US warns Syrian regime against carrying out gas attacks
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The fact that Assad may still have chemical weapons shows "either Russia is incompetent or in cahoots with Assad," Mattis said.
Regime forces have been pounding Eastern Ghouta for nearly three weeks in an assault that has killed over 1,000 civilians.
Mattis also took aim at Russia, which has been propping up Assad's regime since 2015 and carrying out military operations in rebel-held areas.
Assad "could not be in power absent Russia's unfortunate veto in the UN years ago and the Russians' full-throated military support for Assad," he said.
Mattis declined to say whether the use of gas would represent some sort of trigger that would prompt a US military response.
"The president has full political manoeuver room to take the decision that he believes appropriate," he said.
"There are other Western nations that have been in contact with us that are watching this very closely and are completely aligned with us and what I just said - that it would be very unwise for someone to use gas."
Eastern Ghouta is home to around 400,000 people living under a crippling regime siege since 2013.
The United Nations has demanded a month-long ceasefire there to allow for aid to be brought in and for desperately sick and wounded civilians to receive treatment.