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1980. 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. . 1982. All five leukemias in the control group were acute forms, while three in the exposed group were chronic myeloid leukemia. 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. Whole-body radium retention in humans. The loss is more rapid from soft than hard tissues, so there is a gradual shift in the distribution of body radium toward hard tissue, and ultimately, bone becomes the principal repository for radium in the body. The poorest fit, and one that is unacceptable according to a chi-squared criterion, was obtained for I = C + D2. 1976. When plotted, the model shows a nonlinear dose-response relationship for any given time after exposure. i is 226Ra intake, and D s is 226Ra skeletal dose. Evans15 listed possible consequences of radium acquisition, which included leukemia and anemia. 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. The cause of paranasal sinus and mastoid air cell carcinomas has been the subject of comment since the first published report,43 when it was postulated that they arise ''. This will extend the zone of irradiation out into the marrow, beyond the region that is within alpha particle range from bone surfaces. Your comment on the increased blood flow is certainly part of the process, especially for acute (recent) injuries. In effect, essentially all the 220 Rn that diffuses into the pneumatized air space decays there Before it can be cleared, but essentially all the 222Rn that reaches the pneumatized air space is cleared before it can decay. 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. 1985. 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. 1981. i) with 95% confidence that total risk lies between I The difference between mucosal and epithelial thickness gives the thickness of the lamina propria a quantity of importance for dosimetry. 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. Risk per person per gray versus mean skeletal dose. 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. The times to tumor appearance for bone sarcomas induced by 224Ra and 226,228Ra differ markedly. When radium levels in urine and feces are measured, by far the largest amount is found in the feces. While five cases of leukemia were observed among 681 adults who received an average skeletal dose of 206 rad, none were observed among 218 1 to 20-yr-olds at an average skeletal dose of 1,062 rad. The principal factors that have been considered are the nonuniformity of deposition within bone and its implications for cancer induction and the implications for fibrotic tissue adjacent to bone surfaces. 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. Deposition (and redeposition) is not uniform and tissue reactions may alter the location of the cells and their number and radiosensitivity. 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. Parks, J. Farnham, J. E. Littman, and M. S. Littman. 1959. Because bone cancer is an early-appearing tumor, the risk, so far as is now known, disappears within 25 yr after exposure. Regardless of the functions selected as envelope boundaries, however, the percent uncertainty in the risk cannot be materially reduced. Tumor frequencies for axial and appendicular skeleton are shown in Table 4-1. Bean, J. Why does radium accumulate in bones?-Radium accumulates in bones because radium essentially masks itself as calcium. i - 3.6 10-8 Little research on the chemical form of radium in body fluids appears to have been conducted. A total of 9.2 cases would be expected to occur naturally in such a population. The complete absence of other, less-frequent types of naturally occurring carcinoma that represent 16% of the carcinomas of specific cell type in the SEER52 study and 39% of the carcinomas in the review by Batsakis and Sciubba4 provides further evidence for perturbation of the distribution of carcinoma types by alpha radiation. From this, we can conclude that much, and perhaps all, of the difference in radiosensitivity between juveniles and adults originally reported was due to the failure to take into account competing risks and loss to follow-up. Posted by: Comments: 0 Post Date: June 8, 2021 . In contrast, 226Ra delivers most of its dose while residing in bone volume, from which dose delivery is much less efficient. This method of selection, therefore, made such cases of questionable suitability for inclusion in data analyses designed to determine the probability of tumor induction in an unbiased fashion. The third analysis that corrects for competing risks was performed by Chemelevsky et al.9 using a proportional hazards model. provided an interesting and informative commentary on the background and misapplications of the linear nonthreshold hypothesis.17. 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. On the basis of minimum and median appearance times, they concluded that the appearance times do not change with dose. National Research Council (US) Committee on the Biological Effects of Ionizing Radiations. 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 standard deviation for each point is shown. Argonne National Laboratory. Source: International Commission on Radiological Protection (ICRP).29. 1975. Not long afterward, Mays and Spiess45 published a life-table analysis in which cumulative incidence was computed annually from the date of first injection by summing annual tumor occurrence probabilities. The linear functions obtained by Rowland et al.67 were: where D Published by at 16 de junio de 2022. 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. Radium-226 adheres quickly to solids and does not migrate far from its place of release. i = 100 Ci to a value of 480 at D 2 Clearance through the ventilatory ducts is rapid when they are open. Below this dose level, the chance of developing a radium-induced tumor would be very small, or zero, as the word threshold implies. 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. 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. Leukemia has not often been seen in the studies of persons who have acquired internally deposited radium. However, calcium is ubiquitous in the human body, so small amounts of radium may accumulate in other tissues, causing toxicity. 1980. The layer was 8- to 50-m thick, was sometimes a cellular, and sometimes contained cells or cell remnants within it. Annual Report No. 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. Importantly, because alpha particles have a very short range (<100 m), there is limited damage to surrounding normal tissues, including bone marrow [ 7, 9 ]. The identities of these cells are uncertain, and their movements and life cycles are only partly understood. 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. The thickness of the simple columnar epithelium, including the cilia, is between 30 and 45 m. 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. For exposure at environmental levels, the distinction between hot spots and diffuse radioactivity is reduced or removed altogether. Some of these complications, such as osteopenia, are reversible and severity is dose dependent. Radium is present in soil, minerals, foodstuffs, groundwater, and many common materials, including many used in construction. All members of the world's population are presumably at risk, because each absorbs radium from food and water; as a working hypothesis, radiation is assumed to be carcinogenic even at the lowest dose levels, although there is no unequivocal evidence to support this hypothesis. The collective volume of one set of ethmoid air cells is about 3.5 cm3; there are nine cells on the average,92 for an average volume per cell of 0.4 cm3. 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. why does radium accumulate in bones?coastal plains climate. Figure 4-2 is a summary of data on the whole-body retention of radium in humans.29 Whole-body retention diminishes as a power function of time. Their induction, therefore, cannot be influenced by dose from the airspace as can the induction of carcinomas by 226Ra in humans. Since radium is present at relatively low levels in 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. 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. al.,61,62 with time to death by bone cancer and average skeletal dose rate as the response and dose parameters, respectively. These percentages contrast sharply with the results for beagles injected with 226Ra, in which osteosarcomas were about equally divided between the axial and appendicular skeletons and one-quarter of the tumors appeared in the vertebrae.90, Histologic type has been confirmed by microscopic examination of 45 tumors from 44 persons exposed to 226,228Ra for whom dose estimates are available; there were 27 osteosarcomas, 16 fibrosarcomas, 1 spindle cell sarcoma, and 1 pleomorphic sarcoma. Groer and Marshall20 estimated the minimum time for osteosarcoma appearance in persons exposed to high doses of 226Ra and 228Ra. Retention in tissues decreases with time following attainment of maximal uptake not long after intake to blood. Roughly 900 persons who were treated with Peteosthor as children or adults during the period 19461951 have been followed by Spiess and colleagues8486 for more than 30 yr and have shown a variety of effects, the best known of which is bone cancer. It does, however, deposit in soft tissue and there is a potential for radiation effects in these tissues. 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 l, respectively) of an envelope of curves that provided acceptable fits to the data, as judged by a chi-squared criterion. The subjects used in this analysis were all women employed in the radium-dial-painting industry at an average age of about 19 yr. This argues for the interaction of doses and in the extreme case for squaring the cumulative dose. There is a 14% probability that the expected number of tumors lies within the shaded region, defined by allowing the parameter value in Equation 416 to vary by 2 standard errors about the mean, and a 68% probability that it lies between the solid line that is nearly coincident with the upper boundary of the shaded region and the lower solid curve. 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. Nevertheless, the time that bone and adjacent tissues were irradiated was quite short in comparison to the irradiation following incorporation of 226Ra and 228Ra by radium-dial workers. A common reaction to intense radiation is the development of fibrotic tissue. Investigation of other dosimetric approaches is warranted. The probability of survival for cells adjacent to the endosteal surface and subjected to the estimated average endosteal dose for this former radium-dial painter was extremely small. A. Egsston. The dosimetric differences among the three isotopes result from interplay between radioactive decay and the site of radionuclide deposition at the time of decay. Although the conclusions to be drawn from Evans' and Mays' analyses are the samethat a linear nonthreshold analysis of the data significantly overpredicts the observed tumor incidence at low dosesthere is a striking difference in the appearance of the data plots, as shown in Figure 4-4, in which the results of studies by the two authors are presented side by side. However, the mucosa may have been irradiated by the alpha rays from the radiothorium that was fixed in the adjacent periosteum. The typical adult maxillary cavity has a volume of about 13 cm3; one frontal sinus has a volume of about 4.0 cm3, and one sphenoid sinus has a volume of about 3.5 cm3. If a dose-protraction effect were included in the analysis, there might be a reversal of the original situation, with adults having the greater radiosensitivity. Incident Leukemia in Located Radium Workers. There is a 95% probability that the expected number lies between the dashed boundaries. The first comprehensive graphical presentations of the dose-response data were made by Evans.15 In that study both tumor types (bone sarcoma and head carcinoma) were lumped together, and the incidence data were expressed as the number of persons with tumor divided by the total number known to have received the same range band of skeletal radiation dose. Rowland et al.69 examined the class of functions I = (C + D local 36 elevator apprenticeship. 1978. Because of internal remodeling and continual formation of haversian systems, these cells can be exposed to buried radioactive sites. i + Di The take and release of activity into and out of the surface compartment was studied quantitatively in animals and was found to be closely related to the time dependence of activity in the blood.65 Mathematical analysis of the relationship showed that bone surfaces behaved as a single compartment in constant exchange with the blood.37 This model for the kinetics of bone surface retention in animals was adopted for man and integrated into the ICRP model for alkaline earth metabolism, in which it became the basis for distinguishing between retention in bone volume and at bone surfaces. 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. Two extensive studies of the adverse health effects of 224Ra are under way in Germany. For this reason, the total average endosteal dose is probably the best measure of carcinogenic dose. 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. Because CLL is not considered to be induced by radiation, the latter case was assumed to be unrelated to the radium exposure. 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. i is the total systemic intake of 226Ra plus 2.5 times the total systemic intake of 228Ra, expressed in microcuries. analysis are closely parallel and, as might be expected, lead to the same general conclusion that the response at low doses [where exp(-D) 1] is best described by a function that varies with the square of the absorbed dose. Higher doses of radium have been shown to cause effects on the blood (anemia), eyes (cataracts), teeth (broken teeth), and bones (reduced bone growth). They fit mathematical functions of the general form: in which all three coefficients (, , ) were allowed to vary or one or more of the coefficients were set equal to zero. 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. 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. 35, A proportional hazards analysis of bone sarcoma rates in German radium-224 patients, Introduction to Stochastic Processes in Biostatistics, Development and Anatomy of the Nasal Accessory Sinuses in Man, The Nose: Upper Airway Physiology and the Atmospheric Environment, Radium poisoning; a review of present knowledge, The effect of skeletally deposited alpha-ray emitters in man. The use of a table for each starting age group provides a good accounting system for the calculation. The third analysis was carried out by Raabe et. 1978. ." 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. This may lead to negative values at low exposures. A three- or four-inch pipe pulls radon from underneath the house and vents it outside. Further, a dose-response relationship is suggested for total leukemia with increasing levels of radium contamination. ANL-84-103. 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. The increase of median tumor appearance time with decreasing dose rate strengthens the case for a practical threshold. 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 frequencies for different bone groups are axial skeleton-skull (3), mandible (1), ribs (2), sternebrae (1), vertebrae (1), appendicular skeleton-scapulae (2), humeri (6), radii (2), ulnae (1), pelvis (10), femora (22), tibiae (7), fibulae (1), legs (2; bones unspecified), feet and hands (5; bones unspecified). 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. Since it is not yet possible to realistically estimate a target cell dose, it has become common practice to estimate the dose to a 10-m-thick layer of tissue bordering the endosteal surface as an index of cellular dose. Dose-response relationships of Evans et al. 1985. 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, where D In communities where wells are used, drinking water can be an important source of ingested radium. In the case of the longer-half-life radium isotopes, the interpretation of the cancer response in terms of estimated dose is less clear. For example, the central value of total risk, including that from natural causes, is I = (10-5 + 6.8 10-8 The removal of the difference came in two steps associated with analyses of the influence of dose protraction on tumor induction. Health Risks of Radon and Other Internally Deposited Alpha-Emitters: Beir IV, The bone-cancer risk appears to have been completely expressed in the populations from the 1940s exposed to, The committee recommends that the follow-up studies of the patients exposed to lower doses of. The average dose for the exposed group, based on patients for whom there were extant records of treatment level, was 65 rad. If this were substituted for the tumor rate caused by 224Ra exposure in Table 4-7 and the survival rate of those exposed to 224Ra were adjusted to the corresponding value (0.9998), survival in the presence of 224Ra exposure after 25 yr would be 777,293, with 3,272 deaths attributable to the 224Ra exposure. It shows no signs of significant secretory activity but is always moist. The kinetics of radon accumulation in the pneumatized air spaces are determined by the kinetics of radium in the surrounding bone, the rate of diffusion from bone through the intervening tissue to the air cavity, and the rate of clearance through the ventilatory ducts and the circulatory system. In addition to the primary radiationalpha, beta, or bothindicated in the figures, most isotopes emit other radiation such as x rays, gamma rays, internal conversion electrons, and Auger electrons. Leukemias induced by prolonged irradiation from Thorotrast (see Chapter 5) have appeared from 5 to more than 40 yr after injection, similar to the broad distribution of appearance times associated with the prolonged irradiation with 226,228Ra. Because of its preference for bone, radium is commonly referred to as a bone seeker. The expected number of leukemias for the adult group was two, but the authors point out that the drugs often taken to suppress the pain associated with ankylosing spondylitis are suspected of inducing the acute forms of leukemia. 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. This assumes the 224Ra dose-response analyses described above and further assumes that tumors are fatal in the year of occurrence. Various radiation effects have been attributed to radium, but the only noncontroversial ones are those associated with the deposition of radium in hard tissues. For 228Ra the dose rate from the airspace to the mastoid epithelium was about 45% of the dose rate from bone. 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. The risk envelopes defined by these analyses are not unique. why does radium accumulate in bones? 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. 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 dose is delivered continuously over the balance of a person's lifetime, with ample opportunity for the remodeling of bone tissues and the development of biological damage to modulate the dose to critical cells. The alternative is to reanalyze all of the data on tumor induction for 224Ra by using the new algorithm before it is applied it to dose calculations for risk estimation in a population group different from the subjects in the study by Spiess and Mays.85. The points with their standard errors result from the proportional hazards analysis of Chemelevsky et al. Home; antique table lamps 1900; why does radium accumulate in bones? The fundamental reason for this is the chemical similarity between calcium and radium. Relative Frequencies for Radium-Induced and Naturally Occurring Tumors by Age Group. 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. Over age 30, the situation is different. 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. For t less than 5 yr, M(D,t) is essentially 0 because of the minimum latent period. This is the first report of an explicit test of linearity that has resulted in rejection. 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." At the low exposures that occur environmentally and occupationally, exposure to radium isotopes causes only a small contribution to overall mortality and would not be expected to perturb mortality sufficiently to distort the normal mortality statistics. These cells are within 3080 m of endosteal bone surfaces, defined here as the surfaces bordering the bone-bone marrow interface and the surfaces of the forming and resting haversian canals. A., P. Isaacson, R. M. Hahne, and J. Kohler. For nonstochastic effects, apparent threshold doses vary with health endpoint. The cumulative tumor risk (bone sarcomas/106 person-rad) was similar in the juvenile and adult patients under the dosimetric assumptions used. 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 second, which used the deep-well data from the prior study, examined cancer incidence as a function of radium content of the water.

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