Superboy encounters his first fragment of red kryptonite in Adventure Comics #252 (July 1958). The meteor is ejected accidentally from a spaceship intent on invading Earth from another dimension and Superboy has to keep vigil until the invasion is attempted. This kryptonite is “ten times the radiation power of ordinary kryptonite!”, so I guess they hadn’t quite established that each fragment of red kryptonite has a different effect.