McCarthy said the EPA will investigate and seek an independent review of the spill, though she offered no details.
"We are going to be fully accountable for this in a transparent way," she said at a press conference. "The EPA takes full responsibility for this incident. No agency could be more upset."
When asked if the EPA will investigate itself as vigorously as it would a private company, McCarthy said, "We will hold ourselves to a higher standard than anybody else."
The EPA said the spill occurred August 5 when one of its teams was using heavy equipment to enter the Gold King Mine, a suspended mine north of Durango.
Instead of entering the mine and beginning the process of pumping and treating the contaminated water inside as planned, the team accidentally caused it to flow into the nearby Animas and downstream to other states.
The EPA's slow response angered local and state officials as well as farmers, native Americans and others who live near the river.
Buster Jaquez, 83, has lived and farmed by the river near Farmington, New Mexico, since 1967. He relies on well water for his home and to irrigate his farm, and for drinking water for his livestock. He said he doesn't know what he will do without a clean water source. He also worries about the possible long-term effects.
Later Wednesday, the attorneys general for Colorado, Utah and New Mexico said they might sue the federal government individually or collectively, though Colorado Attorney General Cynthia Coffman said, "It is too early to know if litigation is necessary or appropriate."
She said she's encouraged tests show the river seems to be returning to normal, with no fish or insect kills. The mustard color caused by the heavy metals is also clearing up around Durango.
Attorney generals from Utah and New Mexico joined Coffman in Durango on Wednesday. In a statement, the Utah Attorney General's office said that all three states support an independent review of the mishap in addition to the EPA's review.
The long-term effects on the river are difficult to measure, Coffman said.
"Often fish do not form signs of contamination and poison from these levels of heavy metal for two or three years at least," Coffman said.
Utah Gov. Gary R. Herbert declared a state of emergency, directing state agencies to help local communities affected by the spill.
"I am deeply disappointed by the actions of the Environmental Protection Agency. It was a preventable mistake, and they must be held accountable," he said. "With potential long-term implications, the emergency proclamation will allow us to continue to support affected businesses and communities."
Utah Attorney General Sean Reyes said he's encouraged the EPA is taking responsibility, but is not ruling out a lawsuit against the federal government.
"Any good lawyer will tell you that before you start to talk about a claim you need to know what the damage is," Reyes said.
Fears of serious health risks quickly surfaced, but Colorado Department of Public Health and Environment Executive Director Larry Wolk
said Tuesday the river is returning to normal.
McCarthy repeated those findings Wednesday, saying the river appeared to be returning to "pre-incident conditions."
On Wednesday, the chairmen of the House Oversight and Subcommittee on the Interior called for the EPA to investigate the Colorado spill.
"The EPA should be held to the same benchmark that applies to those it regulates," wrote U.S. Reps. Jason Chaffetz of Utah and Cynthia M. Lummis of Wyoming in a letter to EPA Inspector General Arthur Elkins.