Chapter Three

Concluding Remarks and Future Research

After examining the chemical and physical nature of DU, this report has surveyed the literature related to the health effects of DU through both external and internal exposure. Potential health effects were divided into those associated with radiation and with heavy-metal toxicology.

Few studies to date in the literature have focused directly on DU. On the other hand, there is a wealth of literature related to natural and enriched uranium. This literature provides many relevant insights because the heavy-metal chemical toxicity of DU is the same as that of natural and enriched uranium. Further, both natural and enriched uranium are far more radioactive than DU. Therefore, if no adverse health effects to natural uranium are reported, one may reasonably conclude the same will be the case for DU.

Radiation Effects

The literature review examined the extensive published data on radiation that has looked at the relationship between exposure to uranium through various pathways--inhalation, ingestion, and external exposure--and possible health effects. Available information includes data on human exposure to natural uranium through the normal pathways of diet and inhalation, studies of miners and millers in the uranium industry, findings on animals, and some studies relating directly to Gulf War veterans.

From the scientific literature it is concluded that:

• Although any increase in radiation to the human body can be calculated to be harmful from extrapolation from higher levels, there are no peer reviewed published reports of detectable increases of cancer or other negative health effects from radiation exposure to inhaled or ingested natural uranium at levels far exceeding those likely in the Gulf. This is mainly because the body is very effective at eliminating ingested and inhaled natural uranium and because the low radioactivity per unit mass of natural uranium and DU means that the mass of uranium needed for significant internal exposure is virtually impossible to obtain.
• External radiation in the form of alpha radiation cannot penetrate cloth or skin and would therefore have no negative health effect. Beta and gamma radiation, which can have negative health effects, have been measured at levels below those expected to be of concern.
• Large variations in exposure to radioactivity from natural uranium in the normal environment have not been associated with negative health effects.
• Radiation-related effects from embedded fragments will depend on the size of the fragment and its proximity to vital organs.
• The cohort of individuals, about half of whom have embedded fragments, who are being followed at the Baltimore VA Medical Center as part of the DU Follow-Up Program, represents a group of Gulf War veterans who received the highest levels of exposure to DU during the Gulf War. Although many of these veterans have health problems related to their injuries in the Gulf War and those with embedded fragments have elevated urinary uranium levels, researchers to date do not find adverse health effects they relate to radiation from DU, but several perturbations in biochemical and neuropsychological testing have been correlated with elevated urinary uranium, the clinical significance of which is unclear (McDiarmid, 1998b).

Heavy-Metal Toxicological Effects

Uranium in the form of the isotopically depleted metal used for military purposes in the Gulf War presents primarily a potential chemical rather than radiological hazard. Like most heavy metals, uranium possesses a high chemical affinity for proteins and other biological molecules. It normally is taken up into the body through the lungs (via inhalation) or intestine (via ingestion) but in military settings may also penetrate the body as fragments. These slowly dissolve, posing a risk of chemical exposure.

The kidneys show special sensitivity to the chemical toxicity of uranium. While this does not exclude the possibility of the metal inflicting functional lesions in other organ systems, the first adverse chemical effects following high or prolonged exposure to uranium are found in the kidney. Proximal tubular function in particular is depressed, but lesions in other nephron segments have also been reported. In the case of high exposures, renal function can serve as a sensitive biomonitor.

The literature provides the following insights:

• Exposure to uranium and other heavy metals in large doses can cause changes in renal function and at very high levels result in renal failure.
• In spite of these findings, no increased morbidity or frequency of end-stage renal disease has been observed in relatively large occupational populations chronically exposed to natural uranium at concentrations above normal ambient ones.
• As indicated above, the individuals being followed as part of the DU Follow-up Program at the Baltimore VA Medical Center who were exposed to aerosolized DU and in about half the cases to embedded fragments, represent a sample of individuals who received some of the highest exposure to DU in the Gulf War. Researchers report no adverse renal effects due to DU exposure, although most individuals with embedded fragment have elevated urinary uranium levels, but several perturbations in biochemical and neuropsychological testing have been correlated with elevated urinary uranium, the clinical significance of which is unclear (McDiarmid, 1998b).

Research

Although there is already a large body of literature on natural uranium, below we list some areas likely to prove fruitful in enhancing our knowledge of the health effects of DU. We encourage additional research into both the effects of exposure and long-term epidemiology studies to further our understanding of the health effects of DU. Among other research, the following areas of inquiry would be useful:

• It would be helpful to conduct further long-term epidemiological studies in veterans of the Gulf War to the degree that the availability of exposure information permits such research.
• Because risk assessment has advanced greatly since many of the standards for both occupational and population exposures were developed, reexamination of those standards and refined dose response end points by these organizations would be helpful.
• Research to better understand the mechanisms and dose response of exposure to DU on renal function would be helpful. Attempts should be made to correlate nephrotoxicity with renal uranium concentration following different modes and levels of exposure. Knowledge of cortical concentration would be more informative than total renal uranium levels. The U.S. Transuranium Registry is a continuing source of these data (Kathren and Ehrhart, 1998). It is also important to continue work to understand the mechanism by which natural and depleted uranium exert toxic effects on the body. This would include work to understand the nature and toxicological significance of the separate uranium pools kinetically identified in the kidney. Modern techniques should permit analysis of distribution of the toxic metal in the kidney, and more-sophisticated dose-effect studies than those relying on total tissue concentration at one arbitrary time are appropriate.
• The work of the DU Follow-Up Program being conducted and expanded at the Baltimore VA Medical Center is important and needs to continue. The cohort and research represents the best opportunity to study the effects of human exposure to DU over time that is now available.
• Although ionizing radiation from DU is in the form of alpha particles, the decay products emit gamma and beta radiation that could affect those in proximity to DU weapons. Although research to date has indicated that levels of exposure are significantly below occupational levels, ongoing efforts to study the levels of exposure from such radiation to soldiers in proximity to DU weapons or armor should continue, especially as weapons and weapon systems vary over time.
• A research protocol should be developed to study troops in the next situation in which they are likely to be exposed to DU. This would include urinalysis of a sample of individuals with oversampling of those likely to be exposed (e.g., troops in charge of damaged tank cleanup) before deployment, and tests immediately after significant exposure and for some time. Once exposure information is obtained, following health outcomes over time in well-designed epidemiology studies would provide needed information.
• In the meantime, although there is already a large body of literature on natural uranium, animal studies that simulate exposure to DU in a chemical form consistent with exposure from weapons and via various pathways (inhalation, ingestion, and embedded) at various levels to study health effects and various diagnostic techniques would enhance understanding of possible health effects if any, limits of exposure, and mechanisms of action.

In conclusion, the use of DU munitions and armor is likely to expand greatly over the coming years, both in the U.S. military and in other countries. It is therefore important to continue research to further our knowledge of any potential health risks that might result from different levels and pathways of exposure.

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