An investigation was under way today into how untreated sewage and cyanide made its way into part of one of the country's major rivers.
Thousands of fish have already died and more wildlife is at risk following the "pollution incident" in the River Trent in Staffordshire.
The Environment Agency yesterday issued a warning for people and animals to keep out of the river between Stoke-on-Trent and Yoxall, after the pollution made it a potential health risk.
A spokeswoman said: "This is due to untreated sewage and cyanide at levels that are potentially a cause for concern, especially with regard to fish, wildlife and animals. Thousands of fish have already died.
"The warning to stay out of the river applies to everyone, including farmers, anglers, dog walkers, boaters and anyone using the river for work or pleasure.
"We have also received advice from the Food Standards Agency that people should stop extracting water temporarily so water should not be taken out of the river for any reason."
She said it was also important to keep all animals away from the water, including farm animals and dogs.
"We are tracking the pollution as it moves downstream," the spokeswoman added.
"It is likely to travel downstream of Yoxall (today), reaching Burton on Trent area late (this afternoon) by which time it will have been diluted so the risk may well have reduced."
She said officers were monitoring the situation.
The Environment Agency was working with "key partners", she said.
An investigation has been launched into the cause, but she said this could not be discussed for legal reasons.
The RSPCA urged members of the public not to go near any animals in distress but instead to report any sightings to the charity.
A spokeswoman said: "What we're trying to advise members of the public to do is if they see any animals in distress not to go near them but to report them to our Cruelty and Advice line, like details of where, what and so on.
"We will probably be having a team go to the area and we will be getting involved with the Environment Agency and other agencies.
"We expect there will be quite a big clean-up operation involved.
"For those people with livestock we would remind them to get them away from the area as safely as possible."
Anyone who spots animals in difficulty is asked to call the RSPCA's Cruelty and Advice line on 0300 1234 999.
The Environment Agency manages fisheries, flood defence, navigation, recreation and nature conservation. In Scotland, the River Purification Boards control river pollution.
The Water Resources Act 1991 allows the Environment Agency to police the use of water in England and Wales.
Just last month in a separate incident, water company Severn Trent Water was fined almost £7,000 for allowing pollution to enter the River Trent after a prosecution brought by the Environment Agency.
The company was fined £6,700 and ordered to pay costs of £2,777.80 at Stafford Magistrates Court after pleading guilty to causing sewage pollution to enter the River Trent.