Limit to number of items using 'IN' SQL syntax in arcmap/arcpy?

I’m writing a python script that uses 'NOT IN ('a', 'b', ...)' statements on very large lists (like comparing 500 items in one feature class against >10k items in another) and am getting weird unexpected results (sometimes it works, sometimes it doesn’t and it corrupts the geodatabase…?!?).

I’ve looked and can’t find any ArcMap/arcpy documentation on how large a list can be using IN/NOT IN syntax and was wondering if anyone knew. Using ArcGIS 10.3.1 with 64-bit python.

Update: All of the data in question is stored in file geodatabases.