Mine generally stays about 90F above ambient when I'm towing.
If your E450 is stock and you stay within the rating, you probably have nothing to worry about. The hottest trans temps I ever see are actually doing things like backing a trailer up a driveway after getting off the freeway. Towing on the highway, even in the mountains, is never a problem.
But it is still a good idea to monitor. I have a Banks trans temp gauge mounted in my A-pillar. You can also plug something in like the ScanGauge-2 which monitors the data stream through your OBD2 port.