Embedded Weapons-Grade Tungsten Alloy Shrapnel Rapidly Induces Metastatic High-Grade Rhabdomyosarcomas in F344 Rats

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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.

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To integrate recent understandings of the mechanisms of genotoxicity and carcinogenicity of the different cobalt compounds. A narrative review of the studies published since the last IARC assessment in 1991 (genotoxicity, experimental carcinogenesis, and epidemiology). Two different mechanisms of genotoxicity, DNA breakage induced by cobalt metal and especially hard metal particles, and inhibition of DNA repair by cobalt (II) ions contribute to the carcinogenic potential of cobalt compounds. There is evidence that soluble cobalt (II) cations exert a genotoxic and carcinogenic activity in vitro and in vivo in experimental systems but evidence in humans is lacking. Experimental data indicate some evidence of a genotoxic potential for cobalt metal in vitro in human lymphocytes but there is no evidence available of a carcinogenic potential. There is evidence that hard metal particles exert a genotoxic and carcinogenic activity in vitro and in human studies, respectively. There is insufficient information for cobalt oxides and other compounds. Although many areas of uncertainty remain, an assessment of the carcinogenicity of cobalt and its compounds requires a clear distinction between the different compounds of the element and needs to take into account the different mechanisms involved.

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Author and article information

Journal

Journal ID (nlm-ta): Environ Health Perspect

Title: Environmental Health Perspectives

Publisher: National Institue of Environmental Health Sciences

ISSN (Print): 0091-6765

Publication date (Print): June 2005

Publication date (Electronic): 15 February 2005

Volume: 113

Issue: 6

Pages: 729-734

Affiliations

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

Author notes

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.

Article

Publisher ID: ehp0113-000729

DOI: 10.1289/ehp.7791

PMC ID: 1257598

PubMed ID: 15929896

SO-VID: 02e1b67e-047d-42a4-bbdd-e7c91f21c3e5

Copyright © This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original DOI.

Embedded Weapons-Grade Tungsten Alloy Shrapnel Rapidly Induces Metastatic High-Grade Rhabdomyosarcomas in F344 Rats

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Most cited references 30

Arsenic: health effects, mechanisms of actions, and research issues.

Nickel carcinogenesis.

Update on the genotoxicity and carcinogenicity of cobalt compounds.

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