This discussion will be devoted to matters that have a quantitative effect on the estimation of endosteal tissue dose. Cumulative incidence, computed as the product of survival probabilities in the life table,10 was used as the measure of response with errors based on approximations by Stehney. The paranasal sinuses are cavities in the cranial bones that exchange air and mucus with the nasal cavity through a small ostium. In this analysis, there were one or more tumors in the six intake groups with intakes above 25 Ci and no tumors observed in groups with intakes below 25 Ci. Some of these complications, such as osteopenia, are reversible and severity is dose dependent. Spontaneously occurring bone tumors are rare. The linear functions obtained by Rowland et al.67 were: where D 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. In a more complete development, Schlenker73 investigated the dosimetry of sinus and mastoid epithelia when 226Ra or 228Ra was present in the body. The importance of this work lies in the fact that it shows the maximum difference in radiosensitivity between juvenile and adult exposures for this study. Rowland et al. 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. Rowland et al.66 plotted and tabulated the appearance times of carcinomas for five different dosage groups. In discussing these cases, Wick and Gssner93 noted that three cases of bone cancer were within the range expected for naturally occurring tumors and also within the range expected from a linear extrapolation downward to lower doses from the Spiess et al.88 series. Leukemia has been seen in the Germans exposed to 224Ra, but only at incidence rates close to those expected in unexposed populations. 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. Petersen, N. J., L. D. Samuels, H. F. Lucas, and S. P. Abrahams. Their induction, therefore, cannot be influenced by dose from the airspace as can the induction of carcinomas by 226Ra in humans. A clear implication of these data is that the connective tissue in the mastoid is thinner than the connective tissue in the paranasal sinuses. The analysis is most relevant to the question of practical threshold and will be discussed again in that context. Unless physically trapped in a matrix, radon diffuses rapidly from its site of production. Schlenker, R. A., and B. G. Oltman. The total thickness of the mucosa, based on the results of various investigators, ranges from 0.05 to 1.0 mm for the maxillary sinuses, 0.07 to 0.7 mm for the frontal sinuses, 0.08 to 0.8 mm for the ethmoid sinuses, and 0.07 to 0.7 for the sphenoid sinuses. The radium content in the bodies of 185 of these workers was measured. Posted by: Comments: 0 Post Date: June 8, 2021 . In the subject without carcinoma, the measured radium concentration in the layer adjacent to the bone surface was only about 3 times the skeletal average. i is 226Ra intake, and D i The data are subdivided into three groups based on the 226Ra intake. However, the change was not so great as to alter the basic conclusion that the data have too little statistical strength to distinguish between various mathematical expressions for the dose-response curve. An acceptable fit, as judged by a chi-squared criterion, was obtained. The analysis was not carried out for carcinoma risk, but the conclusions would be the same. The work by Raabe et al.61,62 permits the determination of a practical threshold dose and dose rate. For each of the seven intake groupings in this range (e.g., 0.51, 12.5, 2.55), there was about a 5% chance that the true tumor rate exceeded 10-3 bone sarcomas per person-year when no tumors were observed, and there was a 48% chance that the true tumor rate, summed over all seven intake groups exceeded the rate predicted by the best-fit function I = (10-5 + 6.8 10-8 Raabe et al. 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. 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. This duct is normally closed, and clearance By this pathway is negligible. s. The analysis of Rowland et al.67 assumes that tumor rate is constant with time for a given intake D The fundamental reason for this is the chemical similarity between calcium and radium. 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. 1. D 1976. 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). Thus, most data analyses have presented cancer-risk information in terms of dose-response graphs or functions in which the dependent variable represents some measure of risk and the independent variable represents some measure of insult. The analysis shows that the minimum appearance time varies irregularly with intake (or dose) and that the rate of tumor occurrence increases sharply at about 38 yr after first exposure for intakes of greater than 470 Ci and may increase at about 48 yr after first exposure for intakes of less than 260 Ci. Calcium can accumulate in the arterial plaque that develops after an injury to the vessel wall. 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. For 228Ra the dose rate from the airspace to the mastoid epithelium was about 45% of the dose rate from bone. The points with their standard errors result from the proportional hazards analysis of Chemelevsky et al. Direct observation in vivo of retention in these three compartments is not possible, and what has been learned about them has been inferred from postmortem observations and modeling studies. The results of this series of studies of bone sarcoma incidence among 224Ra-exposed subjects extending over a period of 15 yr underscore the importance of repeated scrutiny of unique sets of data. 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. The statistical uncertainty in the coefficient is determined principally by the variance in the high-dose data, that is, at exposure levels for which the observed number of tumors is nonzero. When these ducts are open, clearance is almost exclusively through them. As with 226,228Ra, the curves in Figure 4-8 can be used to establish confidence limits for risk estimates at low doses, although it is to be understood that these limits are not unique, because the shape of the dose-response curve is unknown. Kolenkow30 presented his results as depth-dose curves for the radiation delivered from bone but made no comment on epithelial cell location. The risk envelopes defined by these analyses are not unique. Hindmarsh, M., M. Owen, J. Vaughan, L. F. Lamerton, and F. W. Spiers. 1980. . The calculated dose from this source was much less than the dose from bone. i), based on year of entry. Thus, the absence of information on the tumor probability as a function of person-years at risk is not a major limitation on risk estimation, although a long-term objective for all internal-emitter analyses should be to reanalyze the data in terms of a consistent set of response variables and with the same dosimetry algorithm for both 224Ra and for 226Ra and 228Ra. 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. Hasterlik, R. J., L. J. Lawson, and A. J. Finkel. By measuring the radium content of 50 private wells in 27 selected counties, the counties were divided into 10 low-exposure and 17 high-exposure groups. 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. Rundo, J., A. T. Keane, H. F. Lucas, R. A. Schlenker, J. H. Stebbings, and A. F. Stehney. Argonne, Ill.: When examined in this fashion, questions arise. With only two exceptions, average skeletal dose computed in the manner described at that time has been used as the dose parameter in all subsequent analyses. In the model, this dose is directly proportional to the average skeletal dose, and tumor rate is an analog of the response parameter, which is bone sarcomas per person-year at risk. This report indicates that the age- and sex-adjusted osteosarcoma mortality rate for the total white population in the communities receiving elevated levels of radium for the period 19501962 was 6.2/million/yr; that of the control population was 5.5. Animal data supplemented by models are required to estimate retention in the human bone surface, and human data combined with models of gas accumulation are applied to the pneumatized space compartment. In general, the data from humans suffice to establish radium retention in the bone volume compartment. (c). The third patient was reported to contain 45 g of radium. ; 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 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. None of these findings are in agreement with the long-term studies of higher levels of radium in the radium-dial workers. 1986. All five leukemias in the control group were acute forms, while three in the exposed group were chronic myeloid leukemia. The equations based on year of first measurement of body radioactivity are: With attention now focused on exposure levels well below those at which tumors have been observed, it is natural to exploit functions such as those presented above for radiogenic risk estimation. Littman, M. S., I. E. Kirsh, and A. T. Keane. Locations of Bone Sarcomas among Persons Exposed to 224 Ra and 226,228Ra for Whom Skeletal Dose Estimates Are Available. It should be noted that if tumor rate were constant for a given dose, it could not be constant for a given intake because the dose produced by a given intake is itself a function of time; therefore, the tumor rate would be time dependent. 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. Radium . An internally deposited radioactive element may concentrate in, and thus irradiate, certain organs more than others. Separate retention functions are given for each of these compartments. 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. Radon is known to accumulate in homes and buildings. Florida has substantial deposits of phosphate, and this ore contains 238U, which in turn produces 226Ra and 222Rn. For the presentation of empirical data, two-dimensional representations are the most convenient and easiest to visualize. 16/06/2022 . Raabe et al. With life-long continuous intake of dietary radium, the distinction between hot spot and diffuse activity concentrations is diminished; if dietary intake maintains a constant radium specific activity in the blood, the distinction should disappear altogether because blood and bone will always be in equilibrium with one another, yielding a uniform radium specific activity throughout the entire mineralized skeleton. 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. Littman et al.31 report a single value of 17 m for the lamina propria in a person who had contracted mastoid carcinoma. Some 35 carcinomas of the paranasal sinuses and mastoid air cells have occurred among the 4,775 226,228Ra-exposed patients for whom there has been at least one determination of vital status. The intersection of the line with the appearance time axis provides an estimate of the minimum appearance time. There may be an excess of leukemia among the adults, but the evidence is weak. Schumacher, G. H., H. J. Heyne, and R. Fanghnel. 1982. Source: Mays and Spiess.45, Risk per person per gray versus mean skeletal dose. Further, a dose-response relationship is suggested for total leukemia with increasing levels of radium contamination. 228Ra intake was excluded because it was assumed that 228Ra is ineffective for the production of these carcinomas. Importantly, because alpha particles have a very short range (<100 m), there is limited damage to surrounding normal tissues, including bone marrow [ 7, 9 ]. Argonne National Laboratory, Comparable examples can be given for each expression of Rowland et al. i = 0.05 Ci, the total systemic intake in 70 yr for a person drinking 2 liters of water per day at the Environmental Protection Agency's maximum contaminant level of 5 pCi/liter, the ratio is 4,700. Incident Leukemia in Located Radium Workers. 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 of December 1982, the average followup time was 16 yr for patients injected after 1951 with lower doses of 224Ra for the treatment of ankylosing spondylitis.93 Of 1,426 patients who had been traced, the vital status for 1,095 of them was known. Rowland, R. E., A. F. Stehney, and H. F. Lucas, Jr. Parks, J. Farnham, J. E. Littman, and M. S. Littman. i 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. These authors concluded that there was no relationship between radium level and the occurrence of leukemia. 1971. Radium is present in soil, minerals, foodstuffs, groundwater, and many common materials, including many used in construction. l - 0.7 10-5) are used to determine a range of values based on the envelope boundaries, a measure of the uncertainty in estimated bone sarcoma risk at low doses can be formed as: where I is the best-fit function [0.7 10-5 + 7.0 10-8 In an additional group of 37 patients who were treated with radium by their personal physicians, two blood dyscrasias were found. 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. a. In a more complete series of measurements on normal persons and persons exposed to low 226,228Ra doses, Harris and Schlenker21 reported total mucosal thicknesses between 22 and 134 m, with epithelial thicknesses in the range of 3 to 14 m and lamina propria thicknesses in the range of 19 to 120 m. Calculations for 226Ra and 228Ra are similar to the calculation with the asymptotic tumor rate for 224Ra. Cells with a fibroblastic appearance similar to that of the cells lining normal bone were an average distance of 14.9 m from the bone surface compared with an average distance of 1.98 m for normal bone. For the functions of Rowland et al. 1984. The data points in Figure 4-7 for juveniles and adults are not separable from one another, and the difference between juvenile and adult radiosensitivity has completely disappeared in this analysis. why does radium accumulate in bones? Pool, R. R., J. P. Morgan, N. J.
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