More than 100 firefighters are battling a large chemical factory fire that is sending thick black smoke across Melbourne's north and likely to burn for days.
MFB chief officer Dan Stephens says the yet to be controlled blaze in Thornycroft Street, Campbellfield, is "highly challenging" and likely to be a "protracted incident".
Mr Stephens likened it to the toxic West Footscray fire last August, which took almost a day to control.
"This is likely to be a protracted incident that will be ongoing for a number of days," he told reporters.
The fire ignited about 6.40am, forcing nearby businesses to evacuate and an advisory for people in Broadmeadows, Campbellfield, Coolaroo, Dallas and Somerton to stay indoors.
Boilermaker Alexander Powell, 28, who works next to the factory, heard the explosion through his earplugs.
"About a quarter to seven we heard a yell, we could see the roof on fire," he told AAP.
"There was a large fireball probably about 40 storeys high. I was wearing earplugs at the time, the noise was enormous, you could feel the heat bearing down on you, so we moved away.
"I was surprised the firefighters were so scared of it."
Dave from the nearby suburb of Wollert, told 3AW radio he saw a "massive explosion that looked like a mushroom cloud".
The address is registered to Bradbury Industrial Services, a toxic waste disposal company whose licence was suspended by the environment watchdog on March 20 for compliance issues.
The firm, which specialises in treating solvent and other waste from paint and related industries - is banned from taking in more waste, but can process what already exists in it until it complies with licence requirements.
At an inspection on March 13, EPA officers found the company was storing more waste than allowed under its EPA licence and storage containers not adequately labelled that were being handled outside an appropriate area.
Mr Stephens says an LPG tank is stored nearby the factory site, but crews have measures in place to protect it.
The fire is sending a large volume of black smoke towards the CBD and witnesses reported seeing plumes as far as Clayton and Coldstream.
"(With) the nature of the hazardous materials in the premise, flammable liquids, we do have a number of running fuel fires which has caused the fire to spread beyond the premise. But we've managed to contain that," Mr Stephens said.
People in the advisory area are urged to ensure all exterior doors, windows and vents are closed and heating and cooling systems are off.
About 30 people self evacuated before crews arrived to find the 30-metre by 30-metre factory fully alight.
One man was taken to hospital for an eye injury.
Paramedics and EPA staff are at the scene, as aerial appliances tackle the fire from above.
