David Cameron has blasted as "complete fiction" a former Tory leader's claim that Britain could obtain an improved reform deal from the EU by voting Leave in the referendum.
In a significant blow to the Prime Minister's campaign to keep Britain in the EU, Michael Howard said Mr Cameron's renegotiation of the UK's membership had "met with failure" and urged voters to back withdrawal.
And Government minister Andrea Leadsom, who is campaigning for the UK to quit, dismissed as "unlikely" Chancellor George Osborne's assessment that leaving the EU would cause a "profound economic shock" for Britain.
Lord Howard, a former mentor of Mr Cameron, used an article in the Daily Telegraph to argue that the UK should vote for Brexit to "shake Europe's leaders out of their complacency", arguing there would be "a significant chance that they would ask us to think again".
Mr Cameron has dismissed talk of a second referendum as being "for the birds", insisting he would respond to a Leave vote by immediately triggering Article 50 of the Lisbon Treaty, which sets out a two-year process for negotiating terms for withdrawal.
But Lord Howard suggested he could pause the process by up to a month for EU leaders to come back with a better deal for Britain.
"I think it is quite likely that during that month they would say let's talk some more, let's see if we can reach a different agreement and perhaps you could have a second referendum. If, after a month or so they don't, then Article 50 would have to be triggered and negotiations to leave would begin," he told BBC Radio 4's Today programme.
But the Prime Minister insisted that voters will be making "a single decision, a final decision" on June 23.
Asked about Lord Howard's comments during a visit to an aviation factory near Cardiff, the PM said: "This idea that there is some third way - as some are suggesting - between in and out, that we vote out in order to have another renegotiation, another referendum, I think that is a complete fiction.
"It's a very simple question on the ballot paper - you either remain in the European Union or you leave the European Union. I think people really to need understand that it's a single decision, it's a final decision, and there are only two choices."
Meanwhile, the Chancellor warned about the economic impact of Brexit during a visit to Shanghai for a summit of G20 finance ministers.
"You have seen the value of the pound fall and it reminds us all that this is not some political parlour game, this is about people's jobs and their livelihoods and their living standards," said Mr Osborne.
"In my judgment as Chancellor, leaving the EU would represent a profound economic shock for our country, for all of us, and I'm going to do everything I can to prevent that happening."
But Ms Leadsom, a minister in the Department for Energy and Climate Change, disputed the Chancellor's claims, telling BBC Radio 4's World At One programme: "A profound economic shock is unlikely and I think that it is unthinkable that Europe would somehow stop trading with the UK were we to leave the European Union."
Unconfirmed reports suggested that the world's most powerful economies may signal their concern over the prospect of Brexit with a statement in the official communique issued at the end of the G20 meeting on Saturday.
Mr Cameron visited the London headquarters of the Britain Stronger In Europe campaign before heading to Wales on the latest of his regional visits to promote the Remain message, which will take him to Northern Ireland on Saturday and Scotland next week.
He was still short of obtaining the symbolically important public backing of more than half of Tory MPs, according to a survey by the Press Association.
Some 158 of the Prime Minister's 329 Commons colleagues have declared they will vote to "remain" in the EU and 130 have said they will back Brexit. York Outer MP Julian Sturdy and Woking's Jonathan Lord became the latest MPs to declare, announcing they would vote to leave the EU.
Downing Street confirmed that a series of Government papers will be published "over the coming weeks", assessing issues including the costs and benefits of being in the EU, the rights and obligations of membership, the alternative arrangements available outside the 28-nation bloc and the process for departure.
The papers, promised during the passage of legislation paving the way to the referendum, will be prepared by civil servants and signed off by ministers and will offer a "fact-based, balanced" view of the issues so that voters can make an informed choice, said Mr Cameron's spokeswoman. Ministers campaigning for withdrawal will not be given access to the papers.