Toxicokinetic assessment of inhaled silver nanoparticles using particle number as metric and oxidative stress measurements

The toxicity and kinetics of nanoparticles (NPs) have been related to their physical and chemical properties. To better understand their fate and reactivity in the body, intrinsic properties of NPs (size, shape, surface area, particle number) and mobility properties (agglomeration) need to be evaluated. A systematic study of the toxicokinetics of inhaled silver (Ag) NPs and the evolution of malondialdehyde (MDA) marker of oxidative stress over time was performed by testing the effect of the particle number as metric and using the rat as an experimental model. Aerosols of Ag NPs with lower- and higher-total particle numbers but with the same mass concentration (15 mg/m3) and initial particle size (20 nm) were generated with a nose-only inhalation unit, and exposure conditions (including size distribution) were monitored. Rats were placed in the inhalation unit for six consecutive hours (some rats sacrificed at 3 h) and the time courses of elemental Ag in lungs, blood, extrapulmonary tissues and excreta were determined over a 14-day period. Microscopy characterization showed that Ag NPs used for aerosol generation had two kinds of shape: spherical shape or elongated (like a rugby ball). Monitoring of size distribution of (agglomerated) particles in the aerosol revealed that the median aerodynamic diameter was slightly greater for the lower-count (92 nm; 1.6 × 105 p/cm3) compared to the higher-count of particles (81 nm; 3.5 × 105 p/cm3). Higher peak levels of Ag element were observed in lungs (2–5 times higher at all times), blood (2–3 times higher) and GI tract (2–3 times higher) of rats exposed to the aerosol with lower-total particle number. However, some similarities in the kinetics were observed between the two conditions, such as the relative tissue distribution, time-to-peak levels (Tmax) and excretion profiles. In both conditions, only a fraction of the inhaled dose was quantitated in the lungs, and the observed lung time-course showed that Ag continued to reach the lungs several hours after the end of the inhalation period. Following inhalation, Ag NPs were excreted mainly in feces and a minor fraction was recovered in urine. For Ag NPs, some particle characteristics were documented earlier to have an impact their toxicity. However, in our study, there was no difference in malondialdehyde (MDA) levels in blood and lungs between the two exposure conditions tested. Further investigations are needed to confirm if the biodistribution pattern of Ag NPs an