A whole animal model for investigation of ingested nanoplastic mixtures and effects on genomic integrity and health

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Project Summary/Abstract Microplastics (MP, plastic particles < 5 mm) are pervasive in the environment and an emerging health concern. MPs have the ability to accumulate chemical pollutants from the environment and contribute to bioaccumulation of pollutants, making their consumption potentially hazardous. MPs have been found in nearly all human tissue and specifically, nanoplastics (NPs, ≤ 1 µm) are of alarming concern due to the ability to enter mammalian cells. Current research into the physiological or pathological effects of nanoplastic pollutant exposure is limited, and the human risks of ingestion of NPs alone or combined with environmental chemicals are unknown. The long-term goal is to understand the impact of NP exposure on biological systems. The overall objectives in this application are to (i) establish Caenorhabditis elegans (C. elegans) as a novel model system for NP-chemical mixture research and (ii) to test the ability and impact of NPs as a delivery vehicle for environmental chemicals. The central hypothesis is that NPs, which have absorbed environmental chemicals, will promote DNA damage and subsequent changes in physiology. The rationale for this project is that chemical pollutants like pesticides and phthalates are genotoxic and become concentrated in nanoplastics in the environment. Furthermore, model organisms such as C. elegans can consume NPs and the chemicals contained in them are absorbed by the animal. Two specific aims are proposed to test the central hypothesis: 1) Determine DNA damaging effects of NPs and absorbed environmental chemicals and 2) Determine the physiological consequence of NPs and absorbed environmental chemical exposure. Under the first aim, protocols will be established to quantify chemical absorption in NPs, and to verify absorption and metabolism of ingested chemicals in C. elegans. Additionally, we will evaluate DNA damage induced by NP-chemical mixtures by assessing frequency and location of mutations using an established fluorescent-based reporter. For the second aim, C. elegans exposed to NP-chemical mixtures will be observed for known physiological defects due to the NPs and chemicals alone, with the hypothesis that combined effects will be more severe. Furthermore, we will correlate the presence of DNA damage in specific tissues, with the observed phenotypic changes after NP-chemical exposure. The research proposed in this application is innovative, in the applicant’s option, because it focuses on systematic and rigorous methods to assess and determine the combined effects of NP and environmental chemical toxicology on the cellular level in vivo and in a whole animal, a system that is currently not available. The proposed research is significant because it is expected to provide strong scientific justification for continued studies to prevent negative health outcomes due to NP-chemical mixture exposure and will inform exposure limits on nanoplastics and environmental chemical pollutants. Ultimately such knowledge has the potential to greatly add to our understanding of the additive toxicology of NPs and environmental chemicals and their risks to human health.