That would do it. Checking a save for 3 different playthroughs, either just before or after the final fight, they were at day 16 (74 hours), day 24 (113 hours) and day 34 (160 hours).
There is no pause function, and unfortunately, no way to clean up or recover handles that are no longer used (if the item was destroyed or consumed). Reverting to an earlier save may help (if you stop leaving the game running in the background and trading whenever you have a few minutes), but there is no way to tell for sure how far back would be safe (it would depend on how much trading/looting/crafting would be undone by reverting, and how much loot generation would be unavoidable while replaying and continuing through the rest of the game). There is no way to fix this issue in the save itself.
When the item generation system was first designed, the number of handles seemed to be practically unlimited, so there was no reason to make it overly complicated by reusing handles, etc. As development progressed, the game grew significantly (even then nobody hit the limit in the original release, until after the EE was out; the playtime was over 550 hours) and changes in the EE increased the demand for handles (more items being classified as global, rather than local). This resulted in the limit being reachable by a great deal of crafting/trading/looting, or leaving the game running and checking trading periodically.
