D The best fit was obtained for the functional form I =(C + D) exp(-D), an unacceptable fit was obtained for I = C + D2, and all other forms provided acceptable fits. Calculations for 226Ra and 228Ra are similar to the calculation with the asymptotic tumor rate for 224Ra. Cancer of the paranasal sinuses and mastoid air cells has been associated with 226,228Ra exposure since the late 1930s43 following the death of a radium-dial painter who had contracted epidermoid carcinoma of the epithelium lining of the ethmoid air cells.3. Radium . i between 0.5 and 100 Ci. The shaded region emphasizes that standard errors obtained by least-square fitting underestimate the uncertainty in risk at low doses. While the report of Mays et al.50 dealt with persons injected with 224Ra between 1946 and 1950, the study of Wick et al.95 examined the consequences of lower doses as a treatment for ankylosing spondylitis and extended from 1948 to 1975. As stated earlier, average hot-spot concentrations are about an order of magnitude higher than average diffuse concentrations, leading to the conclusion that the doses to bone surface tissues from hot spots over the course of a lifetime would also be about an order of magnitude higher than the doses from diffuse radioactivity. Because of its short radioactive half-life, about 90% of the 224Ra atoms that decay in bone decay while on the surfaces.40. The distribution of tumor types is not likely to undergo major changes in the future; the group of 226,228Ra-exposed patients at high risk is dwindling due to the natural mortality of old age and the rate of tumor appearance among 224Ra-exposed patients has dropped to zero in recent years.46. Parks. The excess death rate due to bone cancer for t > 5 yr is computed from: Effect of Single Skeletal Dose of 1 rad from 224Ra Received by 1,000,000 U.S. White Males at Age 40. As a convenient working hypothesis, in several papers it has been assumed that the linear form is the correct one, leading to analyses that are illuminating and easily understood. Here the available dose-response relationships are presented in terms of the number of microcuries that reach the blood. Because bone cancer is an early-appearing tumor, the risk, so far as is now known, disappears within 25 yr after exposure. s is the average skeletal dose from 226Ra plus 1.5 times the average skeletal dose from 228Ra, expressed in rad. The points with their standard errors result from the proportional hazards analysis of Chemelevsky et al. Mays, C. W., T. F. Dougherty, G. N. Taylor, R. D. Lloyd, B. J. Stover, W. S. S. Jee, W. R. Christensen, J. H. Dougherty, and D. R. Atherton. why does radium accumulate in bones? Radium deposited in bone irradiates the cells of that tissue, eventually causing sarcomas in a large fraction of subjects exposed to high doses. Most of the 220Rn (half-life, 55 s) that escapes bone surfaces decay nearby, as will 216Po (half-life 0.2 sec). Leukemia has been seen in the Germans exposed to 224Ra, but only at incidence rates close to those expected in unexposed populations. All five leukemias in the control group were acute forms, while three in the exposed group were chronic myeloid leukemia. Based on epizootiological studies of tumor incidence among pet dogs, Schlenker73 estimated that 0.06 tumors were expected for 789 beagles from the University of Utah beagle colony injected with a variety of alpha emitters, while five tumors were observed. Martland,42 summarizing his studies of radium-dial painters, mentioned the development of anemias. In the Evans et al. For the analyses based on intake, the equation that gives an acceptable fit is: where I is bone sarcomas per person-year at risk, and D This is not a trivial point since rate of loss could be greatly affected by the high radiation doses associated with hot spots. The mucosal lining of the mastoid air cells is thinner than the lining of the sinuses. 2)exp(-1.1 10-3 The decay products of radium, except radon, are atoms of solid materials. The resultant graph of dose-response curve slopes versus years of follow-up is shown in Figure 4-6. 1978. In a report by Finkel et al.,18 mention is made of seven cases of leukemia and aplastic anemia in a series of 293 persons, most of whom had acquired radium between 1918 and 1933. e . Fact Sheet #29 Radium-226 ( 226Ra) Page 3 of 3 The most frequent symptoms for mastoid air cell tumors were ear blockage or discharge and hearing loss. Abstract. There is no doubt that male and female lung cancers appear to increase with an increase in the radium content of the water, but in the case of female lung cancers the levels were never as great as observed for those who drank surface water. Radium has an affinity for hard tissue because of its chemical similarity to calcium. 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. When the U.K. radium-luminizer study for the induction of myeloid leukemia is examined,5 it is seen that among 1,110 women there are no cases to be found. When radiogenic risk is determined by setting the natural tumor rate equal to 0 in the expressions for total risk and by eliminating the natural tumor rate (10-5/yr) from the denominator in Equation 4-14, the value of the ratio increases more slowly, reaching 470 at D Calcium can accumulate in the arterial plaque that develops after an injury to the vessel wall. This ratio increases monotonically with decreasing endosteal dose, from 1.8 at 500 rad to 220 at 25 rad, which is the lower boundary of the lowest dose cohort used in Schlenker's74 analysis. The data have been normalized to the frequency for osteosarcoma and limited to the three principal radiogenic types: osteosarcoma, chondrosarcoma, and fibrosarcoma. Source: Mays and Spiess.45, Risk per person per gray versus mean skeletal dose. i - 3.6 10-8 Negative values have been avoided in practical applications by redefining the dose-response functions at low exposure levels. There may be an excess of leukemia among the adults, but the evidence is weak. The second analysis is that of Marshall and Groer,38 in which a carefully constructed theoretical model was fitted to bone-cancer incidence data. i is IN (t - 10) for t 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. ; Volume 35, Issue 1, of Health Physics; the Supplement to Volume 44 of Health Physics; and publications of the Center for Human Radiobiology at Argonne National Laboratory, the Radioactivity Center at the Massachusetts Institute of Technology, the New Jersey Radium Research Project, the Radiobiology Laboratory at the University of California, Davis, and the Radiobiology Division at the University of Utah. The standard deviation for each point is shown. For this reason, diffuse radioactivity may have been the primary cause of tumor induction among those subjects in whom bone cancer is known to have developed. Since uranium is distributed widely throughout the earth's crust, its daughter products are also ubiquitous. Following entry into the circulatory system from the gut or lungs, radium is quickly distributed to body tissues, and a rapid decrease in its content in blood occurs. (c). Book, and N. J. When radium levels in urine and feces are measured, by far the largest amount is found in the feces. i = 100 Ci to 700 at D The functional form in the analysis of Rowland et al. The original cases of radium poisoning were discovered by symptom, not by random selection from a defined population. These relationships have important dosimetric implications. The most inclusive and definitive study of leukemia in the U.S. radium-dial workers was published by Spiers et al.83 By including all the dial workers, male and female, who entered the industry before 1970, a total of 2,940 persons who could be located, they were able to document a total of 10 cases of leukemia. Summary of virtually all available data for adult man. Under age 30, the relative frequencies for radiogenic tumors are about the same as those for naturally occurring tumors. He also described the development of leukopenia and anemia, which appeared resistant to treatment. For male bladder cancer only, the highest radium level produced a higher cancer rate than was observed for those consuming surface water. He took into account the dose rate from 226Ra or 228Ra in bone, the dose rate from 222Rn or 220Rn in the airspaces, the impact of ventilation and blood flow on the residence times of these gases in the airspaces, measured values for the radioactivity concentrations in the bones of certain radium-exposed patients, and determined expected values for radon gas concentrations in the airspaces. In a more complete development, Schlenker73 investigated the dosimetry of sinus and mastoid epithelia when 226Ra or 228Ra was present in the body. It does, however, deposit in soft tissue and there is a potential for radiation effects in these tissues. Although this city draws its water from Lake Michigan, where the radium concentration is reported as 0.03 pCi/liter, the age- and sex-adjusted osteosarcoma mortality rate was 6.3/million/yr, which is larger than that found for the towns with elevated radium levels in their water. If cell survival is an exponential function of alpha-particle dose in vivo as it is in vitro, then the survival adjacent to the typical hot spot, assuming the hot-spot-to-diffuse ratio of 7 derived above, would be the 7th power of the survival adjacent to the typical diffuse concentration. Schlenker74 examined the uncertainties in risk estimates for bone tumor induction at low intakes and found it to be much greater than would be determined from the standard deviations in fitted risk coefficients. ;31 adopted a spherical shape for the air cavities; and considered air cavity diameters from 0.2 mm, representing small mastoid air cells, up to 5 cm, representing large sinuses. Figure 4-5 shows the results of this analysis, and Table 4-3 gives the equations for the envelope boundaries. i) with 95% confidence that total risk lies between I He placed the total thickness of connective tissue plus epithelium at between 5 and 20 m. Importantly, because alpha particles have a very short range (<100 m), there is limited damage to surrounding normal tissues, including bone marrow [ 7, 9 ]. However, no mention of such cases appear in his report. The radiogenic risk equals the total risk given by one of the preceding expressions minus the natural tumor risk. Data points fall along a straight line when the tumor rate is constant. The rate for the control group was 1.14; the probability of such a difference occurring by chance alone was reported as 8 in 100. As with Evans et al. In a subsequent analysis,46 the data on juveniles and adults were merged, and an additional tumor was included for adults, bringing the number of subjects with tumors and known dose to 48. If radium is ingested or inhaled, the radiation emitted by the radionuclide can interact with cells and damage them. u and I If the tumors are nonradiogenic, then the linear extrapolation gives a substantial over prediction of the risk at low doses, just as a linear extrapolation of the 226,228Ra data overpredict the risk from these isotopes at low doses.17,44. Were it not for the fact that these cancers were not seen at radium intakes hundreds to thousands of times greater in the radium-dial painter studies, they might throw suspicion on radium. 226Ra and 228Ra are also heavily concentrated on bone surfaces at short times after intake. . The rarity of naturally occurring mucoepidermoid carcinoma, contrasted with its frequency among 226,228Ra-exposed subjects, suggests that alpha-particle radiation is capable of significantly altering the distribution of histologic types. For nonstochastic effects, apparent threshold doses vary with health endpoint. 1978. Recall that the preceding discussion of tumor appearance time and rate of tumor appearance indicated that tumor rate increases with time for some intake bands, verifying a suggestion by Rowland et al.67 made in their analysis of the carcinoma data. This change had no effect on the fitted value of , the free parameter in the linear dose-response function. The error bars on each point are a greater fraction of the value for the point here than in Figure 4-6, because the subdivision into dose groups has substantially reduced the number of subjects that contributes to each datum point. Rowland, R. E., A. F. Stehney, A. M. Brues, M. S. Littman, A. T. Keane, B. C. Patten, and M. M. Shanahan. e is the endosteal dose. Comparable examples can be given for each expression of Rowland et al. Schlenker and Smith80 also reported incomplete retention for 212Pb and concluded that the actual endosteal dose rate 24 h after injection varied between about one-third and one-half of the equilibrium dose rate for their experimental animals. Deposits in the bone with nonuniform distribution, following the decay of 226Ra in the bone. This is sometimes in the form of a three-dimensional dose-time-response surface, but more often it is in the form of two-dimensional representations that would result from cutting a three-dimensional surface with planes and plotting the curves where intersections occur. Estimates of the cumulative tumor rate (incidence) versus time after first injection were obtained, and when those for juveniles and adults in comparable dose groups were compared, no difference in either the magnitude or the growth of cumulative tumor rate with time was found between the two age groups. This change occurred in 19251926 following reports and intensive discussion of short-term health effects such as ''radium jaw" in some dial painters. Over age 30, the situation is different. In some cases, this is the age at death and in others this is the age at which the presence of the tumor can be definitely established from the information available. For the Mays and Lloyd44 function, this consists of setting the radiogenic risk equal to the total risk rather than to the total risk minus the natural risk. Unless bone cancer induced by 226Ra and 228Ra is a pure, single-hit phenomenon, some interaction of dose increments is expected, although perhaps it is a less strong interaction than is consistent with squaring the total accumulated intake when intake is continuous. The most likely explanation is that tissue damage to the skeleton, at high doses, alters the retention pattern, primarily through the reduction in skeletal blood flow that results from the death of capillaries and other small vessels and through the inhibition of bone remodeling, a process known to be important for the release of radium from bone. Data on tumor locations and histologic type are presented in Table 4-4. The upper curve of the 68% envelope is nearly coincident with the upper boundary of the shaded envelope. This was because the dose rate from most hot spots is rapidly reduced by the overgrowth of bone with a lower and lower specific activity during the period of appositional bone growth that accompanies hot spot formation. 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. It is absorbed from the soil by plants and passed up the food chain to humans. The half-life for tumor appearance is roughly 4 yr in this data set, giving an approximate value for r of 0.18/yr. For example, if D The asymptotic value of this function is 200 bone sarcomas/million person-rad, which is considered applicable both to childhood and adult exposure. l That Define the Dose-Response Envelopes in Figure 4-5. i Source: International Commission on Radiological Protection (ICRP).29. Why does radium accumulate in bones?-Radium accumulates in bones because radium essentially masks itself as calcium. Raabe et al. No firm conclusions about the constancy or nonconstancy of tumor rate should be drawn from this dose-response analysis. They reported that about 50% of the Haversian systems in the os pubis were hot spots, while hot spots constituted only about 2% of the Haversian systems in the femur shaft. 1975. At high radiation doses, whole-body retention is dose dependent. 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. In addition, they reported a tumor rate of 1.8%/yr for these subjects exposed to high doses and suggested that the sample of tumor appearance times investigated had been drawn from an exponential distribution. 1978. i is 226Ra intake, and D s is 226Ra skeletal dose. The relative frequencies for fibrosarcomas induced by 224Ra and 226,228 Ra are also different, as are the relative frequencies for chondrosarcomas induced by 226,228Ra and naturally occurring chondrosarcomas. Leukemia has not often been seen in the studies of persons who have acquired internally deposited radium. 1978. National Academies Press (US), Washington (DC). 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. The data on human soft-tissue retention were recently reviewed.74 The rate of release from soft tissue exceeds that for the body as a whole, which is another way of stating that the proportion of total body radium that eventually resides in the skeleton increases with time. 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%. The higher values of the ratios were associated with shorter exposure times, usually the order of a year or less. The poorest fit, and one that is unacceptable according to a chi-squared criterion, was obtained for I = C + D2. The remaining two cases were aplastic anemias; these latter two cases and one of the CML cases were not available for study, and hence no measurements of radium content in the workers' bodies were available. Clearly, under these assumptions, dose from radon and its daughters in the airspaces would be of little radiological significance. 1982. In a similar study on bone from a man who had been exposed to radium for 34 yr, they found concentration ratios in the range of 116.25 Rowland and Marshall65 reported the maximum hot-spot and average concentrations for 12 subjects. These constitute about 85% of the subjects with bone sarcoma on which the most recent analyses have been based. D The half lives are 3.5 days for radium-224, 1,600 years for radium-226, and 6.7 years for radium-228, the most common isotopes of radium, after which each forms an isotope of radon. Presumably, if dose protraction were taken into account by the life-table analysis, the difference between juveniles and adults would vanish. With 228Ra, dose delivery is practically all from bone volume, but the ranges of the alpha particles from this decay series exceed those from the 226Ra decay series, allowing 228Ra to go deeper into the bone marrow and, possibly, to irradiate a larger number of target cells. Thereafter, tumors appear at the rate M(D,t). The third patient was reported to contain 45 g of radium. In this way, some problems of selection bias could be avoided, because most radium-dial workers were identified by search, and coverage of the radium-dial worker groups was considered to be high. s, where D local 36 elevator apprenticeship. D At low doses, the model predicts a tumor rate (probability of observing a tumor per unit time) that is proportional to the square of endosteal bone tissue absorbed dose. Separate retention functions are given for each of these compartments. These were plotted against a variety of dose variables, including absorbed dose to the skeleton from 226Ra and 228Ra, pure radium equivalent, and time-weighted absorbed dose, referred to as cumulative rad years. The probability of such a difference occurring by chance was 51%. Annual Report No. Radon is gaseous at room temperature and is not chemically reactive to any important degree. It is not known whether the similarity in appearance time distribution for the two tumor types under similar conditions of irradiation of bone marrow is due to a common origin. The cilia transport mucus in a more or less continuous sheet across the epithelial surface toward the ostium.13. Ally Gesto > Blog > Uncategorized > why does radium accumulate in bones?. Occasionally, data from several studies have been analyzed by the same method, and this has helped to illuminate similarities and differences in response among 224Ra, 226Ra, and 228Ra. Radiogenic tumors in the radium and mesothorium cases studied at M.I.T. An ideal circumstance would be to know the dose-response relationships in the absence of competing causes of death and to combine this with information on age structure and age-specific mortality for the population at large. The question remained open, however, whether the health effects were threshold phenomena that would not occur below certain exposure or dose levels, or whether the risk would continue at some nonzero level until the exposure was removed altogether.