U.S. Action Plan for Acrylamide, Activities and Progress
Terry Troxell, Ph.D., and Lauren Posnick, Sc.D.
March 16, 2003
FAO/WHO Seminar on Acrylamide in Food
(1) Title Slide
(2) This presentation includes information on (1) the history and timetable of events surrounding acrylamide in food, (2) the U.S. FDA Action Plan, and (3) FDA data on acrylamide levels in food. Dr. Petersen and the FDA have collaborated in developing presentations to cover U.S. efforts. Dr. Petersen’s presentation includes information on the FDA exposure assessment and the FDA will not duplicate such information in this presentation.
(3) The major international concern over acrylamide started with the report by Swedish scientists in April of last year that acrylamide can be found in a wide range of foods as a result of cooking, particularly carbohydrate-rich foods cooked at high temperatures. This finding received a great deal of attention because acrylamide is a known human neurotoxicant and potential carcinogen. Also, acrylamide was detected at higher levels than other carcinogens produced through cooking.
(4) Since the announcement, there have been worldwide efforts to develop methods for measuring acrylamide levels in food. The FDA/CFSAN method, developed by Dr. Steven Musser (Steven.Musser@cfsan.fda.gov) and colleagues, was posted on the FDA website initially on June 20, 2002.
Another key early international step was the WHO/FAO consultation in June 2002, in which three FDA experts participated.
(5) Another response seen internationally has been national and regional meetings on acrylamide. In the U.S., the FDA held a public meeting and a federal interagency research meeting in September 2002. Holding a public meeting so soon after the April announcement is consistent with FDA’s goal of open, transparent communication with the public. FDA also held two meetings of all or part of its Food Advisory Committee in December 2002 and February 2003. The Food Advisory Committee (FAC) is a group of experts from outside FDA who met to review and critique FDA’s plan.
FDA representatives have also been active in attending non-FDA meetings, including an international workshop in October coordinated by JIFSAN/NCFST (Joint Institute for Food Safety and Applied Nutrition/National Center for Food Safety and Technology - these are FDA consortia with the University of Maryland and Illinois Institute of Technology, respectively). Dr. Petersen’s presentation will address this workshop.
(6) This slide shows an overview of the U.S. response. The U.S. developed a method, tested a wide variety of foods, prepared an exposure assessment, and laid out plans for needed toxicology research.
(7) This slide continues the overview of the U.S. response. The U.S. is conducting formation research and encouraging research by industry and academia. The ultimate goal of the U.S. efforts is a risk assessment incorporating new data that will provide the scientific basis for appropriate risk management.
(8) The next set of slides go through the FDA Action Plan in more detail. The Action Plan outlines FDA’s goals and planned activities on acrylamide in food over the next several years.FDA presented the Draft Action Plan for public and expert comment at its September and December meetings. The plan was revised based on comments and presented to the Food Advisory Committee in February 2003. FDA will finalize the plan based on the Committee’s comments, although the Plan is still a flexible document and may be updated in the future. Copies of the revised action plan are available at this meeting or can be accessed from FDA’s food web site, www.cfsan.fda.gov, under the program area "Pesticides and Chemical Contaminants." This area of the website also includes other acrylamide information, such as the analytical method and testing results.
(9) The overall goal of the action plan is: Through scientific investigation and risk management decision making, prevent and/or reduce potential risk of acrylamide in foods to the greatest extent feasible.
(10) Under the overall goal, there are seven major subgoals:
----Subgoal 1: Develop more rapid or inexpensive screening methods and seek AOAC validation on FDA’s current method. There are a number of excellent methods being used to measure acrylamide in foods, including GC/MS methods. The FDA is using a very sensitive LC/MS/MS method for testing now, and is also looking into developing an LC/UV screening method. Whatever method is used, it is critical that method developers and users control for potential interferences.
----Subgoal 2: Research mechanisms of formation and possible means of reduction.
(11) Subgoal 3: Assess dietary exposure in the U.S. by measuring levels of acrylamide in foods and modeling exposure from these data.
(12) Subgoal 4: In summary form, the fourth subgoal is to gather new and available data on acrylamide and human health and perform a quantitative risk assessment of acrylamide in food.
(13) Subgoals 5 and 6: FDA’s fifth and sixth subgoals are to develop and foster public/private partnerships for gathering acrylamide data, and to keep the public and industry informed about acrylamide risk.
(14) Subgoal 7: Finally, FDA’s last subgoal is to provide all the essential elements for risk analysis—i.e., risk assessment, risk communication, and risk management.
(15) The Action Plan is divided up by areas. These are the specific action areas included in the plan. This is an overview—the next several slides highlight some elements in the Plan.
(16) Measuring exposure: FDA has done extensive testing so far on foods purchased in the Washington, D.C. area. FDA plans to expand testing to foods gathered across the U.S., including regional specialties. This testing will encompass 400-500 more samples, and will be done through a contract administered by JIFSAN. FDA is also testing foods from its Total Diet Study market basket, which will enable FDA to estimate acrylamide exposure from the average diet and to track changes in acrylamide levels over time. FDA will conduct further testing in fiscal year ’04, as needed to fill in gaps in our data distributions.
Through the WHO/FAO Acrylamide Infonet operated by JIFSAN, FDA hopes to substantially expand the database on levels of acrylamide in foods eaten by U.S. consumers. These data will lead to better exposure assessments and provide insights for researchers on formation and reduction.
(17) Key information is needed in the toxicology area. Bioavailability: FDA needs information on bioavailability of acrylamide in food versus water, as bioavailability was previously studied in water. High-dose versus very low-dose exposures: During high-dose exposures, as in animal studies, a fraction of the acrylamide is known to be metabolized via the P450 pathway to glycidamide, which is thought to be the ultimate carcinogen. At very low dose exposures, as in food exposure, the fraction of acrylamide metabolized by this pathway may be substantially different. Therefore, more information is needed about metabolism at very low-dose exposures more consistent with food.
(18) Biomarkers/adducts: Acrylamide and its metabolite glycidamide react with hemoglobin in red blood cells to form adducts. These adducts can be measured as biomarkers of acrylamide exposure, and we need to understand the levels of adducts that form after acrylamide exposure. We also need to understand the relationship between these hemoglobin adducts, which are probably nontoxic, and the adducts that form with DNA, which are potentially genotoxic. And we need animal to human comparisons that can relate cancer production and adduct levels in animals at high doses with lower adduct levels and low-dose exposures in humans.
(19) Most of this information on adducts, bioavailability, and metabolism can be gained in a relatively short time, 1-2 years. FDA’s National Center for Toxicological Research is also planning to conduct a chronic carcinogenicity bioassay, which should provide new information about the carcinogenic effects of acrylamide in animals. On germ cell toxicity, other federal agencies in the U.S. are planning studies.
Neurotoxicity was not cited as an area of concern by the June 2002 FAO/WHO expert consultation. Discussions at subsequent conferences suggested further information in the area of neurotoxicity and neurodevelopmental effects would be useful. FDA and other U.S. government agencies are looking into studies in this area.
(20) Epidemiology is a newer area of the FDA action plan. Epidemiology could provide interesting information, but it may be very difficult to detect small risks with this method, such as risks associated with the relatively low exposures to acrylamide that occur through food. FDA is considering involvement in epidemiology studies or using information gathered by others from epidemiology studies, in the following areas: occupational studies, prospective cancer studies, and case-control studies.
(21) As was mentioned before, FDA has been actively testing food samples for acrylamide.About 400 food samples have been analyzed to date. More than 35 different food types have been tested. More testing is planned for the future as mentioned previously.
(22) Some foods have little or no acrylamide, such as infant formula, baby cereal, fish and chicken, and condensed and liquid milk.Other foods have acrylamide, but in variable amounts.
(23) This slide shows acrylamide results presented at FDA’s December 2002 Food Advisory Committee meeting. Some important points are: (1) Some categories, such as chips, have higher acrylamide levels than others. (2) Within categories, there is a great deal of variability in acrylamide levels (e.g., chips, crackers). (3) Variability is also substantial from brand-to-brand and also lot-to-lot for a specific product. Further, in a study of potato chips, FDA found substantial day-to-day variability for chips made on the same production line and with the same potato cultivar grown on the same farm. This may be due to the effect of storage conditions on asparagine and glucose levels in potatoes. These natural components of foods are believed to be responsible for the majority of acrylamide formation under appropriate high temperature cooking conditions.
(24) This slide shows more examples of variability within food groups. An important point about this variability is that it suggests that there are ways to make products so that they have lower acrylamide levels.
(25) Along with others, FDA is looking at what factors affect formation of acrylamide. Learning about these factors could contribute to identifying ways to reduce acrylamide levels or control formation.Some factors that have been identified already are food composition and processing conditions. The next several slides show examples of the effects of temperature and time.
(26) This slide shows experiments performed at FDA’s National Center for Food Safety and Technology, a collaborative program between FDA and the Illinois Institute of Technology. In potato chips fried for 4 min, acrylamide levels increased with frying temperature, from 27 ppb at 160 C to 326 ppb at 180 C. Browning also increased. In other words, in this system, acrylamide concentrations increase with temperature.
(27) This slide of experiments shows that in potato chips fried at 180 C for 3.5 to 5 min, acrylamide levels increased with time, from 12 ppb to 973 ppb. Thus acrylamide levels also increase with cooking time, in this system. (Acrylamide levels for the 4 min/180 C tray are lower than in the previous slide because this experiment was done on a different day.)
(28) Another experiment looking at time shows a similar trend of increasing acrylamide levels with cooking time in frozen French fry style potatoes baked at home. Acrylamide levels increased from 11 ppb at 15 minutes baking at 450 C to 1326 ppb at 30 minutes, and almost 5000 ppb at 45 minutes. Rather than focusing on time and temperature in the oven, the key factor in acrylamide formation is the temperature that the food attains. That is what drives the acrylamide formation reaction, which is the same kind of reaction that causes browning and desirable flavor development in these foods.
Another important realization from experiments of this type is that even if food processors find ways to reduce acrylamide levels, a substantial amount of exposure can be introduced through home cooking. Exposure may vary with consumer preferences for degree of browning in cooking.
(29) Data summary: FDA has measured acrylamide in a wide range of products. Acrylamide was detected in a variety of foods and at a variety of levels. In some foods, no acrylamide was detected.
(30) Data summary: FDA has found variability between food categories and within food categories, as well as between diffferent brands.
The variability in levels of acrylamide in similar foods suggests that there are ways to make products that will minimize acrylamide formation.
(31) FDA’s current dietary message for acrylamide is 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."
FDA does not have the science to provide targeted advice to consumers on reducing acrylamide levels in home cooked foods. Some of our research will try to answer questions on the relationship between the degree of browning and acrylamide formation in home cooking.
In addition, any advice must be carefully constructed and delivered so that consumers are not exposed to larger risks in following the advice. For example, if we give advice for consumers to not overcook foods, some consumers may react broadly to it and not cook meat and poultry adequately, potentially resulting in a greater risk of foodborne disease that has very serious consequences for susceptible populations.
Another example would be that cereals and breads, important staples of the diet, are significant contributors to acrylamide exposure. Consumers who avoided eating these foods may encounter greater risks because they would have less fiber and other beneficial nutrients in their diets.
(32) In closing, this presentation:
Reviewed the timetable of events leading up to development of FDA’s Action Plan for acrylamide in food.
Reviewed the goals and key action points in the Action Plan, and
Reviewed data from FDA’s survey of acrylamide levels in food and preliminary formation work.