The raw water supply for the northern KwaZulu-Natal town of Dundee and surrounding areas has been poisoned with cyanide, uThukela Water said on Friday.
The spill was discovered on Thursday morning when cows died after drinking from a stream near a site outside Newcastle, spokesman Dumisani Thabethe said.
Residents appeared to have escaped harm so far.
"There is no one who has been reported to have been affected by the spillage," he said.
Thabethe said: "We are told that about 11 cows have died, but by late evening it was 50, but I am not too sure about the accuracy of the figures.
"Our concern is people getting water directly from the river."
As a precaution, uThukela Water broadcast a warning on the Newcastle community radio station on Thursday.
The spill might have come from a site where synthetic rubber was being manufactured, but this was still being investigated, Thabethe said.
The Ngagane river was flushed with water from the Ntshingwayo dam on Thursday in an attempt to dilute the chemical content.
Water was being released from the dam at 16,000 litres per second.
Thabethe said HTH, chlorine used in domestic swimming pools, was poured into the river before it was flushed.
"They were hoping to stimulate a chemical reaction between the HTH and the cyanide."
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