Matt, I really don't want to get you to change your mind but……
Filling up that void with epoxy
fillers, or ping pong balls or whatever seems awfully permanent to me. Once filled, you are never going to get the space back - at least not without a shipload of effort in removing whatever you finally put in.
Perhaps good low down space is readily available on a 42'er but I am used to smaller boats (~30') where all space is highly valuable. I can't help thinking that one day you (or even the NP) might want to use that space.
I understand your concerns about a big air gap but what about thinking of ways to mitigate these concerns rather than just filling up the space.
I am thinking that first re-seal the bottom and sides of the space with epoxy
resin then putting a sealed cover over the space (as if you were making a tank in the space). Put a big sealed inspection
plate in the top cover. Done well, it will be airtight and thus water
tight. Nothing should ever get in there and if it somehow does, you have the big inspection hatch
to deal with it.
As suggested earlier, you could fit a permanent pickup pipe (say 25mm) in it to pump out the stuff that will never get in there
and really, that should only be water
This is the lightest and probably cheapest solution and covers all you requirements except your fear of fluid penetration. It is no different than building a water or fuel tank
except we want the inside to be empty rather than full.
Just my 2 cents