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Embedded Weapons-Grade Tungsten Alloy Shrapnel Rapidly Induces Metastatic High-Grade Rhabdomyosarcomas in F344 Rats
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...
Autores principales: | , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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National Institue of Environmental Health Sciences
2005
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1257598/ https://www.ncbi.nlm.nih.gov/pubmed/15929896 http://dx.doi.org/10.1289/ehp.7791 |
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author | Kalinich, John F. Emond, Christy A. Dalton, Thomas K. Mog, Steven R. Coleman, Gary D. Kordell, Jessica E. Miller, Alexandra C. McClain, David E. |
author_facet | Kalinich, John F. Emond, Christy A. Dalton, Thomas K. Mog, Steven R. Coleman, Gary D. Kordell, Jessica E. Miller, Alexandra C. McClain, David E. |
author_sort | Kalinich, John F. |
collection | PubMed |
description | 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. |
format | Text |
id | pubmed-1257598 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2005 |
publisher | National Institue of Environmental Health Sciences |
record_format | MEDLINE/PubMed |
spelling | pubmed-12575982005-11-08 Embedded Weapons-Grade Tungsten Alloy Shrapnel Rapidly Induces Metastatic High-Grade Rhabdomyosarcomas in F344 Rats Kalinich, John F. Emond, Christy A. Dalton, Thomas K. Mog, Steven R. Coleman, Gary D. Kordell, Jessica E. Miller, Alexandra C. McClain, David E. Environ Health Perspect Research 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. National Institue of Environmental Health Sciences 2005-06 2005-02-15 /pmc/articles/PMC1257598/ /pubmed/15929896 http://dx.doi.org/10.1289/ehp.7791 Text en http://creativecommons.org/publicdomain/mark/1.0/ Publication of EHP lies in the public domain and is therefore without copyright. All text from EHP may be reprinted freely. Use of materials published in EHP should be acknowledged (for example, ?Reproduced with permission from Environmental Health Perspectives?); pertinent reference information should be provided for the article from which the material was reproduced. Articles from EHP, especially the News section, may contain photographs or illustrations copyrighted by other commercial organizations or individuals that may not be used without obtaining prior approval from the holder of the copyright. |
spellingShingle | Research Kalinich, John F. Emond, Christy A. Dalton, Thomas K. Mog, Steven R. Coleman, Gary D. Kordell, Jessica E. Miller, Alexandra C. McClain, David E. Embedded Weapons-Grade Tungsten Alloy Shrapnel Rapidly Induces Metastatic High-Grade Rhabdomyosarcomas in F344 Rats |
title | Embedded Weapons-Grade Tungsten Alloy Shrapnel Rapidly Induces Metastatic High-Grade Rhabdomyosarcomas in F344 Rats |
title_full | Embedded Weapons-Grade Tungsten Alloy Shrapnel Rapidly Induces Metastatic High-Grade Rhabdomyosarcomas in F344 Rats |
title_fullStr | Embedded Weapons-Grade Tungsten Alloy Shrapnel Rapidly Induces Metastatic High-Grade Rhabdomyosarcomas in F344 Rats |
title_full_unstemmed | Embedded Weapons-Grade Tungsten Alloy Shrapnel Rapidly Induces Metastatic High-Grade Rhabdomyosarcomas in F344 Rats |
title_short | Embedded Weapons-Grade Tungsten Alloy Shrapnel Rapidly Induces Metastatic High-Grade Rhabdomyosarcomas in F344 Rats |
title_sort | embedded weapons-grade tungsten alloy shrapnel rapidly induces metastatic high-grade rhabdomyosarcomas in f344 rats |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1257598/ https://www.ncbi.nlm.nih.gov/pubmed/15929896 http://dx.doi.org/10.1289/ehp.7791 |
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