A huge cloud of dark smoke clouds bellows above a fire behind a police block at the BASF chemical plant site in Ludwigshafen, Germany, 17 October 2016.

At least two employees are dead while two people are missing and another six people have been severely injured following a violent explosion and fire on Monday at the world's biggest chemical company, BASF, in western Germany.

Police have called on residents in the city of Ludwigshafen, where the sprawling BASF complex is located, and the nearby city of Mannheim to stay indoors and suggested they close all windows and doors and shut down air-conditioning and ventilation systems.

"The situation is still very confusing and changes from minute to minute," said BASF medical director Stefan Lang.

The company said it was still seeking to determine the exact cause of the blast, which occurred during work on a pipeline route for transporting products for processing from the company's Rhine river port to production sites.

"We will, of course, make every effort to find out quickly," said BASF plant manager Uwe Liebelt.

Sirens rang out as emergency services descended on the vast 10-square-kilometre BASF complex late morning Central European time as a large plume of dark smoke billowed over what is the world's largest chemical site.

The fire is now under control but it will take until this evening to successfully dampen down, said Ludwigshafen fire brigade chief Peter Friedrich.

The fire brigade had been battling fire in the company's port area when the explosion occurred, officials said.

Liebelt said that the accident did not pose any measurable threat to the general population.

But he said there was still no detailed information about which chemical substance had originally caught fire.

Liquid gases as well as flammable liquids are also loaded at the port.

BASF said the site's two steam cracker units – the heart of the company's operations in Ludwigshafen which are used in the production of key chemical components - have been shut down for safety reasons.

But BASF said that it was not at this stage considering the costs to the company of the fire and explosion. "The economic damage is not my biggest problem today," said Liebelt.

Motorists have also been asked to avoid the area around the complex where more than 39,000 employees work - about one third of BASF's total global workforce. An emergency hotline has been set up.

Police have, however, ruled out a terrorist attack.

The BASF plant was also hit by a major explosion two years ago, which left two workers dead and 22 people injured.

BASF, which has a corporate history dating back 150 years, had total sales last year of about 70 billion euros (77 billion dollars).

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