Pharmacokinetics of radiolabeled tungsten (¹⁸⁸W) in male Sprague-Dawley rats following acute sodium tungstate inhalation

Abstract

Aerosol cloud formation may occur when certain tungsten munitions strike hard targets, placing military personnel at increased risk of exposure. Although the pharmacokinetics of various forms of tungsten have been studied in animals following intravenous and oral administration, tungsten disposition following inhalation remains incompletely characterized. The objective of this study was to evaluate the pharmacokinetics of inhaled tungstate (WO₄) in rats. Male, 16-wk-old, CD rats (n = 7 rats/time point) underwent a single, 90-min, nose-only exposure to an aerosol (mass median aerodynamic diameter [MMAD] 1.50 μm ) containing 256 mg W/m³ as radiolabeled sodium tungstate (Na₂¹⁸⁸WO₄). ¹⁸⁸W tissue concentrations were determined at 0, 1, 3, 7, and 21 days postexposure by gamma spectrometry. The thyroid and urine had the highest ¹⁸⁸W levels postexposure, and urinary excretion was the primary route of ¹⁸⁸W elimination. The pharmacokinetics of tungsten in most tissues was best described with a two-compartment pharmacokinetic model with initial phase half-lives of approximately 4 to 6 h and a longer terminal phase with half-lives of approximately 6 to 67 days. The kidney, adrenal, spleen, femur, lymph nodes, and brain continued to accumulate small amounts of tungsten as reflected by tissue:blood activity ratios that increased throughout the 21-day period. At day 21 all tissues except the thyroid, urine, lung, femur, and spleen had only trace levels of ¹⁸⁸W. Data from this study can be used for development and refinement of pharmacokinetic models for tungsten inhalation exposure in environmental and occupational settings.

Keywords::

• Inhalation
• kinetics
• tungsten

Acknowledgements

The authors thank the Animal Care Unit and Necropsy staff at The Hamner. We express special thanks to Horace Parkinson and Trista Kohel for their assistance during necropsy. Special thanks to Elise Barber for her assistance making nose plugs. Thanks to Kristen Attard for her assistance with the aerosol generation system and necropsy set ups. This work was supported by the Office of Naval Research reimbursable Work Unit number 60761. The views expressed in this article are those of the authors and do not reflect the official policy or position of the Department of the Navy, Department of Defense, or the U.S. government. This article is approved for public release, distribution unlimited. Some authors are military service members (or employees of the U.S. government). This work was prepared as part of their official duties. Title 17 U.S.C. §105 provides that “Copyright protection under this title is not available for any work of the United States Government.” Title 17 U.S.C. §101 defines a U.S. government work as a work prepared by a military service member or employee of the U.S. government as part of that person’s official duties.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.