title: Acute sodium tungstate inhalation is associated with minimal olfactory transport of tungsten (188W) to the rat brain.
abstract: 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 Na(2)(188)WO(4) aerosol (256 mg W/m(3)). Rats had the right nostril plugged to prevent nasal deposition of (188)W 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 (188)W found on the left and right sides of the nose and brain and blood to determine the contribution of olfactory uptake to brain (188)W levels. Respiratory and olfactory epithelial samples from the side with the occluded nostril had significantly lower end-of-exposure (188)W levels confirming the occlusion procedure. Olfactory bulb, olfactory tract/tubercle, striatum, cerebellum, rest of brain (188)W levels paralleled blood (188)W concentrations at approximately 2-3% of measured blood levels. Brain (188)W concentrations were highest immediately following exposure, and returned to near background concentrations within 3 days. A statistically significant difference in olfactory bulb (188)W concentration was seen at 3 days post-exposure. At this time, (188)W 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 (188)W 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.
authors.affiliation: Colgate-Palmolive Company, Piscataway, NJ, United States.
authors.forename: Pheona M
authors.initials: PM
authors.lastname: Radcliffe
authors.forename: Ayodele O
authors.initials: AO
authors.lastname: Olabisi
authors.forename: Dean J
authors.initials: DJ
authors.lastname: Wagner
authors.forename: Teresa
authors.initials: T
authors.lastname: Leavens
authors.forename: Brian A
authors.initials: BA
authors.lastname: Wong
authors.forename: Melanie F
authors.initials: MF
authors.lastname: Struve
authors.forename: Gail D
authors.initials: GD
authors.lastname: Chapman
authors.forename: Erin R
authors.initials: ER
authors.lastname: Wilfong
authors.forename: David C
authors.initials: DC
authors.lastname: Dorman
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols; D000818:Animals; D003342:Corpus Striatum / Q000378:metabolism*; D008297:Male; D009833:Olfactory Pathways / Q000378:metabolism*; D010902:Pituitary Gland / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution; D017973:Tungsten Compounds / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D000336:Aerosols; D017973:Tungsten Compounds; C025399:sodium tungstate(VI); C045951:tungstate