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. 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. 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. We make safe shipping arrangements for your convenience from Baton Rouge, Louisiana. Thus, there is a potential for the accumulation of large quantities of radon. They point out that there is no information on individual exposure to radium from drinking water, nor to other confounding factors. 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. The third analysis that corrects for competing risks was performed by Chemelevsky et al.9 using a proportional hazards model. Evans15 listed possible consequences of radium acquisition, which included leukemia and anemia. Groer and Marshall20 estimated the minimum time for osteosarcoma appearance in persons exposed to high doses of 226Ra and 228Ra. 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 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. e is the endosteal dose. 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. 1. They conclude that the incidence of myeloid and other types of leukemia in this population is not different from the value expected naturally. why does radium accumulate in bones? The sinus ducts are normally open but can Be plugged by mucus or the swelling of mucosal tissues during illness. 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. Rowland et al.67 have reported the only separate analyses of paranasal sinus and mastoid carcinoma incidence. i = 0.5 Ci. 1978. 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. 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. as result of the local effects of the radon . Equally important is ensuring the availability of information on the rate at which tumors have occurred in the populations at risk. However, no mention of such cases appear in his report. 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. All towns, 1,000 to 10,000 population, with groundwater supplies. The average skeletal doses were later calculated to be 23,000 and 9,600 rad, respectively, which are rather substantial values. Such cells could accumulate average doses in the range of 100300 rad, which is known to induce transformation in cell systems in vitro. 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. 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. Bean, J. The theory of bone-cancer induction by alpha particles38 offers some insights. A common reaction to intense radiation is the development of fibrotic tissue. These estimates are based on retention integrals74 and relative distribution factors40 that originate from retention and dosimetry models. As with Evans et al. The intersection of the line with the appearance time axis provides an estimate of the minimum appearance time. > 10 yr and 0 for t < 10 yr. Data on tumor locations and histologic type are presented in Table 4-4. The increase of median tumor appearance time with decreasing dose rate strengthens the case for a practical threshold. Also, mortality statistics as they now exist include the effect of environmental exposures to radium isotopes. A more complete description of the radium-dial painter data and parallel studies with radium in laboratory animals, particularly the rat, would do much to further such efforts. A total of 9.2 cases would be expected to occur naturally in such a population. This is sometimes in the form of a three-dimensional dose-time-response surface, but more often it is in the form of two-dimensional representations that would result from cutting a three-dimensional surface with planes and plotting the curves where intersections occur. For 224Ra tumors have been observed between 3.5 and 25 yr after first exposure, with peak occurrence being at 8 yr. 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. 1972. Schlenker74 examined the uncertainties in risk estimates for bone tumor induction at low intakes and found it to be much greater than would be determined from the standard deviations in fitted risk coefficients. Various radiation effects have been attributed to radium, but the only noncontroversial ones are those associated with the deposition of radium in hard tissues. 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. The type of dose used is stated for each set of data discussed. Wick et al.95 reported on another study of Germans exposed to 224Ra. 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. 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. 1957. Dose-response data were fitted by a linear-quadratic-exponential expression: where D is estimated systemic intake. Mygind, N., M. Pedersen, and M. H. Nielsen. Only the beta and gamma rays, which were of low intensity compared to the alpha rays, emitted by these radioactive materials in the adjacent bone could have reached these cells. 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. Schumacher, G. H., H. J. Heyne, and R. Fanghnel. 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. What I can't discover is why our body prefers these higher atomic weight compounds than the lower weight Calcium. 1966. 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. 1973. 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. Rundo, J., A. T. Keane, and M. A. Essling. Equations for the dose rate averaged over depth, based on a simplified model of alpha-particle energy loss in tissue, were presented by Littman et al.31 for dose delivered by radium in bone and by radon and its daughters in an airspace with a rectangular cross section. Mays, C. W., H. Spiess, and A. Gerspach. National Academies Press (US), Washington (DC). For animals given a single injection, hot spots probably played a role similar to that played by diffuse radioactivity. Raabe et al. 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. 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. Proper handling procedures are necessary to avoid radiation risks. Three-dimensional representation of health effects data, although less common, is more realistic and takes account simultaneously of incidence, exposure, and time. D why does radium accumulate in bones? The points with their standard errors result from the proportional hazards analysis of Chemelevsky et al.9. Radium-induced carcinomas in the temporal bone are always assigned to the mastoid air cells, but the petrous air cells cannot be logically excluded as a site of origin. Postmortem skeletal retention has been studied in animals and in the remains of a few humans with known injection levels.