Thesis (Ph.D.)--University of Washington, 2016-12Recent technological developments have employed the use of a wide array of nano-scaled materials referred to generally as engineered nanomaterials (ENMs). Silver nanoparticles (AgNPs) are ENMs that are nano-sized particles of silver. Silver has also long been noted for its antimicrobial properties, however recent advances in the ability to synthesize AgNPs have led to a surge of use in consumer and commercial products. Applications of AgNPs range from use in clothing, food storage, pacifiers, toys, washing machines, cooking tools, personal care products, cleaning products, and paints. While AgNPs are integrated into these products, usage and time, or even their own functional design may cause the release of silver nanoparticles from the products and may result in human and environmental exposure to silver and silver nanoparticles. The goal of my dissertation work was to add to the growing body of literature to assess potential risks to human health from exposure to AgNPs. In this work, we assessed potential health risks to workers exposed to AgNPs using literature on AgNP toxicity and exposure in the workplace. We use these data to model and analyze dose response and critical effects and characterize the potential risk to workers and suggest an occupational exposure limit (OEL) to protect workers from adverse health effects. We found that the liver is the most sensitive target organ to AgNPs, and that exposures in the workplace may exceed the level determined to prevent adverse liver effects. Next, we investigated the potential for AgNPs to affect potentially sensitive populations by disrupting neurodevelopment using a three dimensional organotypic mouse midbrain in vitro model. We found that developing neural cultures are adversely affected by AgNP exposure and that developmental stage at the time of exposure significantly affects the extent of toxicity. We found developing neural cultures were more sensitive to smaller AgNPs and we observed no significant difference between AgNPs with different coatings. We also found evidence that the toxicity observed may have resulted from uptake and association of AgNPs with cell cultures, rather than through dissolution of particles in culture medium. Finally, we show how in vitro studies of inorganic ENMs can be applied to risk assessment to inform potential susceptibility such as age or genetic susceptibility using a case study of cadmium-containing quantum dot ENMs with applications for AgNP risk assessment
