Health Risks of Radon and Other Internally Deposited Alpha-Emitters BEIR IV (1988) / Chapter Skim
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5 Thorium
5 Thorium
Pages 245-275
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From page 245... ...
Deposition resulted in continuous alpha-particle irradiation throughout life at a low dose rate. Patients who received alpha-radiation exposure due to radiologically administered Thorotrast in the late 1920s through 1955 have been followed in epidemiological surveys in Germany,5i Portugal,5 245
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From page 246... ...
The average body content of thorium-232 is about 80 mBq, 60~o of which can be found in the skeleton. Associated annual effective dose equivalent is estimated at about 3 ,uSv (1 Sv = 100 rem)
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From page 248... ...
Ra(lon-220 and its decay products (hippo, 2~2Pb, nimbi, memo, and 208 Th) are responsible for an additional annual effective dose equivalent of about 0.22 mSv, 90~o of which is a result from indoor exposure.
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From page 249... ...
Following intravenous injection, thorium of high specific activity deposits mainly on bone surfaces, from which its release appears to be very slow. In the special case of Thorotrast, in which macroquantities of 232Th in colloidal form are injected, it is the physical form that controls its deposition in the cells of the reticuloendothelial system rather than the chemical properties.
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From page 250... ...
With increasing amounts of Thorotrast injected, an increase in the effective average aggregate diameter and a corresponding decrease in the fraction of alpha-energy emitted by the aggregate are found.50 Table 5-2 shows the mean tissue doses in the liver and red bone marrow based on measurements from the German Thorotrast study50 and indicates the magnitude of dose modification to tissue afforded by the selfabsorption of the alpha particles in thorium dioxide aggregates. For example, in the case of the liver, an increase in the injected quantity of Thorotrast by a factor of 10 is associated with only a fourfold increase in annual radiation dose.
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From page 251... ...
THORIUM 251 FIGURE 5-2 High-resolution autoradiograph of liver autopsy specimen of a 60-yr-old male who died of hemangioendothelioma in the liver 15 yr after a 75-ml Thorotrast injection for hepatolienography. Magnification, X 1,250; oil · ~ immersion.
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From page 252... ...
Based on the tissue distribution of 232 Th in Thorotrast-exposed patients and the mean concentration of 232 Th in various organs of Thorotrast-exposed patients, Figure 5-3 ~ from the study of Kaul and Noffz22) illustrates the mean steady-state alpharadiation dose rates in the liver, spleen, and red bone marrow.
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From page 253... ...
and alpha rays from 232Th and 228Th emitted from autopsy samples make it possible to estimate the steady-state activity ratio of thorium daughters to 232Th. The steady-state activity ratio of 228 Th to 232 Th can be determined from an alpha~ray energy spectrum and that of 224 Ra to 228Th and 228 Ra can be determined from a gamma-ray energy spectrum.2i For estimation of average absorbed dose in an organ, the distribution of Thorotrast aggregate sizes must be assumed.
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From page 254... ...
The high dose rate to the endosteal layer in bone is due to the thorium dioxide in adjacent bone marrow and transiocation of 224Ra from deposits in the reticuloendothelial system to bone surfaces. For the West German patients, the mean latent period was 30 yr, the mean absorbed dose in the liver was 824 red (range, 384-1,391 red)
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From page 255... ...
In these experiments, 232 Th was enriched with different fractions of 230Th to allow variation in dose rate for constant volumes of Thorotrast injected or varying volumes for a constant burden of radioactivity. They found that the frequency of liver and spleen tumors following a single injection of Thorotrast followed a linear dependence on radiation dose rate, but was not correlated with the volume of Thorotrast injected.
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From page 256... ...
The volume of injected Thorotrast, given a constant dose rate, had only a slight influence on the number of tumors induced. The experimental evidence from studies on laboratory animals suggests that Thorotrast-induced tumors appear to arise in large measure from the effects of radiation, and that the carcinogenic effect may not be directly related to the physical presence of the particulate material in the tissues, to the chemical properties of thorium, or to the fibrotic tissue formed by cells killed by the radiation.
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From page 257... ...
Studies of the bones of beagle dogs receiving single intravenous injections of 228Th have shown that the histopathological changes preceding the development of osteosarcomas are similar to those caused by 239Pu and 226 Ra and those in radium-bearing humans. High radiation doses altered the vasculature and circulation and caused bone necrosis, bone resorption, reduced bone formation, and marrow fibrosis.~9 26 Lloyd et al.24 cletermined toxicity ratios for bone sarcoma induction at low dose rates and at Tow total doses in life-span observations of beagles, injected as young adults, for incorporated 228 Th relative to that for 226Ra.
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From page 258... ...
There are five epidemiological follow-up studies of Thorotrastexposed patients, namely, the German Thorotrast study,46-5i the Japanese Thorotrast cases,20 2i 29-32 the Thorotrast exposed patients in Portugal, 5 i7 the Danish Thorotrast study,- and the American study.
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From page 259... ...
The shortest latency interval for leukemia was 5 yr. The estimated accumulated dose to the red bone marrow is estimated TABLE 5-3 The German Thorotrast Study: Causes of Death in Examined and Nonexamined Patients (Combined)
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From page 260... ...
The results of the German Thorotrast ~tudy,5t when compared with those of the Portuguese,5 Danish,'t and Japanese32 studies, show similar excess rates of liver cancers and leukem~a.27 28 Doseeffect relationships for liver cancers and leukemias have been observed in the West German study (Figure 5-4~.5~ However, the influence of the dose rate to bone marrow on the leukemia incidence cannot, as yet, be established. The cumulative incidence of liver cancers and leukemias plotted against time after Thorotrast injection (Figure 54)
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From page 261... ...
FIGURE 5-4 The German Thorotrast study. Cumulative incidence of liver tumors Stolid line)
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From page 262... ...
FIGURE 5-5 The German Thorotrast study. Cumulative incidence of liver tumors in examined Thorotrast-treated patients with different liver dose rates.
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From page 263... ...
; for liver cancers, the range was 29-34 yr; for leukemias it was about 20 yr.5 t7 THE JAPANESE THOROTRAST STUDY An epidemiological study is being conducted in Japan of 282 patients who were given Thorotrast for angiography and hepatolienography during World War ll.20923929-32 Their follow-up now extends to 38-46 yr post-Thorotrast administration. The amount of Thorotrast injected intravascularly in 159 cases ranged from 1.0 to 139 m]
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From page 264... ...
of cases To Malignant tumors 75 28.8a 94 7.3 Hepatic tumors 50 19.2U 6 0.5 Other 25 9.6 88 6.8 Blood diseases 4 1.5a 2 0.2 Liver cirrhosis 16 6.1U 17 1.3 Other diseases 67 25.7 243 18.8 Total dead cases 180 69.0a 446 34.6 Total living cases 74 28.3 844 65.4 Untraced cases 7 2.7 — — Total cases 261 100.0 1,290 100.0 ap c 0.001. SOURCE: Modified from Mori et al.32 and blood diseases are in accord with the findings of the German Thorotrast study.49 50 In the Japanese Thorotrast study,3i the absorbed dose rate in the liver, spleen, and bone marrow was estimated for 71 autopsy cases of Thorotrast-treated patients who died from cholangiocarcinoma, hemangioendothelioma, liver cell carcinoma, liver cirrhosis, and blood and other diseases.
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From page 265... ...
SOURCE: Mori et al.3i In the patients exposed to Thorotrast intravascularly, the dose rates to the liver estimated in 96 cases ranged from 2 to 69 rad/yr; the mean absorbed dose was 919.6 red (standard deviation [SDi, 409.0 red) for 67 malignant hepatic tumors, 958.6 red (SD, 251.6 red)
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From page 266... ...
There have been 93 liver cancers versus 0.89 expected, and 23 leukemias versus 3.12 expected. There also appeared to be an excess of lung cancer (19 observed versus 9.1 expected)
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From page 267... ...
Other forms of thorium would be subject to different pharmacodynamics, and thus, the dose distribution and health ejects would be different. In order to calculate the risk of dying by liver cancer after Thorotrast injection, it is necessary to know the size of the Thorotrast population cohort, the average dose to the liver per year, the number of persons dead at time t, the number of liver cancers at time t, and finally the number of liver cancers in the control group at time t.
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From page 268... ...
An example calculation of the risk is given In the box entitled Example Risk Estimate for Liver Cancer in the German Thorotrast Study." Using these assumptions, excess lifetime risks have been calculated for liver cancer for the three different Thorotrast studies, namely, the German, the Japanese, and the Portuguese studies. These risks are shown in Table 5-6.
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From page 269... ...
x 2,334 = 413 Risk per 106 person-red = 413/1,380,950 = # 300/106 personrad TABLE 5-6 Estimated Liver Cancer Risks from Thorotrast Thorotrast Expected Excess Person-Rad- Risk/106 Study Liver Cancers Wasted Dose Person-Rad German 413 1.30 X 106 300 Japanese 67 0.256 X 106 260 Portuguese 111 0.40 X 106 280 quite different from the dose distributions associated with Thorotrast aggregates, and the risk values will also be different. Faber6 ~ 9 estimated the excess rate of liver cancer in adults as 4.2 cases/year/106 person-red.
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From page 270... ...
Rowland and Rundo37 have calculated that a typical intravascular injection of 25 m! of Thorotrast gave an average dose rate from transiocated 224 Ra of about 1 rad/yr to the marrow-free skeleton of an adult.
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From page 271... ...
Further, some of the decay products of the complicated thorium series are soluble, transIocate, and are bone seekers. Thus, average dose to the tissues may be an inappropriate parameter, and calculations based on terminal burdens do not necessarily represent the radiation dose that may be responsible for initiating malignant processes.
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From page 272... ...
status of the Danish Thorotrast study. Health Phys.
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From page 273... ...
1983. Estimated absorbed dose in tissues and radiation effects in Japanese Thorotrast patients.
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From page 274... ...
Recent results of the German Thorotrast study.
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From page 275... ...
1983. Recent results of the German Thorotrast studyepidemiological results and dose effect relationships in Thorotrast patients.
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