Sam,
I'd make sure your lead MQL flow excludes this list initialy. If a lead from the List matches existing leads, then you can legitimately do what you want with that lead.
So if you only upload your list, send out your email, and then delete those records immediately you would be fine.
Usually I recommend adding that list to a suppression list or Suspending them until you plan to use them again.
Just make sure you know the response rates, etc before you remove the non responders from your database.