The chemical is sold under the brand name NutraSweet, among others.
The study, conducted by a team of Italian scientists, demonstrates that aspartame is particularly potent when animals are exposed in utero and during development. The rats were exposed to the sweetener at levels above and below the recommended daily maximums for people.
The research was published online this month in Environmental Health Perspectives, a U.S. government sponsored, peer-reviewed journal.
This study raises "serious questions about the safety of the artificial sweetener aspartame," said Mike Jacobson, executive director for the Center for Science in the Public Interest, a public health watchdog group based in Washington, D.C.
He is hoping the Food and Drug Administration will take notice and re-evaluate the artificial sweetener.
But the Calorie Control Council, an industry group, disagrees. Beth Hubrich, a registered dietitian for the council, said the methodology was faulty, and she expressed concern that the study would unnecessarily alarm people.
"It is difficult to understand why the National Institute of Environmental Health Safety would publish such studies in Environmental Health Perspectives when the design and execution did not follow guidelines set up by the National Toxicology Program," Hubrich wrote in an e-mail.
The study, from the European Ramazzini Foundation of Oncology and Environmental Sciences -- an independent, non-profit foundation based in Bologna, Italy -- indicated that cancers, including lymphomas, leukemias and breast cancer, were more common in rats exposed to the sweetener than in animals that were not exposed. And there was dose-related response.
"On the basis of our scientific data, we believe that aspartame should be avoided as much as possible, especially by pregnant women and children," Morando Soffritti, the lead researcher on the study, wrote in an e-mail.
The acceptable daily intake of aspartame is 50mg per kilogram of body weight in the U.S., and 40mg per kilogram of body weight in the European Union.
For a 150-pound U.S. adult, that is about 18 cans of diet soda each day. For a 50-pound child, it is closer to six cans a day.
But aspartame is not just in diet sodas. It is also in yogurts, sugar-free desserts, gums and medicines. Therefore, it is likely that one's daily aspartame consumption is often underestimated, according to Soffritti.
To investigate the effects of the sweetener on rats, Soffritti and his team separated pregnant females into three groups. One group was given feed with a high dose of aspartame (100mg/kg body weight), another group was fed a lower dose (20mg/kg body weight) and the third group had no sweetener.
Feeding was initiated on the 12th day of pregnancy.
The mother rats were killed after weaning their pups, and their offspring were allowed to live until they died of natural causes. The offspring got the same feed as their mothers.
In all, 400 rats were examined in this study.
When the offspring died, they were examined for cancer and disease. The researchers looked at their skin, fat, mammary glands, brains, pituitary glands and salivary glands.
The Italian team discovered a statistically significant dose-related increase of malignant tumors in rats who were fed the artificial sweetener. The high-dose group showed statistically significant increases in tumors -- as much as 15 percentage points higher in males -- while the low-dose group showed non-significant increases in lymphomas and leukemias in both sexes, and breast cancers in females.
The results, Soffritti said, "call for urgent reconsideration of regulations governing the use of aspartame as an artificial sweetener."
"This is not just an opinion," he said, "but in the U.S., it is also the law."
The Delaney Clause of the Food Additives Amendment of 1958 mandates that any food additive shown to cause cancer in people or in laboratory animals -- as demonstrated in rigorous safety tests -- should be considered unsafe by the Food and Drug Administration.
"The law was designed to protect citizens with a zero cancer risk standard," Soffritti wrote in an e-mail. "Now that aspartame has been demonstrated to induce cancer in animals, it follows that aspartame is not safe as a food additive for humans. Human consumers should not only be warned, but also protected from this risk."
The same research group published a similar study in 2005. However, the scientists did not expose animals prenatally in that experiment. This new study, they say, provides more sensitivity and strength to the aspartame-cancer link.
Others, however, beg to differ. James Swenberg, professor of environmental sciences and engineering at the University of North Carolina, said the group did not follow the National Toxicology Program's methodology, and therefore, the results were suspect.
He said letting the animals die of natural causes -- and not killing them at two years, as the toxicology program does -- could confound, or at least confuse the findings.
He said when tissue gets old, as it does in long-lived rats, it is hard to make precise and accurate pathology reports.
"That's really less than optimal," he said.
The FDA agreed. In a letter drafted in April, the agency concluded that despite the Italian group's work published in 2005, aspartame should still be considered safe. In response to the 2007 study, the FDA said it has not found evidence to support a change in its conclusions about the safety of aspartame.
Devra Davis, an epidemiologist at the University of Pittsburgh Cancer Institute, said the work done by the Italian group was cutting edge, and the researchers' methodology was "the wave of the future."
"You kill a rat at two years, that's comparable to killing a person at 60," she said.
Let them live the entirety of their lives, and you're following the animals into the equivalence of their 80s, she said, adding "some of us are concerned about life after our 60s."
She said the Italian team was "among the premier research groups in the world." And she said that "it would be a mistake not to take this study seriously."
Robin Mackar, a National Toxicology Program spokeswoman, did not respond to a request for comment.
KNOWING YOUR LIMIT
The acceptable daily intake of aspartame is 50 milligrams per kilogram of body weight. What that means:
For a 150-pound U.S. adult: About 18 cans of diet soda per day. For a 50-pound child: About six cans.
But aspartame is not only found in diet sodas. It is also in "light" yogurts, sugar-free desserts, gums and medicines.
From the July 2, 2007, Prepared Foods e-Flash