The central nervous system (CNS) is partially protected from circulating toxicants by the blood-brain barrier. However, for xenobiotics which are excluded from the CNS the olfactory pathway provides an alternative route of passage into the brain. Thus, in the olfactory epithelium the primary olfactory neurons have dendrites in contact with the nasal lumen and axons which project to the olfactory bulbs. Materials which come into contact with the olfactory epithelium may be taken up in the primary olfactory neurons and transported to the olfactory bulbs and even further into other areas of the brain. The article deals with the uptake and transport of metals in the olfactory system. Metals discussed are mainly manganese, cadmium, nickel, aluminum, zinc, cobalt and mercury. Among these metals manganese has a unique capacity to be taken up via the olfactory pathway. Thus, following transport along the primary olfactory neurons to the olfactory bulbs manganese continues via secondary and tertiary olfactory neurons and further connections to all parts of the brain and even into the spinal cord. Cadmium is transported along the axons of the primary olfactory neurons to the olfactory bulb, but this metal appears unable to leave the terminal arborizations of the axons in the glomeruli of the bulb. Studies with nickel, zinc, cobalt and mercury indicate that these metals are transported along the primary olfactory neurons and accumulated in the olfactory nerve layer and the glomerulular layer of the bulbs. In addition, low levels of these metals leave the terminations of the primary olfactory neurons. There is evidence that mercury also may undergo axonal transport in the primary olfactory neurons following uptake in these neurons from the systemic circulation. This may be a part of a more general ability of mercury to be taken up in neurons with access to the systemic circulation and reach the CNS via transport in these neurons. There is evidence that aluminum is transported along the olfactory pathway, but the fate of this metal in the olfactory system is not yet known in detail. The olfactory pathway is a route by which metals may circumvent the blood-brain barrier and reach the central nervous system. The possibility that uptake and transport of metals in the olfactory pathways may induce olfactory dysfunction and neurotoxicity should be taken into account in risk assessments of occupational metal exposure via inhalation.
