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A building collapse occurred at a construction site in the township of Tongaat about 4:30 p.m. local time, at the end of the working day and after many workers had left on Tuesday.
Police said one woman was confirmed dead at the scene and three people remained unaccounted for.
KwaZulu-Natal Premier Senzo Mchunu said he was shocked by the "horrific accident" and expressed confidence an investigation into its cause would be quickly carried out.
In a statement describing the collapse as "calamitous," the Department of Labour said its acting director, deputy director of inspection and enforcement and the commissioner for its Compensation Fund were visiting the site.
The South African Press Association (Sapa) said the search and rescue operation had been called off so that the department could move some of the rubble.
It quoted a police spokeswoman as saying it was possible that more people were trapped in the debris.
Speaking from the scene Tuesday, Crisis Medical operations director Neil Powell told CNN the construction work had been taking place beside a shopping mall.
"It's unknown exactly what caused the collapse. There was a large amount of scaffolding and cement foundation that collapsed onto some of the construction workers," Powell said.
He said those taken to a hospital for treatment had suffered injuries ranging from moderate to critical.
Max Foster speaks with Neil Powell of Crisis Medical who is on the scene of a deadly building collapse in South Africa.