Sen. Lindsey O. Graham (R-S.C.) said Saturday that fellow presidential candidate Donald Trump's derogatory commentary has begun inflicting permanent and possibly fatal damage to the Republican Party brand and urged GOP leaders to stop "tiptoeing" around the billionaire businessman and to confront him directly and unequivocally.

In an interview with The Washington Post, Graham said Trump's personal attacks on Fox News anchor Megyn Kelly after she questioned him in Thursday night's primary debate were "an affront to all women" and undermine the Republican Party's urgent mission to appeal to more women voters.

“I think we’ve crossed that Rubicon, where his behavior becomes about us, not just him," Graham said. "I hope the party leadership will push hard. I hope that those seeking the nomination to be the standard bearer will unequivocally reject this. People gave Mr. Trump a pass on the [debate] stage. I understand that to a point, but we’ve crossed a line here that can’t be ignored. There can be no more tiptoeing around this.”

Graham's comments came after Trump hurled insults at Kelly in a Friday night appearance on CNN. He called her a "lightweight" and suggested that she asked him aggressive and "ridiculous" questions in the debate.

"You could see there was blood coming out of her eyes, blood coming out of her wherever," Trump said on CNN. On Saturday morning, he and his campaign issued statements claiming that Trump was referring to Kelly's nose.

Graham, a long-serving senator from South Carolina, was relegated to the undercard debate on Thursday because of his poor standing in national polls. He said the party's deep bench of talented candidates is being overshadowed and undermined by Trump, who helped draw a record cable television audience for the main debate.

"Everything is being placed in jeopardy by the antics of Mr. Trump and we’re at a crossroads as a party," Graham said. "The good news is that 24 million people watched the Republican debate. The bad news is that 24 million people watched the Republican debate."

Graham urged his fellow presidential candidates, as well as party leaders like Republican National Committee Chairman Reince Priebus, to state clearly that Trump's message "is not who we are, not where we're going to take the country and not what we believe."

“It’s just like driving by a car wreck without rendering aid," Graham said. "Donald Trump is an out of control car driving through a crowd of Republicans and somebody needs to get him out of the car. I just don’t see a pathway forward for us in 2016 to win the White House if we don’t decisively deal with this.”

Republican leaders have tread carefully in dealing with Trump, worried about alienating or angering him out of fear that he might run as an independent candidate in next year's general election and take votes away from the Republican nominee. In Thursday's debate, Trump memorably refused to vow to support the eventual nominee, saying he wanted to keep his "leverage."

But Graham said GOP leaders need to "take the leverage away and not be afraid to speak honestly and directly about this problem."

“He’s a bully," Graham said. "He intimidates people by calling them bad names. Like every other bully, he’ll meet his fate only when good people say, 'Enough.' Donald Trump, enough already. Take your ball and go home.”

This is not Graham's first time unloading on Trump. He condemned the billionaire real estate mogul and reality television star last month after he belittled the Vietnam War service of Sen. John McCain (R-Ariz.), a close friend and supporter of Graham's.