Pulmonary response to intratracheal instillation of fine or ultrafine carbon black or titanium dioxide: role of surface area.
Sager-TM; Porter-D; Castranova-V
Toxicologist 2008 Mar; 102(1):305-306
Nanparticles are characterized by having a high surface area per mass. Therefore particle surface area may play an important role in determining the biological activity of nanoparticles. However problems arise because nanoparticles tend to agglomerate into microm sized particles when suspended in PBS. Our previous studies found that such agglomeration in PBS results in inaccurate dose delivery this leads to misinterpretation of toxicity of the particulate being assessed. We found that acellular BALF is effective in dispersing nanoparticles without masking the particles biological surface activity. After establishing an accurate protocol for dispersing nanosized particles, assessment of the inflammatory and cytotoxic potential of ultrafine and fine carbon black and TiO2 was conducted. Fisher rats were exposed by intratracheal instillation to varying doses of ultrafine and fine carbon black or TiO2. At 1,7, or 42 days post-exposure, inflammatory and cytotoxic potential of each particle type was compared on both an equal mass dosage (mg/rat) as well as an equal surface area dosage (cm2 of particles per cm2 of alveolar epithelium). The findings of the study show that on an equal mass basis the ultrafine particles were significantly more inflammogenic and cytotoxic than the fine sized particles. However, when doses were equalized based on surface area of particles given, the ultrafine particles were only slightly more inflammogenic and cytotoxic when compared to the fine sized particles. It was also noted that at 1 day postexposure, with a dose equalized to surface area, the carbon black particles and the TiO2 particles exhibited similar inflammogenic potential. Over the post-exposure time course of 42 days pulmonary toxicity of both the ultrafine and fine particles tended to resolve. However at 42 days post-exposure the TiO2 was significantly more potent than the carbon black particles. In conclusion this study suggests that surface area of particles may be a more accurate dose metric for pulmonary toxicity studies than mass of particles.
Particulates; Particulate-dust; Cell-biology; Biological-factors; Biological-monitoring; Biological-transport; Biological-effects; Biological-function; Cellular-reactions; Respiratory-hypersensitivity; Respiratory-irritants; Respiratory-system-disorders; Pulmonary-disorders; Pulmonary-system-disorders; Pulmonary-system; Nanotechnology
The Toxicologist. Society of Toxicology 47th Annual Meeting and ToxExpo, March 16-20, 2008, Seattle, Washington