Protecting children's health by applying novel approaches to assess urban and rural drinking water - SUMMARY We live in an era of contaminated drinking water. Potable water reuse, climate change, population growth, and intensive farming are factors that drive this contamination. Concurrently drinking water contaminants have been linked with epidemic diseases such as cancer, obesity, dysregulation of the gastrointestinal systems, impaired mental functions, and other developmental and reproductive diseases. Toxic pollutants in drinking water are particularly hazardous for fetal and infant health. They are more vulnerable to harmful contaminants because their organs and tissues are still developing. Previous studies have targeted gut microbiota as an active player of that association. However, the mechanisms underlying these impairments remain poorly defined due to challenges associated to the identification of microbiome-mediated relationships between external factors (i.e., diet and contaminants) and host metabolism. Due to the massive number of organic micropollutants, monitoring using targeted chemical analyses alone is insufficient to assess drinking water quality, covering only a very small subset of the chemicals. Finally, current health risks of drinking water contaminants are typically assessed one chemical at a time, an approach that misses the health impacts of co-occurring contaminants in drinking water and their potential synergistic effects. My central hypothesis is that current tap and well water quality assessments underestimate our exposure to organic contaminants in drinking water and their impact on fetal and infant health. My long-term goals are to (1) improve drinking water quality assessments, by applying high- throughput identification and prioritization strategies of contaminant mixtures, as well as (2) elucidate causal relationships between drinking water contaminants and negative health outcomes in children, specifically those related to neurological conditions. Current knowledge of the risks associated with drinking water contaminants is limited due to the challenges associated with their detection, identification, and testing. Therefore, my overall objectives for this application are to (1) apply high-resolution mass spectrometry (HRMS) and in vitro and in vivo effect-directed analysis (EDA) to expand the coverage of current water monitoring strategies; (2) select and prioritize chemical candidates based on their occurrence, abundance, and toxicity; (3) evaluate associations among prioritized contaminants and water sources according to zip code and open source information found in the Oregon Drinking Water Services at the Public Health Division Website; (4) identify gut metabolites whose variation explains the association between specific gut microbes and zebrafish endpoints; (5) and provide a comprehensive list of prioritized chemicals and mixtures found in rural and drinking water in Oregon. This study will help members from the EPA and DEQ make better informed decisions related to further chemical regulations in drinking water. This application responds to the first theme of the NIEHS strategic plan 2018-2023, Advancing Environmental Health Sciences (EHS), by studying the effects of contaminant mixtures of emerging concern, predictive toxicology, and microbiome responses.
