Quite possibly the mod sounds take up more bytes than the default sounds, so you might be running into memory/paging/loading issues or hitting a threshold in the game's sound engine (i guess that despite the altered samples the way it all operates is still based on the default sound engine).
I haven't installed any mods yet so i'm just guessing here, but what you describe seems to be a classic my-system-has-run-out-of-"ooomph"-to-run-this scenario, similar to people with non-modded installations that are having the same problems in lower spec PCs.
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