I have an activity that opens up 40+ slots. From a destination queue.
However I would like to exclusively lock the item to a user after they have opened it.
Why 40+ slots? If you limit the Activity to 1 slot, all 40+ users will still receive a worklist item but the first user to open the work item will be the only one allowed to work with it - depending on what you use for the client event UI. If your client event UIs are aspx pages, you should see the above behaviour, InfoPath client events however behave differently.

In order to apply a timeout, I would add an escalation that calls an external assembly utilizing K2MNG.dll to release the 'Open' worklist item - thereby resetting the status of all 40+ worklistitems to 'Available'.
Please Note: I haven't tested this solution - just an idea!!

HTH,
Ockert