I did not reconvert from ePub to ePub. And I didn't think of trying an LRF. Thanks, I will put both of those in my toolbox for future cases.
But in the meantime I think I may have solved this another way...
I got to wondering, why is this ePub file so large? I started poking around trying to see where all this size comes from. I brought it up again in the Tweak ePub area in Calibre, and specifically looked for an answer to this question. I found that the images folder contained a lot of JPG files, which is as I would expect, those would be the illustrations. But the real space eaters were the SVG files. 96 of them. What are these? I didn't know. I googled and it turns out SVG stands for Scalable Vector Graphics. Just a wild guess, but I suspect the ePub doesn't use these - I bet these are remnants of the Topaz file I converted from.
I already had made a backup of the ePub. So I tried just deleting the *.svg files wholesale. Then I re-assembled the ePub file. This brought its size down from 6.6 MB to 2.0 MB. I deleted the copy on my PRS-350, and sent a fresh copy. I can now page past the point where it was failing before.