Seattle Mariners pitcher Hector Santiago became the first player to be ejected under Major League Baseball's crackdown on illegal substances on Sunday.

Santiago was formally tossed in the fifth inning of the Mariners' road game against the Chicago White Sox following an inspection of his glove.

Santiago was ejected just as he was being replaced by the Mariners with the score tied at 1-1 with the bases loaded.

It marked the first time a player has been thrown out of a game since MLB unveiled new rules designed to deter pitchers from altering the condition of baseballs by applying foreign substances.

Under the crackdown, Santiago now faces an automatic 10-game suspension for the rules breach.

The use of sticky substances by pitchers has come under the microscope since the start of the season as batting averages have plummeted and strikeout rates have soared.

MLB commissioner Rob Manfred said the new rules were necessary to level the playing field after an investigation found widespread use of foreign substances to alter the condition of the ball.

The crackdown has been criticized by players across the league, while some pitchers have reacted angrily during checks of their gloves by game officials.

Manfred said last week, however, the new zero tolerance approach had been well received. He told the New York Times last week he was pleased with the overall results.

"Players in general have been extremely cooperative, the inspections have taken place quickly and between innings," Manfred said.

"Frankly, the data suggests that we are making progress with respect to the issues (in spin rate) that caused us to undertake the effort in the first place."