Metals and Health: A Clinical Toxicological Perspective on Tungsten and Review of the Literature

Voet, Gijsbert B. van der; Todorov, Todor I.; Centeno, José A.; Jonas, Wayne B.; Ives, John A.; Mullick, Florabel G.

doi:10.7205/milmed.172.9.1002

Cited by 60 publications

(28 citation statements)

References 20 publications

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“…The employment of tungsten-alloys in military ammunition has produced a new route of long-term metal exposures as embedded shrapnels, which can be difficult to remove because of their location and/or small size (van der Voet et al, 2007). This long-term exposure could increase the risk of cancer development in injured individuals.…”

Section: Discussionmentioning

confidence: 99%

In vitro profiling of epigenetic modifications underlying heavy metal toxicity of tungsten-alloy and its components

Verma¹,

Xu²,

Jaiswal³

et al. 2011

Toxicology and Applied Pharmacology

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In vitro profiling of epigenetic modifications underlying heavy metal toxicity of tungsten-alloy and its components" (2011 Tungsten-alloy has carcinogenic potential as demonstrated by cancer development in rats with intramuscular implanted tungsten-alloy pellets. This suggests a potential involvement of epigenetic events previously implicated as environmental triggers of cancer. Here, we tested metal induced cytotoxicity and epigenetic modifications including H3 acetylation, H3-Ser10 phosphorylation and H3-K4 trimethylation. We exposed human embryonic kidney (HEK293), human neuroepithelioma (SKNMC), and mouse myoblast (C2C12) cultures for 1-day and hippocampal primary neuronal cultures for 1-week to 50-200 μg/ml of tungsten-alloy (91% tungsten/6% nickel/3% cobalt), tungsten, nickel, and cobalt. We also examined the potential role of intracellular calcium in metal mediated histone modifications by addition of calcium channel blockers/chelators to the metal solutions. Tungsten and its alloy showed cytotoxicity at concentrations N 50 μg/ml, while we found significant toxicity with cobalt and nickel for most tested concentrations. Diverse cell-specific toxic effects were observed, with C2C12 being relatively resistant to tungsten-alloy mediated toxic impact. Tungsten-alloy, but not tungsten, caused almost complete dephosphorylation of H3-Ser10 in C2C12 and hippocampal primary neuronal cultures with H3-hypoacetylation in C2C12. Dramatic H3-Ser10 dephosphorylation was found in all cobalt treated cultures with a decrease in H3 pan-acetylation in C2C12, SKNMC and HEK293. Trimethylation of H3-K4 was not affected. Both tungsten-alloy and cobalt mediated H3-Ser10 dephosphorylation were reversed with BAPTA-AM, highlighting the role of intracellular calcium, confirmed with 2-photon calcium imaging. In summary, our results for the first time reveal epigenetic modifications triggered by tungsten-alloy exposure in C2C12 and hippocampal primary neuronal cultures suggesting the underlying synergistic effects of tungsten, nickel and cobalt mediated by changes in intracellular calcium homeostasis and buffering.Published by Elsevier Inc.

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Section: Discussionmentioning

confidence: 99%

In vitro profiling of epigenetic modifications underlying heavy metal toxicity of tungsten-alloy and its components

Verma¹,

Xu²,

Jaiswal³

et al. 2011

Toxicology and Applied Pharmacology

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“…However, most of these reports have been on its inhibitive effects on iron, carbon steels, and stainless steels (ferrous metals and alloys) [215,[397][398][399][400][401][402][403][404], with only few reports on tunsgtate inhibition of aluminum corrosion [405][406][407][408]. Though the toxicity of tungsten/tungstate have hitherto been considered to be low [409][410][411][412], recent reports have brought it into scrutiny as an emergent toxicant , and thus the likelihood of tungsten/tungstate use coming under strict regulatory control in the near future is significant.…”

Section: Toxicity Concerns With Respect To Plausible Strategies For Mmentioning

confidence: 99%

The Sealing Step in Aluminum Anodizing: A Focus on Sustainable Strategies for Enhancing Both Energy Efficiency and Corrosion Resistance

2020

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Increasing demands for environmental accountability and energy efficiency in industrial practice necessitates significant modification(s) of existing technologies and development of new ones to meet the stringent sustainability demands of the future. Generally, development of required new technologies and appropriate modifications of existing ones need to be premised on in-depth appreciation of existing technologies, their limitations, and desired ideal products or processes. In the light of these, published literature mostly in the past 30 years on the sealing process; the second highest energy consuming step in aluminum anodization and a step with significant environmental impacts has been critical reviewed in this systematic review. Emphasis have been placed on the need to reduce both the energy input in the anodization process and environmental implications. The implications of the nano-porous structure of the anodic oxide on mass transport and chemical reactivity of relevant species during the sealing process is highlighted with a focus on exploiting these peculiarities, in improving the quality of sealed products. In addition, perspective is provided on plausible approaches and important factors to be considered in developing sealing procedures that can minimize the energy input and environmental impact of the sealing step, and ensure a more sustainable aluminum anodization process/industry.Coatings 2020, 10, 226 2 of 55 sealing methods. Furthermore, the applicability of another hitherto popular sealing process; chromate sealing, is currently limited to essential parts in the aerospace industry due to toxicological, health, and environmental implications traced to Cr(VI) employed in the process [7][8][9][10][11][12][13][14][15][16]. On the other hand, the advantages of another industrially utilized sealing process; the nickel fluoride (cold) sealing process is limited by the toxicity of nickel salts which narrows its range of application, and introduces added costs due to post-sealing wastewater treatments and management [17][18][19][20]. Further efforts at sealing anodized aluminum at temperatures lower than that used in hydrothermal (high temperature) sealing, have led to much variety in the chemical constitution and operating temperatures of sealing baths [21]. On the basis of temperature at which the sealing step is carried out, sealing can be classified into three major categories; high temperature, mid-temperature, and room-temperature or cold sealing. In this work sealing at temperatures from 0 to 40 • C is classified as low temperature sealing, from ≥ 40 • C to 70 • C as intermediate or mid temperature sealing, and sealing at temperatures > 70 • C as high temperature sealing.

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“…However, concern regarding the acute and long-term human health and environmental effects of exposure to lead and DU has forced the military in many countries to explore the possibility of using toxicologically-safer metals with comparable material characteristics. Heavy metal tungsten alloy (HMTA)-based materials (containing 90% to 98% tungsten with some mix of nickel (Ni), iron (Fe), copper (Cu), and/or cobalt (Co)) have therefore been recently introduced as potential replacement metals for military applications [6]. Although the toxicological profiles of many of these separate metals are well known, their internalization as embedded fragments retained in soft tissue is an unusual exposure route which may lead to hitherto unseen toxic effects.…”

Section: Introductionmentioning

confidence: 99%

Embedded Fragments from U.S. Military Personnel—Chemical Analysis and Potential Health Implications

Centeno¹,

Rogers²,

Voet³

et al. 2014

IJERPH

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Background: The majority of modern war wounds are characterized by high-energy blast injuries containing a wide range of retained foreign materials of a metallic or composite nature. Health effects of retained fragments range from local or systemic toxicities to foreign body reactions or malignancies, and dependent on the chemical composition and corrosiveness of the fragments in vivo. Information obtained by chemical analysis of excised fragments can be used to guide clinical decisions regarding the need for fragment removal, to develop therapeutic interventions, and to better anticipate future medical problems from retained fragment related injuries. In response to this need, a new U.S Department of Defense (DoD) directive has been issued requiring characterization of all removed fragments to provide a database of fragment types occurring in combat injuries. Objectives: The objective of this study is to determine the chemical composition of retained embedded fragments removed from injured military personnel, and to relate results to histological findings in tissue adjacent to fragment material. Methods: We describe an approach for the chemical analysis and characterization of retained fragments and adjacent tissues, and include case examples describing fragments containing depleted uranium (DU), tungsten (W), lead (Pb), and non-metal foreign bodies composed of natural and composite materials. Fragments obtained from four patients with penetrating blast wounds to the limbs were studied employing a wide range of chemical and microscopy techniques. Available adjacent tissues from three of the cases were histologically, microscopically, and chemically examined. The physical and compositional properties of the removed foreign material surfaces were examined with energy dispersive x-ray fluorescence spectrometry (EDXRF), scanning electron microscopy (SEM), laser ablation inductively-coupled plasma mass-spectrometry (LA-ICP-MS), and confocal laser Raman microspectroscopy (CLRM). Quantitative chemical analysis of both fragments and available tissues was conducted employing ICP-MS. Results: Over 800 fragments have been characterized and included as part of the Joint Pathology Center Embedded Fragment Registry. Most fragments were obtained from penetrating wounds sustained to the extremities, particularly soft tissue injuries. The majority of the fragments were primarily composed of a single metal such as iron, copper, or aluminum with traces of antimony, titanium, uranium, and lead. One case demonstrated tungsten in both the fragment and the connected tissue, together with lead. Capsular tissue and fragments from a case from the 1991 Kuwait conflict showed evidence of uranium that was further characterized by uranium isotopic ratios analysis to contain depleted uranium. Conclusions: The present study provides a systematic approach for obtaining a full chemical characterization of retained embedded fragments. Given the vast number of combat casualties with retained fragments, it is expected that fragment analysis will ha...

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Metals and Health: A Clinical Toxicological Perspective on Tungsten and Review of the Literature

Cited by 60 publications

References 20 publications

In vitro profiling of epigenetic modifications underlying heavy metal toxicity of tungsten-alloy and its components

In vitro profiling of epigenetic modifications underlying heavy metal toxicity of tungsten-alloy and its components

The Sealing Step in Aluminum Anodizing: A Focus on Sustainable Strategies for Enhancing Both Energy Efficiency and Corrosion Resistance

Embedded Fragments from U.S. Military Personnel—Chemical Analysis and Potential Health Implications

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