alan R. Liss. Ra78 Rakic, P. 1978. Neuronal migration and contact guidance in the primate telencephalon. Postgrad. Med. J. 54(Suppl. 1):Z5-40.

OTHER SOMATIC AND FETAL EFFECTS 369 Ro76 Roth, J., M. Brown, M. Catterall et al. 1976. Effects of fast neutrons on the eye. Br. J. Ophthalmol. 60:236-244. Ro82 Ron, E., B. Modan, S. Flora, I. Harkedar, and R. Gureurt. 1982. Mental function following scalp irradiation during childhood. Am. J. Epidemiol. 116:149-160. Ro87 Roesch, W. C. 1987. Reassessment of Atomic Bomb Radiation Dosimetry in Hiroshima and Nagasaki: Final Report. Hiroshima: Radiation Effects Research Foundation. Ru39 Russ, S., and G. M. Scott. Biological effects of gamma-irradiation (Series II). Br. J. Radiol. 12:440-441. Ru78 Rubin, P., and G. W. Casarett. 1978. Clinical radiation pathology, Vols. I and II. Philadelphia: W. B. Saunders. Sa62 Sacher, G. A., and E. Trucco. 1962. A theory of the improved performance and survival produced by small doses of radiation and other poisons. Pp. 244-251 in Biological Aspects of Aging, N. W. Shock, ed. New York: Columbia University Press. Sa66 Sacher, G. A. 1966. The Gompertz transformation in the study of the injury-mortality relationship: application to late radiation effects and aging. Pp. 411-441 in Radiation and Aging, P. J. Lindop and G. A. Sacher, eds. London: Taylor and Francis. Sa70 Sacher, G. A., D. Grahn, R. J. M. Fry et al. 1970. Epidemiological and cellular effects of chronic radiation exposure: A search for relationship. Pp. 13-38 in First European Symposium on Late Effects of Radiation, P. Metalli, ed. Rome: Comitato Nazionale Energia Nucleare. Sa87 Sagan, L. A. 1987. What is hormesis and why haven't we heard about it before. Health Phys. 52:521-525. Sc86a Schull, W. J., and M. Otake. 1986. Effects on Intelligence of Prenatal Exposure to Ionizing Radiation. RERF Technical Report 7-86. Sc86b Schull, W. J., and M. Otake. 1986. Neurological deficit and in utero exposure to the atomic bombing of Hiroshima and Nagasaki: A reassessment and new directions. Pp. 399-419 in Radiation Risks to the Developing Nervous System, H. Kriegel et al., eds. New York: Gustav Fischer Verlag. Sc88 Schull, W. J., M. Otake, and H. Yoshimaru. 1988. Effect on Intelligence Test Score of Prenatal Exposure to Ionizing Radiation in Hiroshima and Nagasaki: A Comparison of the Old and New Dosimetry Systems. Revised Technical Report 3-88. In preparation. Se58 Seltser, R., and P. E. Sartwell. 1958. Ionizing radiation and longevity of physicians. J. Am. Med. Assoc. 166:585-587. Se65 Seltser, R., and P. E. Sartwell. 1965. The influence of occupational exposure to radiation on the mortality of American radiologists and other medical specialists . Am. J. Epidemiol. 81:2-22. Sh76 Shore, R. E., R. E. Albert, and B. S. Pasternack. 1976. Follow-up study of patients treated by x-ray for tinea capitas: Resurvey of post treatment illness and mortality experience. Arch. Environ. Health 1:17-24. Sh88 Shimbun, C. 1988. Threshold dose for severe mental retardation of in utero exposed children determined by RERF study. Personal communication, 14 January. St56 Stewart, A., J. Webb, D. Giles, and D. Hewitt. 1956. Malignant disease in childhood and diagnostic irradiation in utero. Lancet ii:447-448. St58 Stewart, A., J. Webb, and D. Hewitt. 1958. A survey of childhood malignancies. Br. Med. J. 1:1495-1508.

OTHER SOMATIC AND FETAL EFFECTS 370 UN77 United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR). 1977. Sources and Effects of Ionizing Radiation. Report E.77.IX.1. New York: United Nations. UN82 United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR). 1982. Ionizing Radiation: Sources and Biological Effects. Report E.82.IX.8. New York: United Nations. UN86 United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR). 1986. Genetic and Somatic Effects of Ionizing Radiation. Report E.86.IX.9. New York: United Nations. Up60 Upton, A. C., A. W. Kimball, J. Furth, K. W. Christenberry, and W. H. Benedict. 1960. Some delayed effects of atom-bomb radiations in mice. Cancer Res. 20(No. 8, Part II):1-93. Up87 Upton, A. R. 1987. Cancer induction and non-stochastic effects. Br. J. Radiol. 60:1-16. Wa56 Warren, S. 1956. Longevity and causes of death from irradiation in physicians. J. Am. Med. Assoc. 162:464-468. Wa66 Warren, S., and O. M. Lombard. 1966. New data on the effects of ionizing radiation on radiologists. Arch. Environ. Health 13:415-421. Wa75 Walburg, H. E. 1975. Radiation-induced life-shortening and premature aging. Adv. Radiat. Biol. 7:145-179. Wo67 Wood, J. W., K. G. Johnson, Y. Omori, S. Kawamoto, and R. J. Keehn. 1967. Mental retardation in children exposed in utero, Hiroshima and Nagasaki. Am. J. Public Health 57:1381-1390. Ya62 Yamazaki, J. N., L. E. Bennett, and C. D. Clemente. 1962. Behavioral and histological effects of head irradiation in new born rats. In Response of the Nervous System to Ionizing Radiation, T. J. Haley and R. S. Snider, eds. New York: Academic Press. Yo88 Yoshimoto, Y., H. Kato, and W. J. Schull. 1988. Risk of Cancer among in Utero Children Exposed to A-Bomb Radiation: 1950-84. RERF Technical Report 4-88. Hiroshima: Radiation Effects Research Foundation.

Next: 7 Low Dose Epidemiologic Studies »
Health Effects of Exposure to Low Levels of Ionizing Radiation: BEIR V Get This Book
×
Buy Paperback | $125.00
MyNAP members save 10% online.
Login or Register to save!
Download Free PDF

This book reevaluates the health risks of ionizing radiation in light of data that have become available since the 1980 report on this subject was published. The data include new, much more reliable dose estimates for the A-bomb survivors, the results of an additional 14 years of follow-up of the survivors for cancer mortality, recent results of follow-up studies of persons irradiated for medical purposes, and results of relevant experiments with laboratory animals and cultured cells. It analyzes the data in terms of risk estimates for specific organs in relation to dose and time after exposure, and compares radiation effects between Japanese and Western populations.

  1. ×

    Welcome to OpenBook!

    You're looking at OpenBook, NAP.edu's online reading room since 1999. Based on feedback from you, our users, we've made some improvements that make it easier than ever to read thousands of publications on our website.

    Do you want to take a quick tour of the OpenBook's features?

    No Thanks Take a Tour »
  2. ×

    Show this book's table of contents, where you can jump to any chapter by name.

    « Back Next »
  3. ×

    ...or use these buttons to go back to the previous chapter or skip to the next one.

    « Back Next »
  4. ×

    Jump up to the previous page or down to the next one. Also, you can type in a page number and press Enter to go directly to that page in the book.

    « Back Next »
  5. ×

    To search the entire text of this book, type in your search term here and press Enter.

    « Back Next »
  6. ×

    Share a link to this book page on your preferred social network or via email.

    « Back Next »
  7. ×

    View our suggested citation for this chapter.

    « Back Next »
  8. ×

    Ready to take your reading offline? Click here to buy this book in print or download it as a free PDF, if available.

    « Back Next »
Stay Connected!