Article

Urinary and Serum Metal Levels as Indicators of Embedded Tungsten Alloy Fragments

Armed Forces Radiobiology Research Institute, Uniformed Services University, Bethesda, MD 20889-5603, USA.
Military medicine (Impact Factor: 0.77). 09/2008; 173(8):754-8. DOI: 10.7205/MILMED.173.8.754
Source: PubMed

ABSTRACT

Novel metal formulations are being used with increasing frequency on the modern battlefield. In many cases the health effects of these materials are not known, especially when they are embedded as fragments. Imaging techniques, although useful for determining location, provide no information regarding the composition of embedded fragments. In this report, we show that laboratory rats implanted with weapons-grade tungsten alloy (tungsten, nickel, and cobalt) pellets demonstrate significant increases in both urinary and serum levels of tungsten, nickel, and cobalt, which indicates that such measurements can provide information on the composition of embedded fragments. We also propose that, in addition to the requirements promulgated by the recent directive on analysis of metal fragments removed from Department of Defense personnel (Health Affairs policy 07-029), urine and blood/serum samples should be collected from personnel and analyzed for metal content. Such measurements could yield information on the composition of retained fragments and provide the basis for further treatment options.

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Available from: John F Kalinich, Dec 21, 2015
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    • "In rat leg muscle, WNiFe pellets were resistant to corrosion and did not cause tumors; by contrast, WNiCo was extensively corroded, with aggressively metastasizing tumors seen within six months [17] [19]. In these studies, the impact of high serum levels of W, Ni, and Co [13] on the brain was not assessed. However, it has recently been hypothesized that translocation of metals to the brain could potentially exacerbate pre-existing traumatic brain injury [12]. "
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    ABSTRACT: There is increasing evidence that metals have a role in the etiology of diverse neurological diseases. This study used PC12 cells as an in vitro model to examine the toxicity of tungsten alloys that have important military applications. Initially, the relative concentrations of tungsten (W), nickel (Ni), and cobalt (Co) mobilized from pellets of a weapons-grade tungsten alloy incubated in physiologically relevant solutions were determined. Dosing solutions of soluble metal salts that were equivalent in ratio to those mobilized from these alloy pellets were used to treat nerve growth factor (NGF) differentiated PC12 cells. Treatments consisted of single (W, Ni or Co), paired (W/Ni, W/Co or Ni/Co) or complete (W/Ni/Co) metal exposures for 24 h followed by measurement of cytotoxicity, viability, and microarray analysis to examine their impact on survival and viability, global gene expression, and biological processes. Gene expression changed dramatically with addition of NGF. Addition of Ni or Co either singly or in combination further impacted gene expression. An observed additive effect of Ni and Co on gene expression was unaffected by the addition of W. The work showed that tungsten, as found in this tungsten alloy, had minimal relative toxicity as compared to the other alloy components when used either alone or in combination.
    Full-text · Article · Dec 2015 · Toxicology Reports
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    • "In rat leg muscle, WNiFe pellets were resistant to corrosion and did not cause tumors; by contrast, WNiCo was extensively corroded, with aggressively metastasizing tumors seen within six months [17] [19]. In these studies, the impact of high serum levels of W, Ni, and Co [13] on the brain was not assessed. However, it has recently been hypothesized that translocation of metals to the brain could potentially exacerbate pre-existing traumatic brain injury [12]. "

    Full-text · Article · Nov 2015 · Toxicology Reports
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    • "Furthermore, WNC 91–6–3 itself has also been investigated and, when implanted into the thigh muscles of F344 rats all animals developed aggressive rhabdomyosarcomas that metastasized to the lung within 4 to 5 months (Kalinich et al., 2005). It is believed that the mechanism of toxicity of these materials is related to preferential dissolution of the binding alloy into biological fluids resulting in the release of high concentrations of nickel and cobalt ions, which are detectable in urine of rats following implantation with pellets of alloy WNC 91–6–3 (Kalinich et al., 2008; Schuster et al., 2012). WNF 97–2–1 pellets in contrast do not contain cobalt and also display far less corrosion in rat muscles , leading to lower concentrations of metals detectable in urine and no elevated cancer rate (Schuster et al., 2012). "
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    ABSTRACT: The tungsten alloy 91% tungsten, 6% nickel and 3% cobalt (WNC 91-6-3) induces rhabdomyosarcoma when implanted into rat thigh muscle. To investigate whether this effect is species-specific human HSkMc primary muscle cells were exposed to WNC 91-6-3 particles and responses were compared with those from a rat skeletal muscle cell line (L6-C11). Toxicity was assessed by the adenylate kinase assay and microscopy, DNA damage by the Comet assay. Caspase 3 enzyme activity was measured and oligonucleotide microarrays were used for transcriptional profiling. WNC 91-6-3 particles caused toxicity in cells adjacent to the particles and also increased DNA strand breaks. Inhibition of caspase 3 by WNC 91-6-3 occurred in rat but not human cells. In both rat and human cells, the transcriptional response to WNC 91-6-3 showed repression of transcripts encoding muscle-specific proteins with induction of glycolysis, hypoxia, stress responses and transcripts associated with DNA damage and cell death. In human cells, genes encoding metallothioneins were also induced, together with genes related to angiogenesis, dysregulation of apoptosis and proliferation consistent with pre-neoplastic changes. An alloy containing iron, WNF 97-2-1, which is non-carcinogenic in vivo in rats, did not show these transcriptional changes in vitro in either species while the corresponding cobalt-containing alloy, WNC 97-2-1 elicited similar responses to WNC 91-6-3. Tungsten alloys containing both nickel and cobalt therefore have the potential to be carcinogenic in man and in vitro assays coupled with transcriptomics can be used to identify alloys, which may lead to tumour formation, by dysregulation of biochemical processes.
    Full-text · Article · Jan 2015 · Toxicology and Applied Pharmacology
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