Long-term exposure to arsenic, and the co-occurrence of uranium, in public and private drinking water: associations with cardiovascular and chronic kidney diseases in the California Teachers Study

PROJECT SUMMARY/ABSTRACT The overarching objective of this proposal is to evaluate changes in levels of arsenic and uranium in public and private drinking water over several decades across the state of California, and to elucidate the relationship between long-term exposure to these contaminants and the risk of cardiovascular diseases (stroke, acute myocardial infarction) and chronic kidney disease in a large prospective cohort. Inorganic arsenic (As) naturally occurs in soil and groundwater globally. While arsenic in drinking water (wAs) is regulated in US community water supplies, the maximum contaminant level was recently reduced and enforced beginning in the early 2000s. Rural populations, however, rely on private wells which are not regulated for contaminants and may contain higher levels of wAs found in groundwater. Exposure to As has been linked to systemic inflammation and endothelial dysfunction, as well as kidney damage. A limited but growing body of evidence suggests that low-to-moderate levels of wAs present in the US increases the risk of cardiovascular disease (CVD) outcomes, including stroke and myocardial infarction. Few epidemiologic studies have evaluated the association between wAs and chronic kidney disease (CKD), a prevalent disease found at higher rates of unknown cause in some rural regions of California. Another drinking water contaminant, uranium (wU), which naturally occurs in groundwater, shares similar toxicologic properties to wAs and is particularly nephrotoxic. Given wU may co- occur with wAs, exposure to elevated levels of both contaminants may exacerbate the risk of CVD and CKD. In collaboration with the California Office of Environmental Health Hazard Assessment, a geospatial dataset of annual wAs and wU levels (1990-2020) has been developed using measurements from community water supplies and private wells, and spatially allocated to water system boundaries and private groundwater grids (1x1 mile grids), respectively. Our study proposes to first evaluate spatiotemporal trends and the co- occurrence of wAs and wU in community water supplies and private wells across California. We will leverage the geospatial dataset to estimate long-term residential drinking water levels of wAs and wU for participants in the California Teachers Study cohort (enrolled in 1995-96). We will conduct two epidemiologic studies evaluating the association between exposure to wAs and the prospective risks of CVD (including stroke and acute myocardial infarction) and CKD (stage 3 CKD to end stage renal disease) incidence/mortality. We will assess whether risk is greater for participants with the highest exposure levels of both wAs and wU. In summary, our study will describe trends in wAs and wU over time for both public and private water sources, identify regions in California with elevated exposure, as well as contribute to limited knowledge about exposure to low-to-moderate wAs levels and joint exposure to wU and the risks of CVD and CKD in the US.