Spiers, F. W., H. F. Lucas, J. Rundo, and G. A. Anast. Several general sources of information exist on radium and its health effects, including portions of the reports from the United Nations Scientific Committee on the Effects of Atomic Radiation; The Effects of Irradiation on the Skeleton by Janet Vaughan; The Radiobiology of Radium and Thorotrast, edited by W. Gssner; The Delayed Effects of Bone Seeking Radionuclides, edited by C. W. Mays et al. For the percent of exposed persons with bone sarcomas, Mays and Lloyd44 give 0.0046% D Tumor frequencies for axial and appendicular skeleton are shown in Table 4-1. In this expression, C is the natural carcinoma rate and D is the systemic intake or mean skeletal dose. As an example, the upper boundaries of the 95% confidence envelope for total cumulative incidence corrected for competing risks are: Dose-response envelopes for 224Ra from equation 416. Here the available dose-response relationships are presented in terms of the number of microcuries that reach the blood. The sinus ducts are normally open but can Be plugged by mucus or the swelling of mucosal tissues during illness. why does radium accumulate in bones? - sercemzarodzina.pl (a), Mays and Lloyd (b), and Rowland et al. As dose diminishes below the levels that have been observed to induce bone cancer, cell survival in the vicinity of hot spots increases, thus increasing the importance of hot spots to the possible induction of bone cancer at lower doses. Carcinomas of the frontal sinus and the tympanic bulla, a portion of the skull comparable to the mastoid region in humans, have appeared in beagles injected with radium isotopes and actinides. Such negative values follow logically from the mathematical models used to fit the data and underscore the inaccuracy and uncertainty associated with evaluating the risk far below the range of exposures at which tumors have been observed. 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. An approximate approach would be to take the population as a function of age and exposure and apply the dose-response relationship to each age group, taking into account the projected survival for that age group in the coming years. 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. The third analysis was carried out by Raabe et. Calcium can accumulate in the arterial plaque that develops after an injury to the vessel wall. 1980. To circumvent this problem, two strategies have been developed: (1) classification of the cases according to their epidemiological suitability, on a scale of 1 to 5, with 5 representing the least suitable and therefore the most likely to cause bias and 1 representing the most suitable and therefore the least likely to cause bias; and (2) definition of subgroups of the whole population according to objective criteria presumably unrelated to tumor risk, for example, by year of first exposure and type of exposure. Annual Report No. 1978. Since it is the bombardment of target tissues and not the absorption of energy by mineral bone that confers risk, the apparent carcinogenic potency of these three isotopes differs markedly when expressed as a function of mean skeletal absorbed dose, which is a common way of presenting the data. Rowland, R. E., A. F. Stehney, and H. F. Lucas, Jr. why does radium accumulate in bones? - feelfreefromdisability.com Evans et al. why does radium accumulate in bones? - rybmscaffolding.co.uk National Research Council, 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. In contrast, mean skeletal dose changes with time, causing a gradual shift of cases between dose bands and confusing the intercomparison of data analyses carried out over a period of years. Phosphorites are rocks that are made of apatite, a mineral with the formula C a X 5 ( P O X 4) X 3 ( F, C l, O H). 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. 1978. 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. In the subject with carcinoma, he observed a hot layer of bone beginning about 2 m from the surface and extending inward a distance greater than the alpha-particle range. Higher doses of radium have been shown to cause effects on the blood (anemia), eyes (cataracts), teeth (broken teeth), and bones (reduced bone growth). 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. ;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. The thickness of the simple columnar epithelium, including the cilia, is between 30 and 45 m. For comparison with the values given previously for juveniles and adults separately, this is 2.0% incidence per 100 rad, which is somewhat higher than either of the previous values. Argonne National Laboratory. 2)exp(-1.1 10-3 There is no assurance that women exposed at a greater age or that men would have yielded the same results. The frequency distribution for appearance times shows a heavy concentration of paranasal sinus and mastoid carcinomas with appearance times of greater than 30 yr. For bone tumors there were approximately equal numbers with appearance times of less than or greater than 30 yr.67 Based on the most recent summary of data, 32 bone tumors occurred with appearance times of less than 30 yr among persons with known radiation dose and 29 tumors had occurred with appearance times of 30 yr or greater. Rowland et al.66 plotted and tabulated the appearance times of carcinomas for five different dosage groups. Research should continue on the cells at risk for bone-cancer induction, on cell behavior over time, including where the cells are located in the radiation field at various stages of their life cycles, on tissue modifications which may reduce the radiation dose to the cells, and on the time behavior and distribution of radioactivity in bone. The third analysis that corrects for competing risks was performed by Chemelevsky et al.9 using a proportional hazards model. Committee on the Biological Effects of Ionizing Radiations (BEIR). The two bones of the forearm are the radius and the ulna. When an excess has occurred, there exist confounding variables. This large difference has prompted theoretical investigations of the time dependence of hotspot dose rate and speculations on the relative importance of hot-spot and diffuse components of the radioactivity distribution for tumor induction. 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. 1985. The most frequent symptoms for mastoid air cell tumors were ear blockage or discharge and hearing loss. Rowland et al.67 performed a dose-response analysis of the carcinoma data in which the rate of tumor occurrence (carcinomas per person-year at risk) was determined as a function of radium intake. Decay series for radium-228, a beta-particle emitter, and radium-224, an alpha-particle emitter, showing the principal isotopes present, the primary radiations emitted (, , or both), and the half-lives (s = second, m = minute, h = hour, d = day, y = year), b. ." Two extensive studies of the adverse health effects of 224Ra are under way in Germany. Unless there is a bias in the reporting of carcinomas, it is clear that carcinomas are relatively late-appearing tumors. s is the sum of the average skeletal doses for 226Ra and 228Ra, in rad. Recent analyses with a proportional hazards model led to a modification of the statement about the adequacy of the linear curve, as will be discussed later. The removal of the difference came in two steps associated with analyses of the influence of dose protraction on tumor induction. 1982. Decay series for radium-226 showing the primary radiations emitted and the half-lives. When the average exposure period is several hundred days, as it was for humans exposed to 226,228Ra, there will be only a minor reduction of hot-spot dose rate because the blood level is maintained at a high average level for the whole period of formation of most hot spots.67 Autoradiographs from radium cases with extended exposures such as those published by Rowland and Marshall65 bear this out and form a sharp contrast to autoradiographs of animal bone following single injection36 on which the model of hot-spot burial was based. In a review of the papers published in the United States on radium toxicity, and including three cases of radium exposure in Great Britain, Loutit34 made a strong case "that malignant transformation in the lymphomyeloid complex should be added to the accepted malignancies of bone and cranial epithelium as limiting hazards from retention of radium." 1978. Human health studies have grown from a case report phase into epidemiological studies devoted to the discovery of all significant health endpoints, with an emphasis on cancer but always with the recognition that other endpoints might also be significant. Summary of virtually all available data for adult man. 1986. There is a 95% probability that the expected number lies between the dashed boundaries. The success achieved in fitting dose-response functions to the data, both as a function of intake and of dose, indicates that the outcome is not sensitive to assumptions about tumor rate. 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. 1981. Further, a dose-response relationship is suggested for total leukemia with increasing levels of radium contamination. Knowing the death rate as a function of time for each starting age then allows the impact of radiation exposure to be calculated for each age group and to be summed for the whole population. 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. The other 98% passes out through the bowel. Spiess, H., H. Poppe, and H. Schoen. Stebbings et al.89 published results of a mortality study of the U.S. female radium-dial workers using a much larger data base. It should be borne in mind that hot-spot burial only occurs to a significant degree following a single intake or in association with a series of fractions delivered at intervals longer than the time of formation of appositional growth sites, about 100 days in humans. One of these was panmyelosis, and the other was aplastic anemia; the radium measurements for these two cases showed body contents of 10.5 and 10.7 Ci, respectively. A., P. Isaacson, W. J. Hausler, and J. Kohler. Rowland et al.67 have reported the only separate analyses of paranasal sinus and mastoid carcinoma incidence. Thus, while leukemia and diseases of the blood-forming organs have been seen following treatment with 224Ra, it is not clear that these are consequences of the radiation insult or of other treatments experienced by these patients. increases with decreasing intake from 1.7 at D 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. Your comment on the increased blood flow is certainly part of the process, especially for acute (recent) injuries. It may be some time before this group yields a clear answer to the question of radium-induced leukemia. Effects of radiation on bone - PubMed Included in the above summary are four cases of chronic lymphocytic or chronic lymphatic leukemia. 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. Categories . When the model is used for radium, careful attention should be paid to the constraints placed on the model by data on radium retention in human soft tissues.74 Because of the mathematical complexity of the retention functions, some investigators have fitted simpler functions to the ICRP model. The presentation and analysis of quantitative data vary from study to study, making precise intercomparisons difficult. A total of 66 sarcomas have occurred in 64 subjects among 2,403 subjects for whom there is an estimate of skeletal dose; fewer than 2 sarcomas would be expected. Junho 16, 2022 yardistry gazebo 12x10 yardistry gazebo 12x10 It later appears in the urine and feces, with the majority of excretion occurring by the fecal route. Some 55 sarcomas of bone have occurred in 53 of 898 224Ra-exposed patients whose health status is evaluated triennially.46 Two primary sarcomas occurred in 2 subjects. 1959. When the study was restricted to the 360 measured cases, one case of leukemia was found in a woman with a radium intake greater than 50 Ci. An additional three cases were found in the 19301949 cohort, yielding a standard mortality ratio of 221. D In communities where wells are used, drinking water can be an important source of ingested radium. 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. D Restated in more modern terms, the residual range from bone volume seekers (226Ra and 228Ra) is too small for alpha particles to reach the mucosal epithelium, but the range may be great enough for bone surface seekers (228Th), whose alpha particles suffer no significant energy loss in bone mineral;78 long-range beta particles and most gamma rays emitted from adjacent bone can reach the mucosal cells, and free radon may play a role in the tumor-induction process. 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. He emphasized that current recommendations of the ICRP make no clear distinction between the locations of epithelial and endosteal cells and leave the impression that both cell types lie within 10 m of the bone surface; this leads to large overestimates of the dose to epithelial cells from bone. 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. The difference between mucosal and epithelial thickness gives the thickness of the lamina propria a quantity of importance for dosimetry. Because CLL is not considered to be induced by radiation, the latter case was assumed to be unrelated to the radium exposure. in the expiratory air . why does radium accumulate in bones? Dose-response relationships of Evans et al. a. Hasterlik22 and Hasterlik et al.23 further elucidated the role of radon by postulating that it can diffuse from bone into the essentially closed airspaces of the mastoid air cells and paranasal sinuses and decay there with its daughters, adding an additional dose to the epithelial cells. This change occurred in 19251926 following reports and intensive discussion of short-term health effects such as ''radium jaw" in some dial painters. In contrast, 226Ra delivers most of its dose while residing in bone volume, from which dose delivery is much less efficient. When the time dependence of bone tumor appearance following 224Ra exposure is considered an essential component of the analysis, then an approximate modification of the dose-response relationship can be made by taking the product of the dose-response equation and an exponential function of time to represent the rate of tumor appearance: where F(D) is the lifetime risk, as specified by the analyses of Spiess and Mays85 and r is a coefficient based on the time of tumor appearance for juveniles and adults in the 224Ra data analyses. An analysis of the tumor appearance time data for carcinomas based on hazard plotting has been as employed by Groer and Marshall20 to analyze bone tumor rate in persons exposed to high doses from radium. As a response parameter, the number of bone sarcomas that have appeared divided by the number of persons known to have been exposed within a dose group was used. Wick, R. R., D. Chmelevsky, and W. Gssner. With the present state of knowledge, a single dose-response relationship for the whole population according to isotope provides as much accuracy as possible. why does radium accumulate in bones? - teppeifc.com Radon is gaseous at room temperature and is not chemically reactive to any important degree. For male bladder cancer only, the highest radium level produced a higher cancer rate than was observed for those consuming surface water. This type of analysis was used by Evans15 in several publications, some of which employed epidemiological suitability classifications to control for case selection bias. The ratio of the 95% confidence interval range, for radiogenic risk, to the central value. why did jasmine richardson kill her family. When the radiogenic risk functions (I 1984. The subjects used in this analysis were all women employed in the radium-dial-painting industry at an average age of about 19 yr. 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. Whether due to competing risks, dose protraction, or a combination, it is clear that differential radiosensitivity for this group of subjects is a hypothesis that cannot be supported. This curve and the data points are shown in Figure 4-7. Rowland, R. E., and J. H. Marshall. 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. why does radium accumulate in bones? - allygestao.com.br as result of the local effects of the radon . The final report of this study by Petersen et al.56 reported on the number of ''deaths due in any way to malignant neoplasm involving bone." Wolff, D., R. J. Bellucci, and A. The outcome of the fitting procedure was presented in graphic form, with total unweighted estimated systemic intake of 226Ra and 228Ra normalized to body weight as the dose parameter. Shifting to a different algorithm for dose calculation would, at a minimum, require demonstration that the new algorithm gives the same numerical values for dose as the Spiess and Mays85 algorithm for subjects of the same age and sex. Rundo, J., A. T. Keane, H. F. Lucas, R. A. Schlenker, J. H. Stebbings, and A. F. Stehney. It shows no signs of significant secretory activity but is always moist. -kx), and a threshold function. 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 s. The analysis also yields good fits to the data. A similar situation exists for female breast cancer. Harris, M. J., and R. A. Schlenker. 1976. Littman et al.31 report a single value of 17 m for the lamina propria in a person who had contracted mastoid carcinoma. 1969. The ratio of the 95% confidence interval range for radiogenic risk to the radiogenic risk defined by the central value function. In the first dose-response analyses, average skeletal dose was adopted as the dose parameter, and details of the dose calculations were presented. The cumulative tumor risk (bone sarcomas/106 person-rad) was similar in the juvenile and adult patients under the dosimetric assumptions used. 1958. a. Carcinomas of the Paranasal Sinuses and Mastoid Air Cells among Persons Exposed to 226,228Ra and Currently Under Study at Argonne National Laboratory. 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 There may be an excess of leukemia among the adults, but the evidence is weak. Argonne National Laboratory, This type of analysis updates the one originally conducted for this group of subjects in which juvenile radiosensitivity was reported to be a factor of 2 higher than adult radiosensitivity. The fundamental reason for this is the chemical similarity between calcium and radium. Four of the five leukemias occurred in patients with ankylosing spondylitis; two were known to be acute; it is not known whether the other three were acute or chronic. and those done earlier was division of the radium-exposed subjects into subpopulations defined by type of exposure, that is, radium-dial workers (mostly dial painters), those medically exposed, and others. i The sinus and mastoid carcinomas in persons exposed to. The ethmoid sinuses form several groups of interconnecting air cells, on either side of the midline, that vary in number and size between individuals.92 The sinus surfaces are lined with a mucous membrane that is contiguous with the nasal mucosa and consists of a connective tissue layer attached to bone along its lower margin and to a layer of epithelium along its upper margin. Whether the practical threshold represents a dose below which the tumor risk is zero, or merely tiny, depends on whether the minimum tumor appearance time is an absolute boundary below which no tumors can occur or merely an apparent boundary below which no tumors have been observed to occur in the population of about 2,500 people for whom radium doses are known. As with other studies, the shape of the dose-response curve is an important issue. Evans, R. D., A. T. Keane, R. J. Kolenkow, W. R. Neal, and M. M. Shanahan. The authors drew no conclusions as to whether the leukemias observed were due to 224Ra, to other drugs used to treat the disease, or were unrelated to either. Error bars on the points vary in size, and are all less than about 6% cumulative incidence (Figure 4-4). They point out that there is no information on individual exposure to radium from drinking water, nor to other confounding factors. The picture that emerges from considerations of cell survival is that hot spots may not have played a role in the induction of bone cancers among the 226,228Ra-exposed subjects, but they would probably play a role in the induction of any bone cancer that might occur at significantly lower doses, for example, following an accidental occupational exposure. Separate retention functions are given for each of these compartments. 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. How are people exposed to radium? The asymptotic value of this function is 200 bone sarcomas/million person-rad, which is considered applicable both to childhood and adult exposure. i) with 95% confidence that total risk lies between I 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. Radium is present in soil, minerals, foodstuffs, groundwater, and many common materials, including many used in construction. There is evidence that 226,228Ra effects on bone occur at the histological level for doses near the limit of detectability. There were 1,501 exposed cases and 1,556 ankylosing spondylitis controls. Radium has an affinity for hard tissue because of its chemical similarity to calcium. In the data analyses that lead to these equations, a 10-yr latent period is assumed for carcinoma induction. 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. Before concern developed over environmental exposure, attention was devoted primarily to exposure in the workplace, where the potential exists for the accidental uptake of radium at levels known to be harmful to a significant fraction of exposed individuals. why does radium accumulate in bones? - dzenanhajrovic.com Some 87 bone sarcomas have occurred in 85 persons exposed to 226,228 Ra among the 4,775 persons for whom there has been at least one determination of vital status. The purpose of this chapter is to review the information on cancer induced by these three isotopes in humans and estimate the risks associated with their internal deposition. Figure 4-5 shows the results of this analysis, and Table 4-3 gives the equations for the envelope boundaries. The radium concentration in this layer was 50 to 75 times the mean concentration for the whole skeleton. 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. Petersen, N. J., L. D. Samuels, H. F. Lucas, and S. P. Abrahams. If this reduction factor applied to the entire period when 224Ra was resident on bone surfaces and was applicable to humans, it would imply that estimates of the risk per unit endosteal dose, such as those presented in the Biological Effects of Ionizing Radiation (BEIR) III report,54 were low by a factor of 23. The linear relationship that provided the best fit to the data predicted a tumor rate lower than the rate that had been observed recently, and led the authors to suggest that the incidence at long times after first exposure may be greater than the average rate observed thus far. why does radium accumulate in bones? - jonhamilton.com According to the latest life-table analysis, the risk to juveniles (188 32 bone sarcomas/106 person-rad) is 1.4 times the risk to adults (133 36 bone sarcomas/106 person-rad). The exclusion of exhumed subjects removed from analysis 23 of the 759 individuals in the population and 1 of the 21 carcinomas that had occurred among them. Hindmarsh, M., M. Owen, J. Vaughan, L. F. Lamerton, and F. W. Spiers. After 25 yr, there would be 780,565 survivors in the absence of excess exposure to 224Ra and 780,396 survivors with 1 rad of excess exposure at the start of the follow-up period, a difference of 169 excess deaths/person-rad, which is about 15% less than the lifetime expectation of 200 10-6/person-rad calculated without regard to competing risks. 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. The radium, once ingested, behaves chemically like calcium and, therefore, deposits in significant quantities in bone mineral, where it is retained for a very long time. 1978. . . The times to tumor appearance for bone sarcomas induced by 224Ra and 226,228Ra differ markedly. u = 10-5 + 1.6 10-5 Environmental Research Division. In Table 4-1 note the low tumor yield of the axial compared with the appendicular skeleton. At high radiation doses, whole-body retention is dose dependent. Florida has substantial deposits of phosphate, and this ore contains 238U, which in turn produces 226Ra and 222Rn. 2 for D For 226Ra and 228Ra the constant tumor rates given by Rowland et al.68 as functions of systemic intake are computed for the intake of interest, and the results are worked out with a table such as Table 4-7. PDF Radium-226 (226Ra) - Washington State Department of Health The analysis took into account tumors appearing between 14 and 21 yr after the start of exposure in 43 subjects that received a known dose.
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