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Researchers have found 24,990sq km of "dead zones", or oxygen-depleted water, in the Gulf of Mexico this summer, the biggest area since tracking of the annual phenomenon began.
They say humans are mostly to blame for the dead waters, and that increased planting of corn to make ethanol is adding to the problem.
Ethanol is a motor fuel distilled from corn and promoted as a more environmentally friendly alternative to petrol.
The dead zones, which have been appearing each summer since at least 1970, threaten marine life and have altered the gulf's ecology, scientists say.
Researchers have been checking them each year since 1985.
Usually, they find only one large zone each year, just off the Louisiana coast where the Mississippi River empties into the gulf.
But this summer, a separate zone has developed off Texas.
Recent measurements show the Louisiana dead zone covered about 20,461sq km, and the Texas zone was 4532sq km - a total of 24,990sq km.
The previous largest amount was 22,002sq km found in 2002, Nancy Rabalais, chief scientist for the Louisiana Universities Marine Consortium, said on Friday.
The Louisiana dead zone is caused mostly by nitrogen-based fertilisers carried by the Mississippi from America's farm belt into the Gulf, she said.
The nitrogen feeds the growth of algae, which depletes oxygen from the water.
The US Department of Agriculture said in March that corn planting would rise 15 per cent this year because of increased demand for ethanol.
Corn needs more fertiliser than other crops, which is probably why tests have found more nitrogen in the Mississippi this year, Dr Rabalais said.
She said only the Baltic Sea had a larger "man-made" dead zone than the Gulf, but it was about four times bigger.
The Texas dead zone was caused by heavy rains that filled the Gulf with fresh water, said Texas A&M University oceanographer Steve DiMarco.
The fresh water sat on top of salt water "like oil and water" and prevented it being oxygenated by air.
Water in the dead zones could not support most life, Mr DiMarco said, and problems were appearing on the Texas coast - "I'm getting reports of some fish kills".
Dr Rabalais said dead zones reduce the amount and variety of marine life and, as a result, had changed the Gulf of Mexico ecosystem, possibly permanently.
The dead zones formed in the calm summer waters and broke up when summer doldrums ended or a hurricane churned through the gulf, she said.
- Reuters