One thing I forgot to mention. Up until very recently, floors in residential homes were designed with a load factor of 40 lbs per sq ft for the 1st floor and 30 lbs per sq ft upper floors. This is based on a deflection factor of L360 (meaning the floor can sag 1" in 360" and not be overloaded. If you were to put something overweight in the center of the span, expect a deflection of more than that. It probably won't fail but sometimes a sag isn't desireable.
Usually, the refrigerator is the heaviest thing for it size in a house. If the safe is no heavier than a frig, you should be OK but expect a little sag if it is in the middle 1/3 of the span. This is with board lumber. TJI's, trusses or engineered lumber is different.