coughlin_acrylamide_international frying symposium_february 2013
TRANSCRIPT
Acrylamide in Foods: A Review of the Science and Future Considerations
James R. Coughlin, Ph.D.President, Coughlin & Associates
Aliso Viejo, [email protected]
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?