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Every research scientist knows that discovery often depends as much on happenstance--serendipity--as it does on methodical searching. If a group of researchers from Stockholm didn't know it earlier, they certainly learned the lesson over the last five years. The presence of acrylamide bound to hemoglobin in laboratory workers who perform polyacrylamide gel electrophoresis--a commonly used method to separate and analyze proteins-- wasn't necessarily surprising, but when Emma Bergmark of Stockholm University also found it in people who didn't work with the reagent, it was indeed puzzling.1 So a group led by Margareta Tornqvist, also of Stockholm University, decided to find out how the chemical-- a known neurotoxin and possible human carcinogen--found its way into the bloodstream of John and Jane Andersson.
Preliminary data indicated that acryl-amide levels are much lower in wild animals, so the researchers wondered if people ingest it in food. And, because it is also found in tobacco smoke, they suspected that high- temperature heating might be involved. To find out, they fried rat food and, after feeding it to animals for one to two months, compared the amount of acrylamide in the rats' blood to levels in those fed an unfried diet. Not surprisingly, the amount of acrylamide-hemoglobin adduct was 10 times higher in rats on a fried food regimen when measured by combined gas chromatography and massspectrometry.2 The level was also similar to that detected previously in human controls, further strengthening the hypothesis that there's more than ketchup on french fries.
The group's next step was to actually measure acrylamide in cooked food, and what they found set off alarm bells from Scandinavia to San Francisco. First announced in a press release last April and formally published by the American Chemical Society in August,3 the researchers discovered an average of 0.4 mg/kg of acrylamide in restaurant-prepared fries, and potato chips weighed in at 1.7 mg/kg. Just to be sure, the team used two methods to measure acryl-amide instead of one, and their numbers were reproducible. Oven baking is also a problem; acryl-amide is even in break- fast cereals.
Interestingly, cooked protein-rich foods, such as chicken or fish, contain far less acrylamide, while fried beet roots have more--in other words, it's carbohydrates that count. Acrylamide doesn't accumulate after boiling, so frying and baking are necessary. "I would say that boiling at 100°C is the only safe cooking method," advises Tornqvist. That might not sit well with an increasingly obese public whose appetite for fast food seems insatiable.
REVERBERATIONS It didn't take long for the fat to hit the fire. The United Nations' Food and Agriculture Organization (FAO) quickly issued a press release after the April Stockholm announcement, saying it was "too early to reach any conclusions" from the study. FAO welcomed further research at the international level. Meanwhile, the World Health Organization (WHO) called for a consultation panel to examine the issue. By early June, both the British and Norwegian governments confirmed the Swedish findings. Said the British Food Standards Agency, "What is important now is to identify research required to understand the formation of acrylamide, how it might affect people, and what may need to be done as a result." While the British did not recommend immediate changes in diet, the Norwegians asked citizens "not to fry food too hard ... to be on the safe side."
On June 25, Michael Jacobson of the Washington, DC-based Center for Science in the Public Interest asked the US Food and Drug Administration (FDA) to "advise people to cut back on foods that ... are most contaminated." Calling it "a serious health problem" that deserves urgent action, Jacobson claimed that acrylamide in American foods "may be causing several thousand cancers per year."
In responding to Jacobson's letter, the FDA said it was awaiting further data, noting that three of its scientists were participating in the WHO consultation that week. FDA and the US Environmental Protection Agency (EPA) posted methods to measure acrylamide in food, and a German company offered to test for it. The National Food Processors Association urged all those involved to "let science lead the way," and not "jump to conclusions ... or use this issue to advance political or activist agendas."
All this caught the attention of the press, of course. As of August 1, Lexis-Nexis Academic Universe, an Internet information provider, listed 98 articles on the subject in major newspapers.
The WHO panel, conducted jointly with FAO, recognized that food-borne acrylamide is "a major concern in humans," and proposed an international data-sharing network called Acrylamide in Food to gather more information.4 It also listed several ways to reduce risk, including a balanced diet with "a moderate consumption of fried and fatty foods." But without more research, the question remains: What really is the risk?
WHERE'S THE BEEF? Acrylamide is a reactive three-carbon molecule used for nearly 50 years in the plastics industry. The polymer, polyacrylamide, is a gel-like material known to most biologists as a substrate for separating proteins. It is also an ingredient in all sorts of things, including inks, cosmetics, adhesives, and the absorbent material in diapers. About 100 million pounds of it were produced in 1992. But far and away the largest use of polyacrylamide is as a flocculant to clarify drinking water and wastewater. Polymer preparations aren't pure, so at least some soluble monomer leaches into the water. After ingestion, acrylamide rapidly makes its way into body fluids and tissues where, in higher doses, it can act as a neurotoxin and reproductive poison. It also causes tumors in rats. Most is excreted, though, bound to a common metabolite called glutathione.
For humans, WHO estimates an excess lifetime acrylamide cancer risk of one in 100,000 at a consumption of 0.5 µg of acryl-amide per liter of water. The EPA requires less than 0.5 ppb in drinking water. But acrylamide also passes through the lungs and skin--every biochemist knows to wear gloves when preparing gels. The US Occupational Safety and Health Administration limits airborne exposure to 0.03 mg/m3 per 8 hours.
A HEALTHY DOSE OF PERSPECTIVE Between 1987 and 1993, 40,000 pounds of acrylamide--primarily from plastics plants--contaminated land and water resources, according to EPA estimates. Fortunately, acrylamide's reactivity means that it doesn't accumulate in the environment; it degrades in a matter of days. But with acrylamide routinely found in the environment, including drinking water, how dangerous are the small quantities found in food? James Klaunig, director of the State Department of Toxicology at Indiana University-Purdue University in Indianapolis, works on acryl-amide and minimizes the risk of any health fallout for people. It's a relatively weak carcinogen in rats, he thinks, requiring high doses and long-term exposure to cause tumors.
Marvin Friedman agrees. He is a toxicologist and science adviser with Saint- Etienne, France-based SNF Floerger, the world's largest producer of polyacrylamide. Friedman attended a meeting in Washington, DC, during which people from the chemical industry revealed what is known about the substance to representatives from federal agencies and the food industry. Says Friedman, "There's a long history of research from industry, but the food people didn't know about it. They said, 'We wish we had this information before the WHO meeting.'"
Photo: Courtesy of Indiana University School of Medicine
According to Friedman, experts have concluded that "the rat cancer model isn't relevant to [humans]. The risk is overrated." Besides, nobody has documented acryl-amide carcinogenicity in humans, despite epidemiological studies on workers routinely exposed to the monomer. "Only limited human population data are available for acrylamide, and these provide no evidence of cancer risk from occupational exposure," concluded the FAO/WHO panel. "My own take is it's not a problem because of the dose/response effect," and because levels are so low in food, adds Klaunig.
For all that toxicologists think they know about acrylamide, they have no idea how it's formed during frying and baking. The industrial process uses acrylonitrile as a precursor, but it's doubtful the chemical occurs in food. "I'm comfortable with the data [on acrylamide]--what's being seen is there," admits Klaunig. "I'm not sure how it's produced." Other experts are equally perplexed, though Klaunig rules out an environmental contaminant. And the British Food Standards Agency recently nixed food packaging as a source. Friedman, who has "heard all sorts of postulates" about how it is formed during cooking, says, "I suspect there's an awful lot of research going on" to solve the mystery.
Barry A. Palevitz (firstname.lastname@example.org) is a contributing editor.
1. E. Bergmark, "Hemoglobin adducts of acrylamide and acrylonitrile in laboratory workers, smokers and non-smokers," Chemical Research in Toxicology, 10:78-84, 1997.
2. E. Tareke et al., "Acrylamide: a cooking carcinogen?" Chemical Research in Toxicology, 13:517-22, 2000.
3. E. Tareke et al., "Analysis of acrylamide, a carcinogen formed in heated foodstuffs," Journal of Agricultural and Food Chemistry, 50:4998-5006, 2002
4. World Health Organization, "FAO/WHO consultation on the health implications of acrylamide in food," June 25-27, 2002, available online at www.who.int/fsf/Acrylamide/SummaryreportFinal.pdf.