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Tissue distribution patterns of solubilized metals from internalized tungsten alloy in the F344 rat

1 Internal Contamination and Metal Toxicity Program, Armed Forces Radiobiology Research Institute, Uniformed Services University, 8901 Wisconsin Avenue, Bethesda, Maryland 20889-5603, USA
2 Current address: Department of Veterans Affairs, Manchester Veterans Affairs Medical Center, 718 Smyth Road, Manchester, New Hampshire 03104, USA

Special Issues: Metal Contamination in the Environment

Because of its unique physical and chemical properties, tungsten has been increasingly utilized in a variety of civilian and military applications. This expanded use also raises the risk of human exposure through internalization by various routes. In most cases the toxicological and carcinogenic properties of these tungsten-based compounds are not known nor are the dissolution biokinetics and ultimate fate of the associated metals. Using a laboratory rodent model system designed to assess the health effects of embedded metals, and a tungsten alloy comprised of tungsten (91.1%), nickel (6.0%), and cobalt (2.9%), we investigated the tissue distribution patterns of the metals over a six month period. Despite its perceived insolubility, tungsten rapidly solubilized from the implanted metal fragments, as did nickel and cobalt. All three metals distributed systemically over time with extremely elevated levels of all three metals found in kidney, liver, and spleen. Unexpectedly, tungsten was found to cross the blood-brain and blood-testis barriers and localize in those tissues. These results, along with recent reports suggesting that tungsten is a tumor promoter, raises serious concerns as to the long-term health effects of exposure to tungsten and tungsten-based compounds.
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1. van der Voet GB, Todorov TI, Centeno JA, et al. (2007) Metals and health: a clinical toxicological perspective on tungsten and review of the literature. Mil Med 172: 1002-1005.    

2. Agency for Toxic Substances and Disease Registry (ATSDR) (2005) Toxicological profile for tungsten. Atlanta, GA: U.S. Department of Health and Human Services, Public Health Service.

3. United States Fish and Wildlife Service, Nontoxic shot regulations for hunting waterfowl and coots in the U.S.. Available from: www.regulations.gov/#!documentDetail;D=FWS-R9-MB-2011-0077-0009.

4. Kraabel BJ, Miller MW, Getzy DM, et al. (1996) Effects of embedded tungsten-bismuth-tin shot and steel shot on mallards (Anas platyrhynchos). J Wildlife Dis 32: 1-8.    

5. Kelly ME, Fitzgerald SD, Aulerich RJ, et al. (1998) Acute effects of lead, steel, tungsten-iron, and tungsten-polymer shot administered to game-farm mallards. J Wildlife Dis 34: 673-687.    

6. Mitchell RR, Fitzgerald SD, Aulerich RJ, et al. (2001) Hematological effects and metal residue concentrations following chronic dosing with tungsten-iron and tungsten-polymer shot in adult game-farm mallards. J Wildlife Dis 37: 459-467.    

7. Mitchell RR, Fitzgerald SD, Aulerich RJ, et al. (2001) Reproductive effects and duckling survivability following chronic dosing with tungsten-iron and tungsten-polymer shot in adult game-farm mallards. J Wildlife Dis 37: 468-474.    

8. Mitchell RR, Fitzgerald SD, Aulerich RJ, et al. (2001) Health effects following chronic dosing with tungsten-iron and tungsten-polymer shot in adult game-farm mallards. J Wildlife Dis 37: 451-458.

9. Brewer L, Fairbrother A, Clark J, et al. (2003) Acute toxicity of lead, steel, and an iron-tungsten-nickel shot to mallard ducks (Anas platyrhynchos). J Wildlife Dis 39: 638-648.

10. Kerley CR, Easterly CE, Eckerman KF, et al. (1996) Environmental acceptability of high-performance alternatives for depleted uranium penetrators. ORNL/TM-13286. Oak Ridge National Laboratory. Available from: http://www.osti.gov/scitech/biblio/464128-environmental-acceptability-high-performance-alternatives-depleted-uranium-penetrators.

11. Kalinich JF, Emond CA, Dalton TK, et al. (2005) Embedded weapons-grade tungsten alloy shrapnel rapidly induces metastatic high-grade rhabdomyosarcomas in F344 rats. Environ Health Perspect 113: 729-734.    

12. Schuster BE, Roszell LE, Murr LE, et al. (2012) In vivo corrosion, tumor outcome, and microarray gene expression for two types of muscle-implanted tungsten alloys. Toxicol Appl Pharmacol 265: 128-138.    

13. Emond CA, Vergara VB, Lombardini ED, et al. (2015) Induction of rhabdomyosarcoma by embedded military-grade tungsten/nickel/cobalt not by tungsten/nickel/iron in the B6C3F1 mouse. Int J Toxicol 34: 44-54.    

14. Koutsospyros A, Braida W, Christodoulatos C, et al. (2006) A review of tungsten: From environmental obscurity to scrutiny. J Hazard Mater 136: 1-19.    

15. Gbaruko BC, Igwe JC (2007) Tungsten: Occurrence, chemistry, environmental, and health exposure issues. Global J Environ Res 1: 27-32.

16. Ogundipe A, Greenberg B, Braida W, et al. (2006) Morphological characterization and spectroscopic studies of the corrosion behaviour of tungsten heavy alloys. Corr Sci 48: 3281-3297.    

17. Dermatas D, Braida W, Christodoulatos C, et al. (2004) Solubility, sorption, and soil respiration effects of tungsten and tungsten alloys. Environ Forensics 5: 5-13.    

18. Bednar AJ, Jones WT, Boyd RE, et al. (2008) Geochemical parameters influencing tungsten mobility in soils. J Environ Qual 37: 229-233.    

19. Strigul N (2010) Does speciation matter for tungsten ecotoxicology? Ecotoxicol Environ Safety 73: 1099-1113.

20. Institute of Laboratory Animal Resources (2010) Guide for the Care and Use of Laboratory Animals. 8th edition. Washington, DC: National Academy Press.

21. Rao GN (1996) New diet (NTP-2000) for rats in the National Toxicology Program toxicity and carcinogenicity studies. Fund Appl Toxicol 32: 102-108.    

22. Hockley AD, Goldin JH, Wake MJC, et al. (1990) Skull repair in children. Pediatric Neurosurg 16: 271-275.

23. Johansson CB, Hansson HA, Albrektsson T (1990) Qualitative interfacial study between bone and tantalum, niobium or commercially pure titanium. Biomaterials 11: 277-280.    

24. Strecker EP, Hagan B, Liermann D, et al. (1993) Iliac and femoropopliteal vascular occlusive disease treated with flexible tantalum stents. Cardiovasc Intervent Radiol 16: 158-164.    

25. Emond CA, Vergara VB, Lombardini ED, et al. (2015) The role of the component metals in the toxicity of military-grade tungsten alloy. Toxics 3: 499-514.    

26. Witten ML, Sheppard PR, Witten BL (2012) Tungsten toxicity. Chemico-Biol Interact 196: 87-88.    

27. Rubin CS, Holmes AK, Belson MG, et al. (2007) Investigating childhood leukemia in Churchill County, Nevada. Environ Health Perspect 115: 151-157.

28. Kalinich JF, Vergara VB, Emond CA (2008) Urinary and serum metal levels as indicators of embedded tungsten alloy fragments. Mil Med 173: 754-758.    

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

30. Miller AC, Xu J, Prasanna PGS, et al. (2002) Potential late health effects of the heavy metals, depleted uranium and tungsten, used in armor piercing munitions: comparison of neoplastic transformation and genotoxicity using the known carcinogen nickel. Mil Med 167: 120-122.

31. Kalinich JF, Kasper CE (2014) Do metals that translocate to the brain exacerbate traumatic brain injury? Med Hypoth 83: 558-562.

32. Leggett RW (1997) A model of the distribution and retention of tungsten in the human body. Sci Total Environ 206: 147-165.    

33. Emond CA, Kalinich JF (2012) Biokinetics of embedded surrogate radiological dispersal device material. Health Phys 102: 124-136.

34. Endoh H, Kaneko T, Nakamura H, et al. (2000) Improved cardiac contractile functions in hypoxia-reoxygenation in rats treated with low concentration Co2+. Am J Physiol Heart Circ Physiol 279: H2713-H2719.

35. Rakusan K, Cicutti N, Kolar F (2001) Cardiac function, microvascular structure, and capillary hematocrit in hearts of polycythemic rats. Am J Physiol Heart Circ Physiol 281: H2425-H2431.

36. Fastje CD, Harper K, Terry C, et al. (2012) Exposure to sodium tungstate and Respiratory Syncytial Virus results in hematological/immunological disease in C57BL/6J mice. Chemico-Biol Interact 196: 89-95.    

37. Kelly ADR, Lemaire M, Young YK, et al. (2013) In vivo tungsten exposure alters B-cell development and increases DNA damage in murine bone marrow. Toxicol Sci 131: 434-446.    

38. Jalaguier-Coudray A, Cohen M, Thomassin-Piana J, et al. (2015) Calcifications and tungsten deposits after breast-conserving surgery and intraoperative radiotherapy for breast cancer. Eur J Radiol 84: 2521-2525.    

39. Bolt AM, Sabourin V, Molina F, et al. (2015) Tungsten targets the tumor microenvironment to enhance breast cancer metastasis. Toxicol Sci 143: 165-177.    

40. Harris RM, Williams TD, Hodges NJ, et al. (2011) Reactive oxygen species and oxidative DNA damage mediate the cytotoxicity of tungsten-nickel-cobalt alloys in vitro. Toxicol Appl Pharmacol 250: 19-28.    

41. Bardack S, Dalgard CL, Kalinich JF, et al. (2014) Genotoxic changes to rodent cells exposed in vitro to tungsten, nickel, cobalt, and iron. Int J Environ Res Pub Health 11: 2922-2940.    

42. Harris RM, Williams TD, Waring RH, et al. (2015) Molecular basis of carcinogenicity of tungsten alloy particles. Toxicol Appl Pharmacol 283: 223-233.    

43. Laulicht F, Brocato J, Cartularo L, et al. (2015) Tungsten-induced carcinogenesis in human bronchial epithelial cells. Toxicol Appl Pharmacol 288: 33-39.    

44. Guandalini GS, Zhang L, Fornero E, et al. (2011) Tissue distribution of tungsten in mice following oral exposure to sodium tungstate. Chem Res Toxicol 24: 488-493.    

45. McInturf SM, Bekkedal MYV, Wilfong E, et al. (2011) The potential reproductive, neurobehavioral and systemic effects of soluble sodium tungstate exposure in Sprague-Dawley rats. Toxicol Appl Pharmacol 254: 133-137.    

46. Radcliffe PM, Leavens TL, Wagner DJ, et al. (2010) Pharmacokinetics of radiolabeled tungsten (188W) in male Sprague-Dawley rats following acute sodium tungstate inhalation. Inhalation Toxicol 22: 69-76.    

47. McDonald JD, Weber WM, Marr R, et al. (2007) Disposition and clearance of tungsten after single-dose oral and intravenous exposure in rodents. J Toxicol Environ Health A 70: 829-836.    

48. NTP Range-Finding Report: Immunotoxicity of Sodium Tungstate Dihydrate in Female B6C3F1/N Mice (CASRN: 10213-10-2) National Toxicology Program, U.S. Department of Health and Human Services. Available from: ntp.niehs.nih.gov/testing/types/imm/abstract/i03038/index.html.

49. U.S. Environmental Protection Agency (2008) Emerging contaminant tungsten. Fact sheet 505-F-070-005. Available from: http://nepis.epa.gov/Exe/ZyPDF.cgi/P1000L3K.PDF?Dockey=P1000L3K.PDF.

Copyright Info: © 2016, John F. Kalinich, et al., licensee AIMS Press. This is an open access article distributed under the terms of the Creative Commons Attribution Licese (http://creativecommons.org/licenses/by/4.0)

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