If you go purely by the weights the Axis/Vegas seems sufficient for the E-350 chassis. When I weighed my Axis fully loaded with fuel & water & our stuff & us I was still 1000 lbs below GVWR. I'm sure that is why they didn't go with the 450 (its not like its a huge cost save anyway: a F-350 is only a few hundred $$ more than an equivalently configured F-250).
Granted they do everything they can to even save off $0.01...
Now if you are questioning the GVWR value given from Ford for the E-350 that is an entirely different discussion (and perhaps part of the reason the vans finally dropped the Econoline chassis altogether).
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