title: The relationship of particle size to olfactory nerve uptake of a non-soluble form of manganese into brain.
abstract: The essential element, manganese, can produce chronic neuromotor impairment related to basal ganglia (BG) damage when it is presented in excessive quantities. The uptake and elimination patterns of manganese following ingestion have been well studied and, under normal conditions, excretion appears to keep manganese levels under tight control. Less is known about inhalation exposure, but it has been proposed that the lung might serve as a long-term reservoir for manganese transport into blood. Recent data suggest that a third route of exposure, transport by the olfactory nerve directly to the brain, might have importance in toxicology since such a route would bypass liver uptake and biliary excretion of manganese. In this study, we sought to determine how particle size and the use of a poorly soluble form of manganese might influence net systemic absorption of manganese dust and the potential role of the olfactory nerve in transport of manganese dioxide. Rats were exposed in nose-only exposure chambers to manganese dioxide (MnO2) aerosols of 1.3 and 18 microm mass median aerodynamic diameter (MMAD). The concentration of aerosols was kept constant at 3 mg/m3 as Mn. Following 15 days of exposure (five times per week for 3 weeks), rats were euthanized and tissues harvested for manganese determination carried out by graphite furnace atomic absorption spectroscopy. Small-particle MnO2 exposure resulted in an elevation in olfactory bulb manganese concentration, presumably through uptake by the olfactory nerve, but the effect was highly variable. While small increases in cortical and neostriatal manganese levels were also observed in these rats, they did not reach statistical significance. By contrast, there was no evidence of olfactory nerve MnO2 uptake in rats receiving the large-particle exposure.
authors.affiliation: Department of Occupational and Environmental Health and Pharmaceutical Sciences, College of Pharmacy, Oklahoma Center for Toxicology, University of Oklahoma Health Sciences Center, Oklahoma City 73190, USA. fechter@ouhsc.edu
authors.forename: Laurence D
authors.initials: LD
authors.lastname: Fechter
authors.forename: David L
authors.initials: DL
authors.lastname: Johnson
authors.forename: Robert A
authors.initials: RA
authors.lastname: Lynch
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D001921:Brain / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D017895:Manganese Compounds / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D009832:Olfactory Nerve / Q000378:metabolism*; D010316:Particle Size; D051381:Rats; D020318:Rats, Long-Evans; D012995:Solubility
chemical_list: D017895:Manganese Compounds