Multi-walled carbon nanotubes (MWCNT) and fine crystalline silica are largely used in the manufacture of composites and as blasting abrasives. While the widespread application and economic benefits of manufacturing such materials are highly promising, their adverse effects on the nervous system have not been fully investigated. Populations at greatest risk for exposure are industrial workers involved in the manufacturing, handling or utilization of such materials. Here, we evaluated the potential neurotoxic effects of exposure to MWCNT (67nm diameter, 5-13µm length) and silica (<2µm) in a murine model. Exposure (by pharyngeal aspiration) of mice to MWCNT (10, 20 or 40µg/mouse) or silica (1mg/mouse) elicited neuroinflammation in discrete brain areas. Specifically, the expression of CCL2, TNFá and IL6 increased (2 to 10-fold; P<0.05) in the olfactory bulb, hippocampus and frontal cortex, within 24h following exposure. This inflammatory outburst is a consequence of microglial activation, in response to perturbation of the neuronal microenvironment and function. Silica also induced the expression of IL1alpha, OSM, TLR2 and FGF2, effects not observed with MWCNT at the doses tested. In addition, both MWCNT and silica induced region-selective expression of metallothioneins I and II (>2-fold, P<0.05), metal binding proteins that are regulated by inflammatory stress signals and afford protection against oxidative injury. Whether the region-specific neurotoxicity observed following pharyngeal aspiration is due to systemic responses or possible redistribution of these materials to the brain remains enigmatic. In summary, our findings indicate that exposure to engineered nanoand fine particles can elicit neuroinflammatory changes.
Physical-reactions; Risk-analysis; Risk-factors; Dose-response; Chemical-analysis; Chemical-composition; Chemical-hypersensitivity; Chemical-reactions; Pharmacodynamics; Blasting-agents; Neuropathy; Nervous-system; Nervous-system-function; Materials-handling; Work-environment; Industrial-environment; Industrial-exposures; Industrial-factory-workers; Industrial-hazards; Animal-studies; Breathing; Air-contamination; Olfactory-disorders; Oxidative-processes; Oxidative-metabolism; Particulates; Nanotechnology
The Toxicologist. Society of Toxicology 46th Annual Meeting and ToxExpo, March 25-29, 2007, Charlotte, North Carolina