Nanoparticle Delivery and Dosimetry: The Unsolved Mysteries in Inhalation Toxicology

Both aerosolized delivery and dosimetry of nanoparticles are often perceived as major challenges in inhalation nanotoxicology studies.
State-of-the-art methods of aerosolized delivery and dosimetry of nanoparticles for in vitro and in vivo studies are presented including the VITROCELL CLOUD & flexiVent system for aerosol delivery and the Quartz Crystal Microbalance & ISDD/DG in silico particokinetics models for dosimetry.
The following fundamental misconceptions and truths related to in vitro and in vivo nanoparticle dosimetry will be addressed:
1) Not mass but surface area is the most relevant dose metric for many particle types. The relevance of other dose metrics will be discussed as well.
2) Not particle concentration (e.g. cm2/m3 or cm2/mL) but cell/tissue-delivered particle dose (cm2) should be used for dosimetry.
3) The delivered dose should be normalized to a tissue-specific metric such as surface area of exposed tissue (e.g. cm2-particles/cm2-tissue).
The validity of these statements will be demonstrated by grouping of some 70 different nanomaterials into toxicity classes based on acute and chronic in vivo data from the literature.
Taking advantage of these innovative methods and concepts will not only solve the “mysteries” of nanoparticle delivery and dosimetry, it will also facilitate direct translation of in vitro and in vivo dose-response data into human equivalent exposure limits which are essential for risk management of nanomaterials.