U.S. Environmental Protection Agency


Date of this Version



NeuroToxicology 33 (2012) 838–841



Copyright 2011 Elsevier Inc. All rights reserved.


The effects of inhaled particles have focused heavily on the respiratory and cardiovascular systems. Most studies have focused on inhaled metals, whereas less information is available for other particle types regarding the effects on the brain and other extra-pulmonary organs. We review here the key available literature on nanoparticle uptake and transport through the olfactory pathway, the experimental data from animal and in vitro studies, and human epidemiological observations. Nanoparticles (<0.1µm in one dimension) may easily reach the brain from the respiratory tract via sensory neurons and transport from the distal alveoli into the blood or lymph as free particles or inside phagocytic cells. These mechanisms and subsequent biologic responses may be influenced by the chemical composition of inhaled particles. Animal studies with ambient particulate matter and certain other particles show alterations in neuro-inflammatory markers of oxidative stress and central neurodegeneration. Human observations indicate motor, cognitive, and behavioral changes especially after particulate metal exposure in children. Exposure to co-pollutants and/or underlying disease states could also impact both the biokinetics and effects of airborne particles in the brain. Data are needed from the areas of inhalation, neurology, and metal toxicology in experimental and human studies after inhalation exposure. An increased understanding of the neurotoxicity associated with air pollution exposure is critical to protect susceptible individuals in the workplace and the general population.