The rules exempted aircraft with 4 piston engines or 3 turbine engines from having to comply with rules applicable to twins. Regulations would have been playing catch up with increased aircraft performance and range, a Super Constellation refuelling in Shannon for the Atlantic crossing had a reasonably high chance of suffering an engine failure en route and this would have necessitated a careful drawing up of regulations applying to twins with similar engines.
Regulators are normally quite conservative and the reliability of the relatively new jet engine was still unproven so it was reasonable for them to require some demonstrated in service statistics before granting any exemptions
Early twin jet performance would not allow an Atlantic crossing where as today it’s routine for the B737Max. Long haul jets of the B707/DC8 class needed 4 engines due to the relatively low power of the 1950s era power plants.
Routes routinely flown today simply didn’t exist back in the early days as there was no demand.
Other factors need to be considered for EDTO, such as passenger illness or failure of the vacuum toilet system. Even something mundane such as the galley ovens going U/S could cause problems on a 19 hour flight.