Acute sodium tungstate inhalation is associated with minimal olfactory transport of tungsten (188W) to the rat brain

Olfactory transport of represents an important mechanism for direct delivery of certain metals to the central nervous system (CNS). The objective of this study was to determine whether inhaled tungsten (W) undergoes olfactory uptake and transport to the rat brain. Male, 16-week-old, Sprague–Dawley rats underwent a single, 90-min, nose-only exposure to a Na2188WO4 aerosol (256mgW/m3). Rats had the right nostril plugged to prevent nasal deposition of 188W on the occluded side. The left and right sides of the nose and brain, including the olfactory pathway and striatum, were sampled at 0, 1, 3, 7, and 21 days post-exposure. Gamma spectrometry (n=7 rats/time point) was used to compare the levels of 188W found on the left and right sides of the nose and brain and blood to determine the contribution of olfactory uptake to brain 188W levels. Respiratory and olfactory epithelial samples from the side with the occluded nostril had significantly lower end-of-exposure 188W levels confirming the occlusion procedure. Olfactory bulb, olfactory tract/tubercle, striatum, cerebellum, rest of brain 188W levels paralleled blood 188W concentrations at approximately 2–3% of measured blood levels. Brain 188W concentrations were highest immediately following exposure, and returned to near background concentrations within 3 days. A statistically significant difference in olfactory bulb 188W concentration was seen at 3 days post-exposure. At this time, 188W concentrations in the olfactory bulb from the side ipsilateral to the unoccluded nostril were approximately 4-fold higher than those seen in the contralateral olfactory bulb. Our data suggest that the concentration of 188W in the olfactory bulb remained low throughout the experiment, i.e., approximately 1–3% of the amount of tungsten seen in the olfactory epithelium suggesting that olfactory transport plays a minimal role in delivering tungsten to the rat brain.