Thinking outside the lung: alternate routes of nanoparticle exposure.
Nurkiewicz-TR; Stapleton-PG; Minarchick-V; Chen-BT; Cumpston-A; McKinney-W; Frazer-D; Castranova-V
Toxicologist 2012 Mar; 126(Suppl 1):197
Multi-walled carbon nanotubes (MWCNT) are widely used to enhance existing material properties; however, more recently their potential as a drug delivery mechanism and other biomedical applications has been investigated. Studies have traditionally focused on the lung, but other exposure routes may be equally important in this regard. Sprague-Dawley rats were exposed to filtered air (control), aerosolized MWCNT with count mode aerodynamic diameter of 420 nm via a single day 5- hour exposure at concentrations of 4.6 + / - 0.2 mg/m3 which produced calculated pulmonary depositions of 20 + / - 1 microg. Other rats were gavaged 600 microg/rat in a 300 microl sterile saline suspension with 5% FBS. Coronary arterioles from the left anterior descending artery distribution and mesenteric arterioles were isolated for reactivity assessments (approximately 170 microm in diameter) based on responses to transmural pressure and to increasing concentrations of phenylephrine (PE), acetylcholine (Ach), A23187, and spermine NONOate (SPR) 24-hours post MWCNT exposure. There were no significant differences observed between groups or microvascular beds in the endothelium-independent responses to SPR and PE indicating smooth muscle sensitivity to nitric oxide and adrenergic responses were intact in both vascular beds. In the coronary arterioles, reactivity of the exposure groups were significantly different than control with respect to the endothelium-dependent reactivity (ACh, A23187, myogenic response); while, in the mesenteric arterioles ACh and A23187 were significantly different. The gavage and inhalation exposures routes were significantly different at the highest concentration of ACh and show an upward shift in myogenic responsiveness. These findings indicate that the endothelium-dependent microvascular impairments that follow MWCNT exposure via the gut, are equal to or greater than those observed in the lung.
Nanotechnology; Health-hazards; Hazardous-materials; Toxic-materials; Biomedical-engineering; Drugs; Hospital-equipment; Medical-treatment; Medicinal-chemicals; Laboratory-animals; Laboratory-techniques; Laboratory-testing; Aerosol-particles; Air-flow; Particle-aerodynamics; Particle-counters; Exposure-levels; Cardiovascular-system; Heart
The Toxicologist. Society of Toxicology 51st Annual Meeting and ToxExpo, March 11-15, 2012, San Francisco, California