KANSAS CITY, Missouri (Reuters) - Critics say it’s a chemical that could cause infertility or cancer, while others see it speeding the growth of super weeds and causing worrying changes to plants and soil. Backers say it is safe and has made a big contribution to food production.

Young maize seedlings are seen in the corn greenhouse at the Monsanto Research facility in Chesterfield, Missouri in this October 9, 2009 file photo. REUTERS/Peter Newcomb

It’s glyphosate, the key - but controversial - ingredient in Roundup herbicide and the top selling weed killer used worldwide. For more than 30 years, glyphosate has been embraced for its ability to make farming easier by wiping out weeds in corn, soybean and cotton fields, and for keeping gardens and golf courses pristine.

But the chemical touted as a safe, affordable and critical part of global food production, is now at a crossroads.

Amid rising voices of alarm, regulators in the United States and Canada are conducting a formal review of glyphosate’s safety, lawsuits are pending and some groups are calling for a global ban.

“Glyphosate’s days are numbered,” said Paul Achitoff, a lawyer for Earthjustice, an environmental law firm that last month sued the U.S. Department of Agriculture in part over concerns about heavy glyphosate use.

Agricultural seeds and chemicals giant Monsanto Co introduced the chemical to the world in 1974 and has made billions of dollars over the years from Roundup as well as from the “Roundup Ready” corn, soybeans and cotton the company has genetically engineered to survive dousings of glyphosate.

Last year alone, Monsanto made more than $2 billion in sales of Roundup and other glyphosate-based herbicides, though revenues have been in decline amid competition from generic makers since the company’s glyphosate patent expired in 2000.

“I think it would be difficult to overstate the contribution that glyphosate has made and will continue to make to farming,” said Monsanto executive vice president of sustainability Jerry Steiner. “It is a phenomenal product.”

Many top U.S. farmer organizations say glyphosate is too beneficial to give up. But critics say glyphosate may not be as safe as initially believed, and farmers should be fearful.

Environmentalists, consumer groups and plant scientists from several countries are warning that heavy use of the chemical over the years is causing dangerous problems for plants, people and animals alike.

The Environmental Protection Agency is examining the issue and has set a deadline of 2015 for determining if glyphosate should continue to be sold or in some way limited. The EPA is working closely with regulators in Canada as they also assess the ongoing safety and effectiveness of the herbicide.

“The agency plans to re-evaluate risks from glyphosate and certain inert ingredients to humans and the environment during the registration review process,” the EPA said in a written statement. The agency declined to make anyone available to discuss the review.

Meanwhile, Monsanto and its corporate agricultural rivals are scrambling to roll out different herbicides as well as new herbicide-tolerant crops that they hope will halt the advance of weed resistance and silence critics.

“Glyphosate resistance has built up to quite concerning levels in the United States,” said John Ramsay, chief financial officer of Switzerland-based plant sciences company Syngenta, one of many companies introducing glyphosate alternatives.

“It is not surprising that with every single farmer pouring glyphosate over virtually every acre, plant life is going to have something to say about it,” he said.

It all spells potentially big changes for world agriculture and the profits of those companies playing in the chemicals and seeds arena.

A FAVORITE WITH FARMERS

World annual spending on herbicide totals more than $14 billion, with more than $5 billion of that spent in the United States alone, according to the EPA.

Thanks to the spread of herbicide-resistant crops, herbicide use has been increasing rapidly, a factor environmental and consumer groups find particularly concerning.

More than 2 billion lbs of herbicide were used globally in 2007, with one quarter of that total - 531 million lbs - used in the United States in that timeframe, according to a report issued in February by the EPA.

And of the more than two dozen top herbicides on the market, glyphosate dominates all with more than 750 U.S. products containing the chemical.

The top users are farmers. In 2007 alone, for instance, as much as 185 million lbs of glyphosate was used by U.S. farmers, double the amount used only six years earlier. The next most popular herbicide - atrazine - has less than half the amount of usage of glyphosate, according to EPA data.

Already more than 130 types of weeds have developed levels of herbicide resistance in more than 40 U.S. states, more resistant weeds than found in any other country. Experts estimate glyphosate-resistant weeds have infested close to 11 million acres (4.5 million hectares), threatening U.S. farmers’ yields.

On March 18, a cross section of consumer and environmental groups filed another in a series of lawsuits against the U.S. Department of Agriculture for the agency’s approval of more Roundup Ready crops.

The latest suit, which targets Roundup Ready alfalfa, involves a range of concerns, including “the cumulative impact of increased herbicide load on the environment... and the creation of Roundup Ready ‘super weeds’ that become immune to the herbicide Roundup because of overuse.” Yet more Roundup Ready crops will “cause grave harm to neighboring crops, native plants, microorganisms and biodiversity,” the suit states.

Monsanto has acknowledged the spreading weed resistance problems, which are particularly bad for U.S. cotton and soybean growers. And last month Monsanto and Germany-based BASF announced a new collaboration to develop alternative herbicide formulations using “dicamba” and to create dicamba-tolerant soybeans, corn, cotton and canola.

The advent of new herbicides isn’t assuaging critics though. They worry that this may only make the problems with weed resistance worse, because the new herbicides are being used on top of glyphosate, not instead of it, putting even more chemicals into the soil.

“That is going to spell big problems... even larger problems with herbicide-resistant weeds,” said Center for Food Safety analyst Bill Freese. “It will just accelerate this toxic spiral of increased pesticide use.”

ASSESSING THE RISKS

Along with the problem of herbicide-resistant weeds, health-related alarms have been raised by several scientists.

In January, well-known plant pathologist and retired Purdue University professor Don Huber sent a letter to U.S. Agriculture Secretary Tom Vilsack warning of tests that indicated glyphosate could be contributing to spontaneous abortions and infertility in pigs, cattle and other livestock.

Scientists in Argentina last year published a study saying glyphosate caused malformations in frog and chick embryos.

Other scientists, both from private institutions and from the federal government, have said research shows harmful effects of glyphosate products on soil organisms, on plants, and on certain animals. A 2008 lawsuit filed by the Center for Biological Diversity said glyphosate was harmful to California’s red-legged frog and the EPA subsequently agreed it was “likely to adversely affect” the frog.

The Institute of Science in Society has called for a global ban on glyphosate, citing research showing the chemical has “extreme toxicity,” including indications it can cause birth defects. It also submitted a report to EPA.

Another study being looked at by the EPA cited detectable concentrations of glyphosate in the urine of farmers and their children in two U.S. states. Higher levels were found in farmers who did not wear protective clothing when they used glyphosate or who otherwise improperly handled it. The EPA said it will consider data from that study “more fully” as part of its ongoing risk assessment.

The agency also said it is looking at a study partly sponsored by the EPA and the National Institutes of Health (NIH) that found some users of glyphosate were observed to have a higher risk of multiple myeloma, a cancer affecting bone marrow, than people who never used the chemical. The two-fold increased risk was considered “non-significant” and EPA said the findings were preliminary and based on a small number of cases but it is still part of the review.

Monsanto has said repeatedly that glyphosate is safe and it has said studies by Huber and other scientists are invalid.

The EPA also has discounted the validity of many of the studies cited in biomedical literature and by opponents. But it acknowledged there are areas that need more evaluation and has said it wants more data on human health risk and risks to certain endangered species.

“We look closely at every study to determine whether the results are scientifically sound, regardless of the source,” EPA officials said in a written statement.

The EPA is not doing its own studies, instead evaluating information from others. Much of the data is coming from the agricultural chemicals industry as part of a registration review program that aims to examine each registered pesticide every 15 years.

The agribusiness giants, including Monsanto, Syngenta, Dow Chemical, and BASF, have formed a 19-member task force to generate the data the EPA is seeking.

Another factor rankling opponents is that the EPA is using a lower safety standard than they argue it should.

Though the Food Quality Protection Act requires the EPA to use an extra tenfold (10X) safety factor to protect infants and children from effects of the pesticide, the agency determined there was adequate data available to show that the margin of safety for glyphosate could be reduced to only a 1X factor.

The EPA’s Office of Pesticide Programs is in charge of the review and has three main options -- continued approval of glyphosate with no changes; canceling the registration to ban its use in the United States; or continue as an approved product but with some modifications for its use.

The agency said it wants all the relevant data gathered by the summer of 2012 and expects to have a final decision no earlier than 2015.

Canada is likewise re-evaluating glyphosate and is coordinating with the United States to “harmonize the assessments,” the EPA said.

Both supporters and detractors say it is uncertain what the future holds for the world’s favorite weedkiller.

Wellesley College professor and food expert Professor Robert Paarlberg said critics are fueled more by dislike for Monsanto than real evidence of harm.

“The critics would do well to spend more time talking to farmers, who continue find glyphosate a safe and convenient way to control weeds,” Paarlberg said.

The science argues otherwise, according to Huber, who has asked USDA to conduct in-depth research on glyphosate’s effects. Huber was heavily criticized by Monsanto after his January letter to the USDA but he sent a second letter to Vilsack on March 30, reiterating his concerns.

“We are experiencing a large number of problems in production agriculture in the U.S. that appear to be intensified and sometimes directly related to genetically engineered crops, and/or the products they were engineered to tolerate - especially those related to glyphosate,” Huber wrote. “A large reduction in glyphosate usage would be a prudent consideration.”