personally i think the margin is similar for both, as regards to a 22lr and a centrefire, because with a 22lr you have a very light bullet, if it isnt placed in the exact spots on a fox it can cause suffering, so you need to know your limitations, its similar with small centrefires such as 222's as the bullet is still light but isnt affected as much untill at a longer distance. you also have room for little errors as a centrefire will cause more damage, its all about confidence in yourself at shooting at longer distances, me personally would be happy enough to go drop a fox at 50-60 with a 22l