Synthesis of Environmentally Relevant Nanoplastics and their Toxicological Consequences Mediated by Environmental Pollutants and Biomolecule Adsorption - Project Summary / Abstract Plastic waste is a global environmental and health concern. Degradation of plastics results in the generation of micro- and nanoplastics which are currently ubiquitous within the environment and have diverse properties in terms of composition, shape, size, and inclusion of manufacturing additives. Humans are exposed to micro- and nanoplastics through numerous routes of exposure including oral, inhalation, and dermal via their presence within water, foods, and air. Measurable amounts of plastic particulates have been found in human volunteers in various tissues and safety evaluations of representative nanoplastics utilizing cell culture and animal models have demonstrated the potential for toxicity. The consequential biological and adverse health effects associated with these emerging nanoplastic exposures are not well understood. Currently, most toxicity assessments evaluating nanoplastics utilize pristine representative polystyrene nanoparticles which may not represent environmental exposure scenarios and the biological mechanisms induced following exposures. To address this significant limitation, we have developed a novel procedure to reproducibly generate micro- and nanoplastics of increased environmental relevance from common plastic waste materials. Our assessment supports these plastic particles have appropriate physicochemical properties (composition, size, shape, charge) and induce differential in vitro toxicity including cytotoxicity, inflammation, and oxidative stress. This procedure for generating nanoplastics is innovative and allows for the investigation of fundamental and translatable mechanisms of toxicity. Specifically, evidence suggests nanoplastics can adsorb hazardous environmental contaminants on their surface enhancing their toxicity. This adsorption is likely governed by properties of the nanoplastic and the environmental contaminant. Further, following entry into the body particulates associate biomolecules which may facilitate unique cellular interactions and toxicity. Our ability to produce environmentally relevant nanoplastics with differing physicochemical properties allows for the evaluation these nanoplastic-environmental contaminant and biomolecule interactions which may govern subsequent toxicological consequences. Our preliminary data support physicochemical modifications influence environmental contaminant and biomolecule association influencing cellular interactions and responses. This proposal examines the hypothesis that environmentally relevant nanoplastics will induce toxicity dependent on physicochemical variations (composition and size) via modulation of environmental contaminant and biological interactions. The hypothesis will be tested through completion of two main goals: 1) Quantification of nanoplastic interactions with common environmental contaminants and the toxicological consequences; and 2) Determination of nanoplastic-biomolecule interactions modifying cellular responses. These interactions represent key initial regulators and mechanisms governing subsequent cell recognition and toxicity. Completion of the project will generate new knowledge of environmental significance necessary for the understanding of nanoplastic human health effects.
