Food and Drug Administration, HHS.
Notice; request for comments and scientific data and information.
The Food and Drug Administration (FDA) is requesting comments and scientific data and information on acrylamide in food. Acrylamide is a chemical that can form in some foods during certain types of high-temperature cooking. FDA is seeking information on practices that manufacturers have used to reduce acrylamide in food and the reductions they have been able to achieve in acrylamide levels. FDA is considering issuing guidance for industry on reduction of acrylamide levels in food products.
Submit comments and scientific data and information by November 24, 2009.
Submit written comments and scientific data and information to the Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852. Submit electronic comments and scientific data and information to http://www.regulations.gov.Start Further Info
FOR FURTHER INFORMATION CONTACT:
Lauren Posnick Robin, Center for Food Safety and Applied Nutrition (HFS-317), Food and Drug Administration, 5100 Paint Branch Pkwy., College Park, MD 20740, 301-436-1639.End Further Info End Preamble Start Supplemental Information
In 2002, scientists in Sweden announced the discovery of the chemical acrylamide in a variety of heated foods (Ref. 1). Further research subsequently determined that acrylamide can form in some foods during certain types of high-temperature cooking (Refs. 2 and 3). Acrylamide in food is a concern because it has been found to be carcinogenic in rodents and is therefore considered a potential carcinogen for humans (Refs. 4 and 5).
Since the identification of acrylamide in food, research around the world has centered on measuring acrylamide exposure in the diet, studying the toxicology and epidemiology of acrylamide exposure, and reducing (mitigating) acrylamide levels in food. Information on FDA's activities on acrylamide can be found on FDA's Web site (Ref. 6). FDA's research program has focused on toxicology but has also included research on mitigation for consumers (Ref. 7). Based on this research and other findings, FDA added information to its Web site in 2008 for consumers interested in reducing their acrylamide exposure from food. However, FDA's general advice for acrylamide and eating is for consumers to adopt a healthy eating plan consistent with the Dietary Guidelines for Americans (Refs. 6 and 8). The Dietary Guidelines for Americans suggests a diet that emphasizes fruits, vegetables, whole grains, and fat-free or low-fat milk and milk products; includes lean meats, poultry, fish, beans, eggs, and nuts; and is low in saturated fats, trans fats, cholesterol, salt (sodium), and added sugars.
FDA has not issued guidance for manufacturers on reducing acrylamide in food. However, it is anticipated that new information will soon be available about the toxicology of acrylamide, which may confirm acrylamide's carcinogenicity in laboratory animals. International efforts to develop approaches to acrylamide mitigation are also beginning to prove successful. Moreover, FDA is aware that at least some manufacturers in the United States are seeking ways to reduce acrylamide in their products. For these reasons, FDA is considering issuing guidance for industry on reduction of acrylamide levels in food products.
This document summarizes information available to FDA about acrylamide formation, exposure, toxicology, levels in food, and techniques to mitigate acrylamide. This notice also identifies areas in which additional data and information would be helpful to FDA in learning more about acrylamide mitigation techniques and levels of acrylamide in food. These areas are outlined in more detail in section II of this document.
B. Formation and Exposure
Acrylamide forms in foods primarily from a reaction between asparagine, an amino acid, and reducing sugars such as glucose and fructose. This reaction is part of the Maillard reaction, which leads to color, flavor, and aroma changes in cooked foods (Refs. 2, 3, and 9). Acrylamide formation usually occurs at elevated temperatures used when frying or baking (above 120 °C (248 °F)) and in low moisture conditions, although acrylamide has also been identified in some fruit and vegetable products heated at lower temperatures or higher moisture conditions (Refs. 10 through 13). Also, formation occurs primarily in plant-based foods, notably potato products such as French fries and potato chips; coffee; and cereal-grain-based foods such as cookies, crackers, breakfast cereals, and toasted bread.
Thousands of food samples have been analyzed for acrylamide since 2002. Based on its own database of acrylamide levels in U.S. foods (Refs. 12 and 13), FDA estimates acrylamide intake for the average U.S. consumer as 0.4 microgram/kilogram body weight/day (μg/kg-bw/d) (Ref. 14). International estimates for the average consumer range from 0.2 to 1.4 μg/kg-bw/d (Ref. 15). Based on estimates from different countries, the Joint Food and Agriculture Organization/World Health Organization (FAO/WHO) Expert Committee on Food Additives (JECFA) identified an average acrylamide intake of 1 μg/kg-bw/d for the general consumer and 4 μg/kg-bw/d for high consumers (Ref. 4).
Based on measured levels of acrylamide in certain foods and on how frequently these foods are consumed in the United States, FDA identified the following 10 foods (in ranked order) that contribute the most acrylamide to the U.S. diet: French fries (restaurant prepared), French fries (oven baked), potato chips, breakfast cereals, cookies, brewed coffee, toast, pies and cakes, crackers, and soft (nontoasted) breads (Ref. 14). The JECFA evaluation concurred that the major foods contributing to total exposure for most countries were French fries, potato chips, coffee, pastry and sweet cookies, and breads and toasts (Ref. 4).
Several international toxicology evaluations of acrylamide have been completed since the identification of Start Printed Page 43135acrylamide in food in 2002 (Refs. 4 and 5). An initial FAO/WHO consultation in 2002 called the presence of acrylamide in food “a major concern” based on acrylamide's ability to induce cancer and heritable mutations in laboratory animals. In 2005, an international evaluation of acrylamide by JECFA identified margins of exposure (MOEs) for acrylamide of 300 for general consumers and 75 for high consumers. JECFA considers the MOE of 300 calculated for acrylamide to be low for a compound that is genotoxic and carcinogenic and concluded that the levels of acrylamide in food were of concern.
Under the sponsorship of the National Toxicology Program, FDA's National Center for Toxicological Research (NCTR) embarked in 2002 on a series of new toxicology assays for acrylamide. These studies were designed to address deficiencies in earlier carcinogenicity studies and to provide more reliable data on potential carcinogenic risk of acrylamide and other potential effects of acrylamide exposure. The work at NCTR includes long-term carcinogenicity bioassays of acrylamide and its metabolite glycidamide in mice and rats, as well as toxicokinetic, bioavailability, mutagenicity, and neurodevelopmental studies (Refs. 16 through 34). NCTR's work also includes the development of a physiologically based pharmacokinetic model for acrylamide and glycidamide (Refs. 19 and 34).
D. Reduction of Acrylamide Levels in Food
Since the discovery of acrylamide in food in 2002, the international research community has explored numerous strategies for reducing acrylamide levels in food products. This work is summarized in the scientific literature (e.g., Refs. 35 through 48), as well as in guidance materials prepared by industry, other governments, and international organizations. Notable guidance materials include the Acrylamide “Toolbox” produced by the Confederation of Food and Drink Industries of the European Union (CIAA) (Ref. 49), CIAA “Toolbox” brochures on selected foods for small- and medium-sized businesses (Refs. 50 through 54), the “Review of Acrylamide Mitigation in Biscuits, Crackers and Crispbread” produced by the Association of the Chocolate, Biscuits, and Confectionary Industries of the European Union (CAOBISCO) (Ref. 55), and “Guidelines to Authorities and Consumer Organisations on Home Cooking and Consumption” and “Manual on strategies to food industries, restaurants, etc., to minimize acrylamide formation” produced by the Heat-Generated Food Toxicants: Identification, Characterization and Risk Minimisation (HEATOX) Project (Refs. 56 and 57). The Codex Committee on Contaminants in Foods (CCCF) has also prepared a Code of Practice for the Reduction of Acrylamide in Foods (Ref. 58), with the U.S. Delegation to CCCF participating in preparation of the code of practice as co-lead of the document working group.
Research on acrylamide mitigation has focused on reducing acrylamide in potato products, cereal-grain-based products (e.g., baked goods), and coffee through interventions directed at raw materials, additional ingredients, and processing (Ref. 58). As a result of this research, effective mitigation measures have been identified for reducing acrylamide levels in some potato and cereal products; however, no proven mitigation measures have been devised for coffee (Refs. 49 and 58).
Potato products. For potato products, mitigation practices directed at raw materials focus on controlling reducing sugar levels, for example: (1) Selecting potato cultivars that are low in reducing sugars, (2) checking sugar levels of incoming potato lots using chemical analysis or fry testing, (3) storing potatoes above 6 °C (43 °F) to avoid low-temperature sweetening, (4) using reconditioning to lower sugar levels in stored potatoes, and (5) avoiding use of immature potatoes, which have higher sugar levels. Other mitigation practices for potato products address additional ingredients, including using the enzyme asparaginase to reduce levels of the acrylamide precursor asparagine, partially substituting potato ingredients with nonpotato ingredients, and formulating recipes to include ingredients such as sodium pyrophosphate and calcium salts (Refs. 49 and 58). Finally, acrylamide mitigation practices for potato products also address processing steps. For French fries, such practices include: (1) Washing or blanching (with or without added ingredients such as sodium pyrophosphate and cation salts), (2) cutting thicker potato pieces, (3) removing fines (fine pieces of potato), (4) setting fryer temperature no higher than 175 °C (347 °F), and (5) cooking fries to a golden yellow color rather than a golden brown color. For potato chips, such practices include: (1) Optimizing time and temperature cooking conditions, (2) cooking to a golden yellow color, (3) utilizing vacuum frying or flash frying with rapid cooling, and (4) using optical sorting to remove darker chips (Refs. 49 and 58).
Cereal grain products. In cereal-grain-based foods, strain selection and agronomic practices targeted at reducing asparagine levels in raw materials (such as ensuring adequate sulfur fertilization) show potential to reduce acrylamide (Refs. 49 and 58). Mitigation measures directed at additional ingredients include use of asparaginase to deplete asparagine and partial substitution of higher-asparagine flours (e.g., wheat, rye) with lower-asparagine flours (e.g., rice). Substitution of whole-grain flours with highly processed flours can also reduce acrylamide, but use of highly processed flours does not provide the nutritional benefits associated with whole-grain flours. Other ingredient-directed measures that may reduce acrylamide in baked goods include substitution of ammonium-based raising agents with potassium- and sodium-based raising agents, avoidance of reducing sugars during baking, addition of calcium salts, and modification of the use of minor ingredients (e.g., spices) and rework (Refs. 49 and 58). Processing changes shown to decrease acrylamide in cereal-based foods include adjusting the time-temperature profile of baking processes, extending dough fermentation times, controlling final moisture content, and not over-baking or over-toasting foods (Refs. 49 and 58).
E. Levels of Acrylamide in Food
Measured acrylamide levels in food are summarized in multiple databases, publications, and evaluations (e.g., Refs. 4, 12, 13, and 59). Levels of acrylamide in food vary widely, from undetectable amounts in some cereal grain- and potato-based products (e.g., untoasted bread and mashed potatoes) to more than 5000 μg/kg in a cereal grain product (e.g., grain-based coffee substitute) (Refs. 12 and 13). Acrylamide levels also can vary widely within individual food types (e.g., Ref. 12). For example, in data collected by FDA, levels of acrylamide in potato chips varied from nearly 120 μg/kg to over 1200 μg/kg (Ref. 12). There may also be considerable variation within different lots of the same product due to variation in raw materials and processing conditions. Despite the wide range of acrylamide levels for a given food, the availability of proven mitigation practices (Refs. 49 through 58) suggests that it may be feasible to recommend, for some foods, levels for acrylamide that all manufacturers should be capable of achieving.
II. Request for Comments and for Scientific Data and Information
FDA is seeking additional scientific data and information on (1) methods for Start Printed Page 43136reducing acrylamide levels in food and (2) reductions that manufacturers have been able to achieve in acrylamide levels. Accordingly, FDA invites all interested parties to submit comments and scientific data and information on the topics identified. FDA is also seeking specific data and other information on the following questions:
A. Methods for Reducing Acrylamide Levels in Food
1. Are you (manufacturers) currently taking any steps to reduce acrylamide levels in your food products? If yes, what methods are you using? Please list mitigation methods by food type (e.g., potato chip) and, where possible, by product line (e.g., potato chip line one). It is not necessary to identify product line by brand name. Please provide as many details as possible, including being specific about changes to methods, e.g., identify new and previous frying temperatures rather than simply indicating that the frying temperature was lowered.
2. Which methods, if any, have not proved successful or cost-effective for reducing acrylamide in your products? Please identify food types and/or product lines for which particular methods have not proved successful or cost-effective. Where possible, identify the reasons these methods have not proved successful or cost-effective.
3. What changes in ingredients (e.g., addition of cation salts, amino acids, or spices; blanching with sodium pyrophosphate; substitution of grains or sugars; replacement of ammonium bicarbonate) have proved effective and feasible in lowering acrylamide levels in your products? Please provide specific details about product types and manufacturing process changes.
4. Do you use asparaginase to lower acrylamide levels in any of your products? If so, in which of your products has asparaginase proved effective and feasible in lowering acrylamide levels? Please provide specific details about product types and manufacturing process changes.
5. What changes in precooking parameters (e.g., blanching, fermentation) and cooking parameters (e.g., time and temperature of cooking, final moisture content) have proved effective and feasible in lowering acrylamide levels in your products? Please provide specific details about product types and manufacturing process changes. Are techniques such as flash frying and vacuum frying feasible methods of acrylamide reduction?
6. What mitigation methods might be more or less appropriate for small manufacturers? Please provide a rationale for your response.
7. Do you monitor acrylamide formation and reduction? If yes, what endpoint (e.g., browning, measurement of acrylamide levels) do you use?
8. What are standard practices in the United States for delivery, storage, temperature control, reconditioning, and screening (e.g., by fry testing) of potatoes? What potato cultivars in the United States are appropriate for production of French fries, potato chips, and other potato-based snacks? What cultivars are not acceptable for producing these products and/or roasting or frying potatoes at home? Is it appropriate to specify an acceptable level of reducing sugars in incoming lots of potatoes and, if so, what level is appropriate?
9. What changes have you made, if any, to the instructions on food packaging to reduce acrylamide formation during final preparation of food products by consumers?
10. Aside from changes to the instructions on food packaging, are there other steps that manufacturers can take to help consumers reduce acrylamide in food, such as labeling in-store potatoes for appropriate use?
11. Are there other important sources of information on reducing acrylamide levels in food that FDA has not identified in this document? If yes, please identify such sources.
12. Are there any other sources of information about proposed acrylamide mitigation techniques (particularly as applied to U.S. products) that might be more useful or accurate than the information described in this document?
B. Levels of Acrylamide in Food
Among the information that would be helpful to FDA in potentially recommending levels for acrylamide in food is data on reductions achieved by manufacturers using mitigation techniques. Some information on acrylamide levels can be found in existing databases and publications (Refs. 4, 12, 13, and 59), but these databases may reflect, at least in part, acrylamide levels before mitigation measures were applied. Data from more targeted or ongoing sampling plans (e.g., Refs. 60 through 64) and from legal settlements (Ref. 65) may also be useful sources of information on acrylamide levels in food, although some of this information may be limited in scope or applicable primarily to European products.
1. What acrylamide levels have you observed before and after applying mitigation practices? Please break down your data by food type (e.g., potato chip) and, where possible, by product line (e.g., potato chip line one). It is not necessary to identify a product line by brand name. Please include, if possible, measurements of acrylamide levels in individual samples, as well as statistical endpoints (e.g., means, medians, standard deviations). Finally, please identify the acrylamide mitigation measures you used to achieve these reductions.
2. Do you anticipate being able to achieve further reductions by applying different or additional approaches? If yes, please identify the approaches. If no, please explain what limits your ability to further reduce the levels of acrylamide in particular products.
3. What factors, if any, have affected your ability to consistently achieve certain levels of acrylamide or certain percentage reductions?
4. For what food types, if any, would it be appropriate to recommend levels for acrylamide? Please provide an explanation of your response.
5. What reduced acrylamide levels should manufacturers be able to achieve for the following foods: French fries, potato chips, breakfast cereals, coffee, and cookies and other baked goods? What reduced acrylamide levels should manufacturers be able to achieve for other potato- or corn-based snacks?
6. What additional factors, if any, should FDA consider if it recommends levels for acrylamide in foods?
7. Are there important sources of information that FDA has not identified in this document on levels of acrylamide in food and reductions in acrylamide levels achieved by manufacturers? If yes, please identify such sources.
8. Are there any other sources of information about attainable levels of acrylamide in food that might be more useful or accurate than the information described in this notice?
Interested parties may submit to the Division of Dockets Management (see ADDRESSES) written or electronic comments regarding this document. Submit a single copy of electronic comments or two paper copies of any mailed comments, except that individuals may submit one paper copy. Comments are to be identified with the docket number found in brackets in the heading of this document. Received comments may be seen in the Division of Dockets Management between 9 a.m. and 4 p.m., Monday through Friday.Start Printed Page 43137
The following references have been placed on display in the Division of Dockets Management (see ADDRESSES) and may be seen by interested persons between 9 a.m. and 4 p.m., Monday through Friday. (FDA has verified the Web site addresses, but FDA is not responsible for any subsequent changes to the Web sites after this document publishes in the Federal Register.)
1. Tareke, E., P. Rydberg, P. Karlsson, S. Eriksson, and M. Törnqvist, “Analysis of acrylamide, a carcinogen formed in heated foodstuffs,” Journal of Agricultural and Food Chemistry 50: 4998-5006, 2002.
2. Mottram, D.S., B.L. Wedzicha, and A.T. Dodson, “Acrylamide is formed in the Maillard reaction,” Nature 419(6906): 448-449, 2002.
3. Stadler, R.H., I. Blank, N. Varga, F. Robert, J. Hau, P.A. Guy, M.C. Robert, and S. Riediker, “Acrylamide from Maillard reaction products,” Nature 419(6906): 449-450, 2002.
4. Joint FAO/WHO Expert Committee on Food Additives (JECFA), “Summary and conclusions, Sixty-fourth Meeting,” 2005. Accessed online at http://www.who.int/ipcs/food/jecfa/summaries/summary_report_64_final.pdf.
5. Joint FAO/WHO Consultation on Health Implications of Acrylamide in Food, “Health Implications of Acrylamide in Food: Report of a Joint FAO/WHO Consultation,” WHO Headquarters, Geneva, Switzerland, June 25-27, 2002. Accessed online at http://www.who.int/foodsafety/publications/chem/en/acrylamide_full.pdf.
6. U.S. Food and Drug Administration, “Acrylamide in Food.” Accessed online at http://www.fda.gov/Food/FoodSafety/FoodContaminantsAdulteration/ChemicalContaminants/Acrylamide/default.htm.
7. Jackson, L.S., and F. Al-Taher, “Effects of consumer food preparation on acrylamide formation,” Advances in Experimental Medicine and Biology 561: 447-465, 2005.
8. U.S. Department of Health and Human Services, “Dietary Guidelines for Americans,” 2005. Accessed online at http://www.health.gov/dietaryguidelines/dga2005/document/default.htm.
9. Stadler, R.H., “Understanding the formation of acrylamide and other Maillard-derived vinylogous compounds in foods,” European Journal of Lipid Science and Technology 105(5): 199-200, 2003.
10. Amrein, T.M., L. Andres, F. Escher, and R. Amadò, “Occurrence of acrylamide in selected foods and mitigation options,” Food Additives and Contaminants, Supplement 1, 2007: 24(S1): 13-25, 2007.
11. Roach, J.A.G., D. Andrzejewski, M.L. Gay, D. Nortrup, and S.M. Musser, “Rugged LC-MS/MS survey analysis for acrylamide in foods,” Journal of Agricultural and Food Chemistry 51:7547-7554, 2003.
12. U.S. Food and Drug Administration, “Survey Data on Acrylamide in Food: Individual Food Products,” 2002-2006. Accessed online at http://www.fda.gov/Food/FoodSafety/FoodContaminantsAdulteration/ChemicalContaminants/Acrylamide/ucm053549.htm.
13. U.S. Food and Drug Administration, “Survey Data on Acrylamide in Food: Total Diet Study Results,” 2004-2006. Accessed online at http://www.fda.gov/Food/FoodSafety/FoodContaminantsAdulteration/ChemicalContaminants/Acrylamide/ucm053566.htm.
14. DiNovi, M., “The 2006 exposure assessment for acrylamide,” 2006. Accessed online at http://www.fda.gov/Food/FoodSafety/FoodContaminantsAdulteration/ChemicalContaminants/Acrylamide/ucm053566.htm.
15. Council for Agricultural Science and Technology (CAST), “Acrylamide in food,” Issue paper 32, CAST, Ames, Iowa, 2006.
16. Bowyer, J.F., J.R. Latendresse, R.R. Delongchamp, L. Muskhelishvili, A.R. Warbritton, M. Thomas, E. Tareke, L.P. McDaniel, and D.R. Doerge, “The effects of subchronic acrylamide exposure on gene expression, neurochemistry, hormones, and histopathology in the hypothalamus-pituitary-thyroid axis of male Fischer 344 rats,” Toxicology and Applied Pharmacology 230(2): 208-15, 2008.
17. Doerge, D.R., G.G. da Costa, L.P. McDaniel, M.I. Churchwell, N.C. Twaddle, and F.A. Beland, “DNA adducts derived from administration of acrylamide and glycidamide to mice and rats,” Mutation Research 580(1-2): 131-41, 2005.
18. Doerge D.R., N.C. Twaddle, M.I. Boettcher, L.P. McDaniel, and J. Angerer, “Urinary excretion of acrylamide and metabolites in Fischer 344 rats and B6C3F(1) mice administered a single dose of acrylamide,” Toxicology Letters 169(1): 34-42, 2007.
19. Doerge, D.R., J.F. Young, J.J. Chen, M.J. Dinovi, and S.H. Henry, “Using dietary exposure and physiologically based pharmacokinetic/pharmacodynamic modeling in human risk extrapolations for acrylamide toxicity,” Journal of Agricultural and Food Chemistry 56(15): 6031-8, 2008.
20. Doerge, D.R., J.F. Young, L.P. McDaniel, N.C. Twaddle, and M.I. Churchwell, “Toxicokinetics of acrylamide and glycidamide in B6C3F1 mice,” Toxicology and Applied Pharmacology 202(3): 258-67, 2005.
21. Doerge, D.R., J.F. Young, L.P. McDaniel, N.C. Twaddle, and M.I. Churchwell, “Toxicokinetics of acrylamide and glycidamide in Fischer 344 rats,” Toxicology and Applied Pharmacology 208(3): 199-209, 2005.
22. Gamboa da Costa, G., M.I. Churchwell, L.P. Hamilton, L.S. Von Tungeln, F.A. Beland, M.M. Marques, and D.R. Doerge, “DNA adduct formation from acrylamide via conversion to glycidamide in adult and neonatal mice,” Chemical Research in Toxicology 16(10): 1328-37, 2003.
23. Garey, J., S.A. Ferguson, and M.G. Paule, “Developmental and behavioral effects of acrylamide in Fischer 344 rats,” Neurotoxicology and Teratology 27(4): 553-63, 2005.
24. Garey J., and M.G. Paule, “Effects of chronic low-dose acrylamide exposure on progressive ratio performance in adolescent rats,” Neurotoxicology 28(5): 998-1002, 2007.
25. Ghanayem, B.I., L.P. McDaniel, M.I. Churchwell, N.C. Twaddle, R. Snyder, T.R. Fennell, and D.R. Doerge, “Role of CYP2E1 in the epoxidation of acrylamide to glycidamide and formation of DNA and hemoglobin adducts,” Toxicological Sciences 88(2): 311-8, 2005.
26. Manière, I., T. Godard, D.R. Doerge, M.I. Churchwell, M. Guffroy, M. Laurentie, and J.M. Poul, “DNA damage and DNA adduct formation in rat tissues following oral administration of acrylamide,” Mutation Research 580(1-2): 119-29, 2005.
27. Manjanatha, M.G., A. Aidoo, S.D. Shelton, M.E. Bishop, L.P. McDaniel, L.E. Lyn-Cook, and D.R. Doerge, “Genotoxicity of acrylamide and its metabolite glycidamide administered in drinking water to male and female Big Blue mice,” Environmental and Molecular Mutagenesis 47(1): 6-17, 2006.
28. Martins, C., N.G. Oliveira, M. Pingarilho, G. Gamboa da Costa, V. Martins, M.M. Marques, F.A. Beland, M.I. Churchwell, D.R. Doerge, J. Rueff, and J.F. Gaspar, “Cytogenetic damage induced by acrylamide and glycidamide in mammalian cells: correlation with specific glycidamide-DNA adducts,” Toxicological Sciences 95(2): 383-90, 2007.
29. Mei, N., J. Hu, M.I. Churchwell, L. Guo, M.M. Moore, D.R. Doerge, and T. Chen, “Genotoxic effects of acrylamide and glycidamide in mouse lymphoma cells,” Food Chemistry and Toxicology 46(2): 628-36, 2008.
30. Tareke, E., N.C. Twaddle, L.P. McDaniel, M.I. Churchwell, J.F. Young, and D.R. Doerge, “Relationships between biomarkers of exposure and toxicokinetics in Fischer 344 rats and B6C3F1 mice administered single doses of acrylamide and glycidamide and multiple doses of acrylamide,” Toxicology and Applied Pharmacology 217(1): 63-75, 2006.
31. Twaddle, N.C., M.I. Churchwell, L.P. McDaniel, and D.R. Doerge, “Autoclave sterilization produces acrylamide in rodent diets: implications for toxicity testing,” Journal of Agricultural and Food Chemistry 52(13): 4344-9, 2004.
32. Twaddle, N.C., L.P. McDaniel, G. Gamboa da Costa, M.I. Churchwell, F.A. Beland, and D.R. Doerge, “Determination of acrylamide and glycidamide serum toxicokinetics in B6C3F1 mice using LC-ES/MS/MS,” Cancer Letters 207(1): 9-17, 2004.
33. Von Tungeln, L.S., M.I. Churchwell, D.R. Doerge, J.G. Shaddock, L.J. McGarrity, R.H. Heflich, G. Gamboa da Costa, M.M. Marques, and F.A. Beland, “DNA adduct formation and induction of micronuclei and mutations in B6C3F(1)/Tk mice treated neonatally with acrylamide or glycidamide,” International Journal of Cancer 124(9): 2006-15, 2009.
34. Young, J.F., R.H. Luecke, and D.R. Doerge, “Physiologically based pharmacokinetic/pharmacodynamic model for acrylamide and its metabolites in mice, rats, and humans,” Chemical Research in Toxicology 20(3): 388-99, 2007.
35. Amrein, T.M., L. Andres, F. Escher, and R. Amadò, “Occurrence of acrylamide in selected foods and mitigation options,” Food Additives and Contaminants 24(Suppl 1): 13-25, 2007.
36. Claus, A., R. Carle, and A. Schieber, “Acrylamide in cereal products: a review,” Start Printed Page 43138 Journal of Cereal Science 47(2): 118-133, 2008.
37. Friedman, M., and C.E. Levin, “Review of methods for the reduction of dietary content and toxicity of acrylamide,” Journal of Agricultural and Food Chemistry 56(15): 6113-40, 2008.
38. Foot, R.J., N.U. Haase, K. Grob, and P. Gondé, “Acrylamide in fried and roasted potato products: a review on progress in mitigation,” Food Additives and Contaminants 24(Suppl 1): 37-46, 2007.
39. Guenther, H., E. Anklam, T. Wenzl, and R.H. Stadler, “Acrylamide in coffee: review of progress in analysis, formation and level reduction,” Food Additives and Contaminants 24(Suppl 1): 60-70, 2007.
40. Halford, N.G., N. Muttucumaru, T.Y. Curtis, and M.A. Parry, “Genetic and agronomic approaches to decreasing acrylamide precursors in crop plants,” Food Additives and Contaminants 24(Suppl 1): 26-36, 2007.
41. Konings, E.J., P. Ashby, C.G. Hamlet, and G.A. Thompson, “Acrylamide in cereal and cereal products: a review on progress in level reduction,” Food Additives and Contaminants 24(Suppl 1): 47-59, 2007.
42. Morales, F., E. Capuano, and V. Fogliano, “Mitigation strategies to reduce acrylamide formation in fried potato products,” Annals of the New York Academy of Sciences 1126: 89-100, 2008.
43. Muttucumaru, N., J.S. Elmore, T. Curtis, D.S. Mottram, M.A. Parry, and N.G. Halford, “Reducing acrylamide precursors in raw materials derived from wheat and potato,” Journal of Agricultural and Food Chemistry 56(15): 6167-72, 2008.
44. Stadler, R.H., “Acrylamide formation in different foods and potential strategies for reduction,” Advances in Experimental Medicine and Biology 561: 157-169, 2005.
45. Stadler, R.H., and G. Scholz, “Acrylamide: an update on current knowledge in analysis, levels in food, mechanisms of formation, and potential strategies of control,” Nutrition Reviews 62(12): 449-67, 2004.
46. Taeymans, D., A. Andersson, P. Ashby, I. Blank, P. Gondé, P. van Eijck, V. Faivre, S.P. Lalljie, H. Lingnert, M. Lindblom, R. Matissek, D. Müller, R.H. Stadler, A. Studer, D. Silvani, D. Tallmadge, G. Thompson, T. Whitmore, J. Wood, and D. Zyzak. “Acrylamide: update on selected research activities conducted by the European food and drink industry,” Journal of AOAC International 88(1): 234-41, 2005.
47. Taeymans, D., J. Wood, P. Ashby, I. Blank, A. Studer, R.H. Stadler, P. Gondé, P. Van Eijck, S. Lalljie, H. Lingnert, M. Lindblom, R. Matissek, D. Müller, D. Tallmadge, J. O'Brien, S. Thompson, D. Silvani, and T. Whitmore, “A review of acrylamide: an industry perspective on research, analysis, formation, and control,” Critical Reviews in Food Science and Nutrition 44(5): 323-47, 2004.
48. Zhang, Y., and Y. Zhang, “Formation and reduction of acrylamide in Maillard reaction: a review based on the current state of knowledge,” Critical Reviews in Food Science and Nutrition 47(5): 521-542, 2007.
49. Confederation of Food and Drink Industries of the EU (CIAA), “The CIAA Acrylamide ‘Toolbox’, Revision 12,” 2009. Accessed online at http://www.ciaa.be/documents/brochures/ac_toolbox_20090216.pdf.
50. CIAA, “A ‘Toolbox’ for the Reduction of Acrylamide in Biscuits, Crackers & Crispbreads,” 2007. Accessed online at http://www.ciaa.be/documents/others/biscuits-EN-final.pdf.
51. CIAA, “A ‘Toolbox’ for the Reduction of Acrylamide in Bread Products,” 2007. Accessed online at http://www.ciaa.be/documents/others/bread-EN-final.pdf.
52. CIAA, “A ‘Toolbox’ for the Reduction of Acrylamide in Breakfast Cereals,” 2007. Accessed online at http://www.ciaa.be/documents/others/cereals-EN-final.pdf.
53. CIAA, “A ‘Toolbox’ for the Reduction of Acrylamide in Fried Potato Products Potato Crisps,” 2007. Accessed online at http://www.ciaa.be/documents/others/crisps-EN-final.pdf.
54. CIAA, “A ‘Toolbox’ for the Reduction of Acrylamide in Fried Potato Products/French Fries,” 2007. Accessed online at http://www.ciaa.be/documents/others/french%20fries-EN-final.pdf.
55. Association of the Chocolate, Biscuits, and Confectionery Industries of the EU (CAOBISCO), CAOBISCO Review of Acrylamide Mitigation in Biscuits, Crackers and Crispbread, 2006. Accessed online at http://www.caobisco.com/doc_uploads/7254639e.pdf.
56. The HEATOX Project, “Guidelines to Authorities and Consumer Organisations on Home Cooking and Consumption,” 2006. Accessed online at http://www.slv.se/upload/heatox/documents/D59_guidelines_to_authorities_and_consumer_organisations_on_home_cooking_and_consumption.pdf.
57. The HEATOX Project, “Manual on strategies to food industries, restaurants, etc., to minimize acrylamide formation,” 2006. Accessed online at http://www.slv.se/upload/heatox/documents/D60_manual_on_strategies_to_food_industries_restaurants_etc_to_minimise_acrylamide_formation.pdf.
58. Joint FAO/WHO Food Standards Programme Codex Committee on Contaminants in Foods (CCCF), “Draft Code of Practice for the Reduction of Acrylamide in Foods (N06-2006),” In: Report of the 3rd Session of the CCCF, Rotterdam, The Netherlands, March 23-27 2009, ALINORM 09/32/41, 2009, Appendix IV. Accessed online at http://www.codexalimentarius.net/download/report/722/al32_41e.pdf.
59. European Commission Joint Research Centre—Institute for Reference Materials and Measurements, “Monitoring database on acrylamide levels in food,” 2006. Accessed online at http://irmm.jrc.ec.europa.eu/html/activities/acrylamide/database.htm.
60. European Food Safety Authority (EFSA), “Call for occurrence data on acrylamide levels in food,” 2007. Accessed online at http://www.efsa.europa.eu/EFSA/efsa_locale-1178620753812_1178656289168.htm.
61. The Commission of the European Communities, “Commission Recommendation of 3 May 2007 on the monitoring of acrylamide levels in food (2007/331/EC),” Official Journal of the European Union, 12/5/2007, L 123/33-40. Accessed online at http://eur-lex.europa.eu/LexUriServ/site/en/oj/2007/l_123/l_12320070512en00330040.pdf.
62. Bundesamt für Verbraucherschutz und Lebensmittelsicherheit (BVL), “Concept of minimising acrylamide contents in foodstuffs,” 2005. Accessed online at http://www.bvl.bund.de/cln_007/nn_521138/EN/01_Food/04_Acrylamid_en/acrylamid_EN_node.html_nnn=true.
63. Bonneck, S., “Acrylamide Risk Governance in Germany,” In O. Renn and K.D. Walker, Eds., Global Risk Governance, 2008. Accessed online at http://www.irgc.org/IMG/pdf/Chapter_11_Acrylamides_final.pdf.
64. Health Canada, “Health Canada's Acrylamide Monitoring Program,” 2009. Accessed online at http://www.hc-sc.gc.ca/fn-an/securit/chem-chim/food-aliment/acrylamide/monitoring-prog-surveillance-eng.php.
65. Office of the Attorney General, State of California, News release: “Atty. Gen. Brown Settles Potato Chip Lawsuit With Heinz, Frito-Lay & Kettle Foods,” August 1, 2008. Accessed online at https://ag.ca.gov/newsalerts/release.php?id=1595&.Start Signature
Dated: August 17, 2009.
Assistant Commissioner for Policy.
[FR Doc. E9-20495 Filed 8-25-09; 8:45 am]
BILLING CODE 4160-01-S