Written by Anthony Hardie
(91outcomes.com) - The following is a review of select new scientific studies (2009, 2010) related to the health effects of Depleted Uranium (DU). This review is based on the abstracts of published studies publicly available on PubMed.gov, a service of the U.S. National Library of Medicine, which is part of the National Institutes of Health. This review is by no means intended to be perceived as comprehensive, nor does it take into account every single study published on DU during this time period. However, every attempt has been made to provide a balanced and careful review of each of the studies below.
The studies examine the health effects associated with DU that has been embedded/implanted (such as shrapnel) in the body, ingested/swallowed and absorbed into the body, and inhaled into the upper and/or lower respiratory tracts/lungs. One study examines the health effects associated with DU exposure through wounds. None of the studies examines health effects related to skin contact with DU, DU particulate matter, or DU crystalline residue.
Taken together, these studies suggest that there are a number of negative health effects associated with exposure to DU. The nature and severity of these health effects are dependent upon the type, duration, and magnitude of DU exposure, and, for aeresolized DU particulates, the size, composition, and timing of the DU particles inhaled.
First, some terms we’ll be using…
Depleted Uranium (DU). Uranium (U) is a naturally occurring heavy metal that has both radioactive properties caused by the decay of the uranium atom’s nucleus, and chemical properties as a heavy metal. DU is the by-product of the enrichment process, which extracts portions of naturally occurring uranium for nuclear fuel and weapons. DU is what’s left over after enrichment: a form of uranium that 40 percent less radioactive than naturally occurring uranium, but is chemically identical to naturally occurring uranium and other forms of uranium. In addition to a less radioactive form of uranium, the DU used in the U.S. military’s armor plates and munitions also contains trace levels of more radioactive transuranics (neptunium, plutonium, and americium) and fission products (technetium-99). DoD says the levels of these more radioactive transuranics and fission products are in minute quantities and result in” less than a one percent increase in the internal radiation dose. “ More detailed information on DU’s characteristics is available from DoD.
Oxidative Stress (OS). The human body is a careful balancing act. Too much or too little of one thing or another can lead to disastrous consequences. One of these countless balancing acts is with reactive oxygen species (ROS), chemically reactive oxygen-containing molecules most often created by the body as by-products of normal and essential metabolic reaction, and which are needed by the body for immune function and cell signaling. However, an imbalance causing too many ROS can be caused by many factors as results in an inability by the body to detoxify or to repair damage caused by excessive ROS. This resulting condition is called Oxidative Stress (OS), an imbalance that results in damage to one or more cells, tissues, or organs. OS has been found to play a key role in many disease processes.
…And now, on to the studies themselves.
U versus DU. An Italian government study found cytotoxic (cell-killing) and genetic effects at quite low concentrations of uranium (U). The impact was higher with exposures to natural uranium (U) than to DU. (A. Giovanetti et al, 2010)
A study from the University of Nebraska-Kearney (W. Briner et al, 2010) notes, “while depleted uranium is less radioactive than natural uranium, it still retains all the chemical toxicity associated with the original element. In large doses the kidney is the target organ for the acute chemical toxicity of this metal, producing potentially lethal tubular necrosis. In contrast, chronic low dose exposure to depleted uranium may not produce a clear and defined set of symptoms. Chronic low-dose, or subacute, exposure to depleted uranium alters the appearance of milestones in developing organisms. Adult animals that were exposed to depleted uranium during development display persistent alterations in behavior, even after cessation of depleted uranium exposure. Adult animals exposed to depleted uranium demonstrate altered behaviors and a variety of alterations to brain chemistry. Despite its reduced level of radioactivity evidence continues to accumulate that depleted uranium, if ingested, may pose a radiologic hazard.”
The results of a French government study, conducted by France’s Radioprotection and Nuclear Safety Institute, “illustrate that oxidative stress plays a key role in the mechanism of uranium neurotoxicity. They showed that chronic exposure to DU, but not enriched uranium, seems to induce an increase of several antioxidant agents in order to counteract,” the OS in the brain. According to the study authors, “these results demonstrate the importance of the double toxicity, chemical and radiological, of uranium.” (Lestaevel et al, 2009)
DU Genotoxity. Some substances have genotoxic properties – properties that make them harmful to the genetic information (DNA, RNA, chromosomes, etc.) in living creatures. There are three types of genotoxins: 1) Carcinogens (cancer-causing); 2) Mutagens (cause mutations); and, 3) Teratogens (birth-defect causing).
A Chinese government study using rats fed levels of DU, ranging from none to high, found increased concentrations of uranium in the kidneys and ovaries and significant abnormalities in the sperm in those that had consumed the DU. Because these genotoxic changes to the DNA affected ovaries and sperm, the DNA changes were passed on to offspring, even for rats that had consumed only low doses of DU, with the most severe changes in the sperm found in the offspring of the rats exposed to DU, even at low levels. (Y. Hao, 2009)
Another French government study conducted by France’s Radioprotection and Nuclear Safety Institute showed that while enriched uranium has a higher genotoxic ability than DU to cause mutagenic structural changes and breakage in the chromosomes, the genotoxic, mutagenic ability of DU to cause an abnormal number of chromosomes, “remains high.” (C. Darolles, 2010)
A University of Belgrade study conducted on local individuals exposed to DU, and a control group of those not exposed to DU, found that individuals exposed to DU contamination from the war had cell and chromosome damage associated with their DU exposure. (S. Milacic, 2009)
A French study discussed in more detail below found that inhaled DU caused damage to the chromosomes in the cells lining the airways after just 48 hours. (C. La Certe, 2010)
DU Dose-Response. In one Italian government study, the negative effects of DU were observed in greater levels with greater exposures, but the dose-effect relationship was found to be non-linear, meaning not only the negative effects themselves increased with greater doses, but also the rate of negative effects increased with larger doses of the concentration of uranium. (A. Giovanetti, 2010)
Effects of Ingested (Swallowed) DU. A Norwegian University of Life Sciences study examining DU in Kuwait and Kosovo found that a majority of DU is readily absorbed into the body (bioaccessible) when ingested (swallowed). (Lind et al, 2009)
As noted above, a Chinese government study using rats fed levels of DU, ranging from none to high, found increased concentrations of uranium in the kidneys and ovaries and significant abnormalities in the sperm in those that had consumed the DU, and that those changes were passed on to offspring who then exhibited even more dramatic changes In their own reproductive systems. (Hao et al, 2009)
A French government Institute for Radiological Protection and Nuclear Safety study showed changes in rats in the liver’s modulation of cholesterol following ingestion (swallowing) of DU. The study’s authors noted that previous studies showed vitamin D and the brain’s cholesterol metabolisms were affected following chronic ingestion of DU. In this study, high, “chronic” (40 milligrams/liter every day for nine months) doses of DU were swallowed by the rats, and despite changes in the way cholesterol is metabolized, high cholesterol levels were still seen. Of particular note, one of the study’s results was a noted deficiency of a particular enzyme that breaks down cholesterol, leading to hypercholesterolaemia. (R. Racine et al, 2010) The enzyme found to be decreased by DU in this study normally, dramatically increases in the liver with age. (Norlin 2002)
Effects of Inhaled DU. A new study from the Wise Laboratory of Environmental and Genetic Toxicology in Maine found that DU caused cellular death in the cells lining the bronchial airways of human lungs, and caused damage to the chromosomes after just 48 hours. While the scope of the study wasn’t to determine whether DU causes lung cancer, the study results, indicate that if indeed DU does cause lung (specifically bronchial) cancer in humans, the DU, “is likely acting through a mechanism that involves DNA breaks after longer exposures.” (C. La Certe, 2010)
A second study published by the same group found even stronger evidence of the damage caused by DU to human lungs, showing that the cells lining the airways are “transformed by DU and exhibit significant chromosome instability consistent with” the growth of neoplasms -- abnormal growth of cells that, if large enough, are known as “tumors.” Neoplasms are of three types: non-malignant, pre-malignant, and malignant. (H. Xie et al, 2010)
A study by the Quebec-based Uranium Medical Research Center found that following exposure to inhaled DU, “biological samples show the presence of a synthetic mixture of natural uranium and DU.” . (M Valdes, 2009)
A Lovelace Respiratory Research Institute study, part of the U.S. government-led Capstone DU studies, found that inhaled aerosolized DU posed the greatest cancer risk to the lungs, with the lungs receiving nearly all (97%) of the risk posed by inhaled DU. However, even with a relatively long (two hour) exposure to the aerosolized DU, the cancer risk was found to be” 0.42%, low compared with the natural or background risk of 7.35%.” (Hahn et al, 2009)
Another Lovelace Capstone study modeled exposures for M1A1 Abrams tanks hit by DU rounds. The study estimated the greatest risk of inhaled DU exposures, at “a factor of 20” was shown in the case of a one minute exposure in an unventilated Abrams with a DU round perforating then tank’s DU armor, whereas the exposure was only “a factor of two” for a first-responder scenario. (Guilmette et al, 2009) Another Capstone study discussed the methods used to calculate the dose of the aerosolized DU exposures. (Miller et al, 2009)
Another Capstone study found that there was a substantial variability in how inhaled DU is absorbed, “which in part depended on the type of armor being impacted by the DU penetrator and the particle size fraction being tested.” The study further noted that, “although some trends were suggested, the variability noted leads to uncertainties in predicting the solubility of other DU-based aerosols.” (Guilmette and Cheng, 2009)
Variability of DU particle size, shape, solubility, and suspension in air. An earlier Capstone study analyzed the size and shape of DU after the impact of a DU penetrating round against an armored target. Notably, “A few samples seemed to contain small bits of nearly pure uranium metal, which were verified … to have a higher uranium content exceeding that expected for uranium oxides.” Different levels of solubility -- the ability of the DU to be absorbed into the body – were also found. (Krupka et al, 2009)
Another related Capstone study analyzed the size of DU particulate matter in relation to how long it stayed in the air after the impact of a DU round. The study found that the DU particulate matter ranged from “small” (between 0.2 and 1.2 micrometers) and “large” (between 2 and 15 micrometers), with the larger particles settling fairly quickly, while DU particulate matter 1 micrometer and smaller remaining suspended in the air two hours after impact. (Cheng et al, 2009). A related Capstone study found that the amount of uranium in the particulate matter varied with the size of the particulate, “typically with less uranium associated with the smaller particle sizes.” Furthermore, “the results demonstrate that the peak uranium concentration in the aerosol occurred in the first 10 s after perforation, and the concentration decreased in the Abrams tank shots to about 50% within one minute and to less than 2% after 30 minutes,” following impact of the DU penetrating round. (Parkhurst et al, 2009)
The USEPA classifies “inhalable coarse particles” as between 2.5 micrometers and 10 micrometers in diameter, while “Fine particles," such as those found in smoke and haze, are 2.5 micrometers and smaller (also known as PM2.5)(Source: USEPA)
Without regard for the radiologic or toxic properties of DU, according to the New York State Department of Health has this to say about microfine particulate matter in general:
Particles in the PM2.5 size range are able to travel deeply into the respiratory tract, reaching the lungs. Exposure to fine particles can cause short-term health effects such as eye, nose, throat and lung irritation, coughing, sneezing, runny nose and shortness of breath. Exposure to fine particles can also affect lung function and worsen medical conditions such as asthma and heart disease. Scientific studies have linked increases in daily PM2.5 exposure with increased respiratory and cardiovascular hospital admissions, emergency department visits and deaths. Studies also suggest that long term exposure to fine particulate matter may be associated with increased rates of chronic bronchitis, reduced lung function and increased mortality from lung cancer and heart disease. People with breathing and heart problems, children and the elderly may be particularly sensitive to PM2.5. (Source: NY Dept. of Health)
Effects of Implanted/Embedded DU. Urine testing of approximately 1,7000 U.S. veterans found three with evidence of DU in their urine; all three had embedded DU fragments. (CD Dorsey et al, 2009)
Further testing involved, “35 members of a larger cohort of 77 Gulf War I veterans who were victims of depleted uranium (DU) "friendly fire" during combat underwent a 3-day clinical assessment at the Baltimore Veterans Administration Medical Center (VAMC).” The study concluded that, “Sixteen years after first exposure, this cohort continues to excrete elevated concentrations of urine U as a function of DU shrapnel burden. Although subtle trends emerge in renal proximal tubular function and bone formation, the cohort exhibits few clinically significant U-related health effects.” (McDiarmid et al, 2009)
A Fudan University (China) study concluded that kidneys and bone are the primary reservoirs for uranium redistributed from DU fragments embedded in muscle, and “the accumulations in kidney, bone and many other tissues suggest the potential for unanticipated physiological consequences of chronic exposure to DU.” (G. Zhu et al, 2009)
The Fudan study also found that, “uranium concentrations increased with a close correlation to the implanted DU doses and duration of exposure, with a peak at 90 days post-implantation, after which followed by a decreasing period, but still maintained at a relatively high level even at 360 days post- implantation.” (G. Zhu et al, 2009)
Effects of Internally Injected DU. A Japanese National Institute of Radiological Sciences study found that high doses of DU in solution injected under the skin of rats acutely induced severe damage in the DU-injected sites and organs by chemical toxicity within a very short time after DU intake, including depositions of uranium in the liver, kidneys and femur just one hour after DU injection. Severe damage in the organs, including the kidney resulted. (Fukuda et al, 2009)
A second experiment conducted by the Japanese National Institute of Radiological Sciences sought to determine whether a chelating agent was useful in mitigating the damage caused by the high doses of injected DU in solution. The chelating agent worked well when it was administered shortly after the DU injections to cause the excretion of uranium in urine and feces and decreasing the concentrations of uranium in the kidneys and femur. (Fukuda et al, 2009)
Leukemia and DU. A U.S. Department of Defense, Armed Forces Radiobiology Research Institute (AFFRI) study of mice with leukemia induced by chronic internal exposure to DU found that non-genetic factors causing genes to behave (or "express themselves") differently are implicated in DU-induced leukemia. The study found evidence that a form of abnormal activity, called hypomethylation, in the DNA in the spleen was associated with both the chronic internal DU exposure and the onset of leukemia, a new link between DU and leukemia. (Miller et al, 2009)
According to the MIT’s Whitehead Institute for Biomedical research, hypomethylation is “a process that can cause chromosomes to become unstable,” by causing changes in the natural methylation process of the DNA. (Gaudet et al, 2003).
Hypercholesteraemia and DU. As noted above, one recent French study found that hypercholesteraemia as associated with ingested DU due to decreased levels of a key cholesterol-regulating enzyme. (R. Racine et al, 2010)
A major, multi-institutional study undertaken to determine the effects of a natural deficiency of the same enzyme in a particular kindred of Caucasian individuals of English and Celtic decent was found to be associated with a metabolic disorder, hyptertriglyceridemia (increased blood levels of triglycerides, a risk factor for coronary artery disease), and also appeared to be associated with increased risk of cholesterol gallstones. (Pullinger et al, 2002)
DU Exposure Testing. A study reporting the results of urine testing of approximately 1,700 U.S. veterans seeking DU urine testing, using a new and improved method, found only three with evidence of DU in their urine. All three had embedded DU fragments. Based on an underlying assumption that all DU in the body is continually excreted in small amounts in the urine, the study’s authors assert that, “these findings suggest that future DU-related health harm is unlikely in veterans without DU fragments.” (CD Dorsey et al, 2009)
A study by the Quebec-based Uranium Medical Research Center developed a linear model to estimate the lung burden of DU from measurements of DU in 24-h urine samples, years after inhalational exposure to aerosols of DU. This model takes into account the intracellular dissolution of the retained particles and the precipitation of a significant fraction of the dissolved DU as insoluble uranyl phosphates. (M Valdes, 2009)
A U.S. Army Center for Health Promotion and Preventive Medicine (USA CHPPM) Capstone study discussed its development of a test that determines the approximate severity of effect on the kidneys following DU exposure with 85 percent accuracy. The study asserted that, “The primary target for uranium toxicity is the kidney.” (Roszell et al, 2009)
Possible Treatments and Preventions. A group of fungal compounds, one of which might be effective in treating the toxic effects of the OS caused by DU, is currently being used clinically in China and Japan as potent immunological activators and has been shown to be effective in treating diseases like cancer, a range of microbial infections, hypercholesterolaemia (high blood cholesterol), and diabetes (Chen et al, 2007). These fungal compounds are called non-cellulosic beta-glucans and a new Iranian study suggests that one, fungal beta-1-3-D-glucan, as well as silymarin, a compound extracted from the Blessed Milk Thistle plant found worldwide, are drug treatment candidates for preventing against and detoxifying from DU’s OS effects (J. Pourahmad et al, 2010).
A Vanderbilt University Medical Center study found that “DU causes toxicity in a dose-dependent manner,” meaning greater or less DU leads to greater or less toxicity. The study also found that metallothioneins (MTs), which are small proteins that have numerous functions such as metal sequestration, transport, and detoxification, are protective against DU exposure. (GC Jiang et al, 2009)
As noted in the Japanese National Institute of Radiological Sciences study, above, a particular chelating agent was useful in mitigating the damage caused by the high doses of injected DU in solution when it was administered shortly after the DU injections. (Fukuda et al, 2009)
