Some Republicans said they wouldn’t support McCarthy — currently the agency’s top air quality regulator — because she’d enforce President Obama’s recent announcement to regulate the carbon emissions of existing power plants, which create about a third of U.S. greenhouse gas emissions, largely from burning coal.

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“As the head of the EPA’s air division, she’s overseen the implementation of numerous job-killing regulations,” Senate Minority Leader Mitch McConnellAddison (Mitch) Mitchell McConnellGun proposal picks up GOP support Children’s health-care bill faces new obstacles Dems see Trump as potential ally on gun reform MORE (R-Ky.) said ahead of the vote. “These regulations, along with others promulgated by the EPA, have had devastating consequences in states like mine. They’ve helped bring about a depression.”

Senate Environment and Public Works Committee Chairwoman Barbara BoxerBarbara BoxerTrump riles Dems with pick for powerful EPA job Pelosi's chief of staff stepping down Time is now to address infrastructure needs MORE (D-Calif.) criticized Republicans for blocking McCarthy, not because she wasn’t qualified but because they hate the mission of the EPA.

“This battle is not about Gina McCarthyGina McCarthyTrump plans to roll back environmental rule everyone agrees on EPA chief to visit Colorado mine spill site In the fight between Rick Perry and climate scientists, Perry is winning MORE,” Boxer said Thursday. “It’s because a lot of our colleagues would simply say we’d be better off without the EPA.”

Democrats point out that McCarthy’s work on air quality has saved lives and that she is a bipartisan choice because she had worked for former Gov. Mitt Romney (R-Mass.). She was Romney’s under secretary of policy at the Massachusetts Executive Office of Environmental Affairs, and deputy secretary of operations for the cross-cutting Office for Commonwealth Development that Romney created, work that included development of policies on smart growth and climate change.

“Gina McCarthy knows how to bring people together. She knows how to work toward a common goal,” Sen. Richard Blumenthal (D-Conn.) said. “She knows how to get to ‘yes’ and she does it as a tough, fair, balanced, environmental law enforcer. ... Gina McCarthy is as good as it gets in public service.”

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Republicans agreed to hold an up-or-down vote on her nomination as part of a deal to avoid Senate rule changes limiting the minority's right to filibuster executive branch nominees.

Some Republicans were trying to hold up her nomination because they said they wanted guarantees from McCarthy that she would run a more transparent EPA.

Republicans on the Senate Environment and Public Works Committee even boycotted her confirmation hearing in May. Democrats criticized Republicans throughout the process for the boycott and because McCarthy was forced to answer more than 1,000 questions submitted by committee members.

Since then, Vitter, the ranking member, said McCarthy has promised to be more open and work with him on some key concerns of his.

Boxer said this is the longest time that the EPA has been without an administrator, since Lisa Jackson stepped down at the beginning of the year.

“The EPA deserves a leader and this woman, Gina McCarthy, deserves a promotion,” Boxer said.

Ben Geman contributed to this article.