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The explosion happened about 7:50 p.m. local time (0050 GMT Thursday) in the city of West, some 320 kilometres north of the Texas capital of Houston.
There are no official casualty figures, but Dr George Smith, the head of Texas Emergency Medical Services in West, said at least 60 were dead and some 170 injured, broadcaster KWTX reported.
West Mayor Tommy Muska told an earlier news conference it had been confirmed at least four or five rescuers and firefighters were missing.
Muska said a fire broke out at the fertilizer plant before the explosion, which devastated surrounding areas, destroying 10 homes and damaging 50 more – it also triggered a 2.1-magnitude earthquake.
Witnesses said an evacuation had already begun before the explosion due to the fire at the plant and that the huge explosion sounded like a nuclear bomb and sent a mushroom cloud into the air.
Rescuers launched a door-to-door search overnight in the area near the explosion, looking for dead or injured.
Waco Police Department spokesman William Swanton told reporters that local authorities are still busy moving people out of the disaster area home by home and business by business, and that evacuation is very cautious, as many buildings have sustained structural damage and could collapse at any time.
Toxic gas is feared to have been released into the air and authorities are worried that a second fertilizer tank may explode.
The cause of the explosion and the earlier fire in the plant is under investigation.
West is a small city of 2,600 residents – half of the town was evacuated after the explosion.