This is my understanding, but some other folks on here do EICR testing professionally so can say more:
Typically the global IR is L+N to E and is a useful first check if anything is really not good.
If you see much higher than Mohm then you know probably all is OK, but if low then you need to do more diagnostics to work out what it is that has pulled the global value down (e.g. lots of ropey cable or very dusty accessories in use that are individually OK but accumulate leackage to an undesirable level globally, or all good bar one damaged circuit, etc)
Doing per-circuit L+N to E is the minimum and (as for global one) safe at 500V as any electronics connected to the main supply has to be safe to at least that level of insulation. For example, typically class-Y capacitors for L-E filters are rated to survive surges to 5kV.
Doing L-N IR testing per-circuit is desirable, but not always practical, on existing installations if you have loads that cannot be easily removed (or you create more risk of faults, etc, by testing that it would fail to reveal if you did not test). Here it is always best to first check at 250V just in case there is low power electronics (USB chargers, LED lights, dimmers that use N, etc) unless you can be very sure everything has been disconnected.
For a new circuit before vulnerable accessories are attached you should test L-N at 500V though.