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.
"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). "
[Show abstract][Hide abstract] 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.
"For Ni-based restorative alloys, patients undergoing Ni–Cr replacement 1 year ago had a higher level of serum Ni than that of controls.15 Other Ni-based implants have also demonstrated significantly increased Ni concentrations in body fluids after the implantation, such as hip prostheses,29 cardiac device,30 spinal instrumentation31 and tungsten alloy.32 "
[Show abstract][Hide abstract] ABSTRACT: This paper aims to investigate if the dental restoration of nickel-chromium based alloy (Ni-Cr) leads to the enhanced excretions of Ni and Cr in urine. Seven hundred and ninety-five patients in a dental hospital had single or multiple Ni-Cr alloy restoration recently and 198 controls were recruited to collect information on dental restoration by questionnaire and clinical examination. Urinary concentrations of Ni and Cr from each subject were measure by graphite furnace atomic absorption spectrometry. Compared to the control group, the urinary level of Ni was significantly higher in the patient group of <1 month of the restoration duration, among which higher Ni excretions were found in those with either a higher number of teeth replaced by dental alloys or a higher index of metal crown not covered with the porcelain. Urinary levels of Cr were significantly higher in the three patient groups of <1, 1 to <3 and 3 to <6 months, especially in those with a higher metal crown exposure index. Linear curve estimations showed better relationships between urinary Ni and Cr in patients within 6-month groups. Our data suggested significant increased excretions of urinary Ni and Cr after dental restoration. Potential short- and long-term effects of Ni-Cr alloy restoration need to be investigated.International Journal of Oral Science (2013) 5, doi:10.1038/ijos.2013.13; published online 5 April 2013.
International Journal of Oral Science 04/2013; 5(1). DOI:10.1038/ijos.2013.13 · 2.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Significant controversy over the environmental and public health impact of depleted uranium use in the Gulf War and the war in the Balkans has prompted the investigation and use of other materials including heavy metal tungsten alloys (HMTAs) as nontoxic alternatives. Interest in the health effects of HMTAs has peaked since the recent discovery that rats intramuscularly implanted with pellets containing 91.1% tungsten/6% nickel/2.9% cobalt rapidly developed aggressive metastatic tumors at the implantation site. Very little is known, however, regarding the cellular and molecular mechanisms associated with the effects of inhalation exposure to HMTAs despite the recognized risk of this route of exposure to military personnel. In the current study military-relevant metal powder mixtures consisting of 92% tungsten/5% nickel/3% cobalt (WNiCo) and 92% tungsten/5% nickel/3% iron (WNiFe), pure metals, or vehicle (saline) were instilled intratracheally in rats. Pulmonary toxicity was assessed by cytologic analysis, lactate dehydrogenase activity, albumin content, and inflammatory cytokine levels in bronchoalveolar lavage fluid 24h after instillation. The expression of 84 stress and toxicity-related genes was profiled in lung tissue and bronchoalveolar lavage cells using real-time quantitative PCR arrays, and in vitro assays were performed to measure the oxidative burst response and phagocytosis by lung macrophages. Results from this study determined that exposure to WNiCo and WNiFe induces pulmonary inflammation and altered expression of genes associated with oxidative and metabolic stress and toxicity. Inhalation exposure to both HMTAs likely causes lung injury by inducing macrophage activation, neutrophilia, and the generation of toxic oxygen radicals.
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