Acrylamide in Foods: A Review of the Science and Future Considerations

James R. Coughlin, Ph.D.President, Coughlin & Associates

Aliso Viejo, Californiajrcoughlin@cox.net

www.linkedin.com/in/jamescoughlin

“7th International Symposiumon Deep Frying”

San Francisco, CaliforniaFebruary 21, 2013

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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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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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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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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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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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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AmmoniaAlkyl aminesAmino acidsProteinsPhospholipids

AldehydesKetonesSugarsCarbohydratesLipids

CarbonylsEstersAmides (Acrylamide)Heterocyclic Compounds

Amine

Carbonyl

Amino-CarbonylInteraction

(Amadori Products)

HEATHEAT

Furans OxazolesPyrroles ImidazolesThiophenes PyridinesThiazoles Pyrazines

Melanoidins(pigments)

Volatile Compounds(aroma chemicals)

General Scheme of Maillard Browning Reaction

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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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

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

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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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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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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“Acrylamide in Foods: A Review of the Science andFuture 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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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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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 noteliminate 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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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-ounceserving 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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Acrylamide Resources for the Food Industry Grocery Manufacturers Association - Acrylamide Facts

http://www.acrylamidefacts.org/

International Food Information Council - Acrylamide Resourceshttp://www.foodinsight.org/Resources/Detail.aspx?topic=AcrylamideResources

Food Drink Europe - Acrylamide “Toolbox”http://www.fooddrinkeurope.eu/publications/category/toolkits/

FDA - Questions and Answershttp://www.fda.gov/Food/FoodSafety/FoodContaminantsAdulteration/ChemicalContaminants/Acrylamide/ucm053569.htm

EFSA - Acrylamidehttp://www.efsa.europa.eu/en/topics/topic/acrylamide.htm

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Benefit-Risk Evaluation –

The “Holistic Approach”

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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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“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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Problems Presented by Focusing on a SingleToxic 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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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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“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 antioxidantproperties

Some MRPs can also induce protective detoxification enzymes, including ones that even detoxify acrylamide (glutathione-S-transferase).

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J. Agric. Food Chem. (2006) 54: 853

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Does Acrylamide in Food Pose a Real Risk toHuman 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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Thank You!

Questions?