Are System Volume Information entries safe to delete if they're flagged as invalid by such as Registry Mechanic?
All entries should be safe to delete, if there really is not any reference to that "flagged as invalid" entrie on your system. For example, if you got "flagged as invalid" reg. entry that points at to Windows\setup1234.exe, and you really don't got that explicit setup1234.exe on your system.
Are System Volume Information entries safe to delete if they're flagged as invalid by such as Registry Mechanic?
Or, would deleting those entries not show up any negative effects until you have the need to use System Restore?
The latter's correct; I'm not familiar with Registry Mechanic myself, but you can easily cripple a Restore Point by having, say, an AV, an uninstaller, or Registry Cleaner (Norton's Disk doctor is a notorious case in point, but it's not alone) tamper with it, resulting in error messages like:
"Windows was unable to restore your computer to..."
... and it never tells you why either...
I don't think it's coincidental that I was posting some time back about a problem I had which "System Restore" couldn't fix.
I'm saying couldn't fix, what actually was happening was I kept getting the message "Windows was unable to restore your computer to...", and it was happening what seemed even to me, to be too often.
Scanning in safe mode, on the face of it, seems to be an exercise worth doing once in a while, but by the same token, also seems fraught with danger if you don't fully understand what it is you're deleting, and I'm afraid I fall into that camp.
I have to say CCleaner really does an outstanding job, even in comparison with reg cleaners double the price... 
Unless you know what you're doing, and are prepared to double-check every second 'orphaned' key or value you're presented with, I wouldn't bother with any other registry cleaner. I run JV16 Power Tools' Reg cleaner alongside CCleaner, but, although it is a good application it still has its fallibilities
When you go to the safe mode, do you log in to the same account, as what your user account is?
When i start up my computer, it goes straight to my user (my name) account. If i choose safe mode, i got option to log in either to my user -or to my Administrator account.
Maybe one final observation on this, which was prompted by this post from CeeCee.
Just out of interest today I scanned with Registry Mechanic normally, and found one entry. I then went into safe mode, logged on with my user account, scanned and came up with the same single entry.
Rebooted back into safe mode, and logged on with the generic "Administrator" account, scanned and found 69 items.
Systematically checked them, and they were all "System Volume Information/restore", and I think the most pertinent point is that this time, the vast majority of them are files still on my hard drive.
I thought this was worth a mention.