Skip to main content
Log in

Tungsten: an Emerging Toxicant, Alone or in Combination

  • Metals and Health (A Barchowsky, Section Editor)
  • Published:
Current Environmental Health Reports Aims and scope Submit manuscript

Abstract

Purpose of review

Tungsten is an emerging environmental toxicant, yet our understanding of the potential risks of exposure on human health is still limited.

Recent findings

In this review, we will discuss populations most at risk of exposure to high concentrations of tungsten. In addition, we will highlight what is known about the toxicity profile of tungsten compounds, based on epidemiological, in vitro, and in vivo studies, focusing on bone, immune, pulmonary, and cancer outcomes. Of note, emerging evidence indicates that tungsten can augment the effects of other stimulants, stressors, and toxicants. Of particular importance may be tungsten-cobalt mixtures that seem to be more toxic than either metal alone. This is important because it means that we cannot just evaluate the toxicity of tungsten in isolation. Finally, we still have limited information of how many of the in vitro and in vivo findings translate to human populations, so it will be important to conduct epidemiology studies in highly exposed populations to adequately address the potential risks of tungsten exposure on human health.

Summary

Together, we discuss recent findings that support further investigation into the toxicities of tungsten alone and in combination with other metals.

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.

Fig. 1

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. EPA, Emerging contaminant tungsten. Fact sheet, in 505-F-070-005. 2008.

  2. NTP, Priority substance list nomination summary—tungsten. 2002.

  3. Agency for Toxic Substances and Disease Registry, A., Toxicological profile for tungsten. 2005. www.atsdr.cdc.gov/toxprofiles/tp186.pdf. Last Accessed: April 29th, 2016.

  4. Keith LS et al. ATSDR evaluation of potential for human exposure to tungsten. Toxicol Ind Health. 2007;23(5-6):309–45.

    Article  CAS  PubMed  Google Scholar 

  5. Rubin CS et al. Investigating childhood leukemia in Churchill County, Nevada. Environ Health Perspect. 2007;115(1):151–7.

    Article  CAS  PubMed  Google Scholar 

  6. Bolt AM et al. Tungsten targets the tumor microenvironment to enhance breast cancer metastasis. Toxicol Sci. 2015;143(1):165–77. This study showed that tungsten remained in the human body years after the original source of the exposure was removed, suggesting that a secondary storage site for tungsten exists. In addition, tungsten promoted murine breast cancer metastasis to the lung by modulating the tumor microenvironment rather than the primary tumor cells.

  7. Gaitens JSK, Condon M, Centeno J, McDiarmid M. Mobilization of metals from embedded fragments in a cohort of US veterans. Society of Toxicology 2015 Annual Meeting abstract 345 2015.

  8. Kraus T et al. Exposure assessment in the hard metal manufacturing industry with special regard to tungsten and its compounds. Occup Environ Med. 2001;58(10):631–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Lemus R, Venezia CF. An update to the toxicological profile for water-soluble and sparingly soluble tungsten substances. Crit Rev Toxicol. 2015;45(5):388–411.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Lassner ESWD. Tungsten—properties, chemistry, technology of the element, alloys, and chemical compounds. New York: Kluwer; 1999.

    Google Scholar 

  11. Weast RC. Handbook of chemistry and physics. 54th ed. Boca Raton: CRC Press; 1973.

    Google Scholar 

  12. CDC, NIOSH pocket guide to chemical hazards. Tungsten. 2010. http://www.cdc.gov/niosh/npg/npgd0645.html. Last Accessed: April 29th, 2016.

  13. OECD SIDS, Tungsten carbide. 2005: [Unpublished Report] Washington, DC. http://www.inchem.org/documents/sids/sids/12070121.pdf. Last Accessed: April 29th, 2016.

  14. RCC NOTOX BV, Determination of the water solubility of sodium metatungstate. 1992: [Unpublished Report] Hertogenbosch, The Netherlands.

  15. Baes Jr CFMRE. The hydrolysis of cations. New York: Wiley; 1978.

    Google Scholar 

  16. Association of State and Territorial Solid Waste Management Official (ASTSWMO), Tungsten Issues Paper. 2011.

  17. Dermatas DBW, Christodoulatos C. Solubility, sorption, and soil respiration effects of tungsten and tungsten alloys. Environ Forensics. 2004;5(1):5–13. www.astswmo.org/Files/Policies_and_Publications/Federal_Facilities/2011-02_FINAL_Tungsten_Issues_2-0.pdf. Last Accessed: April 29th, 2016.

    Article  CAS  Google Scholar 

  18. Koutsospyros A et al. A review of tungsten: from environmental obscurity to scrutiny. J Hazard Mater. 2006;136(1):1–19.

    Article  CAS  PubMed  Google Scholar 

  19. Armstead AL, Arena CB, Li B. Exploring the potential role of tungsten carbide cobalt (WC-Co) nanoparticle internalization in observed toxicity toward lung epithelial cells in vitro. Toxicol Appl Pharmacol. 2014;278(1):1–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Lombaert N et al. Evaluation of the apoptogenic potential of hard metal dust (WC-Co), tungsten carbide and metallic cobalt. Toxicol Lett. 2004;154(1-2):23–34.

    Article  CAS  PubMed  Google Scholar 

  21. Lombaert N et al. In vitro expression of hard metal dust (WC-Co)—responsive genes in human peripheral blood mononucleated cells. Toxicol Appl Pharmacol. 2008;227(2):299–312.

    Article  CAS  PubMed  Google Scholar 

  22. Lombaert N et al. Hard-metal (WC-Co) particles trigger a signaling cascade involving p38 MAPK, HIF-1alpha, HMOX1, and p53 activation in human PBMC. Arch Toxicol. 2013;87(2):259–68.

    Article  CAS  PubMed  Google Scholar 

  23. Anard D et al. In vitro genotoxic effects of hard metal particles assessed by alkaline single cell gel and elution assays. Carcinogenesis. 1997;18(1):177–84.

    Article  CAS  PubMed  Google Scholar 

  24. Lison D, Lauwerys R. In vitro cytotoxic effects of cobalt-containing dusts on mouse peritoneal and rat alveolar macrophages. Environ Res. 1990;52(2):187–98.

    Article  CAS  PubMed  Google Scholar 

  25. Miller AC et al. Neoplastic transformation of human osteoblast cells to the tumorigenic phenotype by heavy metal-tungsten alloy particles: induction of genotoxic effects. Carcinogenesis. 2001;22(1):115–25.

    Article  CAS  PubMed  Google Scholar 

  26. Harris RM et al. Reactive oxygen species and oxidative DNA damage mediate the cytotoxicity of tungsten-nickel-cobalt alloys in vitro. Toxicol Appl Pharmacol. 2011;250(1):19–28.

    Article  CAS  PubMed  Google Scholar 

  27. Verma R et al. In vitro profiling of epigenetic modifications underlying heavy metal toxicity of tungsten-alloy and its components. Toxicol Appl Pharmacol. 2011;253(3):178–87.

    Article  CAS  PubMed  Google Scholar 

  28. Ding M et al. Size-dependent effects of tungsten carbide-cobalt particles on oxygen radical production and activation of cell signaling pathways in murine epidermal cells. Toxicol Appl Pharmacol. 2009;241(3):260–8.

    Article  CAS  PubMed  Google Scholar 

  29. Emond CA et al. Induction of rhabdomyosarcoma by embedded military-grade tungsten/nickel/cobalt not by tungsten/nickel/iron in the B6C3F1 mouse. Int J Toxicol. 2015;34(1):44–54.

    Article  CAS  PubMed  Google Scholar 

  30. Emond CA, Vergara VB, Lombardini ED, Mog SR, Kalinich JF. The role of the component metals in the toxicity of military-grade tungsten alloy. Toxics. 2015;3(4):499–514. This study demonstrated that tungsten/nickel/cobalt pellets were more potent inducers of rhabdomyosarcoma tumors than individual metal components alone or two metal combinations, providing evidence of synergy between tungsten and other metals to promote cancer.

  31. Kalinich JF et al. Embedded weapons-grade tungsten alloy shrapnel rapidly induces metastatic high-grade rhabdomyosarcomas in F344 rats. Environ Health Perspect. 2005;113(6):729–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Mezentseva N, Tungsten. In: Izreal’son ZI, ed. Toxicology of the rare metals. (Toksikologiya redkikh metallov). Jerusalem: Israel Program for Scientific Translations. 1967. AEC-tr 6710: 28–35.

  33. Lasfargues G et al. Comparative study of the acute lung toxicity of pure cobalt powder and cobalt-tungsten carbide mixture in rat. Toxicol Appl Pharmacol. 1992;112(1):41–50.

    Article  CAS  PubMed  Google Scholar 

  34. Roedel EQ et al. Pulmonary toxicity after exposure to military-relevant heavy metal tungsten alloy particles. Toxicol Appl Pharmacol. 2012;259(1):74–86.

    Article  CAS  PubMed  Google Scholar 

  35. Rengasamy A et al. Effects of hard metal on nitric oxide pathways and airway reactivity to methacholine in rat lungs. Toxicol Appl Pharmacol. 1999;157(3):178–91.

    Article  CAS  PubMed  Google Scholar 

  36. De Boeck M et al. In vivo genotoxicity of hard metal dust: induction of micronuclei in rat type II epithelial lung cells. Carcinogenesis. 2003;24(11):1793–800.

    Article  PubMed  Google Scholar 

  37. Coates Jr EO, Watson JH. Diffuse interstitial lung disease in tungsten carbide workers. Ann Intern Med. 1971;75(5):709–16.

    Article  PubMed  Google Scholar 

  38. Naqvi AH et al. Pathologic spectrum and lung dust burden in giant cell interstitial pneumonia (hard metal disease/cobalt pneumonitis): review of 100 cases. Arch Environ Occup Health. 2008;63(2):51–70.

    Article  PubMed  Google Scholar 

  39. Figueroa S et al. Hard metal interstitial pulmonary disease associated with a form of welding in a metal parts coating plant. Am J Ind Med. 1992;21(3):363–73.

    Article  CAS  PubMed  Google Scholar 

  40. Moulin JJ et al. Lung cancer risk in hard-metal workers. Am J Epidemiol. 1998;148(3):241–8.

    Article  CAS  PubMed  Google Scholar 

  41. Wild P et al. Lung cancer mortality in a site producing hard metals. Occup Environ Med. 2000;57(8):568–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Richter VVRM. On hardness and toughness of ultrafine and nanocrystalline hard materials. Int J Refract Met Hard Mater. 1999;17(1-3):141–52.

    Article  CAS  Google Scholar 

  43. Machado BI et al. Characterization and cytotoxic assessment of ballistic aerosol particulates for tungsten alloy penetrators into steel target plates. Int J Environ Res Public Health. 2010;7(9):3313–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Sheppard PR et al. Temporal variability of tungsten and cobalt in Fallon, Nevada. Environ Health Perspect. 2007;115(5):715–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Abraham JL, Hunt A. Environmental contamination by cobalt in the vicinity of a cemented tungsten carbide tool grinding plant. Environ Res. 1995;69(1):67–74.

    Article  CAS  PubMed  Google Scholar 

  46. Xu S et al. Tungsten- and cobalt-dominated heavy metal contamination of mangrove sediments in Shenzhen. China Mar Pollut Bull. 2015;100(1):562–6.

    Article  CAS  PubMed  Google Scholar 

  47. Pang Y et al. Metal mixtures in urban and rural populations in the US: the Multi-Ethnic Study of Atherosclerosis and the Strong Heart Study. Environ Res. 2016;147:356–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. NIOSH, Occupational exposure to tungsten and cemented carbide. 1977. pp. 21–171.

  49. Bachthaler M et al. Corrosion of tungsten coils after peripheral vascular embolization therapy: influence on outcome and tungsten load. Catheter Cardiovasc Interv. 2004;62(3):380–4.

    Article  PubMed  Google Scholar 

  50. Barrett J et al. Endovascular embolization of varicoceles: resorption of tungsten coils in the spermatic vein. Cardiovasc Intervent Radiol. 2000;23(6):457–9.

    Article  CAS  PubMed  Google Scholar 

  51. Barbera A et al. Tungstate is an effective antidiabetic agent in streptozotocin-induced diabetic rats: a long-term study. Diabetologia. 2001;44(4):507–13.

    Article  CAS  PubMed  Google Scholar 

  52. Claret M et al. Tungstate decreases weight gain and adiposity in obese rats through increased thermogenesis and lipid oxidation. Endocrinology. 2005;146(10):4362–9.

    Article  CAS  PubMed  Google Scholar 

  53. Hanzu F et al. Proof-of-concept trial on the efficacy of sodium tungstate in human obesity. Diabetes Obes Metab. 2010;12(11):1013–8.

    Article  CAS  PubMed  Google Scholar 

  54. Clausen JLTS, Larson SL, Bednar AJ, Ketterer M, Griggs CS, Lambert DJ, Hewitt AD, Ramsey CA, Bigl SR, Bailey, RN, Perron NM. Fate and transport of tungsten at Camp Edwards Small Arms Ranges. 2007.

  55. Sadiq MMAA, Althagafi KM. Inter-city comparison of metals in scalp hair collected after the Gulf War 1991. J Environ Sci Health Part A. 1992;27(6):1415–31.

    Google Scholar 

  56. Mamuro TMY, Mizohata Y. Activation analysis of polluted river water. Radioisotopes. 1971;20(3):111–6.

    Article  CAS  Google Scholar 

  57. Pang Y et al. Association of geography and ambient air pollution with urine metal concentrations in six US cities: the Multi-Ethnic Study of Atherosclerosis. Int J Environ Res Public Health. 2016; 13(3).

  58. Schell J, Pardus M. Tungsten and cobalt in Fallon, Nevada: association with childhood leukemia. Environ Health Perspect. 2008;116(5):A196–7. author reply A197.

    Article  PubMed  PubMed Central  Google Scholar 

  59. Seiler RL, Stollenwrk KG, Garbarino JK. Factors controlling tungsten concentrations in ground water, Carson Desert, Nevada. Appl Geochem. 2005;20(2):423–41.

    Article  CAS  Google Scholar 

  60. Tyrrell J et al. High urinary tungsten concentration is associated with stroke in the National Health and Nutrition Examination Survey 1999–2010. PLoS One. 2013;8(11):e77546. This study investigated the association between urinary tungsten concentrations and the prevalence of cardiovascular disease or stroke using data from the NHANES database. They found a strong association between elevated urinary tungsten concentrations and increased prevalence of stroke.

  61. Menke A, Guallar E, Cowie CC. Metals in urine and diabetes in U.S. adults. Diabetes. 2016;65(1):164–71.

    CAS  PubMed  Google Scholar 

  62. Feng W et al. Association of urinary metal profiles with altered glucose levels and diabetes risk: a population-based study in China. PLoS One. 2015;10(4):e0123742.

    Article  PubMed  PubMed Central  Google Scholar 

  63. Navas-Acien A et al. Metals in urine and peripheral arterial disease. Environ Health Perspect. 2005;113(2):164–9.

    Article  CAS  PubMed  Google Scholar 

  64. Massachusetts “Department of Environmental Protection (DEP)., Fact sheet: tungsten and tungsten compounds. 2006.

  65. Sanitary rules and norms of Russian Federation. 1996: Moscow.

  66. CDC, Second national report on human exposure to environmental chemicals, in HSDHHS, CDC, National Center for Environmental Health. 2003.

  67. Canada H. Second report on human biomonitoring of environmental chemicals in Canada. 2013.

  68. Paschal DC et al. Trace metals in urine of United States residents: reference range concentrations. Environ Res. 1998;76(1):53–9.

    Article  CAS  PubMed  Google Scholar 

  69. Occupational Safety and Health Administration, O., Tungsten and cobalt in workplace atmospheres (ICP Analysis). 2013. www.osha.gov/dts/sltc/methods/inorganice/id213/id213.html. Last Accessed: April 29th, 2016.

  70. Lagarde F, Leroy M. Metabolism and toxicity of tungsten in humans and animals. Met Ions Biol Syst. 2002;39:741–59.

    CAS  PubMed  Google Scholar 

  71. Kaye SV. Distribution and retention of orally administered radiotungsten in the rat. Health Phys. 1968;15(5):399–417.

    Article  CAS  PubMed  Google Scholar 

  72. Guandalini GS et al. Tissue distribution of tungsten in mice following oral exposure to sodium tungstate. Chem Res Toxicol. 2011;24(4):488–93.

    Article  CAS  PubMed  Google Scholar 

  73. Kelly AD et al. In vivo tungsten exposure alters B cell development and increases DNA damage in murine bone marrow. Toxicol Sci. 2013;131(2):434–46.

    Article  CAS  PubMed  Google Scholar 

  74. Rajendran N et al. Toxicologic evaluation of tungsten: 28-day inhalation study of tungsten blue oxide in rats. Inhal Toxicol. 2012;24(14):985–94.

    Article  CAS  PubMed  Google Scholar 

  75. Leggett RW. A model of the distribution and retention of tungsten in the human body. Sci Total Environ. 1997;206(2-3):147–65.

    Article  CAS  PubMed  Google Scholar 

  76. Bolt AM et al. Tungsten promotes sex-specific adipogenesis in the bone by altering differentiation of bone marrow-resident mesenchymal stromal cells. Toxicol Sci. 2016.

  77. Ferguson VL et al. Bone development and age-related bone loss in male C57BL/6J mice. Bone. 2003;33(3):387–98.

    Article  PubMed  Google Scholar 

  78. Osterburg AR et al. Sodium tungstate (Na2WO4) exposure increases apoptosis in human peripheral blood lymphocytes. J Immunotoxicol. 2010;7(3):174–82.

    Article  CAS  PubMed  Google Scholar 

  79. Fastje CD et al. Exposure to sodium tungstate and Respiratory Syncytial Virus results in hematological/immunological disease in C57BL/6J mice. Chem Biol Interact. 2012;196(3):89–95.

    Article  CAS  PubMed  Google Scholar 

  80. Frawley RP et al. Immunotoxic effects of sodium tungstate dihydrate on female BCF/N mice when administered in drinking water. J Immunotoxicol. 2016; 1–10.

  81. Guilbert C et al. Exposure to tungsten induces DNA damage and apoptosis in developing B lymphocytes. Leukemia. 2011;25(12):1900–4.

    Article  CAS  PubMed  Google Scholar 

  82. Dunnick KM et al. The effect of tungstate nanoparticles on reactive oxygen species and cytotoxicity in raw 264.7 mouse monocyte macrophage cells. J Toxicol Environ Health A. 2014;77(20):1251–68.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Mazus B, Krysiak C, Buchowicz J. Tungsten particle-induced nicking of supercoiled plasmid DNA. Plasmid. 2000;44(1):89–93.

    Article  CAS  PubMed  Google Scholar 

  84. Ulitzur S, Barak M. Detection of genotoxicity of metallic compounds by the bacterial bioluminescence test. J Biolumin Chemilumin. 1988;2(2):95–9.

    Article  CAS  PubMed  Google Scholar 

  85. Singh I. Induction of reverse mutation and mitotic gene conversion by some metal compounds in Saccharomyces cerevisiae. Mutat Res. 1983;117(1-2):149–52.

    Article  CAS  PubMed  Google Scholar 

  86. Sora S et al. Disomic and diploid meiotic products induced in Saccharomyces cerevisiae by the salts of 27 elements. Mutagenesis. 1986;1(1):21–8.

    Article  CAS  PubMed  Google Scholar 

  87. Miller AC, Page N. Mutagenicity of heavy metals used in military application: comparison of depleted uranium, tungsten, and nickel. Environ Mutagen. 1999. 141.

  88. Laulicht F et al. Tungsten-induced carcinogenesis in human bronchial epithelial cells. Toxicol Appl Pharmacol. 2015;288(1):33–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Schroeder HA, Mitchener M. Life-term studies in rats: effects of aluminum, barium, beryllium, and tungsten. J Nutr. 1975;105(4):421–7.

    Article  CAS  PubMed  Google Scholar 

  90. Wei HJ, Luo XM, Yang SP. Effects of molybdenum and tungsten on mammary carcinogenesis in SD rats. J Natl Cancer Inst. 1985;74(2):469–73.

    CAS  PubMed  Google Scholar 

  91. Luo XM, Wei HJ, Yang SP. Inhibitory effects of molybdenum on esophageal and forestomach carcinogenesis in rats. J Natl Cancer Inst. 1983;71(1):75–80.

    CAS  PubMed  Google Scholar 

  92. Gunnison AF et al. The effect of inhaled sulfur dioxide and systemic sulfite on the induction of lung carcinoma in rats by benzo[a]pyrene. Environ Res. 1988;46(1):59–73.

    Article  CAS  PubMed  Google Scholar 

  93. Tellez-Plaza M et al. Association of global DNA methylation and global DNA hydroxymethylation with metals and other exposures in human blood DNA samples. Environ Health Perspect. 2014;122(9):946–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Johnson JL, Rajagopalan KV, Cohen HJ. Molecular basis of the biological function of molybdenum. effect of tungsten on xanthine oxidase and sulfite oxidase in the rat. J Biol Chem. 1974;249(3):859–66.

    CAS  PubMed  Google Scholar 

  95. Johnson DR et al. Tungsten effects on phosphate-dependent biochemical pathways are species and liver cell line dependent. Toxicol Sci. 2010;116(2):523–32.

    Article  CAS  PubMed  Google Scholar 

  96. Salto R et al. Activation of ERK by sodium tungstate induces protein synthesis and prevents protein degradation in rat L6 myotubes. FEBS Lett. 2014;588(14):2246–54.

    Article  CAS  PubMed  Google Scholar 

  97. Raza R et al. Polyoxometalates as potent and selective inhibitors of alkaline phosphatases with profound anticancer and amoebicidal activities. Dalton Trans. 2012;41(47):14329–36.

    Article  CAS  PubMed  Google Scholar 

  98. Rodriguez-Hernandez CJ et al. Sodium tungstate modulates ATM function upon DNA damage. FEBS Lett. 2013;587(10):1579–86.

    Article  CAS  PubMed  Google Scholar 

  99. Fernandez-Ruiz R et al. Role of sodium tungstate as a potential antiplatelet agent. Drug Des Dev Ther. 2015;9:2777–86.

    Article  CAS  Google Scholar 

Download references

Acknowledgments

This work is supported by grants from the Canadian Institutes of Health Research MOP-137149 and MOP-142227 and the Natural Sciences and Engineering Research Council of Canada RGPIN-2015-04919.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Koren K. Mann.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

This article is part of the Topical Collection on Metals and Health

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bolt, A.M., Mann, K.K. Tungsten: an Emerging Toxicant, Alone or in Combination. Curr Envir Health Rpt 3, 405–415 (2016). https://doi.org/10.1007/s40572-016-0106-z

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40572-016-0106-z

Keywords

Navigation