The key question is, WHAT fifth wheel?
Even the lightest "1/2 ton towable" fifth wheels push the limits of most F-150 trucks, and require some suspension helpers.
If you're talking about the fifth wheel in your signature, you better travel light. Empty it's 8800lbs and has a 1200lb pin weight. That's going to be pushing things both in power and payload capacity, and you may not like how it drives, even after you add LT rated tires, airbags, etc. to the truck.
I'm not particularly concerned about safety, because you will know if it's not safe long before you get into trouble.