ACHRE Report

Part II

Chapter 7


The Context for Nontherapeutic Research with Children

Risk of Harm and Nontherapeutic Research with Children

Beyond Risk: Other Dimensions of the Ethics of Nontherapeutic Research on Children

The Studies at the Fernald School


Chapter 7: Conclusion

If an ethical evaluation of human experiments depended solely upon an assessment of the risks to subjects as they could reasonably be anticipated at the time, the radiation experiments conducted on children reviewed in this chapter would be relatively unproblematic.[97]During this time, the association between radiation exposure and the subsequent development of cancer was not well understood, and in particular, little was known about iodine 131 and the risk of thyroid cancer. Both researchers and policymakers appear to have been alert to considerations of harm and concerned about exposing children to an unacceptable level of risk.

At the same time, however, the scientific community's experience with radionuclides in humans was limited, and this approach to medical investigation was new. Although the available data about human risk were encouraging and the biological susceptibility of children to the effects of radiation was not appreciated, we are left with the lingering question of whether investigators and agency officials were sufficiently cautious as they began their work with children. This is a difficult judgment to make at any point in the development of a field of human research; it is particularly difficult to make at forty or fifty years' remove. Investigators and officials had to make decisions under conditions of considerable uncertainty; this is commonplace in science and in medicine. Although the biological susceptibility of children was not then known, investigators and officials held the view that children should be accorded extra protection in the conduct of human research, and they made what they thought were appropriate adjustments when using children as subjects. If human research never proceeded in the face of uncertainty, there would be no such experiments. How little uncertainty is acceptable in research involving children is a question that remains unresolved. Today, we continue to debate what constitutes minimal risk to children, in radiation and in other areas of research. The regulations governing research on children offer little in the way of guidance, either with respect to conditions of uncertainty about risk or when risks are known.

As best as we can determine, in eleven of the twenty-one experiments we reviewed, the risks were in a range that would today likely be considered as more than minimal, and thus as unacceptable in nontherapeutic research with children according to current federal regulations. It is possible, however, that four of the eleven might be considered acceptable by the "minor increase over minimal risk" standard.[98] In these four experiments, the average risk estimates were between one and two per thousand, the studies were directed at the subjects' medical conditions, and they may well have had the potential to obtain information of "vital importance."

Physical risk to subjects is not the only ethically relevant consideration in evaluating human experiments. With the exception of the studies at Fernald, we know almost nothing about whether or how parental authorization for the remaining nineteen experiments we reviewed was obtained. And with the exception of the Fernald studies and the experiment at Wrentham, we know very little about the children who were selected to be the subjects of this research. Therefore, we cannot comment on the general ethics of these other experiments.

The experiments at Fernald and at the Wrentham School unfairly burdened children who were already disadvantaged, children whose interests were less well protected than those children living with their parents or children who were socially privileged. At the Fernald School, where more is known, there was some attempt to solicit the permission of parents, but the information provided was incomplete and misleading. The investigators successfully secured the cooperation of the children with offers of extra milk and an occasional outing--incentives that would not likely have induced children who were less starved for attention to willingly submit to repeated blood tests.

One researcher speaking almost thirty-five years ago set out the fundamental moral issue with particular frankness and clarity:

. . . we are talking here about first and second class citizens. This is a concept none of our consciences will allow us to live with. . . . The thing we must all avoid is two types of citizenry.[99]

It might have been common for researchers to take advantage of the convenience of experimenting on institutionalized children, but the Committee does not believe that convenience offsets the moral problems associated with employing these vulnerable children as research subjects--now or decades ago.

The Vanderbilt Study

In an exceptionally large study[a] at Vanderbilt University in the 1940s, approximately 820 poor, pregnant Caucasian women were administered tracer doses of radioactive iron. Vanderbilt worked with the Tennessee State Department of Health, and the research was partly funded by the Public Health Service.[b] Today, most women take iron supplements during pregnancy. This experiment provided the scientific data needed to determine the nutritional requirements for iron during pregnancy.

The radioiron portion of the nutrition study, directed by Dr. Paul Hahn, was designed to study iron absorption during pregnancy.[c] The women, who were anywhere from less than ten weeks to more than thirty-five weeks pregnant, were administered a single oral dose of radioactive iron, Fe-59, during their second prenatal visit, before receiving their routine dose of therapeutic iron.[d] On their third prenatal visit, blood was drawn and tests performed to determine the percentage of iron absorbed by the mother. The infants' blood was then examined at birth to determine the percentage of radioiron absorbed by the fetus. The doses to the women were estimated in the study article, using crude dose-estimation methods available at the time, to be from 200,000 to 1,000,000 countable counts per minute.[e] Although the investigators did not estimate doses to the fetuses in the original study, Dr. Hahn later estimated fetal doses to be between 5 and 15 rad. This estimate, however, has been questioned.[f]

There is at least some indication that the women neither gave their consent nor were aware they were participating in an experiment. Vanderbilt study subjects, expressing bitterness at the way they believed they had been treated, testified at an Advisory Committee meeting that the proffered drink, called a "cocktail" by the investigators, was offered with no mention of its contents. "I remember taking a cocktail," one woman said simply. "I don't remember what it was, and I was not told what it was."[g] Although it is not clear what, if anything, the subjects were told, information about the Vanderbilt experiment was available to the general public. In late 1946 news reports appeared in the Nashville press.[h]

The actual risk to the fetuses in the Vanderbilt experiment has long been a matter of study. In 1963-1964, a group of researchers at Vanderbilt found no significant differences in malignancy rates between the exposed and nonexposed mothers.[i] However, they did identify a higher number of malignancies among the exposed offspring (four cases in the exposed group: acute lymphatic leukemia, synovial sarcoma, lymphosarcoma, and primary liver carcinoma, which was discounted as a rare, familial form of cancer). No cases were found in a control group of similar size, and approximately 0.65 cases would have been expected on Tennessee state rates, compared to which the three observed cases is a marginally significant excess. This led the researchers to conclude that the data suggested a causal relationship between the prenatal exposure to Fe-59 and the cancer. The investigators also concluded that Dr. Hahn's estimate of fetal exposure was an underestimation of the fetal-absorbed dose.

A 1969 study, funded by the AEC and conducted by one of the investigators from the 1963-1964 study, attempted to reconstruct the doses of Fe-59 to the fetuses in the original Vanderbilt study.[j] The investigators observed that the one case of leukemia might have been due to radiation damage, but that the doses in the other two cases were low; therefore, the relationship between the radiation exposure and the cancer in those cases might not have been causal. However, the researchers also noted that due to incomplete data, they could not estimate the dose absorbed by the fetus with confidence and that no definitive conclusions could be drawn from this study as to whether these exposures resulted in damage to the fetus.[k]

The Vanderbilt study raises many of the same ethical issues as the experiments reviewed in this chapter. Like these experiments, the Vanderbilt study offered no prospect of medical benefit to the pregnant women or their offspring, raising the question of the conditions under which it is acceptable to put children at risk for the benefit of others, whether before or after birth. What could the investigators reasonably have been expected to know about the risks to which they put their subjects? Did they exercise appropriate caution in exposing fetuses to radiation? What were the pregnant women told, if anything, and was their permission sought? Who were these women, and how were they positioned relative to pregnant women, generally?

The Committee did not have the resources to pursue these questions in both research in which children were the subjects and research in which children were exposed as fetuses. We did establish that the Vanderbilt study was not the only experiment during this period to expose fetuses in research that offered no prospect of medical benefit to them or their mothers. While the Committee did not conduct an exhaustive review of the scientific literature, we did find twenty-seven human radiation studies that included pregnant or nursing women as subjects between 1944 and 1974.[l] Of these studies, eight were considered therapeutic, and nineteen offered no prospect of benefit to the subject. Most of the nineteen were tracer experiments.

These studies were performed in order to examine human physiology during pregnancy or to study the uptake of radioactive substances by fetuses or nursing infants.[m] They generally addressed valid scientific questions that could not be investigated in other populations. Knowledge of fetal exposure to radioiodine, for example, was relevant to issues such as potential harm to the fetus from maternal uptake of radioiodine in diagnostic tests or to estimate the potential effects of environmental exposure to radioiodine on the human fetus. In other studies, radioactive iron was administered to better understand the physiology of maternal and fetal intake of iron during pregnancy.

a . Most of the other tracer studies involving pregnant women and offering no prospect of benefit that were reviewed by the Committee involved fewer than twenty women as subjects.

b . William J. Darby, Director of the Tennessee-Vanderbilt Project et al., Summary Report, Section B, Tennessee-Vanderbilt Nutrition Project, July 1, 1946 to December 31, 1946 (ACHRE No. CORP-020395-A), 97-110. This nutrition study summary report notes, "Considerable expansion of the program of study of maternal and infant nutrition has been made possible by a grant of $9,000 per year which was made by the U.S. Public Health Service. These funds were available beginning November 1, 1946." Ibid., 99. The summary observes that the grant was to be used for additional personnel, including the appointment of Dr. Richard Cannon, an obstetrics resident, to the staff of the Division of Nutrition beginning 1 January 1947. Dr. Cannon's name subsequently appears as an investigator in the medical report discussing the radioiron portion of the study, along with Dr. Paul Hahn's and others.

c . P. Hahn et al., "Iron Metabolism in Human Pregnancy as Studied with the Radioactive Isotope, Fe-59," American Journal of Obstetrics and Gynecology 61 (March 1951): 477-486. The exact years of the radioiron portion of the nutrition study are uncertain. Minutes from a meeting of the nutrition study investigators indicate the study was to begin in September 1945. Tennessee-Vanderbilt Nutrition Project, Nutrition in Pregnancy Study, "Minutes of Meeting for Discussion of Nutrition in Pregnancy Study, August 17, 1945" (ACHRE No. CORP-020395-A), 17A-C. The radioiron study probably began at approximately that time and appears to have continued until sometime in 1947, based on a review of periodic study summaries.

d . The Advisory Committee has not been able to determine whether Dr. Hahn got the radioactive iron used in the study from a private or government source, or both.

e . Counts per minute is a measure of the radioactivity detected by a specific counting instrument. The sensitivities of counting instruments vary; a specific instrument may not "see" and count all the radiation coming from a particular substance. Thus, the total amount of radiation emitted by a substance may be calculated by considering the sensitivity of the counter.

f . Contemporary estimates of the fetal doses by the Committee and others suggest that the fetal effective dose was a few hundred millirems.

g . Wilton McClure, transcript of audio testimony before the Advisory Committee on Human Radiation Experiments, Small Panel Meeting, Knoxville, Tennessee, 2 March 1995, 182.

h . "Iron Doses with Radioactive Isotopes Aid to Pregnancy, Experiment Shows," Nashville Banner, 13 December 1946; "VU to Report on Isotopes," The Nashville Tennessean, 14 December 1946 (ACHRE No. CORP-020395-A).

i . The investigators identified the hospital records of 751 exposed mothers and 771 unexposed controls, as well as 719 exposed offspring and 734 unexposed offspring, and mailed them questionnaires. Of the exposed mothers, 90.4 percent responded, as did 91.45 percent of the unexposed mothers, 88.2 percent of the exposed offspring, and 89.2 percent of the unexposed. Ruth M. Hagstrom et al.,"Long Term Effects of Radioactive Iron Administered During Human Pregnancy," American Journal of Epidemiology 90 (1969): 1-8.

j . Norman C. Dyer and A. Bertrand Brill, "Fetal Radiation Dose from Maternally Administered Fe-59 and I-131," in Radiation Biology of the Fetal and Juvenile Mammal: Proceedings of the Ninth Annual Hanford Biology Symposium at Richland, Washington, May 5-8, 1969, eds. Melvin R. Sikov and D. Dennis Mahlum (Washington, D.C.: GPO, December 1969), 78-88. This study was reviewed in detail by the Committee. The study also investigated fetal absorption of radioiodine because that isotope was and is commonly used in diagnosis and therapy, including in pregnant women.

k . Ibid., 85.

l . All of the nineteen studies reviewed in detail by the Committee were conducted or at least partially funded by the federal government or were supplied with radioisotopes by the AEC. For the earlier years, the Committee relied on the ACHRE experiments database, AEC isotope distribution lists provided by DOE, and relevant biographies. The Committee also consulted relevant medical indexes and computer databases; the isotope distribution lists provided by DOE did not cover these years. While the computer search would have located nontherapeutic tracer experiments for this period as well, very few were identified.

m . Of the nineteen tracer experiments (funded by the government) involving pregnant or nursing women identified by the Committee, only three administered tracer doses to nursing women that offered no prospect of benefit; in at least one of the studies the infants were exposed. In one case, six nursing women were given radioiodine to determine excretion in breast milk, the infants were not given the exposed milk. In another case, two infants were intentionally exposed to the breast milk of their mothers, who were given I-131. An I-131 tracer study on the general population, incidentally included two nursing women. The report indicates that both had been nursing their children, and since there is no indication that the mothers were warned to avoid breastfeeding after the exposure, it is quite probable that the infants were exposed.

Nasopharyngeal Irradiation

Nasopharyngeal irradiation,[a] introduced by S. J. Crowe and J. W. Baylor of the Otological Research Laboratory at the Johns Hopkins University, was employed from 1924 on as a means of shrinking lymphoid tissue at the entrance to the eustachian tubes to treat middle ear obstructions, infections, and deafness. For this treatment, intranasal radium applicators (sealed ampules containing radium salt) were inserted (at least three insertions per treatment cycle) into the nasopharyngeal area for twelve-minute periods.[b] The therapeutic effect of the treatments resulted from the penetrating radiation emitted from the radium source (gamma and beta rays), not from the internal deposition of radium itself. Crowe and his colleagues reported that "under this treatment, the lymphoid tissue around the tubal orifices gradually disappeared, marked improvement or complete return of the hearing followed, and in many the bluish discoloration of the tympanic membrane also disappeared."[c] This method was used for more than a quarter century as a prophylaxis against deafness, for relieving children with recurrent adenoid tissue following tonsillectomy and adenoidectomy, and for children with chronic ear infections. Asthmatic children with frequent upper respiratory infections were also often considered for this type of irradiation.

An average of 150 patients a month, mostly children, were given the treatment at the Johns Hopkins clinic over a period of several years.[d] Many children received the treatment more than once as recurrent lymphoid tissue was considered an indication for treatment.

Crowe and his colleagues reported that the results following irradiation of the nasopharynx alone were not only as good as, but often better than, those following removal of tonsils and adenoids.[e] In review articles, they noted that approximately 85 percent of treated patients responded with decreased numbers of infections and/or improved hearing when treated at young ages. They also concluded that "it is effective, safe, painless, inexpensive and has proved particularly valuable for prevention of certain ear, sinus and bronchial condition in children."[f]

Although early articles by Crowe and colleagues indicate that nasopharyngeal radium treatments were accepted as standard procedure for the prevention of childhood deafness, these treatments, like most standard interventions in medicine, had not been subjected to formal scientific evaluation. A controlled study was conducted from 1948 to 1953 by Crowe and his colleagues to determine "the feasibility of irradiation of the nasopharynx as a method for controlling hearing impairment in large groups of children associated with lymphoid hyperplasia in the nasopharynx; to draw conclusions concerning the per capita cost of such an undertaking as a public health measure."[g] Crowe et al. wrote in an NIH "Notice of Research" that "the procedure of treatment is

not new, as an individual measure; this is the first adequately controlled experiment of sufficient size for accurate statistical analysis."[h]

This work was funded by NIH for the entire period of study. As recorded in an NIH grant application, the study involved approximately 7,000 children screened for hearing impairment.[i] Of those screened, approximately 50 percent were selected for further study based on the chosen criteria for hearing loss. Half of this study group was irradiated with radium, while the other half served as a control group. Crowe and colleagues reportedly concluded from this study (published in 1955) that the radium treatments did shrink swelling of lymphoid tissue and improve hearing.[j] This type of therapy was ultimately discontinued because of newly available antibiotics and the use of transtympanic drainage tubes, as well as awareness of the potential risks of radiation treatment.

In addition to the targeted lymphoid tissue, the brain and other tissues in the head and neck region, including the paranasal sinuses, salivary glands, thyroid, and parathyroid glands are also exposed to significant doses of radiation during the radium treatments, prompting concern that these treated individuals might have been placed at increased risk for radiation-induced cancers at these sites. Dale P. Sandler et al., in their 1982 study of the effects of nasopharyngeal irradiation on excess cancer risk for children treated at the Johns Hopkins clinic, found "a statistically significant overall excess of malignant neoplasms of the head and neck among exposed subjects," based however on only four cases in comparison with 0.57 expected.[k] This excess was accounted for mainly by three brain tumors that occurred in the irradiation subjects. One other malignant tumor, a cancer of the soft palate, was also reported. The Department of Epidemiology at the Johns Hopkins University has undertaken a further follow-up study of the Crowe et al. cohort of children irradiated there, previously studied by Sandler et al.[l] Verduijn et al., in their 1989 study of cancer mortality risk for those individuals (mostly children) treated by nasopharyngeal irradiation with radium 226 in the Netherlands, reported that "the present study has found no excess of cancer mortality at any site associated with radium exposure by the Crowe and Baylor therapy. Specifically,

the finding of Sandler et al. of an excess of head and neck cancer was not found in this study group."[m]

Among the Japanese atomic bomb survivors, no excess of brain tumors was found. However, several studies have noted an increased risk of both benign and malignant brain tumors following therapeutic doses of radiation to the head and neck region during childhood.[n] From the Committee's own limited risk analysis of these experiments, we concluded that the brain and surrounding head and neck tissues would be put at highest risk and estimated the lifetime risk at approximately 4.35 per 1,000 and an increased relative risk of 62 percent.[o]

The Hopkins nasopharyngeal study raises different ethical issues than those posed by the other experiments reviewed in this chapter, all of which offered no prospect of medical benefit to the children who served as subjects. By contrast, the nasopharyngeal irradiation experiment was designed to determine whether children at risk for hearing loss would be better off receiving radiation treatments or not receiving such treatments. A central issue here was whether it was permissible to withhold this intervention from "at risk" children. The application of radium was at this point a common, but scientifically unproven, treatment for children at risk of hearing loss; the risks of the treatment were not well characterized. If it was really unknown which was better for children--receiving radium or no intervention--then the medical interests of the children were best served by being subjects in the research because, as a consequence, they would have a 50 percent chance of receiving the better approach. The nasopharyngeal experiment thus belongs to a class of research the Committee did not investigate--therapeutic research with children.

a . Nasopharyngeal irradiation was studied in adults as well as children. In the early 1940s, 732 submariners were subjects of a controlled experiment designed to test whether nasopharyngeal radium treatments could be used to shrink lymphoid tissue surrounding the eustachian tubes, thereby preventing and treating aerotitis media in submariners by equalizing external and middle ear pressure. This treatment was successful in 90 percent of the cases. H. L. Haines and J. D. Harris, "Aerotitis Media in Submariners," Annals of Otology, Rhinology, and Laryngology 55 (1946): 347-371. In a 1945 journal article, it was noted that a controlled study was considered by the Army Air Forces, but rejected because of the urgent need to treat fliers immediately and keep them flying. However, the published report describes differences between various dose groups, implying an uncontrolled experimental comparison was made. Captain John E. Hendricks et al., "The Use of Radium in the Aerotitis Control Program of the Army Air Forces: A Combined Report by the Officers Participating," Annals of Otology, Rhinology, and Laryngology 54 (1945): 650-724. Tens of thousands of servicemen were subsequently given this nasopharyngeal radium treatment.

Relying on the risk estimate developed in the Sandler study, Stewart Farber, a radiation-monitoring specialist with a background in public health, has projected 51.4 excess brain cancers over a fifty-year period in the 7,613 servicemen irradiated in the Navy and Army Air Forces studies noted above. Stewart Farber, Consulting Scientist of the Public Health Sciences, to Stephen Klaidman, ACHRE Staff, 8 March 1995 ("Nasopharyngeal Radium Irradiation-Initial Radiation Experiments Performed by DOD on 7,613 Navy and Army Air Force Military Personnel during 1944-45"). Alan Ducatman, M.D., of the University of West Virginia School of Medicine, who coauthored a letter with Farber to the New England Journal of Medicine regarding the radium exposure of military personnel, wrote that he found "no convincing evidence of excess cancer in the exposed population." He added, however, "there is also no good evidence for the null hypothesis." Alan Ducatman, West Virginia University School of Medicine, to Duncan Thomas, Member of the Advisory Committee on Human Radiation Experiments, 22 February 1995 ("I'm sorry I could not respond . . .") (ACHRE No. WVU-021795-A).

Han K. Kang, with the Environmental Epidemiology Service of the Veterans Health Administration, is currently conducting a study to assess the feasibility of an epidemiologic study of Navy veterans who received radium treatments. Han K. Kang, Environmental Epidemiology Service, Veterans Health Administration, "Feasibility of an Epidemiologic Study of a Cohort of Submariners Who Received Radium Irradiation Treatment," 23 August 1994. It is not clear, however, that sufficient numbers of treatment-documented personnel can be identified, as a group representing submariners has apparently been able to identify only six former Navy personnel from of a pool of twenty-seven whose records indicate they received radium treatment. (It is not clear whether the data being collected by the VFW with the support of Senator Joesph Lieberman of Connecticut will be from a representative sample of respondents. If, in fact, these data are from a highly nonrepresentative sample, the study may not be considered scientifically valid.) However, the Veterans of Foreign Wars organization apparently is now processing hundreds of surveys filled out by veterans who say they underwent nasopharyngeal radium treatment. Once this task is completed, Senator Lieberman plans to present the data to the Department of Veterans Affairs with a recommendation that an epidemiologic study be conducted.

b . Samuel J. Crowe, "Irradiation of the Nasopharynx," Annals of Otology, Rhinology and Laryngology 55 (1946): 31.

c . Ibid., 30.

d . Ibid., 33.; Dale P. Sandler et al., "Neoplasms Following Childhood Radium Irradiation of the Nasopharynx," Journal of the National Cancer Institute 68 (1982): 3-8.

e . Ibid., 33.

f . Ibid.

g . S. J. Crowe et al., The Johns Hopkins University School of Medicine and School of Hygiene and Public Health, to Federal Security Agency, Public Health Service, National Institutes of Health, July 1948 ("The Efficiency of Nasopharyngeal Irradiation In the Prevention Of Deafness in Children, Notice of Research Project, Grant No. B-19") (ACHRE No. HHS No. 092694-A).

h . Ibid.

i . Ibid.

j . Ibid.

k . For the combination of benign and malignant neoplasms, there were 23 cases, for a relative risk of 2.08 with a 95 percent confidence interval of 1.12 to 3.91. Sandler, "Neoplasms Following Childhood Radium Irradiation," 5.

l . Jessica Yeh and Genevieve Matanowski, fax to Anna Mastroianni (ACHRE), 7 July 1995 ("Nasopharyngeal Power Analysis"), 1-3.

m . Verduijn et al., "Mortality after Nasopharyngeal Irradiation," Annals of Otology, Rhinology, and Laryngology 98 (1989): 843.

n . S. Jablon and H. Kato, "Childhood Cancer in Relation to Prenatal Exposure to Atomic-Bomb Radiation," The Lancet, ii (1970): 1000-1003.; M. Colman, M. Kirsch, and M. Creditor, "Radiation Induced Tumors," in Late Biological Effects of Ionizing Radiation, Vol. 1 (Vienna: International Atomic Energy Agency, 1978), 167-180; R. E. Shore, R. E. Albert, and B. S. Pasternak, "Follow-up Study of Patients Treated by X ray Epilation for Tinea Capitis: Resurvey of Post-Treatment Illness and Mortality Experience," Archives of Environmental Health 31 (1976): 17-24; and C. E. Land,"Carcinogenic Effects of Radiation on the Human Digestive Tract and Other Organs," in Radiation Carcinogenesis, eds. A. C. Upton et al. (New York: Elsevier, 1986), 347-378.

o . The radiation dose estimate to the head and neck region was calculated according to the following assumptions: (1) Source description: 50 mg of radium, active length 1.5 cm, filtered by 0.3 mm of Monel metal. (2) Average treatment: 60mg/hrs; based on three 12-minute treatments (radium applicators inserted through both nostrils)= (12x3x50x2)/60 mins per hour= 60 mg-hrs. (3) Dose rate at points in a central orthogonal plane surrounding the source: for distances up to 5 centimeters dose estimated using published data (Quimby Tables, Otto Glasser et al., Physical Foundations of Radiology, 3d ed. [New York: Paul Hoeber, Inc., 1961]) for linear radium sources with dose increased by 50% to allow for the reduced filtration provided by the applicator wall and converting roentgen to rad by a multiplication factor of 0.93. For distances greater than 5 centimeters, the dose rate is reduced in accordance with the inverse square law, with a proportionality constant of 690 rad-cm2. There was no dose correction for attenuation of the gamma rays by tissue absorbtion, which has been calculated to be about 2%/cm (yielding a dose reduction of about 20% at 10 cm).

The local gamma dose to the head and neck region was assumed to be distributed according to an inverse square law d(r) = 690/r2 rad. The Committee approximated the exposed region of the body by a sphere with radius 10 centimeters. This was felt to be a conservative assumption, because although the dose does not go to zero at the base of the neck, a 10-centimeter sphere would also extend outside the skull. Averaging this dose distribution over the exposed sphere, the average dose to the head was found to be 20.7 rad. The exposed volume is about 4189 cm3, or 29 percent of the total body, so the average whole body dose is about 6.0 rad. Multiplying this by the BEIR V risk coefficient for children exposed at age five, 1.4/1,000 person-rad, produces a lifetime risk of about 8.4/1,000. This calculation assumes that the brain and other head tissues have average radiosensitivity. BEIR V also gives absolute-risk coefficients for brain cancer ranging from 1 to 9 per million person-year-rad, with 3 being a reasonable average. Applying this figure to an average head dose of 20.7 rad, the Committee estimates a lifetime risk of about 4.35/1,000. The corresponding relative risk coefficients average about 3 percent per rad, so this dose would correspond to an excess relative risk of 62 percent.

Table 2. Summary and Risk Analysis for Studies Examined by the Advisory Committee

Primary Author Date of Publ. Title of Study Isotope Number of Children Cancer Risk Risk Estimate (%) Incidence[*]
K. M. Saxena 1965 Thyroid Function in Mongolism I-131 104 Thyroid 0.03 (0.1)
McDougall 1964 Estimation of Fat Absorption from Random Stool Specimens I-131 9 Thyroid 0.06
M. A. Van Dilla 1963 Thyroid Metabolism in Children and Adults Using Very Small (Nanocurie) Doses of Iodine-125 and Iodine-131 I-131 8 Thyroid 0.001
R. T. Morrison 1963 Radioiodine Uptake Studies in Newborn Infants I-131 25 Thyroid 0.15 (0.2)
K. M. Saxena 1962 Minimal Dosage of Iodine Required to Suppress Uptake of Iodine 131 by Normal Thyroid I-131 63 Thyroid 0.10 (0.18)
R. E. Ogborn 1960 Radioactive-iodine Concentration in Thyroid Glands of Newborn Infants I-131 28 Thyroid 0.25 (0.49)
G. S. Kurland 1957 Radioisotope Study of Thyroid Function in 21 Mongoloid Subjects, Including Observations in 7 Parents I-131 24 (17 children) Thyroid 0.15 (1.0)
L. Oliner 1957 Thyroid Function Studies in Children: Normal Values for Thyroidal I-131 Uptake and PBI-131 Levels up to the Age of 18 I-131 83 Thyroid 0.34 (2.3)
E. E. Martmer 1956 A Study of the Uptake of Iodine (Iodine-131) by the Thyroid of Premature Infants I-131 70 Thyroid 0.7 (2.2)
F. Bonner 1956 Studies in Calcium Metabolism: Effect of Phytates on 45-Ca Uptake in Boys on a Moderate Calcium Breakfast Ca-45 57 Total 0.001
A. Friedman 1955 Radioiodine Uptake in Children with Mongolism I-131 129 Thyroid 0.12 (0.82)
C. E. Benda 1954 Studies of Thyroid Function in Myotonia Dystrophica I-131 6 Thyroid 0.02
L. V. Middlesworth 1954 Radioactive Iodine Uptake of Normal Newborn Infants I-131 7 Thyroid 0.20 (0.27)
S. H. Silverman 1953 Radioiodine Uptake in the Study of Different Types of Hypothyroidism in Childhood I-131 34 Thyroid 0.13 (0.6)
P. S. Lavik 1952 Use of Iodine-131 Labeled Protein in the Study of Protein Digestion and Absorption in Children with and without Cystic Fibrosis of the Pancreas I-131 15 Total 0.05
H. W. Scott 1951 Blood Volume in Congenital Cyanotic Heart Disease: Simultaneous Measurements with Evans Blue and Radioactive Phosphorus P-32 20 Total 0.08
L. M. Sharpe 1950 The Effect of Phytates and Other Food Factors on Iron Absorption Fe-55 and Fe-59 17 Total 0.03
W. A. Reilly 1950 Carrier-Free Radioactive Iodine-131 Thyroid Uptake and Urinary Excretion in Normal and Hypothyroid Children I-131 16 Thyroid 0.04 (0.3)
V. C. Kelley 1950 Labeled Methionine as an Indicator of Protein Formation in Children with Lipoid Nephrosis S-35 4 Total 0.02
G. H. Lowrey 1949 Radioiodine Uptake Curve in Humans: II. Studies in Children I-131 26 Thyroid 0.2 (1.0)
E. H. Quimby 1947 Uptake of Radioactive Iodine by the Normal and Disordered Thyroid Gland in Children I-131 54 Thyroid 0.16 (2.2)
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