On Depleted Uranium: Gulf War and Balkan Syndrome
Nuclear Medicine Division and Clinical PET,
King Faisal Specialist Hospital and Research Centre,
Riyadh, Kingdom of Saudi Arabia
The complex clinical symptomatology of chronic illnesses, commonly described as Gulf War Syndrome, remains a poorly understood disease entity with diversified theories of its etiology and pathogenesis. Several causative factors have been postulated, with a particular emphasis on low level chemical warfare agents, oil fires, multiple vaccines, desert sand (Al-Eskan disease), botulism, Aspergillus flavus, Mycoplasma, aflatoxins, and others, contributing to the broad scope of clinical manifestations. Among several hundred thousand veterans deployed in the Operation Desert Storm, 15-20% have reported sick and about 25,000 died. Depleted uranium (DU), a low-level radioactive waste product of the enrichment of natural uranium with U-235 for the reactor fuel or nuclear weapons, has been considered a possible causative agent in the genesis of Gulf War Syndrome. It was used in the Gulf and Balkan wars as an armor-penetrating ammunition. In the operation Desert Storm, over 350 metric tons of DU was used, with an estimate of 3-6 million grams released in the atmosphere. Internal contamination with inhaled DU has been demonstrated by the elevated excretion of uranium isotopes in the urine of the exposed veterans 10 years after the Gulf war and causes concern because of its chemical and radiological toxicity and mutagenic and carcinogenic properties. Polarized views of different interest groups maintain an area of sustained controversy more in the environment of the public media than in the scientific community, partly for the reason of being less than sufficiently addressed by a meaningful objective interdisciplinary research.
words: environmental exposure; leukemia, radiation induced; military personnel;
Persian Gulf syndrome; radiation accidents; radiation genetics; radiometry;
uranium; veterans; war.
The use of uranium as a warfare agent of mass contamination is not that new. Towards the conclusion of World War II, when Japan launched over 6,000 explosive-laden air balloons to the continental United States, there was a serious concern of a possible use of uranium oxide against US megacities in the form of aerosol for mass contamination.
Depleted uranium as a product of the environment of natural uranium for the reactor fuel and nuclear weapons is partially altered by the extraction of U-235 to about one third of natural uranium content (2). This residue, also known as tails, is a radioactive waste with the current stockpiles of over 600,000 metric tons of depleted uranium hexafluoride (UF6 ). UF6 is an unstable toxic chemical, which forms uranyl fluoride (UO2 F2 ) and hydrogen fluoride (HF) if released in atmosphere. It is identified as toxic substance (3) with serious health consequences if inhaled, by both chemical and radiological properties (1). The United States Nuclear Regulatory Commission (NRC) governs the use and transportation of depleted uranium for the use and transfer of maximum of 15 pounds at a given time and 150 pounds in a calendar year. Also, the NRC requires detailed documentation of DU intended use, training of personnel, compliance with health, safety, and environmental standards (4). Depleted uranium is an internal health hazard. By its parenteral entry in the extracellular fluid, it gets incorporated in the target sites of its retention – predominantly skeletal tissue and kidneys, where it exerts nephrotoxicity by its effect on the proximal convoluted tubules. It has also been demonstrated that it induces transformation of human osteoblasts into the neoplastic phenotype in cell culture studies (5). In vivo studies reported mutagenic activity in the experimental animals implanted with DU pellets (5). Human data of spatiotemporal models of mapping cancer mortality reported an elevated lung cancer rate in the vicinity of DU processing facilities (6). Some recent reports indicate the increase in urinary excretion of DU in US Gulf War veterans wounded by the shrapnel during the operation Desert Storm (7). Similar findings were reported in the British, Canadian, and US veterans exposed to DU by inhalation during the Desert Storm Operation, where the presence of DU was verified by the methods of neutron activation analysis (8) and mass spectrometry (9). The isotopic ratio of DU and the presence of U-236 – an uranium isotope not found in nature, in Desert Storm Operation veterans opens yet another compartment of Pandora’s box. It poses an inevitable question of the origin of DU used in the Gulf war, recently further augmented by the finding of traces of plutonium and other actinides (americium, neptunium) in DU shrapnel. The scientific inquiry into DU as a possible etiological factor in the causology of Gulf war and Balkan conflict illnesses has not been met with unbiased scientific criticism.
No Turn Left Unstoned
Some of the arguments relate to the short range of alpha particles (10), the other to the radiation being too low to induce mutagenic and oncogenic effects. Most of the polemics are in the arenas of extremely polarized interest groups on both sides of the fence, each side conspicuously lacking presence of the actual experts on actinides. The opinions are commonly exchanged in the mass media by the non-experts, and often by non-professionals, inevitably ignoring the complexity of DU interactions with the internal environment of stem and dividing transit cell population (11), basic laws of radiation biology and cellular radiosensitivity to alpha interactions (12,13), and effects of organotropic radionuclides in the human body (14), unskillfully navigating through uncharted seas of low level radiation. As usual, truth is often found between the extremes of Confucian pendulum, easier found in the science textbooks than on the Internet screen, which often lacks the basics of chemical synchronization, mitotic selection, fundamentals of the mitotic cell collection, and uniformity of cell cycle, cell culture, survival curves, and cellular response to radiation. The biological effects of DU do not differ from other alpha and beta internally deposited emitters and have to be considered in the light of cellular radiosensitivity as related to the mitotic cycle, with clear concepts of radiosensitivity and radioresistance in different phases of the mitotic cycle. The intermitotic and dividing cell population in the vicinity of final retention sites of depleted uranium includes pluripotent stem cells, hematopoietic system, intestinal villi crypt cells, intermitotic pool in the bone marrow, and basal cells of the skin. The mechanisms of DU interactions are far from being adequately understood even by the experts. Thus, it is perhaps premature to classify DU as a non hazardous substance, even if the proponents manage to master the basics of the host of factors that determine the biological consequences of internal particulate emitters, including dose-rate effects, linear energy transfer, oxygen effects, relative biological effectiveness, repair mechanisms, and damage recovery. Furthermore, the established concepts of cell survival curves are currently being re-examined in the realm of low-dose radiation (15). Radiation-induced cancer incidence at low dose exposure with BEIR (Biological Effects of Ionizing Radiation) and UNSCEAR (United Nations Scientific Committee on the Effects of Atomic Radiation) adopted linear non-threshold curves postulate no safe dose for any exposure to ionizing radiation. But, no threshold hypothesis was more conceptualized on mathematical than biological considerations. Reassessment introduces biphasic curve, addressing the mechanisms of damage of radiosensitive cells. It postulated, by the experimental evidence, that a part of the radiation-damaged cell population would become more susceptible to mutagenic alterations as the dose increases from point zero. It also includes the transformation to neoplastic entities. With further increase of the dose, radiosensitive cells would sustain lethal damage with a consequent fall in mutations. At that point, less sensitive cells would start a new rise in oncogenic events, which, after the second peak, would result in a death of the organism (16). Second event theory, although new, has attracted considerable attention. It postulates that two hits can interact with the same cell. The first one creates high sensitivity phase, and the second further damages the cell in its sensitive phase, with both events occurring during cell replication. This is of importance to contamination with uranium isotopes, where the size of a particle determines the delivered dose. DU particle of 0.2 microns in diameter would deliver an alpha dose equal to annual exposure of 2 mSv, rapidly increasing delivery dose by the increased particle size (16). Current reevaluations of the human and animal data recognize a large error of the conventional models of the risk assessment in the low-level exposure health risk evaluation.
application of the re-examination of low dose effects applied to Chernobyl
accident has identified new relationships between the actual number of
cases with malignant alterations and the numbers predicted by the conventional
model of radiation risk (17). There is a significant increase in the number
of the children with leukemia while being exposed in utero to radionuclides
from Chernobyl fallout. The infant leukemia cohort has been reported in
Scotland (18), Greece (19), United States (20) and Germany (21). It is
being applied to current research on Gulf war legacy, which, unlike multiradionuclide
Chernobyl fallout exposure, is a result of a mass contamination with the
isotopes of a single radionuclide. Naming of the non-existent syndrome
rages in the semantic controversy, which – for the sake of sanity, we may
temporarily call Gulf war illness or Gulf war syndrome.
Several criteria of classification of the Gulf war syndrome have been considered, ranging from the terminology such as Haley’s factor analysis classification in six syndromes (23), to a broad category of Mucocutaneous-intestinal-rheumatic Desert Syndrome, with three major and 17 minor categories (24), or a neuroimmune syndrome (25) – all distinctly different from postraumatic stress syndrome (PTSD), which was for some time meant to phagocytize the Gulf war syndrome (26).
causology includes chemical, biological, and radiological etiology. All
discussion in the literature in a considerable length often lacks objective
analytical support, sometime in Swiftian resemblance of a Gulliver’s encounter
with scientists from an academy proudly explaining their success in the
research of extracting sun-beams from the cucumbers. Be as it is, the DU
research has been lacking for whatever reason, none being the lack of awareness
of its toxic properties and health hazards.
DU shrapnel wounded veterans continue to excrete elevated quantities of
uranium isotopes (33), not many casualties are the consequences of shrapnel
wounds. Shrapnels are of a lesser importance in understanding DU role in
Gulf war illnesses than mass contamination by the inhalation of DU containing
dust, initially described as Al-Eskan disease (35). The effects of uranium-embedded
particles have been known for almost two centuries (36). The causological
correlation between depleted uranium and Gulf war illnesses (37) remains
the most important but unanswered question. The studies of DU role in Gulf
war illnesses have been not only as diversified as the symptomatology of
the illness, bur also inadequately studied (38), not for the want of expertise,
technology, patient population, or resources, but rather due to incapability
to subscribe to Francis Bacon’s Utopian dream of New Atlantis and replace
the politician with the scientist.
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Nuclear Medicine Division and Clinical PET
King Faisal Specialist Hospital and Research Centre
Riyadh, Kingdom of Saudi Arabia
134 - Durakovic: Uranium and Balkan Syndrome Croat Med J 2001;42:130-134)