| Embedded Weapons-Grade Tungsten Alloy Shrapnel Rapidly Induces Metastatic High-Grade Rhabdomyosarcomas in F344 Rats John F. Kalinich,1 Christy A. Emond,1 Thomas K. Dalton,1 Steven R. Mog,2 Gary D. Coleman,3 Jessica E. Kordell,1 Alexandra C. Miller,1 and David E. McClain1 1Heavy Metals Research Team and 2Veterinary Sciences Department, Armed Forces Radiobiology Research Institute, Bethesda, Maryland, USA; 3Division of Veterinary Pathology, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA Abstract
Continuing concern regarding the potential health and environmental effects of depleted uranium and lead has resulted in many countries adding tungsten alloy (WA) -based munitions to their battlefield arsenals as replacements for these metals. Because the alloys used in many munitions are relatively recent additions to the list of militarily relevant metals, very little is known about the health effects of these metals after internalization as embedded shrapnel. Previous work in this laboratory developed a rodent model system that mimicked shrapnel loads seen in wounded personnel from the 1991 Persian Gulf War. In the present study, we used that system and male F344 rats, implanted intramuscularly with pellets (1 mm  2 mm cylinders) of weapons-grade WA, to simulate shrapnel wounds. Rats were implanted with 4 (low dose) or 20 pellets (high dose) of WA. Tantalum (20 pellets) and nickel (20 pellets) served as negative and positive controls, respectively. The high-dose WA-implanted rats (n = 46) developed extremely aggressive tumors surrounding the pellets within 4-5 months after implantation. The low-dose WA-implanted rats (n = 46) and nickel-implanted rats (n = 36) also developed tumors surrounding the pellets but at a slower rate. Rats implanted with tantalum (n = 46) , an inert control metal, did not develop tumors. Tumor yield was 100% in both the low- and high-dose WA groups. The tumors, characterized as high-grade pleomorphic rhabdomyosarcomas by histopathology and immunohistochemical examination, rapidly metastasized to the lung and necessitated euthanasia of the animal. Significant hematologic changes, indicative of polycythemia, were also observed in the high-dose WA-implanted rats. These changes were apparent as early as 1 month postimplantation in the high-dose WA rats, well before any overt signs of tumor development. These results point out the need for further studies investigating the health effects of tungsten and tungsten-based alloys. Key words: cobalt, embedded fragment, nickel, rat, rhabdomyosarcoma, tungsten, tungsten alloy. Environ Health Perspect 113: 729-734 (2005) . doi:10.1289/ehp.7791 available via http://dx.doi.org/ [Online 15 February 2005]
Address correspondence to J. F. Kalinich, Heavy Metals Research Team, AFRRI, 8901 Wisconsin Ave., Bethesda, MD 20889-5603 USA. Telephone: (301) 295-9242. Fax: (301) 295-0292. E-mail: kalinich@afrri.usuhs.mil This work was supported in part by U.S. Army Medical Research and Materiel Command grant DAMD17-01-1-0821. The views and opinions expressed in this report are strictly those of the authors and should not be construed as official U.S. Department of Defense policy. The authors declare they have no competing financial interests. Received 24 November 2004 ; accepted 14 February 2005.
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