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The Saint Louis River was listed as a Great Lakes Area of Concern (AOC) under the Great Lakes Water Quality Agreement (GLWQA) of 1987. The AOC boundary includes the lower 39 miles of the St. Louis River, from upstream of Cloquet, Minnesota, to its mouth at the Duluth/Superior Harbor and Lake Superior, and the Nemadji River watershed. Draining 3,634 square miles of watershed and encompassing a 1,020 square-mile area, the St. Louis River is the second largest U.S.-based AOC. As the largest tributary to Lake Superior, the St. Louis River is vital to the regional economy and encompasses the Port of Duluth-Superior, an essential port for Great Lakes shipping.

Historical industrial use of the river, before the onset of modern pollution laws, has resulted in sediments contaminated with: mercury, dioxins, polychlorinated biphenyls (PCBs), polycyclic aromatic hydrocarbons (PAHs), and other toxins. Pollutants in the AOC are also due to: historical discharges, Superfund sites, discharges from wastewater and from landfills, and other point-source discharges within the AOC.

An impairment of beneficial uses means a change in the chemical, physical or biological integrity of the Great Lakes system sufficient to cause significant environmental degradation. A 1992 Remedial Action Plan determined that nine "beneficial use impairments" existed in the AOC including:


 * Fish Consumption Advisories
 * Degraded Fish and Wildlife Populations
 * Fish Tumors and Other Deformities
 * Degradation of Benthos
 * Restrictions on Dredging
 * Excessive Loading of Sediment and Nutrients
 * Beach Closings and Body Contact Restrictions
 * Degradation of Aesthetics
 * Loss of Fish and Wildlife Habitat

Two of these impairments have been removed from the designation (degradation of aesthetics in 2014, fish tumors and other deformities in 2019) following remediation projects. Reaching these targets will lead to the goal of delisting the AOC, which means the ecological benefits of the St. Louis River have been restored to an acceptable level.