Pharmacokinetics Of Radiolabeled Tungsten (W-188) In Male Sprague-Dawley Rats Following Acute Sodium Tungstate Inhalation

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 (WO 4) 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 mu m) containing 256 mg W/m(3) as radiolabeled sodium tungstate ((Na2WO4)-W-188). W-188 tissue concentrations were determined at 0, 1, 3, 7, and 21 days postexposure by gamma spectrometry. The thyroid and urine had the highest W-188 levels postexposure, and urinary excretion was the primary route of W-188 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 W-188. Data from this study can be used for development and refinement of pharmacokinetic models for tungsten inhalation exposure in environmental and occupational settings.