Nanotechnologies continue to permeate a multitude of industries, with diverse applications ranging from pesticides to fuel additives. The unusual behavior of nanomaterials that drives their innovation also complicates the job of toxicologists tasked with assessing their potential environmental and public health impacts. This dissertation investigates the underlying reasons for uncertainty associated with the biological effects of nanomaterials. Chapter 2 and Chapter 3 focus on nanoparticles present in commercially available pesticide formulations and assess how particle size influences the environmental risk of a pesticide’s active ingredient. These studies reveal a size-specific effect on the toxicity of the nanoparticles despite normalized concentrations of active ingredient and highlight the potential for nanoparticles to mask the hydrophobic behavior of some chemicals. In Chapters 4 and 5, the focus shifts to soybeans and their microbiome as they respond to soils amended with cerium oxide nanoparticles. Utilizing metagenomic software to analyze large data sets and predict changes in ecological functionality, these companion chapters correlate plant growth with bacterial community structure and emphasize the atypical dose-response relationship of nanoparticles in terrestrial systems. Further, they address importance of acknowledging the difference between pristine and aged nanoparticle exposures. This body of work demonstrates the capacity for nanomaterials to confound toxicological assessment if the disconnect between nanomaterial dosimetry and biological response is not accounted for.