Based upon the numerous complaints of owners who tried to improve the ballistics of the parent .250/3000 in their pre-war M99s, there may be problems using .22-250 factory ammo. The classic pre-war M99 cartridges were the .250 and .300 Savages, both factory loaded to mild pressures of ca. 45,000 cup. The .22-250 is factory loaded to 53,000 cup, producing considerably higher breech thrust. When the old boys hotrodded the .250/3000 they got action springing which caused trough extraction, a real problem given the M99's relatively weak extraction (compared to a M70, etc.).
Savage recognized this shortcoming of the M99 and made action changes prior to the introduction of modern high-pressure cartridges in the mid-1950s. The older rifle won't blow up, but it may cause problems at pressures which exceeded its original design strength.
Ackley was a fine gunsmith, I have several rifles he worked on, but even he couldn't fix the M99's springy action. His response was the .250/3000 Ackley Improved cartridge. BTW, Ackley mentions this exact issue with high pressure .250/3000 M99 loads in Volume I of his Handbook.