I have used OtherDrop's replacementblock feature to allow painting blocks into other blocks by right-clicking it with a slime ball. It works really well, but the only issue is that players are permitted to do this anywhere - even if they don't have access to the WorldGuard region.

Here is the configuration that I used to discover this issue:
http://pastebin.com/LBJdx0RA

Would it be possible to honor WorldGuard regions in the future?

OtherDrops should already be honouring WorldGuard permissions and I tested this with the latest WorldGuard, OtherDrops and Spigot 1.8.8 - rightclicking on the slime was rejected. What version of each are you using (did you try the latest dev version of OtherDrops)?

Currently I am using WorldGuard 6.1, Spigot 1.8.8, and OtherDrops 2.8b-dev.1363. I've definitely verified that I am not opped, and don't have access to the region. I have had one of my normal players use replacementblock in regions they don't have access to, just to make sure it wasn't only me. The default player group (which I am testing as) has access to the following WorldGuard permissions:

worldguard.region.info.own.*
worldguard.region.info.member.*
worldguard.region.addowner.own.*
worldguard.region.removeowner.own.*
worldguard.region.addmember.own.*
worldguard.region.removemember.own.*

although I can't imagine any of these to interfere with WorldGuard and replacementblock.

In this example region I am able to use replacementblock as a normal player with no build permissions there: http://puu.sh/mWzUH/b11799523f.png

I am not receiving any console errors or notifications. I am not sure what else I can try to further identify the issue.