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The vote in Colorado on Tuesday was overwhelmingly against the labeling, while Oregon's was much closer.
While the defeats were hard to accept for advocates, it's not the end of the effort to get GMO foods labeled on store shelves, said Joel Warady, chief sales and marketing officer for Enjoy Life Foods, a food producing company in Schiller Park, Illinois, that shuns GMO made products.
"It does set the movement back," Warady said. "But it doesn't set back consumer sentiment on wanting GMO labeling. I think the fight will continue."
Monsanto, which is the world's biggest producer of GMO crop seeds and spent millions to defeat the two measures, was happy at the outcome.
"We're pleased that Colorado and Oregon farmers, food producers, retailers and especially consumers will not be subject to these costly measures and will not be unnecessarily economically impacted by the burden these labels would create," spokeswoman Charla Lord said in an email to CNBC.
GMOs are the result of a laboratory process of taking genes from one species and inserting them into another in an attempt to get desired traits such as resistance to disease or tolerance of pesticides.
Several common ingredients like corn starch and soy protein are predominantly derived from genetically modified crops.
GMOs are present in 60 to 70 percent of foods on U.S. supermarket shelves, according to the Center for Food Safety.
The science around GMO safety and whether they are harmful to humans is far from definitive, as even proponents of labeling admit.
"I can't take a firm stance on whether they are safe are not," said Derek Peterson, CEO of Terra Tech Corp., which develops environmentally friendly agricultural equipment.
"But consumers need to know about GMOs in their food because we don't have all the information," Peterson said.
Had the measures passed, Oregon and Colorado would have been the second and third states to require GMO food labeling.
But it does face legal challenges from food manufactures and organizations like the Grocery Manufacturers Association, the National Association of Manufacturers, International Dairy Foods Association and the Snack Foods Association.
Maine and Connecticut have passed labeling laws—but they only go into effect when five other states in the Northeast pass or legislate their own GMO laws.
Monsanto along with food companies like Kraft Foods, PepsiCo, Kellogg and Coca-Cola reportedly contributed roughly $20 million to defeat the ballots In Oregon and Colorado.
That's said to be triple the money raised by supporters of the initiatives.
They've had a track record of success so far. Last year, a statewide vote on GMO labeling suffered a narrow defeat in Washington state. The year before, an effort in California failed.
"The reason we don't support them is simple. They don't provide any safety or nutrition information and these measures will hurt, not help, consumers,taxpayers and businesses," Monsanto's Lord said.
The cost of GMO labeling, which would supposedly be passed on to consumers, has been used by GMO backers as a key reason to reject labeling.
Warady said that doesn't make sense.
"It's absurd to make that claim about the cost of labeling," he said. "Food products get label changes all the time. Whether it's new product information or something else, it happens a lot."
But just the idea of labeling GMO foods is wrong from the start, said Tim Richards, professor of agribusiness and resource management at Arizona State University.
"It's like putting a skull and crossbones on a food product," Richards said. "GMO labels would be telling people this is toxic while there's no definite proof it is."
Brenda Morrison, a partner at the Denver-based policy analysis firm Engaged Public, said Coloradans may not have been properly prepared to accept the label law.
She conducted a focus group with about 20 eligible voters on the GMO law before Tuesday's vote, and let them hear from both sides.
"The issue wasn't ready for prime time in Colorado," Morrison said. "The proponents had a hard hill to climb on educating people about the law."
"And there was the money spent by opponents," she said. "That was a huge factor in its defeat."
But if anyone thinks the GMO labeling issue is going away, they'd be wrong.
"Last night's decision only strengthens our resolve to fight for the consumers' right to know what's in their food," said Scott Faber, executive director of Just Label It, a proponent of GMO labeling.
And there's some hope for them to build on.
Voters in the Hawaii's county of Maui narrowly approved a measure Tuesday that would prohibit any growth, testing or cultivation of genetically modified or engineered crops and would put a stop to any genetic modification and engineering operations in the county.
That ban would exist until an environmental and public health study is conducted and finds the proposed cultivation practices to be safe and harmless.
However, on Thursday Monsanto said it will file a lawsuit challenging the legality of the measure.