1. Acrylamide in Foods: A Review of the
Science and Future Considerations
James R. Coughlin, Ph.D.
President, Coughlin & Associates
Aliso Viejo, California
jrcoughlin@cox.net
www.linkedin.com/in/jamescoughlin
“7th International Symposium
on Deep Frying”
San Francisco, California
February 21, 2013

2. Presentation Outline
 Acrylamide Background -
 Toxicity, Genotoxicity, Carcinogenicity
 Discovery in Foods in 2002
 Animal Carcinogenicity – newer findings
 Human Epidemiologic Evidence
 Heat-induced Carcinogens in Foods
 Benefit-Risk Evaluation – The “Holistic Approach”
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5. Risk Assessment Paradigm for Chemicals
 Hazard Identification - Determination of adverse effects caused by high
intakes of the chemical (epidemiology, clinical, animal, short-term, etc.)
 Dose-Response Assessment -
 Selection of the critical data set & the “No-Observed-Adverse-Effect-
Level” (NOAEL), and determination of an Uncertainty Factor (e.g., 100)
 Determination of a carcinogen’s animal potency and risk level
 Derive an Acceptable Daily Intake (ADI) or Tolerable Level of Intake
 Exposure (Intake) Assessment - Evaluation of the range and distribution
of human intakes of chemicals
 Risk Characterization -
 Estimation of the fraction of the population exceeding ADI
 Evaluation of the magnitude of potential excess intakes.
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6. The Dose Makes the Poison!
“All things are poison and
there is none which is not a
poison. Solely the dose
differentiates a poison from a
remedy.”
Paracelsus
(1493-1541)
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7. Acrylamide Snapshot: Chemistry and Toxicology
 Occupational neurotoxin in humans; genotoxic / mutagenic in cell
cultures
 Known rat carcinogen, classified as “probable human carcinogen”
 Metabolized to glycidamide (an epoxide), also an animal carcinogen
 Acrylamide & glycidamide can bind to DNA, amino acids and proteins
 DNA adducts  carcinogenic potential
 Blood hemoglobin adducts  biomarker of exposure
 Dietary proteins may reduce acrylamide uptake in humans
 Protective enzymes can detoxify acrylamide and glycidamide
 Discovered by the Swedes in 2002 in hundreds of heat-processed
food products, making up about 40% of our calories.
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8. Swedish Discovery of Acrylamide in Foods
(announced April 2002)
Tareke et al., J. Agric. Food Chem. 50: 4998-5006 (2002)
 Discovered after illness investigations of tunnel workers
exposed to acrylamide in 1997; background levels of
Hemoglobin-acrylamide adducts of non-smoking Swedes
were found to be elevated
 Higher temperature / time / surface area increase levels:
 Carbohydrate-rich foods high: 150 - 4,000 ppb
 Protein-rich foods low, e.g. meats: 5 - 50 ppb
 Not detected in unheated or boiled foods
 Swedish adult acrylamide intake estimated to be 100 μg/day,
but not known to be much lower in most populations.
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9. Acrylamide’s Comparison with other Known
“Cooked Food” Carcinogens
 Late 60’s / early 1970’s - PAH’s in grilled meats, N-nitroso
compounds in cured meats and beer, other trace contaminants
 Late 1970’s - reports on heat-induced “Maillard Browning Reaction”
products and heterocyclic amines (Trp-P1&2, Glu-P1&2, IQ, etc.)
 These contaminants were found –
 in just a very few foods
 at very low parts per billion (ppb) levels
 Big surprise: acrylamide is found in so many foods at much higher
levels, even up to 1,000 to 4,000 ppb.
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10. Ammonia
Alkyl amines
Amino acids
Proteins
Phospholipids
Aldehydes
Ketones
Sugars
Carbohydrates
Lipids
Carbonyls
Esters
Amides (Acrylamide)
Heterocyclic Compounds
Amine
Carbonyl
Amino-Carbonyl
Interaction
(Amadori Products)
HEATHEAT
Furans Oxazoles
Pyrroles Imidazoles
Thiophenes Pyridines
Thiazoles Pyrazines
Melanoidins
(pigments)
Volatile Compounds
(aroma chemicals)
General Scheme of Maillard Browning Reaction

11. Carcinogens in Heated Foods
 For over 40 years, there has been an ongoing worldwide effort to
try to determine the intakes and toxicities of these chemicals and
possible mitigation methods, and to try to understand their true
risk to humans
 This focus has always been on just one chemical at a time
 But health-protective compounds are also produced by heating
foods, and these compounds must be factored into the risk-
benefit evaluation process, as do nutritional benefits
 My own conclusion after almost 40 years of focus on heat-
processed carcinogens:
Cancer warnings on foods are not currently justified,
and any such warnings should be deferred pending the
evaluation of ongoing research efforts.
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12. Food Acrylamide Range (ppb)
Baby food/biscuits ND - 442
Breads/bakery products ND - 364
Cereals 11 - 1057
Chocolate products ND - 909
Coffee (roasted, not brewed) 37 - 374
Coffee (brewed) 5 - 11
Cookies/crackers 26 - 1540
Dairy drinks ND - 43
Dried foods/mixes ND - 1184

13. Food Acrylamide Range (ppb)
French fries 117 - 1325
Fruits/vegetables (canned) ND - 83
Gravies/seasonings ND - 151
Infant formulas ND
Nuts/nut butters ND - 457
Potato chips 117 - 4080
Snacks (other salty) 12 - 1340
Olives 123 - 1925
Prune juice 53 - 326

14. U.S. National Toxicology Program (NTP) Bioassay
of Acrylamide
 U.S. FDA nominated acrylamide and glycidamide for complete toxicology
testing in November 2002 for future risk assessment purposes
 2-year cancer bioassay in rats and mice fed acrylamide in drinking water
(untreated control + 4 treatment doses), with ancillary studies on
metabolism, genotoxicity and toxicokinetics
 Draft Technical Report No. 575 was peer-reviewed by the NTP Peer
Review Panel in April 2011; Panel accepted the conclusions that there
was “Clear Evidence of Carcinogenicity” in male and female rats and
male and female mice; Final Report was issued in July 2012
 For consideration: the observed NTP tumor findings and cancer
potencies may be useful in increasing acrylamide’s acceptable risk level.
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16. Risk Assessment Considerations Based on NTP
 FAO/WHO Joint Expert Committee on Food Additives (JECFA)
acrylamide risk assessment (2010) used preliminary NTP data on
benign tumors in the rat mammary gland and mouse Harderian
gland, but these endpoints are not biologically relevant to human
risk assessment
 JECFA and national authorities should reevaluate acrylamide’s
potential for human risk based on the lower incidences of
relevant NTP malignant rat and mouse tumor endpoints
 I firmly believe that acrylamide is too important and too
widespread a contaminant in the human diet to have its risk
determined by biologically irrelevant rodent tumor endpoints and
with no consideration of the lack of increased risk in humans.
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17. Recent Dietary Epidemiology Studies of
Acrylamide (Human Studies)
 Pelucchi et al. 2011. “Exposure to Acrylamide and Human
Cancer - A Review and Meta-analysis of Epidemiologic
Studies.” Annals Oncology 22: 1487-1499.
 “Conclusions: Available studies consistently suggest a
lack of an increased risk of most types of cancer from
exposure to acrylamide.”
 Lipworth et al. 2012. “Review of Epidemiologic Studies of
Dietary Acrylamide Intake and the Risk of Cancer.” Eur. J.
Cancer Protection 21: 375-386.
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19. “Acrylamide in Foods: A Review of the Science and
Future Considerations”
David R. Lineback, James R. Coughlin and Richard H. Stadler,
Ann. Rev. Food Sci. & Technol. 3: 15-35 (April 2012)
 Most of the major countries of the world have advised consumers
to follow the dietary recommendations for a balanced diet issued
by their food regulatory and public health agencies.
 The data available to date have been insufficient to warrant any
recommendation for a significant change in the dietary
recommendations because of acrylamide.
 Current epidemiological and toxicological evidence are
insufficient to indicate that the amounts of acrylamide consumed
in the normal diet are likely to result in adverse human health
effects, particularly cancer.
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20. Progress on Mitigation Techniques
 Government regulators, university scientists and the food
industry have been working together to develop and
implement ways to reduce the presence of acrylamide
 Food Drink Europe “Toolbox” (2011) guidance summarizes
agronomic, processing and ingredient mitigation techniques,
including enzyme treatments (asparaginase)
 Ongoing research efforts will hopefully continue to lead to
further acrylamide reductions
 However, we will never achieve elimination of acrylamide
from foods, as long as we continue to heat process and cook
our foods.
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21. Acrylamide - Where Do We Go From Here?
 Present naturally in a wide variety of foods since we began to
enjoy the benefits of cooked foods: coffee, baked goods, potato-
products (including chips and fries), whole grains, cereal products
 Recognize that eliminating one single food from the diet will not
eliminate acrylamide completely
 Research will continue to evolve in the U.S. and abroad to provide
better insights on acrylamide’s impact on public health
 FDA’s ongoing Action Plan for acrylamide will identify additional
research needs and any steps, if any, that need to be taken in
regards to assuring food safety
 FDA does not recommend changing your diet due to acrylamide’s
presence, but instead advises consumers to adopt a healthy
eating plan, consistent with the Dietary Guidelines for Americans.
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22. Acrylamide Battleground under California Prop 65
 Listed in 1990 as a carcinogen; “Safe Harbor” level = 0.2 μg/day; must stay
below this level to avoid cancer warnings; if you can detect it, even a 1-ounce
serving of any food exceeds this level
 French fries: Attorney General sued and settled case (2008) against frozen
fries/tater tots and demanded a 50% reduction in levels; fast-food restaurant
fries have had cancer warnings posted for years
 Potato chips: AG settled (2008) the case against chip manufacturers; agreement
to cut levels to 275 ppb by end of 2011 (20 - 85% reductions) to avoid warnings;
no warnings being given
 Cereals: Private “bounty hunter” lawyers sued cereal manufacturers in 2009; the
case is still pending
 “Bounty Hunter” sued coffee shops in 2010 over brewed coffee; 10 x 10-inch
cancer warning placards have been posted; another case now in court against
over 100 coffee roasters for packaged roast coffees.
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24. Acrylamide Resources for the Food Industry
 Grocery Manufacturers Association - Acrylamide Facts
http://www.acrylamidefacts.org/
 International Food Information Council - Acrylamide Resources
http://www.foodinsight.org/Resources/Detail.aspx?topic=Acrylamide
Resources
 Food Drink Europe - Acrylamide “Toolbox”
http://www.fooddrinkeurope.eu/publications/category/toolkits/
 FDA - Questions and Answers
http://www.fda.gov/Food/FoodSafety/FoodContaminantsAdulteration/
ChemicalContaminants/Acrylamide/ucm053569.htm
 EFSA - Acrylamide
http://www.efsa.europa.eu/en/topics/topic/acrylamide.htm
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27. Benefit-Risk Evaluation –
The “Holistic Approach”
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29. Key “Benefit-Risk” Controversies
 Interpretation of rodent cancer bioassays of extreme chemical
doses has been shown to be overly conservative
 Assessing individual food chemicals has been our focus in the
past, but we now need to consider the risks and benefits of
whole foods using a “Holistic Approach”
 Failure to give proper weight to human epidemiology studies
showing little or no increased risk of foods containing the
chemical
 Failure to consider the POSITIVE health benefits of foods
containing only trace levels of carcinogens & toxicants
 Comprehensive benefit-risk assessment is going to be complex,
data-demanding and very expensive.
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30. “Benefit-Risk Evaluation” to Assess the Safety of
Foods Containing Heat-produced Carcinogens
 We’ve been doing it the WRONG WAY for decades, by
simply evaluating the risk of individual chemicals in a
food one by one
 Going forward, I believe the RIGHT WAY is to evaluate
the safety of the whole food by comparing its risks vs.
benefits
 Use the “Holistic Approach” – look at the whole food
 Various “Benefit-Risk” evaluations have recently been
published.
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34. Problems Presented by Focusing on a Single
Toxic Food Chemical
 Consumer confidence in food is eroded by media scares
 Scarce resources do not always go to the most critical risks (trace level
toxicants vs. more critical microbiological and nutritional threats)
 Disruption of business & international trade
 No end in sight…new chemicals are coming to the forefront all the time;
analytical advances drive detection levels to near “zero”; high-dose animal
testing identifies potential health problems that might never occur in
humans
 We don’t have the resources to pursue all these individual chemicals in
food as major issues, like we have with acrylamide
 Can’t toxicology and epidemiology guide us to agree on some
toxicologically insignificant level of a chemical and the benefits of the
whole food? ? I believe they can!
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35. Use the Holistic “Benefit-Risk” Approach
 The beneficial health effects of certain whole foods may outweigh the
effects of trace levels of animal carcinogens and other toxicants in these
foods
 We know we can’t take health benefits into account when we deal with
direct food additives, but we can when dealing with unintentional
contaminants like the heat-produced carcinogens
 We must press global health and regulatory authorities to:
 Use improved toxicology and risk assessment methods on individual
chemicals tested in animals at high doses
 Do more research / evaluation on qualitative and quantitative
assessment of the benefits of whole foods
 Consider the health benefits of protective compounds, both naturally
occurring and produced by heating
 Assess the safety and benefits of the whole food, not just individual
food carcinogens / toxicants one by one.
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36. “Maillard Reaction Products” (MRPs) – Carcinogens vs.
Possible Health-Beneficial Components
 While flavors, aromas, colors and texture of browned foods
depend on the MBR, animal carcinogens are also formed
 But Antioxidants are also produced by the MBR, and they may
protect against diseases linked to oxidative damage (cancer,
diabetes, atherosclerosis, arthritis, inflammation, etc.)
 The brown melanoidin polymers and some heterocyclic
compounds (furan) have been shown to have antioxidant
properties
 Some MRPs can also induce protective detoxification enzymes,
including ones that even detoxify acrylamide (glutathione-S-
transferase).
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37. J. Agric. Food Chem. (2006) 54: 853
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41. Does Acrylamide in Food Pose a Real Risk to
Human Health?
 Risk characterization traditionally includes:
 Rodent cancer bioassay results (like the NTP bioassay)
 Biomarker and metabolic studies in animals and humans
 Bioavailability may be less in human diets than in water
 Need more reliable data on human intake estimates
 But for acrylamide in heated foods…
 Consideration of cancer thresholds and non-linear dose modeling
 Dietary epidemiology studies support lack of human risk globally
 Health-protective, beneficial components of acrylamide-containing
foods and the nutritional value of foods must also be considered in
a benefit-risk evaluation.
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42. Thank You!
Questions?