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Title: Pulmonary toxicity after exposure to military-relevant heavy metal tungsten alloy particles

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 24 h 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.more » 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. -- Highlights: ► Intratracheal instillation of W–Ni–Co and W–Ni–Fe induces lung inflammation in rats. ► W–Ni–Co and W–Ni–Fe alter expression of oxidative stress and toxicity genes. ► W–Ni–Co induces a greater oxidative burst response than W–Ni–Fe in lung macrophages.« less

Authors:
 [1];  [1];  [2];  [2]
  1. Department of General Surgery, Tripler Army Medical Center, Honolulu, HI 96859 (United States)
  2. Department of Clinical Investigation, Tripler Army Medical Center, Honolulu, HI 96859 (United States)
Publication Date:
OSTI Identifier:
22215242
Resource Type:
Journal Article
Journal Name:
Toxicology and Applied Pharmacology
Additional Journal Information:
Journal Volume: 259; Journal Issue: 1; Other Information: Copyright (c) 2011 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0041-008X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; COBALT; DEPLETED URANIUM; HEAVY METALS; INFLAMMATION; INJURIES; IRON; LACTATE DEHYDROGENASE; LUNGS; MACROPHAGES; NEOPLASMS; NEUTROPHILS; NICKEL; NITRIC OXIDE; NITROGEN; OXIDATION; POLYPEPTIDES; RATS; TOXICITY; TUNGSTEN; TUNGSTEN ALLOYS

Citation Formats

Roedel, Erik Q., E-mail: Erik.Roedel@amedd.army.mil, Cafasso, Danielle E., E-mail: Danielle.Cafasso@amedd.army.mil, Lee, Karen W.M., E-mail: Karen.W.Lee@amedd.army.mil, and Pierce, Lisa M., E-mail: Lisa.Pierce@amedd.army.mil. Pulmonary toxicity after exposure to military-relevant heavy metal tungsten alloy particles. United States: N. p., 2012. Web. doi:10.1016/J.TAAP.2011.12.008.
Roedel, Erik Q., E-mail: Erik.Roedel@amedd.army.mil, Cafasso, Danielle E., E-mail: Danielle.Cafasso@amedd.army.mil, Lee, Karen W.M., E-mail: Karen.W.Lee@amedd.army.mil, & Pierce, Lisa M., E-mail: Lisa.Pierce@amedd.army.mil. Pulmonary toxicity after exposure to military-relevant heavy metal tungsten alloy particles. United States. https://doi.org/10.1016/J.TAAP.2011.12.008
Roedel, Erik Q., E-mail: Erik.Roedel@amedd.army.mil, Cafasso, Danielle E., E-mail: Danielle.Cafasso@amedd.army.mil, Lee, Karen W.M., E-mail: Karen.W.Lee@amedd.army.mil, and Pierce, Lisa M., E-mail: Lisa.Pierce@amedd.army.mil. Wed . "Pulmonary toxicity after exposure to military-relevant heavy metal tungsten alloy particles". United States. https://doi.org/10.1016/J.TAAP.2011.12.008.
@article{osti_22215242,
title = {Pulmonary toxicity after exposure to military-relevant heavy metal tungsten alloy particles},
author = {Roedel, Erik Q., E-mail: Erik.Roedel@amedd.army.mil and Cafasso, Danielle E., E-mail: Danielle.Cafasso@amedd.army.mil and Lee, Karen W.M., E-mail: Karen.W.Lee@amedd.army.mil and Pierce, Lisa M., E-mail: Lisa.Pierce@amedd.army.mil},
abstractNote = {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 24 h 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. -- Highlights: ► Intratracheal instillation of W–Ni–Co and W–Ni–Fe induces lung inflammation in rats. ► W–Ni–Co and W–Ni–Fe alter expression of oxidative stress and toxicity genes. ► W–Ni–Co induces a greater oxidative burst response than W–Ni–Fe in lung macrophages.},
doi = {10.1016/J.TAAP.2011.12.008},
url = {https://www.osti.gov/biblio/22215242}, journal = {Toxicology and Applied Pharmacology},
issn = {0041-008X},
number = 1,
volume = 259,
place = {United States},
year = {2012},
month = {2}
}