Inhaled solid ultrafine particles (UFP) are efficiently translocated via neuronal nasolfactory pathways.
Feikert-T; Mercer-P; Corson-N; Gelein-R; Opanashuk-L; Elder-A; Silva-V; Carter-J; Maynard-A; Finkelstein-J; Oberdorster-G
Toxicologist 2004 Mar; 78(S-1):435-436
Clearance pathways for inhaled solid UFP (<100 nm) depositing in the respiratory tract include their translocation to extrapulmonary sites. Our previous results in rats with inhaled ultrafine carbon particles suggested that nasally-deposited solid UFP may be taken up by olfactory rods in the olfactory nasal mucosa and translocated along the olfactory dendrites and axons. Olfactory nerve translocation has been well demonstrated for inhaled soluble metal compounds. In order to test this hypothesis for solid UFP and determine the significance for causing health effects we exposed groups of rats to ultrafine MnO 2 particles (31 nm) in whole-body exposure chambers for up to 11 days, with either both nostrils patent or the right nostril occluded. AAS analysis of Mn in lung, liver, kidney, olfactory bulb and several other brain regions as well as Atlas gene array and antibody protein array analyses of these brain regions were performed. After 11 days of exposure, Mn concentrations in the olfactory bulb were 3.6-fold higher whereas lung Mn concentrations only doubled, and there were also significant increases of Mn in striatum and frontal cortex and cerebellum. With the right nostril occluded, Mn accumulated only in the olfactory bulb of the side with the patent nostril. TN mRNA and protein were significantly increased about 30-fold in the olfactory bulb and showed also increases in the other brain regions associated with increased Mn levels. MIP-2 and NCAM mRNA were also significantly increased. We conclude that the olfactory neuronal pathway is very efficient for translocating inhaled solid UFP to the CNS and that translocated UFP, depending on their chemistry, can cause serious adverse effects. We suggest further that despite differences between the human and rodent olfactory systems this pathway is likely to be operative in humans as well.
Pulmonary-system-disorders; Respiratory-system-disorders; Laboratory-animals; Animal-studies; Animals; Metal-compounds; Exposure-levels; Nanotechnology
Research Tools and Approaches: Exposure Assessment Methods
The Toxicologist. Society of Toxicology 43nd Annual Meeting and ToxExpo, March 21-25, 2004, Baltimore, Maryland