Health Risks of Radon and Other Internally Deposited Alpha-Emitters BEIR IV (1988) / Chapter Skim
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6 Uranium
6 Uranium
Pages 276-302
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From page 276... ...
Uranium ~ also found in phosphate rock, lignite, and monazite sands. The potential health effects of uranium in mining or in refining operations are complicated by the presence of other alpha-emitters in the ore, such as radium and radon.
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From page 277... ...
However, the natural uranium content of lung, liver, kidney, and vertebra was found to be age dependent.~i Cayenne and Welfordii also noted that the skeletal content in their material was only one-tenth of that predicted by the International Commission on Radiological Protection (ICRP)
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From page 278... ...
This discovery resulted in its widespread use as a homeopathic remedy in the treatment of diabetes mellitus because of the mistaken conclusion that the effect was an abnormality of carbohydrate metabolism. However, extensive research soon showed that it was the result of renal damage, and uranium compounds became the agent of choice in the production of chronic renal lesions in experimental animals.
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From page 279... ...
A proportion of the deposited particles remains permanently in the Jung tissue or is stored in the hilar lymph nodes. Larger aerosol particles (> 5 ,um ADD)
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From page 280... ...
However, uranium behaves chemically like calcium, and the skeletal system might be the target organ in the case of enriched uranium. The use of autoradiography with isotopes with high specific activities has provided much experimental information on the mechanism of deposition of uranium in bone.
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From page 281... ...
, in eight terminally ill brain tumor patients (Boston, Mass.) , in studies to investigate bone metabolism in seven patients with different bone diseases, and in healthy control subjects.2t These experiments provided information on the distribution and renal effects of acute exposures, but are of less value in predicting the effects of chronic Tow-level exposure.
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From page 282... ...
The total amounts present in the latter would depend on the uranium content of food and water during life and thus on the geographical area from which the specimens were obtained. Donoghue et al.8 compared the body content of uranium in the case that they reported with that calculated from estimates of occupational exposure during life and the retention values predicted from ICRP models.25 Uranium in the lungs and thoracic lymph nodes were less than 1% of the predicted values.
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From page 283... ...
NEPHROTOXIC EFFECTS In the case of natural uranium, the toxicological data identify the kidney as the target organ, although specific acute toxic effects are associated with the inhalation of certain compounds such as UF4 and UC}4. Studies done after the acute administration of soluble uranium to animals2355 indicated that substantial renal damage occurred when the concentration of uranium in the kidney exceeded 3 Agog of renal tissue.
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From page 284... ...
The lesions in the proximal convoluted tubules result in the appearance of glucose, low-molecular-weight proteins, and amino acids in the urine. These substances are normally reabsorbed from the tubular fluid, and their appearance in urine ~ due mainly to malabsorption by the damaged tubular cells and partly to tubular excretion, but not to increased gIomerular permeability.
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From page 285... ...
Both single and chronic exposures are relevant to human populations. The laboratory experiment of single acute exposure mimics accidental exposures, but chronic exposure experiments are more important in estimating environmental effects or those In working populations.
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From page 286... ...
There is some evidence in mice and dogs that the combination of alpha radiation and chemical toxicity produces a greater nephrotoxic eject than either does seperately.~9 The relevance of this to human risk estimates is difficult to determine. In one of the few studies to show an effect of uranium on humans, Thun et a}.53 evaluated kidney function among uranium mill workers and found a statistically significant excretion of beta-2-microgiobulin and five amino acids.
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From page 287... ...
If there is a linear dose-response relationship32 one could speculate that natural or slightly enriched uranium could also induce bone sarcomas in humans, but the likelihood would be very small because of the low specific activity of natural uranium. Nonetheless, Mays et al.32 have estimated, using toxicity ratios, the risk of bone sarcoma induction from the chronic ingestion of natural uranium, on the basis of an assumed linear dose-response function for 226Ra.
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From page 288... ...
Thus, the most reasonable assumption is that the alpha-emitt~ng uranium isotopes are as effective as 226 Ra in inducing bone sarcomas. This assumption should be experimentally investigated in an animal with appropriate skeletal remodeling properties, such as the dog, with 233U and 232U.
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From page 289... ...
have been studied in rats, dogs, and monkeys by observing animals given brief exposures and after prolonged exposure.27 28 For the insoluble uranium compounds, the lungs and pulmonary lymph nodes were the only organs affected. In monkeys, dogs, and rats, the chronic inhalation of insoluble UO2 at 25 mg/m3 eventually produced fibrosis of lung tissue and malignant lung tumors.
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From page 290... ...
The validity of the latter claim must be assessed in relation to the power of surveys to detect an effect if one were present. In the design of epidemiological studies to investigate health risks due specifically to uranium, and not to concomitant exposure to other substances, it would be reasonable to search for bone, hematopoietic, or lung tumors as an expression of the radiation effect and for the
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From page 291... ...
In an early mortality study by the U.S. Public Health Service of uranium miners and millers in the Colorado Plateau, Wagoner et al.56 reported no apparent increase in mortality in a cohort of 611 white uranium millers who had no apparent previous uraniummining exposure.
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From page 292... ...
The type and solubility of the uranium compounds also changed over time. In the earlier years, insoluble oxides were present with the more soluble chloride (ACID.
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From page 293... ...
In a further analysis of the same cohort, Cookfair et al.7 undertook a case-control study nested within the cohort to examine the risk of lung-cancer death among men who received radiation exposure to the lungs as a result of inhaling uranium dust or the dust of uranium compounds. Cases consisted of the 330 cohort members who died of lung cancer.
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From page 294... ...
Another retrospective study of mortality patterns among a cohort of uranium mill workers was reported by Waxweiler et al.58 Records from seven uranium mills throughout the Colorado Plateau were obtained, and 2,002 men who had worked for at least 1 yr in the mills were selected for study. Only those who stated on their job applications that they had never worked in uranium mining were included; the purpose of this restriction was to examine the health risks of uranium exposure in the absence of uranium mining.
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From page 295... ...
. This corroborated the excess of deaths due to the same malignancies reported in another cohort of uranium rn~lers.2 An occupational etiology was considered plausible toxicologically, because yellow-cake dust and insoluble yellow-cake uranium compounds accumulate in the tracheobronchial lymphatic system after inhalation,828 52 so they constitute a potential source of radiation to the lymphatic glands.
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From page 296... ...
There were no hard data on the extent of exposure to chemical agents or uranium or on smoking histories. In view of these limitations, the study results cannot be accepted as convincing evidence of an excess of nonmalignant respiratory disease due to uranium exposure.
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From page 297... ...
RISK ESTIMATES Uranium presents two separate potential risks due to its nephrotoxic action and as a result of alpha radiation. At present there is little convincing epidemiological evidence that serious renal disease has occurred in human populations as a result of chronic low-level exposure nor of increased rates of malignant tumors.
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From page 298... ...
The importance of such information ~ emphasized by the likelihood that control levels in industry may need to be guided more by the potential for nephrotoxic effects than by the effects of alpha radiation. Quantification of the risks associated with alpha emission during chronic exposure to uranium cannot be determined from published epidemiological studies because of confounding factors and because of the limited power of the surveys to detect increased rates of tumor incidence or mortality.
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From page 299... ...
1953. Toxicity following the parenteral administration of certain soluble uranium compounds.
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From page 300... ...
1969. Mortality of uranium miners in relation to radiation exposure, hard rock mining and cigarette smoking—1950 through 1967.
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From page 301... ...
1983. Dose-response relationships for radium-induced bone sarcomas.
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From page 302... ...
1983. An Epidemiologic Investigation of Nonmalignant Respiratory Disease Among Workers at a Uranium Mill.
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