Accumulation of Cd(II) in the CNS depending on the route of administration: Intraperitoneal, intratracheal, or intranasal

Abstract

The uptake and subsequent neuronal transport of certain heavy metals in the olfactory mucosa may be a major means by which these compounds gain access to the CNS. To contrast olfactory versus blood-borne routes of exposure, three groups (n = 4) of adult Long-Evans rats were exposed to solutions of radiolabeled CdCl₂. Exposure was by one of three routes: unilateral intranasal instillation (IN), intratracheal lavage (IT), or intraperitoneal injection (ip). The dose level for the intranasal route was 30 μl of 1 μM CdCl₂ labeled with 1 μCi ¹⁰⁹Cd. For IT and ip, the dose was 30 μl of 1 μM CdCl₂ diluted to 300 μl in saline and labeled with 1 μCi ¹⁰⁹Cd. Rats were euthanized 24 hr after exposure, tissue samples were taken, and radioactivity was counted. Cd levels were low in the olfactory bulbs of rats exposed either intratracheally or intraperitoneally. However, in rats intranasally exposed, Cd levels were nearly 40× higher in olfactory bulbs ipsilateral to the exposed side than in those on the contralateral side. With all routes of exposure, Cd levels in brain samples were only slightly elevated. These results suggest that for certain airborne toxicants, especially those that are excluded from the CNS by the blood-brain barrier, the olfactory system may provide a direct route of entry into the CNS.