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Coldwater Creek is contaminated with uranium processing residues that were improperly stored near the creek. The Mallinckrodt facility in downtown St. Louis extracted uranium and radium as part of the Manhattan project to develop atomic weapons for the United States. Wastes from this process containing low-level radioactive byproducts were moved and stored at two sites near Coldwater Creek, the St. Louis Airport Site on McDonnell Boulevard and the Hazelwood Interim Storage Site on Latty Avenue. Improper handling, transport, and storage of these wastes led to contamination of Coldwater Creek and other nearby areas.

The United States Army Corps of Engineers (USACE) Formerly Utilized Sites Remedial Action Program (FUSRAP) is responsible for environmental sampling and remediation along Coldwater Creek. Recent investigations performed by USACE discovered contamination in parks and residences along Coldwater Creek.