A physiologically based pharmacokinetic model for ionic silver and silver nanoparticles

Gerald Bachler, Natalie von Goetz, Konrad Hungerbühler

ETH Zurich, Institute for Chemical and Bioengineering, Zurich, Switzerland

Abstract: Silver is a strong antibiotic that is increasingly incorporated into consumer products as a bulk, salt, or nanosilver, thus potentially causing side-effects related to human exposure. However, the fate and behavior of (nano)silver in the human body is presently not well understood. In order to aggregate the existing experimental information, a physiologically based pharmacokinetic model (PBPK) was developed in this study for ionic silver and nanosilver. The structure of the model was established on the basis of toxicokinetic data from intravenous studies. The number of calibrated parameters was minimized in order to enhance the predictive capability of the model. We validated the model structure for both silver forms by reproducing exposure conditions (dermal, oral, and inhalation) of in vivo experiments and comparing simulated and experimentally assessed organ concentrations. Therefore, the percutaneous, intestinal, or pulmonary absorption fraction was estimated based on the blood silver concentration of the respective experimental data set. In all of the cases examined, the model could successfully predict the biodistribution of ionic silver and 15–150 nm silver nanoparticles, which were not coated with substances designed to prolong the circulatory time (eg, polyethylene glycol). Furthermore, the results of our model indicate that: (1) within the application domain of our model, the particle size and coating had a minor influence on the biodistribution; (2) in vivo, it is more likely that silver nanoparticles are directly stored as insoluble salt particles than dissolve into Ag⁺; and (3) compartments of the mononuclear phagocytic system play a minor role in exposure levels that are relevant for human consumers. We also give an example of how the model can be used in exposure and risk assessments based on five different exposure scenarios, namely dietary intake, use of three separate consumer products, and occupational exposure.

Keywords: nanosilver, human exposure, biodistribution, PBPK model, risk assessment, toxicokinetics