“An integrated dispersion preparation, characterization and in-vitro dosimetry methodology for low aspect ratio, engineered nanomaterials”
Instructors: Sandra V. Pirela, Glen DeLoid, Joel Cohen and Philip Demokritou
Download Training Workshop Materials, and view On Demand Video PresentationObjective
The objective of this workshop is to present the emerging tools currently available to nanotoxicologists for quantifying in-vitro particle dosimetry for engineered nanomaterials. This includes a series of brief lectures that will provide the necessary background information/concepts and overview of methods in addition to hands-on training of integrated experimental and computational approaches for in vitro dosimetry. Participants will be trained using a relevant real world case study that demonstrates the applications of the emerging methods presented here.
Introduction
In vitro high-throughput screening platforms based on mechanistic injury pathways have been used for hazard assessment of engineered nanomaterials (ENMs). Toxicity screening and other in vitro nanotoxicology assessment efforts typically compare and rank the bioactivity of nanomaterials relative to each other. It has been shown that ENMs hazard rankings are highly sensitive to variability in poorly standardized dispersion protocols and lack of dosimetry. This sensitivity is largely due to the impact of particle transformations on partico-kinetics that affect bioactivity and delivery of particles to cells. The importance of such dosimetric considerations apply to studies using both cell cultures as well as animal experimental models for toxicology assessments. Thus, extrapolation to humans becomes more reliable once the dose is determined accurately at the site of deposition.
Emerging hybrid, experimental/computational approaches to cellular dosimetry can be used by nanoparticle toxicologists to accurately calculate the delivered to cell dose metrics for various ENMs and in vitro experimental conditions as a function of exposure time. In addition, in vivo lung deposition models allow researchers to estimate the delivered particle dose in any region of the respiratory system, as well as study the implications of particle properties and breathing parameters. More importantly, such dosimetric methodologies enable nanoparticle toxicologists to bring in vitro and in vivo doses to the same scale, an important step towards the development and validation of in vitro cellular screening assays.
