The lightweight carbon-fiber Airbus, 7 meters (yards) longer and able to carry 40 more people than A350s already in service, began a three-hour debut flight at just after 0940 GMT, watched by some of the airline bosses who have invested in the $356 million jet.
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The 366-seat A350-1000 was designed to break Boeing's virtual monopoly in the lucrative "mini-jumbo" segment, typically involving large twin-engined jets carrying 350 people.
It is a larger cousin to the new-generation A350-900, which entered service last year. Both are built from similar advanced materials to Boeing's mid-sized 787 Dreamliner in a race between planemakers for fuel savings and better passenger comfort.
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The aircraft involved in Thursday's Toulouse debut is one of three test planes facing a winter of intensive flight testing before the A350-1000 enters service in the second half of 2017.
Fabrice Bregier, chief executive of Airbus, added he was confident the A350-1000 would be delivered on time next year.
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