Impact of Particle Size on Toxicity, Tissue Distribution and Excretion Kinetics of Subchronic Intratracheal Instilled Silver Nanoparticles in Mice

The unique physicochemical properties of silver nanoparticles (AgNPs) make them useful in a wide range of sectors, increasing their propensity for human exposure, as well as the need for thorough toxicological assessment. The biodistribution of silver, hematological parameters and GSH/GSSG levels in the lung and liver were studied in mice that were intratracheally instilled with AgNP (5 and 50 nm) and AgNO(3) once a week for 5 weeks, followed by a recovery period of up to 28 days (dpi). Data was gathered to build a PBPK model after the entry of AgNPs into the lungs. AgNPs could be absorbed into the blood and might cross the physiological barriers and be distributed extensively in mice. Similar to AgNO(3), AgNP5 induced longer-lasting toxicity toward blood cells and increased GSH levels in the lung. The exposure to AgNP50 increased the GSH from 1 dpi onward in the liver and silver was distributed to the organs after exposure, but its concentration decreased over time. In AgNP5 treated mice, silver levels were highest in the spleen, kidney, liver and blood, persisting for at least 28 days, suggesting accumulation. The major route for excretion seemed to be through the urine, despite a high concentration of AgNP5 also being found in feces. The modeled silver concentration was in line with the in vivo data for the heart and liver.