- 2:20 PM

A Review of the Toxicity of 0.1 to 1 Micron Aerodynamic Diameter Airborne Particles

John Andrew Pickrell1, Larry E. Erickson2, Mermagya Dhakal1, Sigifredo D. Castro2, Ken J. Klabunde3, R. G. Maghirang4, and F. W. Oehme1. (1) Diagnostic Medicine/Pathobiology, Kansas State University, Comparative Toxicology Laboratory, 1800 N Denison, Manhattan, KS 66506, (2) Chemical Engineering, Kansas State University, Manhattan, KS 66506, (3) Chemistry, Kansas State University, Mid Campus Drive, Manhattan, KY 66506, (4) Biological and Agricultural Engineering, Kansas State University, Manhattan, KS 66506

Nanoparticles with 1 dimension < 100 nanometers [nm]; 0.1 microns are so small they have different physical properties, but promising applications. For example, a benefit is that airborne nanomaterials (NM) can condense with and clean smoke from the air more quickly than the smoke would settle without assistance. Because of their microcrystalline structure, a higher portion of their molecules are on the surface and may interact with airborne particles. Such properties would predict that NM would make good filters to agglomerate microbes, metal particles and smoke. Parallel to this application are growing concerns that NM that are poorly soluble particles (PSP) NM may enter the body, show biopersistence, travel to target tissue and cause brain, lung, or heart effects at low concentrations. Alternatively, particles that are not PSP would readily dissolve, have minimal biopersistence, and represent minimal to negligible danger to exposed animals or people. Because manufactured NM are of great benefit, we have great responsibility to consider their potential to produce adverse effects. As an example, metal oxides represent a gradient of solubility with magnesium oxide (MgO) being poorly soluble, and titanium dioxide (TiO2) having almost no solubility in aqueous media. Bicarbonate in aqueous media increases the solubility of MgO. We did not find any reports of soluble titanium carbonates in nature; titanium chloride has low solubility in water. Nanoparticles that enter the brain through the olfactory bulbs have been shown to lie along the optic tracts; as yet there are no reports of their entry into the deep brain. Metal oxides which are soluble may enter deep brain structures as metal ions. At low concentrations metals such as magnesium will act as essential metal ions. Metal oxide NM can be inhaled; a small fraction of them will be sufficiently small to go to deep lung (eg. NA MgO ~8-30% by mass), while a smaller fraction will avoid phagocytosis (~1-5% by mass). However, NA MgO is rapidly dissolved in a lung simulant fluid containing physiological amounts of bicarbonate. NM that avoid phagocytosis are small enough to leave the lung, enter the vascular system and create inflammation of previously damaged atherosclerotic arteries; coronary arteries (CA) are a likely target site. Irritating 21 nm copper nanoparticles are small enough to escape phagocytosis (< 500 nm; 0.5 microns). They have the potential to create such inflammation because CA are directly downstream from the pulmonary artery and aorta. Orally gavaged, soluble cupric chloride nanoparticles caused no damage to the CA vasculature; they were present at high enough concentrations to damage liver, kidney and spleen. Ionic copper and micro copper (17 micron diameter) caused no damage. Microcrystalline size, reflecting surface activity, can lead to respiratory tract injury. By way of comparison, 21 nm TiO2 microcrystals added to tracheal minces, induce increased procollagen production, while 120 nm microcrystals have no effect. Agglomerates of the 21 nm TiO2 particles are ~3,000 nm in diameter, while those of 120 nm monomers are 600 nm in diameter, suggesting that it is microcrystalline, not agglomerate size that induces biochemical fibrosis (increased procollagen and collagen). Natural crystals of silica (silicon dioxide) induced a similar increase in inflammation relative to the amorphous silica with increased aqueous solubility and less biopersistence. Risks of production of metal oxide nanoparticles were compared to that of organic PSP such as carbon black and to other common industrial processes such as battery production and oil refining. Manufactured metal oxide nanoparticles had the lowest potential risk. Carbon black was estimated to have significantly more risk for respiratory disease than preparation of metal oxide nanoparticles. [Research partially funded through the award of a contract from the United States Marine Corps Systems Command to M2 Technologies, Inc.]