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Four people were rushed to hospital, including two firefighters and two workers, after the paint factory on Superior Drive in Dandenong South caught fire about midday.
Strong winds along with excessive black smoke prompted authorities to issue a watch and act alert for residents living in Bangholme, Dandenong South and Lyndhurst.
Residents living near Hammond Road have also been urged to take shelter indoors.
Fire Rescue Victoria Assistant Chief Fire Officer Greg Christison said it was a “challenging and complex” fire.
Although the fire is still burning out of control, Christison said he was hopeful it would be contained in the coming hours.
”The fire involves a factory that has a lot of liquid chemicals in it. Our firefighters are working hard in some arduous conditions,” he told reporters.
Ambulance Victoria transported a 60-year-old man to The Alfred, along with another man.
It’s understood the two men received burns to their upper bodies.
A man in his 40s and another in his 30s were transported by road to Dandenong Hospital in a stable condition with upper-body injuries.
Victoria Police and Ambulance Victoria remain on scene.
Hammond Road remains closed between Bangholme and Greens Road.