In October 1997, inhabitants of the Bjare peninsula in southwestern Sweden began to worry when their cows suddenly became paralyzed and died, and dead fish were found floating in breeding pools.
Suspicion turned to the massive railroad tunnel being bored through the Hallandsås horst, a ridge of porous rock between two faults in the earths crust. Contractors for the national railway agency had been working for months to plug leaks that played havoc not only with tunnel construction, but with the water table in the regions rich farmland.
A national scandal erupted in green-conscious Sweden when news reports revealed the cause: 1,400 tons of a sealant called Rhoca-Gil had been injected into cracks in the tunnel walls, contaminating ground and surface water with the toxic chemical acrylamide. Tunnel workers suffered numbness due to neurotoxicity.
For fear of contamination, milk and milk products from the region were dumped, vegetables were left to rot in the fields, and cattle were slaughtered and burned. Protests, lawsuits, and resignations by government and industry executives soon followed. And although no human deaths were reported, fears linger over possible long-term health effects of acrylamide, which is classified by the International Agency for Research on Cancer (IARC) as a probable human carcinogen.
No wonder, then, that while Americans may have shrugged in response to the Swedish governments April 24 report on acrylamide in cooked foods, Swedes were more concerned.
The surprising new findings, in fact, trace their origins to the tunnel investigation. Margareta Törnqvist, Ph.D., of the Department of Environmental Chemistry at Stockholm University was called in to study the tunnel workers exposure to acrylamide. Using mass spectrometry to measure an acrylamide reaction product bound to hemoglobin in the blood of workers and a control group of subjects without occupational exposure, she was puzzled to find relatively high "background" levels of acrylamide in both groups. The ubiquity of these hemoglobin adducts led to a hypothesis that acrylamide might be ingested in the diet.
In a study published in the June 2000 issue of Chemical Research in Toxicology, Törnqvist and colleagues reported that rats fed fried rat food had much higher levels of the adduct than rats fed uncooked food. The authors concluded that "an evaluation of cancer tests of acrylamide and available data for its metabolism leads to the estimation that the background dose of acrylamide"that is, the amount ingested in food "is associated with a considerable cancer risk."
In an interview, Törnqvist said a press release on these findings was suggested 2 years ago, but she asked the journal not to do it. "We knew there would be so many questions we couldnt answer about human foodstuffs, and great pressure on our small research group," she said. "We didnt want to scare people unnecessarily since we knew too little yet about the problem."
Instead, her group continued to study acrylamide in food, and this year had an article accepted for publication in the Journal of Agricultural and Food Chemistry. They found high levels of acrylamide particulary in fried and potato-based foods. When officials at Swedens National Food Administration saw Törnqvists data, they initiated their own analyses which confirmed the data from Törnqvists group. Potato chips, french fries, biscuits, and crackers had the highest levels, while breads, breakfast cereals, and corn chips had somewhat lower amounts. Boiled foods and animal products (even when fried) had relatively negligible levels.
Acrylamide concentration varied widely across different samples of foodfor example, potato chips ranged from 330 to 2300 micrograms (mg) per kgsuggesting that the concentration of acrylamide is influenced by the method of preparation. Preliminary testing showed that the higher the cooking temperature, the higher the acrylamide concentration. By comparison, World Health Organization guidelines limit drinking water to 1 mg of acrylamide per liter of drinking water and stricter European Union regulations will set the limit at 0.1 mg per liter next year.
When officials at Swedens National Food Administration saw Törnqvists data, they decided not to release the findings from their own analyses on the acrylamide content of various foods along with information on acrylamides toxic effects, its estimated cancer risk, and the agencys progress with studies to better quantify levels in foods. (An English version is online at http://www.slv.se/HeadMenu/livsmedelsverket.asp.)
The National Food Administrations advice is cautious: since fried foods are already believed to be unhealthy, reduce their consumption. Since cereal products are part of a healthy diet, continue to eat them.
Critics have blasted the agency for publicizing data before peer review and raising a cancer scare based on scant evidence that the public could do little to avoid. Some have even accused the agency of exploiting the report for political ends in a bid to restore funding that had been cut.
Magnus Ingelman-Sundberg, Ph.D., deputy chairman of the Division of Molecular Toxicology at the Karolinska Institute, Stockholm, said that the data should have been published in a medical journal of high impact before going to the public because the risk assessment would have been peer reviewed along with the chemical data.
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Leif Busk, Ph.D., head of the Research and Development Department at the National Food Administration, vehemently denied the charge of playing politics, arguing that such transparent tactics would never work anyway.
Busk defended the decision to publicize the results based on the unchallenged status of acrylamide as an animal carcinogen along with "value judgments" about when a potential human health risk is serious enough to alert the public. Although not yet published, the findings have in fact had one round of peer review, he noted. (Törnqvist said her article is undergoing further review at the journal following the release of her findings.)
With the acrylamide data, Busk said, "we are getting a very strong signal of a problemthe strongest signal weve seen with a single chemical entity in food. Something has to be done."
He said that barely contained leaks of Törnqvists findings in weeks preceding the announcement, coupled with the Swedish populations acute awareness of acrylamide after the Hallandsås tunnel fiasco, gave the National Food Administration a responsibility to put the issue in context for the public and prevent a panic reaction.
"The risk analysis at the time [of the tunnel leak in 1997] showed that there was no problem whatsoever for consumers, not a trace of acrylamide in any of the [agricultural] products," he said, "but still, there was mass hysteria in Sweden. So I saw what could happen if [the new findings] came out without our comments."
Busk said the new information is particularly important for the food industry, given the evidence that acrylamide levels might be altered through changes in cooking methods. In fact, he said industry sources have already reported preliminary success in reducing acrylamide levels.
Ingelman-Sundberg attacked both the logic of extrapolating rodent data to humans and the conclusions drawn from such comparisons. He said differences in carcinogen sensitivity and metabolism limit the relevance of interspecies comparisons, but added that a person would have to eat 75 kg of chips per day to get even one-tenth of the lowest observed genotoxic dose in rats (25 mg per kg).
He argued that no epidemiologic evidence supports a role for acrylamide as a human carcinogen. Gary M. Marsh, Ph.D., and colleagues at the University of Pittsburgh studied 8,508 potentially acrylamide-exposed workers in four U.S. chemical plants owned by Cytec Industries. The workers exposure came through inhalation of acrylamide used in manufacturing of polymer products. In the Cytec-supported study, published in the Sept. 1, 2001 Occupational and Environmental Medicine, the Pittsburgh investigators reported finding "little evidence of a causal relation between exposure to acrylamide and mortality from any cancer sites."
Ingelman-Sundberg concluded that Törnqvists findings were "interesting in that a rodent carcinogen was identified in food products, but the risk for human health was extremely much overemphasized" by the agency.
"I think we can never monitor any effect of acrylamide on human cancer," he said, adding that he expects this will prove just another soon-forgotten cancer scare.
Törnqvist and Busk do not share Ingelman-Sundbergs dismissive attitude toward the risk, but both agree that linking acrylamide in food to cancer presents a daunting challenge for epidemiology. Some of the foods, such as bread, are so nearly universally eaten that identifying populations with widely different exposures will be difficult. Acrylamide is also a constituent of tobacco smoke, and the body even seems to makes some of the chemical naturally.
In addition, there is no known rationale for tying acrylamide to any specific type of cancer incidence. Glycidamide, the suspected toxic metabolite of acrylamide, is long-lived and extremely water-soluble and is evenly distributed throughout the body, making it impossible to predict which types of cancer would be most likely to develop. Brain, thyroid, and reproductive system tumors are most commonly seen in rats, but experts said this may not translate to human cancers.
One possibility, Törnqvist said, would be a retrospective study covering the period when french fries and chips gained favor over traditional foods such as boiled potatoes. Another, said Busk, would be to study far-flung populations whose diets are very different. IARCs European Prospective Investigation into Cancer and Nutrition (EPIC) study fits the bill, with data and blood samples on 520,000 people from northern Sweden to southern Greece, and Busk said the EPIC investigators have agreed to help in pursuing the acrylamidefood connection.
Busk said the food agency has initiated discussions with epidemiologists Walter Willett, M.D., Dr.P.H., and Hans-Olov Adami, M.D., Ph.D., at the Harvard School of Public Health, Boston. (Adami also heads the Department of Medical Epidemiology at the Karolinska Institute.)
One lesson from the acrylamide story that may not be obvious, Törnqvist said, is that toxic chemicals are unavoidable, given that they have now been found in foods that have been eaten around the world for millennia, and in some cases, made by the body itself.
"We can never take away the acrylamide, but we can reduce exposure," she said.
WHO will hold an urgent expert consultation this month to address basic questions about acrylamide exposure that need to be answered before any recommendations can be made. In the meantime, according to a WHO release, "None of the results announced April 24 in Sweden would cause WHO to change its basic dietary advice ... eating more fruits and vegetables and less fat-containing foods."
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