[Federal Register Volume 74, Number 164 (Wednesday, August 26, 2009)]
[Notices]
[Pages 43134-43138]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E9-20495]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2009-N-0393]


Acrylamide in Food; Request for Comments and for Scientific Data 
and Information

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice; request for comments and scientific data and 
information.

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SUMMARY: 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.

DATES: Submit comments and scientific data and information by November 
24, 2009.

ADDRESSES: 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.

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.

SUPPLEMENTARY INFORMATION:

I. Background

A. Introduction

    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 [deg]C (248 [deg]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 (microg/kg-bw/d) 
(Ref. 14). International estimates for the average consumer range from 
0.2 to 1.4 microg/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 microg/kg-bw/d for the 
general consumer and 4 microg/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).

C. Toxicology

    Several international toxicology evaluations of acrylamide have 
been completed since the identification of

[[Page 43135]]

acrylamide 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 [deg]C 
(43 [deg]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 [deg]C (347 [deg]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 microg/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 microg/kg to over 
1200 microg/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

[[Page 43136]]

reducing 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?

C. Comments

    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.

[[Page 43137]]

III. References

    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. 
T[ouml]rnqvist, ``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.
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S.M. Musser, ``Rugged LC-MS/MS survey analysis for acrylamide in 
foods,'' Journal of Agricultural and Food Chemistry 51:7547-7554, 
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Acrylamide in Food: Individual Food Products,'' 2002-2006. Accessed 
online at http://www.fda.gov/Food/FoodSafety/FoodContaminantsAdulteration/ChemicalContaminants/Acrylamide/ucm053549.htm.
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Acrylamide in Food: Total Diet Study Results,'' 2004-2006. Accessed 
online at http://www.fda.gov/Food/FoodSafety/FoodContaminantsAdulteration/ChemicalContaminants/Acrylamide/ucm053566.htm.
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15, 2008.
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N.C. Twaddle, and F.A. Beland, ``DNA adducts derived from 
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Mutation Research 580(1-2): 131-41, 2005.
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and hemoglobin adducts,'' Toxicological Sciences 88(2): 311-8, 2005.
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63-75, 2006.
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Doerge, ``Autoclave sterilization produces acrylamide in rodent 
diets: implications for toxicity testing,'' Journal of Agricultural 
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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.
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    Dated: August 17, 2009.
David Horowitz,
Assistant Commissioner for Policy.
[FR Doc. E9-20495 Filed 8-25-09; 8:45 am]
BILLING CODE 4160-01-S