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FDA Draft Action Plan for Acrylamide in Food - February 24, 2003 Update
For more recent information, see FDA Action Plan for Acrylamide in Food.
February 24, 2003
FDA has developed an action plan for acrylamide in food. The action plan outlines FDA's goals and planned activities on the issue of acrylamide in food and includes a timeline of planned meetings. It also discusses FDA's intention to work with other federal agencies and to participate in international efforts. The action plan will guide FDA's activities on the issue of acrylamide over the next several years. FDA made a draft version of the action plan available on the CFSAN website. FDA also presented the draft action plan for public and scientific comment at a public meeting on September 30, 2002, and at a meeting of the Subcommittee on Contaminants and Natural Toxicants of the Food Advisory Committee on December 4-5, 2002. The draft action plan has been revised based on input at these meetings, and FDA is presenting this revised action plan to the full Food Advisory Committee (FAC) on February 24-25, 2003, in order to receive input that will assist FDA in finalizing the plan. FDA will develop future revisions of the plan, as needed, based on public comment from meetings and on knowledge gained from research developments.
On April 24, 2002, researchers at the Swedish National Food Administration and Stockholm University reported finding the chemical acrylamide in a variety of fried and oven-baked foods. The initial Swedish research indicated that acrylamide formation is particularly associated with traditional high temperature cooking processes for certain carbohydrate-rich foods. Since the Swedish report, similar findings have been reported by numerous other countries, including Norway, the United Kingdom, Germany, Canada, and Switzerland. Analysis by the FDA revealed that U.S. results were also in basic agreement with these findings. The discovery of acrylamide in foods is a concern because acrylamide is a potential human carcinogen and genotoxicant, based on high-dose animal studies, and a known human neurotoxicant.
Acrylamide appears to form as a byproduct of high-temperature cooking processes (greater than 120°C or 248°F). It does not appear to be present in uncooked food and is present in low or undetectable levels in foods cooked at lower temperatures, such as by boiling. Research to date suggests that acrylamide formation is particularly likely in carbohydrate-rich foods such as potatoes and cereals. Scientists have identified one mechanism responsible for the formation of acrylamide in carbohydrate-rich foods cooked at high temperatures: a chemical reaction between the amino acid asparagine and certain sugars, both of which are found naturally in foods. The discovery of the asparagine-acrylamide connection may ultimately lead to methods for decreasing acrylamide levels in certain foods. However, at this time, not enough is known about acrylamide formation to identify safe, effective, and practical modifications to food processing techniques that will clearly prevent or reduce formation. Identifying all mechanisms of formation is an important step in identifying ways to reduce or prevent acrylamide formation during cooking.
Exposure and Toxicology
There are significant uncertainties about the impact of acrylamide on public health. People have been eating some of the foods now reported to contain acrylamide for many years. To better assess the risk of acrylamide, more information is needed regarding which foods acrylamide is formed in, levels of acrylamide in foods, dietary exposure to acrylamide, the bioavailability of acrylamide in food, the potential of acrylamide to cause cancer when consumed in food, biomarkers of acrylamide exposure, and acrylamide's potential to cause germ cell mutations and neurotoxic or neurodevelopmental effects.
Acrylamide causes cancer in laboratory animals in high doses. As a result, acrylamide is considered a potential human carcinogen. However, it is not clear whether acrylamide causes cancer in humans at the much lower levels found in food. Scientists have conducted epidemiological studies of people exposed to acrylamide in the workplace and through the diet. The studies did not show increased cancer risk with acrylamide exposure. However, these studies do not rule out the possibility that acrylamide in food can cause cancer because they have limited power to detect this effect. Also, we do not have enough information to rule out the possibility that subtle effects can occur on the developing nervous system at acrylamide doses lower than those that have been studied so far in animals and humans.
In June 2002, the World Health Organization (WHO) and the Food and Agriculture Organization (FAO) convened an expert consultation on acrylamide. The consultation, in which three FDA experts participated, concluded that the presence of acrylamide in food is a major concern, and recommended more research on mechanisms of formation and toxicity. Both the WHO/FAO consultation and the FDA have recommended that people continue to eat a balanced diet rich in fruits and vegetables. The WHO/FAO consultation advised that food should not be cooked excessively, i.e., for too long a time or at too high a temperature, but also advised that it is important to cook all food thoroughly--particularly meat and meat products--to destroy foodborne pathogens (bacteria, viruses, etc.) that might be present.
FDA's Goals and Actions on the Issue of Acrylamide in Foods
Purpose of the Action Plan
FDA has developed an action plan for acrylamide in food. The action plan outlines FDA's goals and planned actions on the issue of acrylamide in food and will guide FDA's activities on the issue of acrylamide over the next several years.
The actions outlined in the plan include developing methods for acrylamide analysis, researching mechanisms of acrylamide formation and means to reduce formation, assessing the dietary exposure of U.S. consumers to acrylamide, gathering new information about the toxicology of acrylamide, assessing the potential risk of acrylamide exposure, and evaluating options for reducing potential risk. Based on information gathered from this work, and especially from information on the risk to human health, FDA will identify appropriate risk management and communication steps.
In carrying out this action plan, FDA will continue to collaborate extensively through public/private partnerships with international organizations, academia, industry, and other stakeholders to gather the most expert knowledge available on the topic. FDA is further committed to a continuing exchange of information with the public as the action plan is undertaken and to the rapid dissemination of any new findings as soon as they are known.
- Develop rapid or inexpensive screening methods and validate confirmatory methods of analysis.
- Identify mechanisms responsible for the formation of acrylamide in foods and identify means to reduce acrylamide exposure.
- Assess the dietary exposure of U.S. consumers to acrylamide by measuring acrylamide levels in various foods and estimating dietary exposure.
- Characterize the potential risks and uncertainties associated with exposure to acrylamide in foods by assessing the available information, by expanding research into acrylamide toxicology to reduce uncertainty, and by performing a quantitative risk assessment with the new information.
- Develop and foster public/private partnerships to gather scientific and technological information and data for assessing the human risk.
- Inform and educate consumers and processors about the potential risks associated with acrylamide throughout the assessment process and as knowledge is gained.
- Provide all the essential elements for risk analysis, i.e., risk assessment, risk communication, and risk management.
- FDA will continue to update and validate its current liquid chromatography/tandem mass spectrometry (LC/MS/MS) methodology as needed. FDA developed its own LC/MS/MS methodology for testing for acrylamide in foods and posted this methodology on the CFSAN website on June 20, 2002. The methodology was updated on July 23, 2002, and a new update will be posted before the February 24-25, 2003 FAC meeting.
- FDA will undertake a peer validation of the method and will submit the results to the AOAC International for publication.
- Researchers at CFSAN will evaluate screening methodologies for more rapid or less expensive detection of acrylamide in the food supply. CFSAN is currently evaluating the feasibility of LC with ultraviolet (UV) detection as a screening method. CFSAN may also consider the feasibility of other screening methods.
Research on formation
- The National Center for Food Safety and Technology (NCFST) in Illinois, a consortium between FDA, the Illinois Institute of Technology, and food-related industries, will investigate mechanisms of acrylamide formation and processes for reducing formation of acrylamide.
- FDA will continue to interact with academia and industry to encourage research on mechanisms of acrylamide formation and effects of process changes on acrylamide levels. FDA is fostering such interactions through NCFST and the Joint Institute for Food Safety and Applied Nutrition (JIFSAN), a consortium between FDA and the University of Maryland.
- NCFST is planning to research the formation of acrylamide during home cooking of toast, French fries, and other foods.
Characterizing the public's exposure to acrylamide involves several components: testing acrylamide levels in food and using data on acrylamide levels to perform an exposure assessment. An initial exposure assessment may highlight areas where more sampling is needed, leading to more testing and an update of the exposure assessment.
- FDA has been testing locally collected foods in its laboratories at the Center for Food Safety and Applied Nutrition (CFSAN).
- In FY03, FDA will test samples collected nationwide by FDA's Office of Regulatory Affairs for analysis by government or non-government laboratories. JIFSAN will administer a contract for FDA for testing approximately 400-500 samples at a private laboratory.
- In FY03, FDA is planning to collect and analyze between 500 and 1000 market basket samples from the FDA Total Diet Study (TDS). In several subsequent years, a smaller subset of samples will be collected and analyzed.
- Further testing may occur in FY04 and beyond based on the findings of the initial survey and formation research. FDA will consult with statisticians on sampling needs.
- CFSAN researchers are deriving exposure estimates of the U.S. population to acrylamide in food. The estimates are derived by combining distributions of acrylamide levels in foods with appropriate food intake distributions using Monte Carlo methodology to provide a distribution of estimated exposures to acrylamide. FDA researchers can predict exposures of the average consumer and high percentile consumer to acrylamide, identify different exposures for different age groups with different diets, and identify which foods contribute most significantly to overall acrylamide exposure.
- The data being used in the exposure assessments are acrylamide levels from samples analyzed at FDA and food consumption data from USDA's 1994-1996, 1998 2-day and 1989-92 3-day CSFII databases on food consumption. Older food consumption data from a Market Research Corporation of America 14-day food frequency survey conducted from 1982-87 are being used to more accurately account for foods eaten less frequently. Additionally, a model of "usual food consumption" is being developed to better reflect lifetime consumption of foods containing acrylamide.
- Exposure estimates will be updated periodically as new data are acquired on acrylamide levels in food. The estimates will incorporate quality data from other sources, e.g., data on foods consumed in the U.S. submitted to JIFSAN for the WHO/FAO Acrylamide Infonet.
Toxicology and Health Effects
Development of new data on toxicology will provide more information about acrylamide and facilitate informed risk management choices. The following are the toxicology research efforts that have been identified to date.
FDA's National Center for Toxicological Research (NCTR) is conducting or planning to conduct the following short-term animal studies:
- Describing the bioavailability of acrylamide from food in both mice and rats. These studies should clarify how acrylamide is absorbed in a food matrix and shed light on the significance of previous toxicology assays in which rats were administered acrylamide in drinking water.
- Identifying acrylamide-related DNA and protein adducts and studying the formation of these adducts in mice and rats exposed to acrylamide. Acrylamide-related adducts are reaction products between acrylamide (and its metabolite glycidamide) and both DNA and proteins.
- FDA NCTR will conduct studies of acrylamide and its reactive metabolite glycidamide under the National Toxicology Program as FDA's high priority chemical selections for fiscal year 2003. A rodent chronic carcinogenicity assay of acrylamide will be a major component of these studies. FDA will also conduct subchronic toxicity studies and supportive mechanistic studies. The suite of planned studies will develop mechanistic, toxicokinetic, and biomarker data to extend the usefulness and low-dose predictive power of the chronic carcinogenicity assay, in addition to generating dose-response data for tumor and adduct (DNA and hemoglobin) formation. The data will also be used with physiologically based pharmacokinetic modeling to reduce uncertainty where possible in low dose extrapolation and to enhance the usefulness of other existing studies for this extrapolation. NCTR is conducting these studies through an interagency agreement between FDA and the National Institutes of Health's (NIH) National Institute of Environmental Health Sciences (NIEHS).
- FDA NCTR is developing plans to study the neurodevelopmental effects of acrylamide exposure.
- NIEHS plans to conduct mechanistic research into germ cell toxicity and neurotoxic effects of acrylamide, including collaboration with NCTR on DNA adduct evaluations.
Human Toxicology and Health Effects
- NCTR will work with the National Center for Environmental Health (NCEH) at the Centers for Disease Control (CDC) to correlate the adduct data from rats with adduct measurements in humans whose only known exposure to acrylamide is through background levels in food or through smoking.
- CDC NCEH is collaborating with FDA to conduct a study of how acrylamide and glycidamide hemoglobin adduct concentrations in volunteer subjects change over several weeks with defined changes in specific food sources of acrylamide in the diet.
FDA will obtain toxicology information from other federal agencies and industry sources.
- CDC NCEH is investigating the use of acrylamide-related protein adducts for monitoring acrylamide exposures in humans. This effort could include monitoring acrylamide and glycidamide adducts in the National Health and Nutrition Examination Survey (NHANES), an ongoing cross-sectional survey that collects biological samples and health data from a nationally representative sample throughout the U.S. The work would begin with blood samples drawn in 2003.
- CDC's National Institute for Occupational Safety and Health (NIOSH) has initiated a pilot study on worker exposures to acrylamide, as a precursor to an epidemiological study of occupational exposures to acrylamide that will consider neurotoxicity and reproductive health.
- A major manufacturer of acrylamide is currently studying the toxicokinetics of orally ingested acrylamide in humans. FDA will seek information from these studies and other external studies to complement its knowledge base on acrylamide toxicology.
Epidemiology studies may be useful in elucidating the relationships among acrylamide levels in food from chemical analysis; dietary intake of acrylamide, as measured by interviews and questionnaires; and biomarkers of acrylamide exposure, such as levels of hemoglobin adducts. Epidemiology studies may also be useful in elucidating relationships between acrylamide exposure through food and disease endpoints in populations. FDA is gathering information on current or planned acrylamide research in the epidemiology community and exploring additional studies.
As noted in the Toxicology section, FDA is seeking information from the following proposed or planned studies that draw on both toxicology and epidemiology:
- Monitoring acrylamide-related hemoglobin adducts in the CDC NHANES survey,
- Correlating NCTR adduct data from rodents with NCEH adduct measurements in humans whose only known exposure to acrylamide is through background levels in food or through smoking, and
- A collaboration between NCEH and FDA to monitor changes in hemoglobin adduct concentrations in volunteers with defined changes in specific food sources of acrylamide.
- Ongoing, prospective cohort studies in the U.S. and other countries monitor large groups of individuals (tens of thousands or more) for associations between risk factors and disease endpoints over a period of years. Some studies have stored frozen biological samples, including red blood cells, collected at the beginning of the study. It may be feasible to compare acrylamide hemoglobin adduct concentrations in cancer cases and controls (nested case control design) in prospective studies to assess whether acrylamide exposure is associated with risk of cancer. Other endpoints such as neurologic status might also be studied. FDA is gathering information on current efforts on acrylamide in prospective studies and exploring the feasibility of designing studies of sufficient power to address the human health risk from acrylamide in food.
- FDA will evaluate all relevant epidemiology studies on acrylamide and integrate relevant information into its risk assessment, including a recent case-control study (Mucci LA, et al., 2003, British Journal of Cancer 88:84-89).
The risk assessment will characterize the potential risk that the presence of acrylamide in food poses to the U.S. population. This information will be used to inform risk managers, to evaluate potential risk reduction options, and to identify any further research needs. The risk assessment will combine data from the exposure assessment and toxicology research.
- The risk assessment will culminate in a document/report. This assessment will be completed when more data are available on exposure and toxicology. For toxicology, the crucial data needs are in the areas of bioavailability, biomarkers, metabolism, and toxicokinetics.
- The risk assessment will use appropriate modeling approaches and will include evaluation of uncertainty in the areas of health effects and exposure.
- As with any risk assessment, it will be revised when there are developments of such significance that would materially change the risk assessment.
FDA will participate in and/or convene, as appropriate, meetings with the goals of (a) gathering public and expert input on acrylamide in food and (b) fostering coordination of research efforts on acrylamide. Examples of meeting activities include the following:
- CFSAN conducted an interagency roundtable of federal public health agencies involved in acrylamide research on September 24, 2002. Participants in the roundtable included the Department of Health and Human Services (FDA, NIEHS, NIOSH, and NCEH), the United States Department of Agriculture (Food Safety Inspection Service, Agricultural Research Service), and the Environmental Protection Agency (EPA). Topics included the results of the WHO consultation, plans for acrylamide toxicology studies at each agency, EPA's reevaluation of its dose-response evaluation for acrylamide, the potential use of biomarkers to monitor acrylamide exposure, epidemiological studies, occupational exposures, and heritable mutagen assays. FDA will plan additional meetings of this interagency group to review ongoing developments relating to acrylamide. As a followup to the September 24 meeting, CDC hosted a meeting on January 27th that focused on the use and harmonization of methods to measure hemoglobin adducts of acrylamide and glycidamide in humans and animals across laboratories currently considering epidemiological or toxicological research on acrylamide.
- FDA convened a Public Meeting, "Assessing Acrylamide in the U.S. Food Supply," on September 30, 2002, to update the public on FDA's activities related to acrylamide in food, to present FDA's draft action plan for acrylamide, and to obtain comments on the plan.
- FDA participated in the JIFSAN/NCFST Workshop, "Acrylamide in Food: What do we need to know? What are the responses?", held on October 28-30, 2002. JIFSAN will continue to run the WHO/FAO Acrylamide Infonet clearinghouse for continued international coordination and data sharing on acrylamide.
- FDA held a meeting of the Subcommittee on Contaminants and Natural Toxicants of the FDA Food Advisory Committee on December 4-5, 2002. At that meeting, FDA presented its draft action plan for acrylamide and preliminary data on acrylamide levels in foods. FDA sought input on the draft action plan, on research and analysis needs, and on exposure and toxicology issues.
- FDA will hold a meeting of the full FDA Food Advisory Committee on February 24-25, 2003. FDA will present its revised action plan, updated to reflect input from the Subcommittee on Contaminants and Natural Toxicants, as well as preliminary data on acrylamide levels in foods and more specific information on ongoing or planned research. FDA will seek input to finalize its action plan on research and analysis needs, and exposure and toxicology issues.
- The Codex Committee on Food Additives and Contaminants is expected to meet March 17-21, 2003, and will include a WHO/FAO workshop on acrylamide for the delegates. The U.S. delegation will work with other delegations to ensure that acrylamide is assessed.
- If invited, FDA scientists will participate in an assessment of acrylamide by the WHO/FAO Joint Expert Committee on Food Additives and Contaminants (JECFA), tentatively planned for 2004.
Inform and Educate the Public
FDA is committed to active risk communication with the public on the issue of acrylamide.
- FDA has held a Public Meeting and a Food Advisory Committee Subcommittee meeting in part to inform the public about its activities on acrylamide. A full Food Advisory Committee meeting will be held in February 2003.
- FDA has posted numerous items on acrylamide on the CFSAN website, including meeting presentations, transcripts, and data on acrylamide levels in food. FDA Consumer magazine published an article on acrylamide for the public in the January/February 2003 issue.
- FDA has issued a dietary message advising consumers to eat a balanced diet, choosing a variety of foods that are low in trans fat and saturated fat, and rich in high-fiber grains, fruits and vegetables.
- As messages are developed and refined, FDA will consider recruiting the aid of diet, nutrition, and home economics organizations, as well as agricultural extension services, in getting its message out to consumers.
- FDA will develop and revise regulatory options as additional knowledge is gained on acrylamide in food. Many of the items in the action plan are geared toward achieving that end.
- FDA will encourage industry to adopt feasible, practical, and safe processes that are successful at reducing acrylamide, if needed.
- FDA will develop and revise consumer messages about dietary choices and cooking methods, as additional knowledge is gained about acrylamide in food. FDA understands the importance of consumer messages that can assist consumers in making informed dietary choices. Any adjustments in consumer messages would be made as dictated by the totality of the science.
The following table highlights the timeline of major activities on acrylamide.
|September 24, 2002||CFSAN-led interagency roundtable of federal public health agencies on acrylamide research.|
|September 30, 2002||"Assessing Acrylamide in the U.S. Food Supply": A public meeting on acrylamide in food.|
|October 28-30, 2002||JIFSAN/NCFST Workshop, "Acrylamide in Food: What do we need to know? What are the responses?"|
|December 4-5, 2002||Meeting of the Subcommittee on Contaminants and Natural Toxicants of the FDA Food Advisory Committee.|
|February 24-25, 2003||Meeting of the full FDA Food Advisory Committee.|
|March 17-21, 2003||Codex Committee on Food Additives and Contaminants meeting.|
|2004||WHO/FAO JECFA acrylamide assessment (tentative).|
|Ongoing or planned|
Exposure assessment studies
Toxicology and epidemiology studies
|*Where applicable. Some dates are tentative or have already occurred.|
This document was issued on February 24, 2003.