A stepwise approach to understanding nanomaterial transformations under situationally relevant conditions.

Given the increasing use of nanomaterials in various consumer products and industrial processes, it is of the utmost importance to better understand potential mechanisms of adverse effects to ensure human health and safety when developing regulations and standard operating procedure with newly developed materials, like nanomaterials. Nanomaterials are materials with one or more dimensions in the nanoscale range that are produced to advance industrial processes, used as an additive in consumer products, and produce novel drug delivery carriers. Standardized toxicological studies focus on newly produced nanomaterial products before they reach the market; however, most of these studies exclusively investigate pristine engineered nanomaterials. The issue with testing pristine engineered nanomaterials is that most environmental and/or human toxicities are induced after nanomaterials undergo transformations, e.g. release of metal ions. The goal of this dissertation was to conduct a comprehensive study of increasingly complex situationally relevant environments on organic and inorganic nanomaterials to understand important insights into nanomaterial transformations and the associated toxicity after exposures in vitro. Situationally relevant conditions occur when nanomaterials are used in products or processes and interact with the surrounding environment, where they then may undergo transformations. These transformations may include distribution with biomolecules or natural organic matter, lipid membranes in cells, high ionic conditions, or changes in temperature, salt concentration, etc. In this study, important physicochemical characterization methods were established for organic and inorganic nanomaterials. Additionally, these nanomaterials were transformed under simulated conditions and examined in increasingly complex environments. Next, the transformed nanomaterials were incubated with an established in vitro liver model to elucidate the relationship between nanomaterial transformations and the associated toxicity after exposure. Finally, transformed nanomaterials were exposed to an in vitro model for steroidogenic disruption to investigate further into adverse effects nanomaterial transformations may have on human health. Ultimately, the aim of this work is to advance the field of toxicology by improving our understanding of nanomaterial transformation mechanisms and to aid in risk assessment and regulations.