ANL-84-103. 1983. In Table 4-1 note the low tumor yield of the axial compared with the appendicular skeleton. In the first dose-response analyses, average skeletal dose was adopted as the dose parameter, and details of the dose calculations were presented. The first case of bone sarcoma associated with 226,228Ra exposure was a tumor of the scapula reported in 1929, 2 yr after diagnosis in a woman who had earlier worked as a radium-dial painter.42 Bone tumors among children injected with 224Ra for therapeutic purposes were reported in 1962 among persons treated between 1946 and 1951.87. There is more information available on the dosimetry of the long-term volume deposit. Home; antique table lamps 1900; why does radium accumulate in bones? With the occasional accidental exposures that occur with occupational use of radium, both hot-spot and diffuse radioactivity are probably important to cancer induction, and the total average endosteal dose may be the most appropriate measure of carcinogenic dose. 1985. 2 for D e Based on Kolenkow's work,30 Evans et al.16 reported a cumulative dose of 82,000 rad to the mucous membrane at a depth of 10 m for the subject with carcinoma. The linear functions obtained by Rowland et al.67 were: where D The data for juveniles and adults was separated into different dose groups, a step not taken with the life-table analysis of Mays and Spiess.45 This, in effect, frees the analysis from the assumption of a linear dose-response relationship, implicit in the Mays and Spiess analysis. Many of the 2,403 subjects are still alive. These are supplemented by postmortem measurements of skeletal and soft-tissue content, observations of radium distribution within bone on a microscale, and measurements of radon gas content in the mastoid air cells. Presumably, if dose protraction were taken into account by the life-table analysis, the difference between juveniles and adults would vanish. The ratios of maximum to average lay in the range 837. In 1952, Aub et al.3 stated that the origin of these neoplasms in mucosal cells that were well beyond the range of the alpha particles emitted by radium, mesothorium, and their bone-fixed disintegration products is also interesting. 1983. The average skeletal dose to a 70-kg male was stated to be 56 rad. In the cohort of 634 women, death certificates indicated that there were three cases attributed to leukemia and aleukemia and four more to blood and blood-forming organs; both were above expectations. Petersen, N. J., L. D. Samuels, H. F. Lucas, and S. P. Abrahams. A different hypothesis for the initiation of radiogenic bone cancer has been proposed by Pool et al.59 They suggest that the cells at risk are the primitive mesenchymal cells in osteons that are being formed. The theory postulates that two radiation-induced initiation steps are required per cell followed by a promotion step not dependent on radiation. A., P. Isaacson, W. J. Hausler, and J. Kohler. i, redefinition is not required to avoid negative expected values, and radiogenic risk is set equal to the difference between total risk and natural risk. (c). In a dosimetric study, Schlenker73 confirmed this by determining the frequency with which the epithelium lay nearer to or farther from the bone surface than 75 m, at which level more than 75% of the epithelial layer in the mastoids would be irradiated. A recent examination of data on whole-body radium retention in humans revealed that the excretion rate diminished with increasing body burden.70 Absolute retention could not be studied, because the initial intake was unknown, but the data imply the existence of a dose-dependent retention similar to that observed in animals. Autoradiographic studies37 of alkaline earth uptake by bone soon after the alkaline earth was injected into animals revealed the existence of two distinct compartments in bone (see Figure 4-3), a short-term compartment associated with surface deposition, and a long-term compartment associated with volume deposition. Hoecker and Roofe28 determined the dose rate produced by the highest concentrations of radium in microscopic volumes of bone from two former radium-dial painters, one who died in 1927 with an estimated terminal radium burden of 50 g 7 yr after leaving the dial-painting industry, and one who died in 1931 with an estimated terminal burden of 8 g 10 yr after last employment as a dial painter. Table 4-5, based on their report, illustrates their results. s, where D For example, if D When the population was later broadened to include all female radium-dial workers first employed before 195069 for whom there was an estimate of radium exposure based on measurement of body radioactivity, a much larger group than female radium-dial workers first employed before 1930 (1,468 versus 759), the only acceptable fit was again provided by the functional form (C + D2) exp(-D). For example, when the risk coefficient is: For functions that lack an exponential factor, such as I = 1.75 10-5 + (2.0 0.6) 10-5 1976. There is little evidence for an age or sex dependence of the cancer risk from radium isotopes, provided that the age dependence of dose that accompanies changes in body and tissue masses is taken into account. Two extensive studies of the adverse health effects of 224Ra are under way in Germany. why does radium accumulate in bones? D For each year, the cumulative incidence so obtained was divided by the average value of the mean skeletal dose for subjects within the group, in effect yielding the slope of a linear dose-response curve for the data. Being an -emitting radionuclide, the radium irradiates bone surface-lining cells and has resulted in an excess incidence of osteogenic sarcomas. what medications become toxic after expiration; why does radium accumulate in bones? The shaded region emphasizes that standard errors obtained by least-square fitting underestimate the uncertainty in risk at low doses. These high ratios emphasize, in quantitative terms, our ignorance of risk at low exposure levels. In summary, hot spots may not have played a role in the induction of bone cancer among members of the radium population under study at Argonne National Laboratory because of excessive cell killing in tissues which they irradiate, and the carcinogenic portion of the average endosteal dose may have been about one-half of the total average endosteal dose. D Schlenker, R. A., and J. E. Farnham. Current efforts focus on the determination of risk, as a function of time and exposure, with emphasis on the low exposure levels where there is the greatest quantitative uncertainty. As the practical concerns of radiation protection have shifted and knowledge has accumulated, there has been an evolution in the design and objectives of experimental animal studies and in the methods of collection, analysis, and presentation of human health effects data. Thus, the spectrum of tumor types appears to be shifted from the naturally occurring spectrum when the tumors are induced by radium. The radioactive half-life of 224Ra is short enough that most of the absorbed dose to target tissues is delivered while it is resident on bone surfaces, a location from which absorbed dose delivery is especially efficient. The subjects used in this analysis were all women employed in the radium-dial-painting industry at an average age of about 19 yr. The asymptotic value of this function is 200 bone sarcomas/million person-rad, which is considered applicable both to childhood and adult exposure. There is no common agreement on which measure is the most appropriate for either variable, making quantitative comparisons between different studies difficult. It is absorbed from the soil by plants and passed up the food chain to humans. Rowland et al. Spiess and Mays85,86 have shown that the distributions of appearance times for leukemias among Japanese atomic-bomb survivors and bone sarcomas induced by 224Ra lie approximately parallel with one another when plotted on comparable scales. The fundamental reason for this is the chemical similarity between calcium and radium. Littman et al.31 report a single value of 17 m for the lamina propria in a person who had contracted mastoid carcinoma. i between 0.5 and 100 Ci. Various radiation effects have been attributed to radium, but the only noncontroversial ones are those associated with the deposition of radium in hard tissues. 1986. This discussion will be devoted to matters that have a quantitative effect on the estimation of endosteal tissue dose. Two cases, by implication, might be considered significant. This keeps it from accumulating inside your home. This is evidenced by the fact that bone tumor incidence rises to 100% with increasing dose. Schlenker74 presented a series of analyses of the 226,228Ra tumor data in the low range of intakes at which no tumors were observed but to which substantial numbers of subjects were exposed. It does, however, deposit in soft tissue and there is a potential for radiation effects in these tissues. Therefore, no judgment can be made as to whether such a layer would develop in response to a single injection of 224Ra or whether the layer could develop fast enough to modify the endosteal cell dosimetry for multiple 224Ra fractions delivered over an extended period of time. The standard deviation for each point is shown. A mechanistic model for alkaline earth metabolism29 was developed by the ICRP to describe the retention of calcium, strontium, barium, and radium in the human body and in human soft tissue, bone volume, bone surfaces, and blood. The term practical threshold was introduced into the radium literature by Evans,15 who perceived an increase of the minimum tumor appearance time with decreasing residual radium body burden and later with decreasing average skeletal dose.16 A plot showing tumor appearance time versus average skeletal dose conveys the impression that the minimum tumor appearance time increases with decreasing dose. Otherwise, the retention in bone is estimated by models. 1976. However, at lower radium intakes, such as those experienced by the British luminizers and the bulk of the U.S. radium-dial workers, incorporated 226Ra does not appear to give rise to leukemia. With environmental radiation, in which large populations are exposed, a spectrum of ages from newborn to elderly is represented. Radium is highly radioactive. Combining this information with results observed with 224Ra may lead to the development of a general model for bone cancer induction due to alpha-particle emitters. The most frequent clinical symptoms for paranasal sinus tumors were problems with vision, pain (not specified by location), nasal discharge, cranial nerve palsy, and hearing loss. The first widespread effort to control accidental radium exposure was the abandonment of the technique of using the mouth to tip the paint-laden brushes used for application of luminous material containing 226Ra and sometimes 228Ra to the often small numerals on watch dials. In the United States there have been at least three attempts to determine whether the populations that drink water containing elevated levels of radium had different cancer experience than populations consuming water with lower radium levels. As the response variable, they used carcinomas per person-year at risk and regressed it against a measure of systemic intake of 226Ra and against average skeletal dose. In press. The data are subdivided into three groups based on the 226Ra intake. This chapter focuses on bone cancer and cancer of the paranasal sinuses and mastoid air cells because these effects are known to be associated with 224Ra or 226,228Ra and are thought to be nonthreshold phenomena. For the percent of exposed persons with bone sarcomas, Mays and Lloyd44 give 0.0046% D Ventilation of the mastoid air cells occurs through the eustachian tube which normally allows little air to move. This is an instance in which an extrapolation of animal data to humans has played an important role. However, no mention of such cases appear in his report. s is the sum of the average skeletal doses for 226Ra and 228Ra, in rad. Based on their treatment of the data, Mays et al.49 made the following observation: ''We have fit a variety of dose-response relationships through our follow-up data, including linear (y = ax), linear multiplied by a protraction factor, dose-squared exponential (y = ax There is no assurance that women exposed at a greater age or that men would have yielded the same results. Simple prescriptions for the skeletal dose from 224Ra as a function of injection level have been given by Spiess and Mays85 and can be used to estimate skeletal dose from estimated systemic intake. Most of the 220Rn (half-life, 55 s) that escapes bone surfaces decay nearby, as will 216Po (half-life 0.2 sec). These limits on radium intake or body content were designed to reduce the incidence of the then-known health effects to a level of insignificance. a. The extreme thinness of the surface deposit has been verified in dog bone, but the degree of daughter product retention at bone surfaces is in question.76 Schlenker and Smith80 have reported that only 525% of 220Rn generated at bone surfaces by the decay of 224Ra is retained there 24 h after injection into beagles. It later appears in the urine and feces, with the majority of excretion occurring by the fecal route. The 9% envelope was obtained by allowing the parameters in the function to vary by 2 standard errors on either side of the mean and emphasizes that the standard errors obtained by least-square fitting underestimate the uncertainty at low doses. Why does radium accumulate in bones?-Radium accumulates in bones because radium essentially masks itself as calcium. Polednak cautioned that the shorter median appearance time at high doses might simply reflect the shorter overall median survival time. Further efforts to refine dose estimates as a function of time in both man and animals will facilitate the interpretation of animal data in terms of the risks observed in humans. It is clear, therefore, that a nonzero function could be fitted to these data but would have numerical values substantially less than 28%. 1959. International Commission on Radiological Protection (ICRP). For this reason, the total average endosteal dose is probably the best measure of carcinogenic dose. D The British patients that Loutit described34 also may have experienced high radiation exposures; two were radiation chemists whose radium levels were reported to fall in the range of 0.3 to 0.5 Ci, both of whom probably had many years of occupational exposure to external radiation. 67,68 based on dose, equations that give an acceptable fit are: where the risk coefficient I equals the number of bone sarcomas per person-year at risk that begin to appear after a 5 yr latent period, and D 1985. Low-level endpoints have not been examined with the same thoroughness as cancer. 1980. The results are shown in Figure 4-8. For 222Rn (whose half-life is very long compared with the time required for untrapped atoms within the body to diffuse into the blood supply), this rapid diffusion results in a major reduction of the radiation dose to tissues. For male bladder cancer only, the highest radium level produced a higher cancer rate than was observed for those consuming surface water. When these ducts are open, clearance is almost exclusively through them. For continuous intake with the dose-squared exponential function for bone sarcoma induction, it is necessary to decide whether to add the cumulative dose and then take the square or to take the square for each annual increment of dose. The authors concluded that bone tumors most likely arise from cells that are separated from the bone surface by fibrotic tissue and that have invaded the area at long times after the radium was acquired. The use of intake as the dose parameter rested on the fact that it is a time-independent quantity whose value for each individual subject remains constant as a population ages. Working from various radium-exposed patient data bases, several authors have observed that carcinomas of the paranasal sinuses and mastoid air cells begin to occur later than bone tumors.16,18,66,71 In the latest tabulation of tumor cases,1 the first bone tumor appeared 5 yr after first exposure, and the first carcinoma of the paranasal sinuses or mastoid air cells appeared 19 yr after first exposure; among persons for whom there was an estimate of skeletal radiation dose, the first tumors appeared at 7 and 19 yr, respectively. As indicated in Annex 7A, the radium-dial painter data can be a useful source of information for extrapolating to man the risks from transuranic elements that have been observed in animal studies. Data on tumor locations and histologic type are presented in Table 4-4. Batsakis, J. G., and J. J. Sciubba. With the analyses presently available, only part of this prescription can be achieved. They conclude from their microscopic measurements that the average density of radium in the portions of the pubic bone studied was about 35 times as great as that in the femur shaft; this subject developed a sarcoma in the ascending and descending rami of the os pubis. Mygind, N., M. Pedersen, and M. H. Nielsen. 1969. Spiess, H., A. Gerspach, and C. W. Mays. The plaque is usually soft to begin with, but eventually tends to harden and become calcified. Spontaneously occurring bone tumors are rare. s = 0.5 rad, which is approximately equal to the lifetime skeletal dose associated with the intake of 2 liters/day of water containing the Environmental Protection Agency's maximum concentration limit of 5 pCi/liter, the expression of Mays and Lloyd44 would predict a total risk of 0.0023%. Risk per person per gray versus mean skeletal dose. i = 100 Ci to a value of 480 at D The primary sources of information on the health effects and dosimetry of radium isotopes come from extensive studies of 224Ra, 226Ra, and 228Ra in humans and experimental animals. . Coverage of other groups, especially those with medical exposure, was considered low, and many subjects were selected by symptom. A plot of the bone sarcoma data for a population subgroup defined as female radium-dial workers first exposed before 1930 is shown in Figure 4-4. Here the available dose-response relationships are presented in terms of the number of microcuries that reach the blood. Because of its short radioactive half-life, about 90% of the 224Ra atoms that decay in bone decay while on the surfaces.40. The first explicit description of the structure of the sinus and mastoid mucosa in the radium literature is probably that of Hasterlik,22 who described it as "thin wisps of connective tissue," overlying which "is a single layer of epithelial cells. Between 1944 and 1951 it was injected in the form of Peteosthor, a preparation containing 224Ra, eosin, and colloidal platinum, primarily for the treatment of tuberculosis and ankylosing spondylitis. As with Evans et al. Since then it has been used with adults as a clinically successful treatment for the debilitating pain of ankylosing spondylitis. The fundamental reason for this is the chemical similarity between calcium and radium. Therefore, calculations of the uncertainty of risk estimates from the standard deviation will be accurate above 25 Ci but may be quite inaccurate and too small below 25 Ci. This cohort was derived from a total of about 1,400 pre-1930 radium-dial workers who had been identified as being part of the radium-dial industry of whom 1,260 had been located and were being followed up at Argonne. provided an interesting and informative commentary on the background and misapplications of the linear nonthreshold hypothesis.17. . s. The analysis also yields good fits to the data. As with other studies, the shape of the dose-response curve is an important issue. This observation was originally made on animals given high doses where retention, at a given time after injection, was found to increase with injection level. For example, if a person is exposed to 226Ra at time zero, the person is not considered to be at risk for 10 yr; the total number of carcinomas expected to occur among N people with identical systemic intakes D i is the total systemic intake of 226Ra plus 2.5 times the total systemic intake of 228Ra, expressed in microcuries. Schlenker, R. A., and B. G. Oltman. In a study of microscopic volumes of bone from a radium-dial painter, Hindmarsh et al.26 found the ratio of radium concentrations in hot spots to the average concentration that would have occurred if the entire body burden had been uniformly distributed throughout the skeleton to range between 1.5 and 14.0, with 3.5 being the most frequent value. When radium levels in urine and feces are measured, by far the largest amount is found in the feces. i is 226Ra intake, and D The ratio of the 95% confidence interval range, for radiogenic risk, to the central value. 1983. For the 27 subjects for whom radium body burden information was available, they estimated that, for airspace thicknesses of 0.5 to 2 cm, the dose from radon and its daughters averaged over a 50-m-thick mucous membrane would be 2 to 5% of the average dose from 226Ra in bone.