It all depends on where they line up and whether or not they are in motion at the snap. Before we get into this, it’s important to remember that the tackle box is defined as 5 yards laterally on either side of the ball and goes from the line of scrimmage all the way back to the offense’s end line. It does not grow or shrink depending on your formation.
If a player is on the line of scrimmage in the tackle box at the snap, he may block low from the front or side in any direction as long as the ball and the blocker have not left the tackle box.
If a player is stationary in the backfield in the tackle box at the snap, he may block low in any direction until he or the ball leave the tackle box. However, unlike a player on the line, he may only block from the front, or “10 to 2”. If he blocks low from the side, it is a foul.
A player who is outside the tackle box or in motion anywhere at the snap is only allowed to block low from the from and away from the original position of the ball. So if the ball is snapped on the right hash, low blocks by these players must be directed away from the right hash or directly upfield. If he blocks low from the side or toward the original position of the ball, it is a foul.
Once the ball or blocker leaves the tackle box, all low blocks must be away from the original position of the ball and from the front no matter where the player was at the snap.
Also, once the ball leaves the tackle box, nobody may block low toward their own end line.