Changing the dose metric for inhalation toxicity studies: Short-term study in rats with engineered aerosolized amorphous silica nanoparticles

Inhalation toxicity and exposure assessment studies for nonfibrous particulates have traditionally been conducted using particle mass measurements as the preferred dose metric (i.e., mg or μg/m3). However, currently there is a debate regarding the appropriate dose metric for nanoparticle exposure assessment studies in the workplace. The objectives of this study were to characterize aerosol exposures and toxicity in rats of freshly generated amorphous silica (AS) nanoparticles using particle number dose metrics (3.7 × 107 or 1.8 × 108 particles/cm3) for 1- or 3-day exposures. In addition, the role of particle size (d50 = 37 or 83 nm) on pulmonary toxicity and genotoxicity endpoints was assessed at several postexposure time points. A nanoparticle reactor capable of producing, de novo synthesized, aerosolized amorphous silica nanoparticles for inhalation toxicity studies was developed for this study. SiO2 aerosol nanoparticle synthesis occurred via thermal decomposition of tetraethylorthosilicate (TEOS). The...