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

Journal Article · Wed Feb 15 04:00:00 EST 2012 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/J.TAAP.2011.12.008· OSTI ID:22215242

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.

• OSTI ID: 22215242
• Journal Information: Toxicology and Applied Pharmacology, Journal Name: Toxicology and Applied Pharmacology Journal Issue: 1 Vol. 259; ISSN TXAPA9; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

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