Skip to main content
Log in

Neurotoxicity of depleted uranium

Reasons for increased concern

  • Published:
Biological Trace Element Research Aims and scope Submit manuscript

Abstract

Depleted uranium (DU) is a byproduct of the enrichment process of uranium for its more radioactive isotopes to be used in nuclear energy. Because DU is pyrophoric and a dense metal with unique features when combined in alloys, it is used by the military in armor and ammunitions. There has been significant public concern regarding the use of DU by such armed forces, and it has been hypothesized to play a role in Gulf War syndrome. In light of experimental evidence from cell cultures, rats, and humans, there is justification for such concern. However, there are limited data on the neurotoxicity of DU. This review reports on uranium uses and its published health effects, with a major focus on in vitro and in vivo studies that escalate concerns that exposure to DU might be associated with neurotoxic health sequelae.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. N. H. Harley, E. C. Foulkes, L. H. Hilborne, A. Hudson, and C. R. Anthony, Depleted Uranium, RAND, Santa Monica, CA (1999).

    Google Scholar 

  2. I. M. Fisenne, P. M. Perry, K. M. Decker, and H. K. Keller, The daily intake of 234,235,238U, 228,230,232Th, and 226,228Ra by New York City residents, Health Phys. 53, 357–363 (1987).

    Article  PubMed  CAS  Google Scholar 

  3. UNSCEAR—United Nations Scientific Committee on the Effects of Atomic Radiation, Sources and Effects of Ionizing Radiation, Vol. I, United Nations, New York, p. 123 (2000).

    Google Scholar 

  4. UNSCEAR—United Nations Scientific Committee on the Effects of Atomic Radiation, Sources and Effects of Ionizing Radiation, Vol. II, United Nations, New York, p. 346 (2000).

    Google Scholar 

  5. Z. Pietrzak-Flis, L. Rosiak, M. M. Suplinska, E. Chrzanowski, and S. Dembinska, Daily intakes of 238U, 234U, 232Th, 230Th, 228Th and 226Ra in the adult population of central Poland, Sci. Total Environ. 273(1–3), 163–169 (2001).

    Article  PubMed  CAS  Google Scholar 

  6. H. Bem, and F. Bou-Rabee, Environmental and health consequences of depleted uranium use in the 1991 Gulf War, Environ. Int. 30, 123–134 (2004).

    Article  PubMed  CAS  Google Scholar 

  7. H. M. Hartmann, F. A. Monette, and I. H. Avci, Overview of toxicity data and risk assessment methods for evaluating the chemical effects of depleted uranium compounds, Hum. Ecol. Risk Assess 6, 851–874 (2000).

    Article  CAS  Google Scholar 

  8. M. D. Sztajnkrycer and E. J. Otten, Chemical and radiological toxicity of depleted uranium, Mil. Med. 169(3), 212–216 (2004).

    PubMed  Google Scholar 

  9. WHO—Department of Protection of the Human Environment, Depleted Uranium: Sources, Exposure and Health Effects, WHO, Geneva.

  10. R. F. Mould, Depleted uranium and radiation-induced lung cancer and leukaemia, Br. J. Radiol. 74, 677–683 (2001).

    PubMed  CAS  Google Scholar 

  11. I. M. Fisenne, P. M. Perry, and N. H. Harley, Uranium in humans, Rad. Prot. Dosim. 24, 127–131 (1988).

    CAS  Google Scholar 

  12. US DoD (Department of Defense), Depleted uranium in the Gulf. Environmental exposure report. Available from http://www.deploymentlink.osd.mil/du_library/du_ii/.

  13. M. A. McDiarmid, J. P. Keogh, F. J. Hooper, et al., Health effects of depleted uranium on exposed Gulf War veterans, Environ. Res. 82, 168–180 (2000).

    Article  PubMed  CAS  Google Scholar 

  14. M. A. McDiarmid, Depleted uranium and public health, Br. Med. J. 322, 123–124, (2001).

    Article  CAS  Google Scholar 

  15. M. A. McDiarmid, S. M. Engelhardt, and M. Oliver, Urinary uranium concentrations in an enlarged Gulf War veteran cohort, Health Phys. 80(3), 270–273 (2001).

    Article  PubMed  CAS  Google Scholar 

  16. M. A. McDiarmid, K. Squibb, S. Engelhardt, et al., Surveillance of depleted uranium exposed Gulf War veterans: health effects observed in an enlarged “friendly-fire” cohort, J. Occup. Envron. Med. 43, 991–1000 (2001).

    Article  CAS  Google Scholar 

  17. M. A. McDiarmid, K. Squibb, and S. M. Engelhardt, Biologic monitoring for urinary uranium in Gulf War I veterans, Health Phys. 87(1), 51–56 (2004a).

    Article  PubMed  CAS  Google Scholar 

  18. H. S. Spencer, D. Osis, I. M. Fisenne, P. Perry, and N. H. Harley, Measured intake and excretion patterns of naturally occurring 238U and calcium in humans, Radiat. Res. 24, 90–95 (1990).

    Article  Google Scholar 

  19. R. H. Gwiazda, K. Squibb, M. McDiarmid, and D. Smith, Detection of depleted uranium in urine of veterans from the 1991 Gulf War, Health Phys. 86(1), 12–18 (2004).

    Article  PubMed  CAS  Google Scholar 

  20. R. E. J. Mitchel and S. Sunder, Depleted uranium dust from fired munitions: physical, chemical and biological properties, Health Phys. 87(1), 57–67 (2004).

    Article  PubMed  CAS  Google Scholar 

  21. P. R. Danesi, A. Bleise, W. Burkart, et al., Isotopic composition and origin of uranium and plutonium in selected soil samples collected in Kosovo, J. Environ. Radioact. 64(2–3), 121–131 (2003).

    Article  PubMed  CAS  Google Scholar 

  22. L. A. Di Lella, L. Frati, S. Loppi, G. Protano, and F. Riccobono, Environmental distribution of uranium and other trace elements at selected Kosovo sites, Chemosphere 56(9), 861–865 (2004).

    Article  PubMed  CAS  Google Scholar 

  23. L. A. Di Lella, F. Nannoni, G. Protano, and F. Riccobono, Uranium contents and (235)U/(238)U atom ratios in soil and earthworms in western Kosovo after the 1999 war, Sci. Total Environ 337(1–3), 109–118 (2005).

    PubMed  Google Scholar 

  24. B. Salbu, K. Janssens, O. C. Lind, K. Proost, L. Gijsels, and P. R. Danesi, Oxidation states of uranium in depleted uranium particles from Kuwait, J. Environ. Radioact. 78 (2), 125–135 (2005).

    Article  PubMed  CAS  Google Scholar 

  25. S. Ihrulj, A. Krunic-Haveric, S. Haveric, N. Pojskic, and R. Hadziselimovic, Micronuclei occurrence in population exposed to depleted uranium and control human group in correlation with sex, age and smoking habit, Med. Arh. 58(6), 335–338 (2004).

    Google Scholar 

  26. M. A. McDiarmid, S. Engelhardt, M. Oliver, et al., Surveillance of depleted uranium exposed Gulf War veterans: a 10-year follow-up, J. Toxicol. Envron. Health 67, 277–296 (2004).

    Article  CAS  Google Scholar 

  27. M. A. McDiarmid, F. J. Hooper, K. Squibb, et al. Health effects and biological monitoring results of Gulf War veterans exposed to depleted uranium, Mil Med. 167(2 Suppl.), 123–124 (2002).

    PubMed  Google Scholar 

  28. H. C. Hodge, Handbook of Experimental Pharmacology: Uranium, Plutonium, Transplutonic Elements, H. C. Hodge, J. N. Stannard, and J. B. Hursh, eds., Springer-Verlag, New York, pp. 5–68 (1973).

    Google Scholar 

  29. D. R. Goodman, Nephrotoxicity: toxic effects in the kidneys, in Industrial Toxicology and Health Applications in the Workplace, P. L. Wilson and J. L. Bur[???]son, eds., Van Nostrand Reinhold, New York (1995).

    Google Scholar 

  30. M. Carrière, L. Avoscan, R. Collins, et al., Influence of uranium speciation on normal rat kidney (NRK-52E) proximal cell cytotoxicity, Chem. Res. Toxicol. 17, 446–452 (2004).

    Article  PubMed  CAS  Google Scholar 

  31. B. L'Azou, M. H. Henge-Napoli, L. Minaro, H. Mirto, M. P. Barrouillet, and J. Cambar, Effects of cadmium and uranium on some in vitro renal targets, Cell. Biol. Toxicol. 18, 329–340 (2002).

    Article  PubMed  Google Scholar 

  32. A. C. Miller, A. F. Fuciarelli, W. E. Jackson, et al., Urinuary and serum mutagenicity studies with rats implanted with depleted uranium or tantalum pellets, Mutagenesis 13(6), 643–648 (1998).

    Article  PubMed  CAS  Google Scholar 

  33. A. C. Miller, W. F. Blakely, D. Livengood, et al., Transformation of human osteoblast cells to the tumorigenic phenotype by depleted uranium-uranyl chloride, Environ. Health Perspect. 106(8), 465–471 (1998).

    Article  PubMed  CAS  Google Scholar 

  34. A. C. Miller, K. Brooks, M. Stewart, et al., Genomic instability in human osteoblast cells after exposure to depleted uranium: delayed lethality and micronuclei formation, J. Environ. Radioact. 64(2–3), 247–259 (2003).

    Article  PubMed  CAS  Google Scholar 

  35. A. Durakovic, On depleted uranium: Gulf War and Balkan Syndrome, Croat. Med. J. 42(2), 130–134 (2001).

    PubMed  CAS  Google Scholar 

  36. A. Durakovic, P. Horan, L. A. Dietz, and I. Zimmerman, Estimate of the time zero lung burden of depleted uranium in Persian Gulf War veterans by the 24-hour urinary excretion and exponential decay analysis, Mil. Med. 168(8), 600–605 (2003).

    PubMed  Google Scholar 

  37. M. A. Kadhim, D. A. Macdonald, D. T. Goodhead, S. A. Lorimore, S. J. Marsden, and E. G. Wright, Transmission of chromosomal instability after plutonium alpha-particle irradiation, Nature 355(6362), 738–740 (1992).

    Article  PubMed  CAS  Google Scholar 

  38. M. A. Kadhim, S. A. Lorimore, M. D. Hepburn, D. T. Goodhead, V. J. Buckle, and E. G. Wright, Alpha-particle-induced chromosomal instability in human bone marrow cells, Lancet 344(8928), 987–988 (1994).

    Article  PubMed  CAS  Google Scholar 

  39. H. Schroder, A. Heimers, R. Frentzel-Beyme, A. Schott, and W. Hoffmann, Chromosome aberration analysis in peripheral lymphocytes of Gulf War and Balkans War veterans, Radiat. Prot. Dosim. 103(3), 211–219 (2003).

    CAS  Google Scholar 

  40. H. Nagasawa and J. B. Little, Induction of sister chromatid exchanges by extremely low doses of alpha-particles, Cancer Res. 52(22), 6394–6396 (1992).

    PubMed  CAS  Google Scholar 

  41. A. C. Miller, S. Mog, L. McKinney, et al., Neoplastic transformation of human osteoblast cells to the tumorigenic phenotype by heavy metal-tungsten alloy particles: induction of genotoxic effects, Carcinogenesis 22(1), 115–125 (2001).

    Article  PubMed  CAS  Google Scholar 

  42. A. C. Miller, J. Xu, M. Stewart, et al., Observation of radiation-specific damage in human cells exposed to depleted uranium: dicentric frequency and neoplastic transformation as endpoints, Radiat. Prot. Dosim. 99(1–4), 275–278 (2002).

    CAS  Google Scholar 

  43. A. C. Miller, K. Brooks, J. Smith, and N. Page, Effect of the militarily-relevant heavy metals, depleted uranium and heavy metal tungsten-alloy on gene expression in human liver carcinoma cells (HepG2), Mol. Cell Biochem. 255, 247–256 (2004).

    Article  PubMed  CAS  Google Scholar 

  44. B. E. Lehnert, E. H. Goodwin, and A. Deshpande, Extracellular factor(s) following exposure to alpha particles can cause sister chromatid exchanges in normal human cells, Cancer Res. 57(11), 2164–2171; erratum 63(6), 1439 (1997).

    PubMed  CAS  Google Scholar 

  45. C. H. Kennedy, C. E. Mitchell, N. H. Fukushima, R. E. Neft, and J. F. Lechner, Induction of genomic instability in normal human bronchial epithelial cells by 238Pu alpha-particles, Carcinogenesis 17(8), 1671–1676 (1996).

    Article  PubMed  CAS  Google Scholar 

  46. R. H. Lin, L. J. Wu, C. H. Lee, and S. Y. Kin-Shiau, Cytogenetic toxicity of uranyl nitrate in Chinese hamster ovary cells, Mutat. Res. 319, 197–203 (1993).

    Article  PubMed  CAS  Google Scholar 

  47. F. F. Hahn, R. A. Guilmette, and M. D. Hoover, Implanted depleted uranium fragments cause soft tissue sarcomas in the muscles of rats, Environ. Health Perspect. 110(1), 51–59 (2002).

    Article  PubMed  CAS  Google Scholar 

  48. C. Voegtlin, and H. C. Hodge, eds., Pharmacology and Toxicology of Uranium Compounds, Part 1, McGraw-Hill, New York (1949).

    Google Scholar 

  49. C. Voegtlin and H. C. Hodge, eds., Pharmacology and Toxicology of Uranium Compounds Part 2. McGraw-Hill, New York (1949).

    Google Scholar 

  50. L. J. Leach, E. A. Maynard, H. C. Hodge, et al., A five-year inhalation study with natural uranium dioxide (UO 2) dust. I. Retention and biologic effect in the monkey, dog and rat, Health Phys. 18(6), 599–612 (1970).

    Article  PubMed  CAS  Google Scholar 

  51. L. J. Leach, C. L. Yuile, H. C. Hodge, G. E. Sylvester, and H. B. wilson, A five-year inhalation study with natural uranium dioxide (UO2) dust. II. Postexposure retention and biologic effects in the monkey, dog and rat, Health Phys. 25(3), 239–258 (1973).

    Article  PubMed  CAS  Google Scholar 

  52. P. Houpert, V. Chazel, F. Pauet, M. H. Henge-Napoli, and E. Ansoborlo, The effects of the initial lung deposit on uranium biokinetics after administration as UF4 and UO4, Int. J. Radiat. Biol. 75(3), 373–377 (1999).

    Article  PubMed  CAS  Google Scholar 

  53. C. Voegtlin and H. C. Hodge, eds., Pharmacology and Toxicology of Uranium Compounds. Part 3. McGraw-Hill, New York (1953).

    Google Scholar 

  54. C. Voegtlin and H. C. Hodge, eds., Pharmacology and Toxicology of Uranium Compounds. Part 4. McGraw-Hill, New York (1953).

    Google Scholar 

  55. N. D. Priest, Toxicity of depleted uranium, Lancet 357, 244–246 (2001).

    Article  PubMed  CAS  Google Scholar 

  56. J. L. Domingo, Reproductive and developmental toxicity of natural and depleted uranium: a review, Reprod. Toxicol. 14, 603–609 (2001).

    Article  Google Scholar 

  57. D. P. Arfsten, K. R. Still, and G. D. Ritchie, A review of the effects of uranium and depleted uranium exposure on reproduction and fetal development, Toxicol. Ind. Health. 17(5–10), 180–191 (2001).

    Article  PubMed  CAS  Google Scholar 

  58. A. W. Abu-Qare and M. B. Abou-Donia, Depleted uranium—the growing concern, J. Appl. Toxicol. 22(3), 149–152 (2002).

    Article  PubMed  CAS  Google Scholar 

  59. T. C. Pellmar, A. F. Fuciarelli, J. W. Ejnik, et al., Distribution of uranium in rats implanted with depleted uranium pellets, Toxicol. Sci. 49, 29–39 (1999).

    Article  PubMed  CAS  Google Scholar 

  60. T. C. Pellmar, D. O. Keyser, C. Emery, and J. B. Hogan, Electrophysiological changes in hippocampal slices isolated from rats embedded with depleted uranium fragments, Neurotoxicology 20(5), 785–792 (1999).

    PubMed  CAS  Google Scholar 

  61. W. Briner and J. Murray, Effects of short-term and long-term depleted uranium exposure on open-field behavior and brain lipid oxidation in rats, Neurotoxicol. Teratol. 27(1), 135–144 (2005).

    Article  PubMed  CAS  Google Scholar 

  62. D. S. Barber, M. F. Ehrich, and B. S. Jortner, The effect of stress on the temporal and regional distribution of uranium in rat brain after acute uranyl acetate exposure, J. Toxicol. Environ. Health A 68(2), 99–111 (2005).

    Article  PubMed  CAS  Google Scholar 

  63. R. H. Lin, W. M. Fu, and S. Y. Lin-Shiau, Presynaptic action of uranyl nitrate on the phrenic nerve-diaphragm preparation of the mouse, Neuropharmacology 27(8), 857–863 (1988).

    Article  PubMed  CAS  Google Scholar 

  64. A. P. Gilman, D. C. Villeneuve, V. E. Secours, et al., Uranyl nitrate: 28-day and 91-day toxicity studies in the Sprague-Dawley rat, Toxicol. Sci. 41(1), 117–128 (1998).

    PubMed  CAS  Google Scholar 

  65. A. P. Gilman, D. C. Villeneuve, V. E. Secours, et al., Uranyl nitrate: 91-day toxicity studies in the New Zealand white rabbit, Toxicol. Sci. 41(1), 129–137 (1998).

    Article  PubMed  CAS  Google Scholar 

  66. A. P. Gilman, M. A. Moss, D. C. Villeuneuve, et al., Uranyl nitrate: 91-day exposure and recovery studies in the male New Zealand white rabbit, Toxicol. Sci. 41(1), 138–151 (1998).

    Article  PubMed  CAS  Google Scholar 

  67. V. Lemercier, X. Millot, E. Ansoborlo, et al., Study of uranium transfer across the blood-brain barrier. Radiat. Prot. Dosim. 105(1–4), 243–245 (2003).

    CAS  Google Scholar 

  68. M. B. Abou-Donia, A. M. Dechkovskaia, L. B. Goldstein, D. U. Shah, S. L. Bullman, and W. A. Khan, Uranyl acetate-induced sensorimotor deficit and increased nitric oxide generation in the central nervous system in rats, Pharmacol. Biochem. Behav. 72, 881–890 (2002).

    Article  PubMed  CAS  Google Scholar 

  69. US Department of Defense, Population representation in the military services, fiscal year 2000. Available from http://www.dod.mil/prhome/poprep2000/html/chapter8/c8_actgender.htm (2000).

  70. F. J. Hooper, K. S. Squibb, E. L. Siegel, K. McPhaul, and J. P. Keogh, Elevated urine uranium excretion by soldiers with retained uranium shrapnel, Health Phys. 77(5), 512–519 (1999).

    Article  PubMed  CAS  Google Scholar 

  71. International Commission on Radiological Protection, Report of the Task Groups on References Man. 23, Pergamon Elmsford, NY (1974).

    Google Scholar 

  72. A. Durakovic, Undiagnosed illnesses and radioactive warfare, Croat. Med. J. 44(5), 520–532 (2003).

    PubMed  Google Scholar 

  73. US DoD (Department of Defense), Depleted uranium in the Gulf. Environmental exposure report. Available from http://www.gulflink.osd.mil/du (1998).

  74. US DoD (Department of Defense), Depleted uranium in the Gulf. Environmental exposure report. Available from http://www.deploymentlink.osd.mil/du_library/du_ii/. (2000).

  75. The Royal Society, The Health Effects of Depleted Uranium Munitions. Part I. The Royal Society, London (2001).

    Google Scholar 

  76. The Royal Society, The Health Effects of Depleted Uranium Munitions. Part II. The Royal Society, London (2002).

    Google Scholar 

  77. The Royal Society, The Health Effects of Depleted Uranium Munitions. Summary. Document 6/62, The Royal Society, London (2002).

    Google Scholar 

  78. E. Weir, Uranium in drinking water, naturally, C. M. A. J. 170(6), 951–952 (2004).

    Google Scholar 

  79. A. C. Miller, M. Stewart, K. Brooks, L. Shi, and N. Page, Depleted uranium-catalyzed oxidative DNA damage: absence of significant alpha particle decay, J. Inorg. Biochem. 91, 246–252 (2002).

    Article  PubMed  CAS  Google Scholar 

  80. M. Yazzie, S. L. Gamble, E. R. Civitello, and D. M. Stearns, Uranyl acetate causes DNA single-strand breaks in vitro in the presence of ascorbate (vitamin C), Chem. Res. Toxicol. 16(4), 524–530 (2003).

    Article  PubMed  CAS  Google Scholar 

  81. M. Taulan, F. Paquet, C. Maubert, O. Delissen, J. Demaille, and M. C. Romey, Renal toxicogenomic response to chronic uranyl nitrate insult in mice, Environ. Health Perspect. 112(16), 1628–1635 (2004).

    PubMed  CAS  Google Scholar 

  82. O. Prat, F. Berenguer, V. Malard, et al., Transcriptomic and proteomic responses of human renal HEK293 cells to uranium toxicity, Proteomics 5(1), 297–306 (2005).

    Article  PubMed  CAS  Google Scholar 

  83. R. Furuya, H. Kumagai, and A. Hishida, Acquired resistance to rechallenge injury with uranyl acetate in LLC-PK1 cells, J. Lab. Clin. Med. 129(3), 347–355 (1997).

    Article  PubMed  CAS  Google Scholar 

  84. S. Mizuno, K. Fujita, R. Furuy, et al., Association of HSP73 with the acquired resistance to uranyl acetate-induced acute renal failure, Toxicology 117(2–3), 183–191 (1997).

    Article  PubMed  CAS  Google Scholar 

  85. J. K. Tolson, S. M. Roberts, B. Jortner, M. Pomeroy, and D. S. Barber, Heat shock proteins and acquired resistance to uranium nephrotoxicity, Toxicology 206(1) 59–73 (2005).

    Article  PubMed  CAS  Google Scholar 

  86. J. F. Kalinich, N. Ramakrishnan, V. Villa, and D. E. McClain, Depleted uranium-uranyl chloride induces apoptosis in mouse J774 macrophages, Toxocology 79, 105–114 (2002).

    Article  Google Scholar 

  87. D. Fahey, Science or science fiction? Facts, myths, and propaganda in the debate over depleted uranium weapons. Available from http://www.antenna.nl/wise/uranium/pdf/dumyths.pdf. (2003)

  88. S. Milacic, D. Petrovic, D. Jovicic, R. Kovacevic, and J. Simic, Examination of the health status of populations from depleted-uranium-contaminated regions, Environ. Res. 95(1), 2–10 (2004).

    Article  PubMed  CAS  Google Scholar 

  89. N. Obralic, F. Gavrankapetanovic, Z. Dizdarevic, et al., The number of malignant neoplasm in Sarajevo region during the period 1998–2002, Med. Arh. 58(5), 275–278 (2004).

    PubMed  Google Scholar 

  90. Z. Karpas, L. Halicz, J. Roiz, et al., Inductively coupled plasma mass spectrometry as a simple, rapid, and inexpensive method for determination of uranium in urine and fresh water: comparison with LIF. Health Phys. 71(6), 879–885 (1996).

    Article  PubMed  CAS  Google Scholar 

  91. J. W. Ejnik, A. J. Carmichael, M. M. Hamilton, et al., Determination of the isotopic composition of uranium in urine by inductively coupled plasma mass spectrometry, Health Phys. 78(2), 143–146 (2000).

    Article  PubMed  CAS  Google Scholar 

  92. A. Ortega, J. L. Domingo, J. M. Llobet, J. M. Tomas, and J. L. Paternain. Evaluation of the oral toxicity of uranium in a 4-week drinking-water study in rats, Bull. Environ. Contam. Toxicol. 42(6), 935–941.

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Jiang, G.C.T., Aschiner, M. Neurotoxicity of depleted uranium. Biol Trace Elem Res 110, 1–17 (2006). https://doi.org/10.1385/BTER:110:1:1

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1385/BTER:110:1:1

Index Entries

Navigation