Nic, I think I can sum up the responses so far by saying:
1) Yes it does affect ball reaction.
2) This could be demonstrated by comparing identical drillings on identical balls with/without an interchangeable thumb on a Determinator.
3) Some posters feel that most of us would not likely notice that difference and that worrying about this is much less important than the overall feel of the grip, as well as the usefulness of an interchangeable thumb system.
4) To answer your latest question, of course the amount of change caused would depend on the shape/density of the core, and its placement relative to the gripping holes, as it does even without an interchangeable thumb.
Basically, if you like using an interchangeable thumb, do so, and don't overly concern yourself with the effect on the ball reaction. Just make adjustments to your layouts, surfaces, balance hole placement and ball selection based on what you see with the interchangeable thumb.
Hope this helps,
Joe