Studies in monkeys with intranasally instilled gold ultrafine particles (UFPs; < 100 nm) and
in rats with inhaled carbon UFPs suggested that
solid UFPs deposited in the nose travel along the olfactory nerve to
the olfactory bulb.
To determine if olfactory translocation occurs for other solid metal UFPs
and assess potential health effects, we exposed groups of rats to manganese (Mn) oxide
UFPs (30 nm; ~ 500 μg/m3) with either both nostrils patent or the right nostril occluded. We analyzed
Mn in lung, liver, olfactory bulb, and other brain regions, and
we performed gene and protein analyses.
After 12 days of exposure with both nostrils patent, Mn concentrations
in the olfactory bulb increased 3.5-fold, whereas lung Mn concentrations
doubled; there were also increases in striatum, frontal cortex, and
cerebellum. Lung lavage analysis showed no indications of lung inflammation, whereas
increases in olfactory bulb tumor necrosis factor-α mRNA (~ 8-fold) and
protein (~ 30-fold) were found after 11 days of
exposure and, to a lesser degree, in other brain regions with increased
Mn levels. Macrophage inflammatory protein-2, glial fibrillary acidic
protein, and neuronal cell adhesion molecule mRNA were also increased
in olfactory bulb. With the right nostril occluded for a 2-day exposure, Mn
accumulated only in the left olfactory bulb. Solubilization of
the Mn oxide UFPs was < 1.5% per day.
We conclude that the olfactory neuronal pathway is efficient for translocating
inhaled Mn oxide as solid UFPs to the central nervous system and
that this can result in inflammatory changes. We suggest that despite
differences between human and rodent olfactory systems, this pathway
is relevant in humans.