The Environmental Protection Agency issued a proposal Friday under the Clean Water Act that would limit mining activity in Alaska’s Bristol Bay watershed — striking a major blow to a project that would rank as one of the world’s largest open-pit mines.

The proposal, which will be subject to a public-comment period until Sept. 19, represents the Obama administration’s latest step to impose restrictions on a massive gold and copper mining project called Pebble Mine. Native Alaskan tribes, commercial fishing operations and environmentalists have sought to block the venture on the grounds that discharge from the operation could harm an area that supports nearly half of the world’s sockeye salmon.

Dennis McLerran, the EPA’s regional administrator for the area, said Friday the agency had concluded that even a mine much smaller than the one envisioned by Pebble’s sponsors would produce “almost unfathomable amounts of rock” that would pose “significant risks to the fragile ecosystem” in Bristol Bay.

The EPA was taking the step “to protect the world’s greatest salmon fishery from what would certainly be one of the world’s largest open-pit mine developments ever conceived of,” McLerran said.

A Canadian-based firm, Northern Dynasty Minerals, is trying to start construction on the project, which it predicts will create 1,000 direct jobs and generate up to $180 million in state revenue.

The mine’s developers have not filed a permit application yet, so EPA based its analysis on the company’s filings with the Securities and Exchange Commission. It based its conclusion on a 0.25 billion ton mine, which is significantly smaller than the project the firm has said it is likely to pursue.

Pebble Partnership CEO Tom Collier said in a statement the restrictions are “misguided and not based on sound science or regulatory precedent,” noting the EPA moved ahead while litigation is pending in federal court. He said the EPA’s action “is causing significant and even critical harm to our business interests and our abilities to fairly advance our project.”

Sen. Lisa Murkowski (R-Alaska) has urged the EPA not to issue a “preemptive veto” against Pebble Mine, while Sen. Mark Begich (D-Alaska) and other Democratic senators from the Pacific Northwest have argued the project poses too great a risk to Bristol Bay’s wild fishery.

Some supporters of the mining industry are concerned the decision could set a precedent that will affect other operations, and a group in Wisconsin has asked the EPA to intervene in a mining project there. But Begich issued a statement Friday saying the decision “applies only to the Pebble deposit” and that he remains “a strong supporter of the mining industry and mines in other regions of Alaska.”

“The limited scope is critical and means the determination would not affect mining or any other resource development project in other parts of the state,” said Begich, who is one of a number of red-state Democrats up for reelection in November.

Tim Bristol, who directs Trout Unlimited’s Alaska program, praised the agency’s move.

“These restrictions will ensure that no unacceptable adverse impacts will occur from mining development in Bristol Bay, the very standard that has been the law of the land for over 40 years,” Bristol said.

Joel Reynolds, Western director for the advocacy group Natural Resources Defense Council, said he did not think the mine’s sponsors would be able to overturn the EPA’s determination because it was based on “a comprehensive, science-based process.”

“Their chances of being able to overturn it are minimal at best,” he said. “Today’s one more nail in the coffin in a project that deserves to die.”