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Rowland, R. E., and J. H. Marshall. Rowland, R. E., A. F. Stehney, and H. F. Lucas, Jr. In summary, the evidence indicates that acquisition of very high levels of radium, leading to long-term body contents of the order of 5 Ci or more, equivalent to systemic intakes of the order of several hundred microcuries, resulted in severe anemias and aleukemias. 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. The complexity of the problem is illustrated by their findings for Chicago. In general, the data from humans suffice to establish radium retention in the bone volume compartment. Deposits in the bone with nonuniform distribution, following the decay of 226Ra in the bone. Meaningful estimates of tissue and cellular dose obtained by these efforts will provide a quantitative linkage between human and animal studies and cell transformation in vitro. EXtensive Experience with human beings and numerous animal experiments have shown beyond doubt that a portion of any quantity of radium which enters the body will be deposited in the bones, and that osteogenic sarcomas are often associated with small quantities of radium which have been fixed in the bone for considerable periods of time (1). Equations for the Functions I . In the Evans et al. 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. u = 10-5 + 1.6 10-5 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. 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. Evans, R. D., A. T. Keane, and M. M. Shanahan. 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. In communities where wells are used, drinking water can be an important source of ingested radium. All five leukemias in the control group were acute forms, while three in the exposed group were chronic myeloid leukemia. The work by Raabe et al.61,62 permits the determination of a practical threshold dose and dose rate. Various radiation effects have been attributed to radium, but the only noncontroversial ones are those associated with the deposition of radium in hard tissues. Some of the lead can stay in the bones for decades; however, some lead can leave the bones and reenter the blood and organs under certain circumstances, for example, during pregnancy and periods of breast-feeding, after a bone 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. 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. i - 3.6 10-8 The ratios of maximum to average lay in the range 837. When the water supplies were divided into three groups levels of 02, 25, and > 5 pCi of 226Ra per liter and the average annual age-adjusted incidence rates were examined for the period 19691978 (except for 1972), certain cancers were found to increase with increasing radium content. Concern over the shape of the dose-response relationship has been a dominant theme in the analyses and discussions of the data related to human exposure to radium. The higher values of the ratios were associated with shorter exposure times, usually the order of a year or less. 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. 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. Thus, there is a potential for the accumulation of large quantities of radon. The weight of available evidence suggests that bone sarcomas arise from cells that accumulate their dose while within an alpha-particle range. The intersection of the line with the appearance time axis provides an estimate of the minimum appearance time. Although the points for adults always lie below those for juveniles, there is always substantial statistical overlap. . Lyman et al.35 do not claim, however, to have shown a causal relationship between leukemia incidence and radium contamination. i + Di Ventilation of the mastoid air cells occurs through the eustachian tube which normally allows little air to move. why does radium accumulate in bones? - teppeifc.com In a more complete development, Schlenker73 investigated the dosimetry of sinus and mastoid epithelia when 226Ra or 228Ra was present in the body. 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 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. This population has now been followed for 34 yr; the average follow-up for the exposed group is about 16 yr. A total of 433 members of the exposed group have died, leaving more than 1,000 still alive. Regardless of the functions selected as envelope boundaries, however, the percent uncertainty in the risk cannot be materially reduced. 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. Carcinomas of the Paranasal Sinuses and Mastoid Air Cells among Persons Exposed to 226,228Ra and Currently Under Study at Argonne National Laboratory. D The pneumatized portion of one mastoid process has a volume of about 9.2 cm3. Commenting on the mucosal thickness data of Ash and Raum,2 Littman et al.31 observed: "If the dimensions of the sinus walls are applicable to the radium cases, it would appear that only a relatively sparse population of epithelial cells in the submucosal glands of the paranasal sinuses would receive significant dose from alpha particles originating in bone.". Radiogenic tumors in the radium and mesothorium cases studied at M.I.T. Evans et al.17 suggested an increase of median tumor appearance time with decreasing dose based on observations of tumors in a group of radium-dial painters, radium chemists, and persons who had received or used radium for medicinal purposes. He pointed out that the reports of Martland4143 describe a regenerative leucopenic anemia, and he stated that "this syndrome has features of atypical (aleukemic) leukemia or myelosclerosis or both.". U.S. white male mortality rates for 1982 from Statistical Abstract of the United States, 106th ed., U.S. Department of Commerce, Washington, D.C., 1986. Therefore, no judgment can be made as to whether such a layer would develop in response to a single injection of 224Ra or whether the layer could develop fast enough to modify the endosteal cell dosimetry for multiple 224Ra fractions delivered over an extended period of time. In 1977 it was estimated that only 15 people died in the United States from cancers of the auditory tube, middle ear, and mastoid air cells.53 Comparable statistics are lacking for cancers of the ethmoid, frontal, and sphenoid sinuses; but mortality, if scaled from the incidence data, would not be much greater than that caused by cancers of the auditory tube, middle ear, and mastoid air cells. i is the total systemic intake of 226Ra plus 2.5 times the total systemic intake of 228Ra, expressed in microcuries. The points with their standard errors result from the proportional hazards analysis of Chemelevsky et al. Radium - Health Risks of Radon and Other Internally Deposited Alpha The calculated dose from this source was much less than the dose from bone. They point out that there is no information on individual exposure to radium from drinking water, nor to other confounding factors. In the simple columnar epithelium, the thicknesses for the lamina propria implied by the preceding information range from about 10 m upward to nearly 1 mm. why does radium accumulate in bones? The eustachian tube provides ventilation for the middle ear and pneumatized portions of the temporal bone. Separate retention functions are given for each of these compartments. 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. 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. 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. 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. Presumably, if dose protraction were taken into account by the life-table analysis, the difference between juveniles and adults would vanish. The radium concentration in this layer was 50 to 75 times the mean concentration for the whole skeleton. Committee on the Biological Effects of Ionizing Radiations (BEIR). The distributions of histologic types for the 47 subjects exposed to 224Ra with bone sarcoma and a skeletal dose estimate are 39 osteosarcomas, 1 fibrosarcoma, 1 pleomorphic sarcoma, 4 chondrosarcomas, 1 osteolytic sarcoma, and 3 bone sarcomas of unspecified type. Rowland et al.66 plotted and tabulated the appearance times of carcinomas for five different dosage groups. Polednak, A. P., A. F. Stehney, and R. E. Rowland. Based on Kolenkow's work,30 Evans et al.16 reported a cumulative dose of 82,000 rad to the mucous membrane at a depth of 10 m for the subject with carcinoma. as result of the local effects of the radon . 's analysis, the 228Ra dose was given a weight 1.5 times that of 226Ra. As revealed by animal experiments and clearly detailed by metabolic models, alkaline earth elements deposit first on bone surfaces and then within the volume of bone. increases with decreasing intake from 1.7 at D The type of dose used is stated for each set of data discussed. 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." A linear function was fitted to the data over the full range of doses, but the fit was rejected by a statistical test for goodness of fit that yielded a P value of 0.02. 1980. 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. 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. Incident Leukemia in Located Radium Workers. The first analysis to take account of competing risks and loss to followup74 was based on a life-table analysis of data collected88 for persons 16 yr of age and older. why did jasmine richardson kill her family. This discussion will be devoted to matters that have a quantitative effect on the estimation of endosteal tissue dose. As with other studies, the shape of the dose-response curve is an important issue. There is more information available on the dosimetry of the long-term volume deposit. 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. For example, if D The subjects used in this analysis were all women employed in the radium-dial-painting industry at an average age of about 19 yr. Over age 30, the situation is different. why does radium accumulate in bones? - dzenanhajrovic.com 1978. 1966. No firm conclusions about the constancy or nonconstancy of tumor rate should be drawn from this dose-response analysis. The individual cells range from 0.1 to more than 1 cm across and are too numerous to be counted. If forms with negative coefficients are eliminated, as postulated by the model, then only (C + D) exp(-D) from this latter group provided an acceptable fit, but it had a chi-squared probability (0.06) close to the rejection level (0.05). Clearance half-times for the frontal and maxillary sinuses are a few minutes when the ducts are open. (a), Mays and Lloyd (b), and Rowland et al. 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. 1981. Finkel, A. J., C. E. Miller, and R. J. Hasterlik. Coverage of other groups, especially those with medical exposure, was considered low, and many subjects were selected by symptom. If the survival adjacent to the diffuse component were 37%, as might occur for endosteal doses of 50 to 150 rad, the hot-spot survival would be 0.09%. 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. Direct observations of the lamina propria indicate that the thickness lies between 14 and 541 m.21. Call simile in romeo and juliet act 1 scene 5| mighty clouds of joy concert or fontana breaking news Summary of virtually all available data for adult man. 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. 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. This work allows one to specify a central value for the risk, based on the best-fit function and a confidence range based on the envelopes. When an excess has occurred, there exist confounding variables. A single function was fitted to these data to describe the change of the dose-response curve slope with the length of time over which injections were given: where y is the number of bone sarcomas per million person-rad and x is the length of the injection span, in months. National Research Council (US) Committee on the Biological Effects of Ionizing Radiations. These 28 towns had a total population of 63,689 people in 1970. The two bones of the forearm are the radius and the ulna. Malignancies of the auditory tube, middle ear, and mastoid air cells (ICD 160.1) make up only 0.0085% of all malignancies reported by the National Cancer Institute's SEER program.52 Those of the ethmoid (ICD 160.3), frontal (ICD 160.4), and sphenoid (ICD 160.5) sinuses together make up 0.02% of all malignancies, or if the nonspecific classifications, other (ICD 160.8) and accessory sinus, unspecified (ICD 160.9), are added as though all tumors in these groups had occurred in the ethmoid, frontal, or sphenoid sinuses, the incidence would be increased only to 0.03% of all malignancies. 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. why does radium accumulate in bones? - nutrir.cl The increase of median tumor appearance time with decreasing dose rate strengthens the case for a practical threshold. Parks, J. Farnham, J. E. Littman, and M. S. Littman. why does radium accumulate in bones? - albakricorp.com Most of the 220Rn (half-life, 55 s) that escapes bone surfaces decay nearby, as will 216Po (half-life 0.2 sec). For 228Ra the dose rate from the airspace to the mastoid epithelium was about 45% of the dose rate from bone. The asymptotic value of this function is 200 bone sarcomas/million person-rad, which is considered applicable both to childhood and adult exposure. Create a gas-permeable layer beneath the slab or flooring.. Schlenker, R. A., and J. H. Marshall. Negative values have been avoided in practical applications by redefining the dose-response functions at low exposure levels. 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 A third compartment, which is not a repository for radium itself but which is relevant to the induction of health effects, consists of the pneumatized portions of the skull bones, that is, the paranasal sinuses and the air cells of the temporal bone (primarily the mastoid air cells), where radon and its progeny, the gaseous decay products of radium, accumulate. 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. Spiess, H., H. Poppe, and H. Schoen. The distribution of histologic types for radium-induced tumors is compared in Table 4-2 with that reported for naturally occurring bone tumors.11 The data have been divided into two groups according to age of record for the tumor. Such cells could accumulate average doses in the range of 100300 rad, which is known to induce transformation in cell systems in vitro. If there were a continuous exposure of 1 rad/yr, the tumor rate would rise to an asymptotic value. 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. 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. 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%. This change occurred in 19251926 following reports and intensive discussion of short-term health effects such as ''radium jaw" in some dial painters. 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. Kolenkow's work30 illustrated many of the complexities of sinus dosimetry and emphasized the rapid decrease of dose with depth in the mucous membrane. 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. The late effects of internally deposited radioactive materials in man, The U.K. radium luminiser survey: Significance of a lack of excess leukemia, The Radiobiology of Radium and Thorotrast, Drinking water and cancer incidence in Iowa, Drinking water and cancer incidence in lowa, Zur Anatomie der Stirnhohlen, Koniglichen Anatomischen Institut za Konigsberg Nr. Rowland, R. E., A. F. Stehney, and H. F. Lucas. 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. 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. 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. These estimates are based on retention integrals74 and relative distribution factors40 that originate from retention and dosimetry models. The data have been normalized to the frequency for osteosarcoma and limited to the three principal radiogenic types: osteosarcoma, chondrosarcoma, and fibrosarcoma. 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. 1952. 4, Radium. 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. Both bones are important for proper motion of the elbow and wrist joints, and both bones serve as important attachments to muscles of the upper extremity. Book, and N. J. In the analysis of radiation-effects data, the alpha particles emitted are considered to be the root cause of damage. 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. However, at lower radium intakes, such as those experienced by the British luminizers and the bulk of the U.S. radium-dial workers, incorporated 226Ra does not appear to give rise to leukemia. i, redefinition is not required to avoid negative expected values, and radiogenic risk is set equal to the difference between total risk and natural risk. i is 226Ra intake, and D Dose is used here as a generic term for the variety of dosimetric variables that have been used in the presentation of cancer incidence data. 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. 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. Learn faster with spaced repetition. 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. 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. 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. In people with radium burdens of many years' duration, only 2% of the excreted radium exits through the kidneys. 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. 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. This is because of the high linear energy transfer (LET) associated with alpha particles, compared with beta particles or other radiation, and the greater effectiveness of high-LET radiations in inducing cancer and various other endpoints, including killing, transformation, and mutation of cells. Finkel et al.18 concluded that the appearance of one case of CML in 250 dial workers, with about 40 yr of follow-up time, would have been above that which was expected. Whether these effects magnify other skeletal problems is unknown, but issues such as these leave the threshold-nonthreshold question open to further investigation.