Gulf War and Health Volume 1: Depleted Uranium, Sarin, Pyridostigmine Bromide, and Vaccines (2000) / Chapter Skim
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Depleted Uranium
Depleted Uranium
Pages 89-168
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From page 89... ...
Beta particles are high-energy electrons; the path length of a beta particle averages O 15 m in air and ~1 cm in solids. Gamma radiation is an external radiation hazard be89
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From page 90... ...
Because of the different percentages of uranium isotopes in depleted uranium (Table 4.1) , its specific activity (14.8 mBq/,ug)
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From page 91... ...
However as discussed above, the chemical properties of depleted uranium are the same as those of the enriched and natural forms. The chemical and physical properties of depleted uranium are ideal for many military and commercial uses.
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From page 92... ...
Known exposure of U.S. personnel to depleted uranium during the Gulf War occurred as the result of friendly fire incidents, cleanup operations, and accidents (including fires)
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From page 93... ...
Some Gulf War veterans, including those with internal DU fragments, are participating in the Depleted Uranium Follow-up Program, a medical surveillance follow-up study, at the Baltimore VA Medical Center (McDiarmid et al., 2000~. There are ongoing efforts to expand this program to include additional veterans.
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From page 94... ...
The amount of uranium that the body absorbs depends largely on the route of exposure and the solubility of the uranium compounds to which the individual is exposed. Insoluble uranium compounds may remain within the pulmonary tissues, especially the pulmonary lymph nodes, for a long time and thus constitute a localized radiological hazard.
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From page 95... ...
The ICRP has developed extensive models of the dosimetry of inhaled radioactive materials (ICRP, 1994~. At the alveolar level, the more soluble uranium compounds (categorized as Type F for fast dissolution [e.g., UFO and uranyl nitrate hexahydrate]
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From page 96... ...
. In animals, the soluble uranium compounds uranyl nitrate hexahydrate (0.5-7 g/kg body weight)
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From page 97... ...
In humans, approximately two-thirds of an intravenous injection of uranium is eliminated from the plasma within 6 minutes, and 99 percent of the uranium is eliminated from the plasma 20 hours after injection (Struxness et al., 1956; Luessenhop et al., 1958~. The kidneys excrete more than 90 percent of hexavalent soluble uranium salt injected intravenously, and less than 1 percent is excreted in the feces.
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From page 98... ...
The half-time of uranium deposited in the lungs of dogs, rats, and monkeys exposed up to 5 years to uranium dioxide dust (5.1 mg U/m33 was approximately 15 months (Leach et al., 19739. Reports from human subjects occupationally exposed to insoluble uranium compounds suggest a two-phase clearance process, consisting of a short phase with a biological half-time between 11 and 100 days and a slow phase of clearance with a biological half-time between 120 and 1,500 days (Hursh and Spoor, 19731.
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From page 99... ...
Cats and dogs exposed for 30 days to 18 mg U/m3 as uranium tetrafluoride or 5 weeks exposure to 9.2 mg U/m3 as uranyl fluoride exhibited rhinitis (Dygert et al., 1949~. Notably, uranium dioxide and triuranium octaoxide, insoluble uranium compounds, did not lead to pulmonary toxicity.
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From page 100... ...
To assess the potential mutagenic effects of long-term exposure to internalized depleted uranium, Sprague-Dawley rats received 20 pellets of either tantalum or DU in various combinations (low DU: 4 DU and 16 tantalum pellets; medium DU: 10 DU and 10 tantalum pellets; high DU: 16 DU and 4 tantalum pellets) (Miller et al., 1998b)
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From page 101... ...
In a 5-year study in dogs and monkeys of inhaled dust containing insoluble uranium dioxide, kidney injury did not occur at exposure levels of 5 mg U/m3 (Leach et al., 1970~. Following a 91-day exposure to uranyl nitrate hexahydrate in drinking water (0.96, 4.8, 24, 120, or 600 mg/L)
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From page 102... ...
(Domingo et al., 1987~. Exposure-related signs of neurotoxicity were not apparent in rats exposed to uranyl nitrate hexahydrate for 91 days at levels up to 600 mg/L drinking water, which is equivalent to a time-weighted average equivalent dose of 37 and 54 mg U/kg body weight per day for male and female rats, respectively (Gilman et al., 1998a)
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From page 103... ...
. The purpose of these experiments was to establish an animal model that would provide insight into the injuries sustained by Gulf War veterans from embedded DU fragments and would make it possible to evaluate the biological effects of intramuscularly embedded DU fragments.
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From page 104... ...
. No gastrointestinal effects occurred in rabbits exposed for 91 days to uranyl nitrate hexahydrate in drinking water (0.96, 4.8, 24, 120, or 600 mg/L)
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From page 105... ...
Rabbits exposed for 91 days to uranyl nitrate in drinking water (0.96, 4.8, 24, 120, or 600 mg/L) did not suffer cardiovascular effects (Gilman et al., 1998b,c)
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From page 106... ...
The section begins with an overview of the studies of uranium miners. The studies in this cohort have limited relevance to the depleted uranium exposures of Gulf War veterans because, as described below, the primary disease-causing exposures for the miners were not to uranium, but to radon.
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From page 107... ...
The principal form of radiation exposure of uranium miners in underground mines has been to inhalation of alpha particles emitted by radon decay products in poorly ventilated mines (NRC, 1999~. Radon progeny are known to increase the risk of lung cancer (NRC, 1999~.
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From page 108... ...
A recent update of the mortality of this cohort examined vital status through December 31, 1990 (Roscoe, 1997~. The study found increased mortality risks in this cohort of 3,238 white male uranium miners for lung cancer (SMR = 580, 95% confidence interval [95% CI]
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From page 109... ...
There were 26 deaths from lymphatic and hematopoietic malignancies versus 27.4 expected; there were 2 deaths from bone cancer compared with 1.38 expected deaths. Studies of uranium miners in Czechoslovakia provide further information on mortality from cancers other than lung cancer and from other diseases (Tomasek et al., 1993, 1994~.
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From page 110... ...
Their exposure history differs from that of uranium miners because they worked in an environment that had little radon gas, an exposure that confounds any attempt to link uranium exposure in mine workers to effects on the lung, an important potential site for disease caused by uranium. The principal exposure of uranium processing workers is to uranium oxides and derivative uranium compounds produced during the uranium refinement process.
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From page 111... ...
Public Health Service (Wagoner et al., 1964) examined cancer mortality in a prospectively identified cohort of uranium miners and millers.
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Film badges, worn by all employees who worked in areas with exposure to radiation, provided a measure of cumulative external radiation. The plant monitored internal radiation by measuring urinary uranium excretion.
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From page 115... ...
They calculated the expected deaths based on statistics for the entire United States. The study examined overall mortality as well as sex- and racespecific mortality rates, but did not categorize workers by job classification as a proxy for radiation exposures.
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From page 116... ...
Uranium Processing Workers—Linde Air Products Company (Dupree et al., 1987J A study by Dupree and colleagues (1987) examined mortality among workers at the Linde Air Products Company Ceramics Plant in Buffalo, New York.
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From page 117... ...
Film badges were the source of external radiation exposure measurements. Individual urine bioassays and environmental sampling of uranium dust provided estimates of internal exposure, expressed as annual lung doses.
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From page 118... ...
Other studies on the Oak Ridge workers that have focused on external radiation exposures in the research laboratory or other settings include Checkoway et al., 1985; Carpenter et al., 1988; Gilbert et al., 1993; and Cardis et al., 1995. Uranium processing workers (1943-1947)
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From page 119... ...
Thus, many employees, especially those involved in the early steps of uranium processing, were heavily exposed to uranium dust. This study addressed the hypothesis that working up to several years in areas with high average levels of uranium dust was associated with increased mortality over a period 25-30 years after employment.
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From page 120... ...
The uranium enrichment process included exposure to enriched uranium, insoluble uranium oxides, and a variety of chemicals including fluorocarbons. Because detailed individual radiation exposure data were not available, workers were classified by the likelihood of exposure (yes, no)
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From page 121... ...
The primary exposure in common among these facilities was to alpha radiation from airborne dust containing insoluble natural uranium compounds. Enriched uranium was present at the Oak Ridge facility from 1943 to 1946, and exposure to radium and radon daughters was also possible at the Mallinckrodt facility.
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From page 123... ...
Radiation film badges give a measure of cumulative exposure but measure only external radiation, which is a greater concern for exposure to enriched uranium than for exposure to natural or depleted uranium. Measuring the internal dose of radiation is more difficult.
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From page 124... ...
They measured the level of uranium exposure in various work sites within the processing plant, using measures of urinary uranium or uranium in ambient dust. This information was used to model the cumulative lung dose per unit time in the work site.
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From page 125... ...
With this approach, the healthy worker effect is more likely to distort estimates of the effect of exposure on health outcomes. Comparison Group Issues Many of the cohort studies of occupationally-exposed workers described in this chapter compared death rates in workers to death rates in the U.S.
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From page 126... ...
(1988~. Table 4.6 outlines the different methods of internal comparisons that have been used in the studies of uranium processing workers.
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From page 127... ...
Poisson regression analysis to describe the joint effects, using a multiplicative main effects model, of the predictor variables (duration of employment, socioeconomic status, radiation exposure, facility, birth year, and length of follow-up) on lung cancer mortality.
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From page 128... ...
The SMRs are all close to or less than 100, indicating that cancer mortality in uranium workers was similar to the comparison group, which was either the entire U.S. male population or the population of the region near the work site.
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From page 130... ...
of follow-up of uranium mill workers. The number of lung cancer deaths was 4 (4.26 expected)
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From page 134... ...
; according to the urinary uranium levels, relatively few workers had high levels of exposure to uranium; and members of the cohort were relatively young at the end of the follow-up period. Uranium Processing Workers Linde Air Products Company (Dupree et al., 19879 There was no increase in lung cancer deaths in this cohort (21 observed, 21.7 expected; SMR 97, 95% CI 60-148~.
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From page 135... ...
However, the author made several new observations about the dose-response relationship and the possible interrelationship of external and internal radiation exposure, as shown in Table 4.10. The author found that an external radiation dose greater than 100 mSv increased cancer mortality for all cancers, lung cancer, and radiation-associated cancers.
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From page 137... ...
Although the radiation exposure data are a major strength of this study, the interpretation of findings for lung cancer risk is limited by the lack of data on smoking and other potential risk factors. Oak Ridge Uranium Processing and Laboratory Workers (From e et al., 1990J This study of uranium enrichment facility and energy research laboratory workers found an SMR for lung cancer of 127, based on 850 observed deaths
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From page 138... ...
Overall, there was no apparent relationship between internal radiation dose, lagged for 10 years, and lung cancer mortality. The only suggestion of an increased risk was for a cumulative internal dose of 25 cGy or more; the relative risk was 2.05, but this figure had extremely wide confidence intervals (0.20-20.70)
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From page 140... ...
The data provide strong evidence that lung cancer risk does not increase up to 25cGy cumulative internal radiation exposure (primarily uranium dust in these operations)
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From page 141... ...
Although studies of uranium miners have shown increased lung cancer mortality, the effect of uranium is difficult to interpret because the miners were simultaneously exposed to radon progeny, a known cause of lung cancer (NRC, 1999~. The lack of direct information on individual workers' exposure to cigarette smoke is an important shortcoming of these studies, since cigarette smoking is generally a predictor of lung cancer.
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From page 142... ...
However, there is inadequate/insufficient evidence to determine whether an association does or does not exist between exposure to uranium and lung cancer at higher levels of cumulative exposure. Lymphatic Cancer The lymphatic system is an important potential target for uranium radiation because inhaled insoluble uranium oxides can remain up to several years in the hilar lymph nodes of the lungs.
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From page 143... ...
Bone Cancer Like the lymphatic system, bone is an important potential target for the effects of uranium because uranium is distributed to the bone, replaces calcium in bone matrix, and may remain in the bone for several years. Studying the effects of uranium exposure on bone cancer is even more difficult than studying lymphoid malignancy because bone cancer is rarer, which means wide confidence intervals for the SMRs and far too few cases to establish useful dose-response relationships.
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From page 144... ...
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From page 145... ...
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From page 147... ...
There are a few case studies with limited information about the effects of orally administered uranium compounds. Oral ingestion of uranyl nitrate at dosages as high as 925 ma, three times per day, did not cause abnormalities on routine urinalysis (Morrow et al., 1980~.
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From page 149... ...
The U.S. Uranium Registry reevaluated the intake and deposition of uranium in three men 38 years after they had been accidentally exposed to soluble uranium compounds in an explosion in 1944 (Kathren and Moore, 19864.
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From page 150... ...
Kidney function was normal in Gulf War veterans with embedded DU fragments, years after exposure, despite urinary uranium concentrations up to 30.74 Gig creatinine (McDiarmid et al., 2000~. creatinine.
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From page 151... ...
. The mortality experiences of uranium processing workers (Table 4.15)
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From page 153... ...
In studies on Gulf War veterans, the search for evidence of neurological effects will require careful neurocognitive measurements, correlation of these with clinical dysfunction, and comparison of exposed veterans to control groups chosen to illuminate various facets of the complex exposure history of Gulf War veterans. Conclusion on Nonmalignant Neurological Disease The committee concludes that there is inadequate/insufficient evidence to determine whether an associations does or does not exist between exposure to uranium and diseases of the nervous system.
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From page 154... ...
In general, more soluble uranium compounds pass into the bloodstream, while less soluble forms remain in the lung or in lymph nodes for months to years. Uranium processing workers are exposed to the more soluble forms of uranium such as uranyl fluoride and uranium tetrachloride, as well as insoluble oxides.
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From page 156... ...
Conclusion on Nonmalignant Respiratory Disease The committee concludes that there is inadequate/insufficient evidence to determine whether an association does or does not exist between exposure to uranium and nonmalignant respiratory disease. Other Health Outcomes The information on other health outcomes in humans comes primarily from case reports of workers or other individuals accidentally exposed to large doses of uranium compounds.
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From page 157... ...
One author reported gonadal endocrine system dysfunction, with significant reduction in testosterone levels in uranium miners (Zaire et al., 1997~. In a subgroup of Gulf War veterans with embedded DU fragments in soft tissues and muscles, semen ejaculates contained uranium (McDiarmid et al., 2000~.
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From page 158... ...
In addition, no cardiovascular effects occurred after one intense accidental inhalational exposure in which neither blood pressure nor pulse rate increased in a man exposed to powdered uranium tetrafluoride for 5 minutes (Lu and Zhao, 1990~. Although the authors did not measure the concentration and mean particle size of the inhaled aerosol, electrocardiograms and chest x-rays were normal shortly after the accident and over a 7.5-Year follow-up period.
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From page 159... ...
Few studies of Gulf War veterans have specifically focused on the effects of uranium. Additionally, the literature on uranium miners is largely not relevant to the study of uranium per se because the primary exposure of this population was to radon progeny, which are known lung carcinogens.
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From page 160... ...
1976. Respiratory disease mortality among uranium miners.
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From page 161... ...
and uranium miners with increased risk for development of SLE. J Rheumatol 25~4~:660~66.
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From page 162... ...
2000. Gulf War Illnesses: Understanding of Health Effects from Depleted Uranium Evolving but Safety Training Needed.
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From page 163... ...
1999. Depleted Uranium: A Review of the Scientific Literature as It Pertains to Gulf War Illnesses.
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From page 164... ...
1969. Mortality of uranium miners in relation to radiation exposure, hard-rock mining and cigarette smoking 1950 through September 1967.
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From page 165... ...
1999. Radiation exposure and cancer mortality in uranium processing workers.
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From page 166... ...
1989. Lung cancer mortality among nonsmoking uranium miners exposed to radon daughters.
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From page 167... ...
1994. Mortality in uranium miners in West Bohemia: A long-term cohort study.
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From page 168... ...
Military Study, 190 Accidental Exposure of Industrial Workers, 191 Matsumoto, Japan, Terrorist Attack, 191 Tokyo, Japan, Terrorist Attack, 193 Gulf War Veterans, 196 Genetic Susceptibility to Sarin Toxicity, 197 CONCLUSIONS REFERENCES .198 199
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