Assessing the pulmonary impacts of two selected amorphous silica nanoparticle size ranges in rats following inhalation exposures
Sayes, C. M., Ostraat, M. L., Reed, K. L., & Warheit, D. B. (2008). Assessing the pulmonary impacts of two selected amorphous silica nanoparticle size ranges in rats following inhalation exposures. In 47th Annual Meeting and ToxExpo, Seattle, WA, March 16-20, 2008, , pp. 305–305. .
Few data have been generated on the pulmonary toxicity of inhaled nanoparticles per se. This research was designed to systematically evaluate the role of nanoparticle size on pulmonary toxicity parameters in rats exposed by inhalation to smaller (30 nm) vs. larger (70 nm) sized silica nanoparticles. The experimental design was divided into four parts: 1) nanoparticle generation, 2)nanoparticle characterization, 3) stability over time, and 4) mammalian pulmonary hazard effects. To initiate this experimentation, aerosol nanoparticle test materials of untreated, as-synthesized, amorphous SiO2 in two different nanoparticle size range populations (i.e. number distributions centered at d50 = 30 nm and d50 = 70 nm) were developed. Each of the size populations was synthesized in situ and upstream of the inhalation apparatus. The aerosolized nanoparticle populations were tested for stability over time by measuring chamber temperatures and humidity. Groups of 5 animals were exposed to 1.5 × 10E7 particles/cm3 for either 1 × 5 hour period or for 3 × 5 hour periods over 3 consecutive days to establish a dose-response relationship at each post-exposure time-point (24 hrs, 1 wk, and 1 mo). We also conducted a flow cytometric assessment of induction of micronuclei in peripheral blood samples. During the nanoparticle aerosol exposures to rats, particle characterization data was collected at t=0, 1, 2.5, 4, and 5 hours. Characterization results demonstrated precise size populations with 5% size distributions; chemical composition (SiO2), surface charge (- 30 mV), and amorphous structure remained identical over the exposure duration. Subsequent post-exposure pulmonary toxicity results (including BAL fluid inflammatory and cytotoxicity endpoints) demonstrated little difference in response to the two different sized nanoparticle-types when comparing exposures to the two different nanoparticle size populations or to sham-exposed air controls. Genotoxicity and lung tissue analysis studies are on-going.