Acrylamide in Foods: Toxicology, Epidemiology and Research InitiativesAcrylamide in Foods: Toxicology, Epidemiology and Research InitiativesSara Hale Henry, P.D., Kathleen M. Koehler, Ph.D., MPH, Center for Food Safety and Applied Nutrition, College Park, MDDaniel R. Doerge, Nat’l. Ctr. for Toxicological Research, Jefferson, ArkansasU.S. Food & Drug AdministrationHemoglobin Adducts in HumansHemoglobin Adducts in Humans• Workers with neurotoxic symptoms• Chinese and Korean workers, polyacrylamide manufacture• Swedish workers, tunnel construction• > 500 to 18,000 picomoles/g globin• Controls with no occupational exposure• Smoking 116 picomoles/g globin• Non-smoking 31 picomoles/g globin• Laboratory workers• Polyacrylamide gels 54 picomoles/g globinAverage Acrylamide per Serving*Average Acrylamide per Serving*48.82 ½ ounces698French Fries, (OB)9.81 slice213Toast2.21 slice44Soft Bread16.41 ounce548Potato Chips22.52 ½ ounces322French Fries, (RF)6.61 ounce222Cookies2.01 cup8Brewed Coffee7.32 ounces133Breakfast CerealAcrylamide,ug per servingApproximateServing Size**Acrylamide,PPB or ug per kg foodFood*FDA exploratory data on acrylamide in foods through Feb 2003**Nutrition Label Serving Sizes (21 CFR 101.12, Table 2)Formation of Acrylamide in FoodFormation of Acrylamide in Food• Side reaction of browning reactions in food• Non-enzymatic browning• Maillard reaction• Reducing sugar (glucose, fructose) + amino acids• Acrylamide formation• Reducing sugar + asparagine• Temperature > 100 deg C• Low moistureFAO/WHO ConsultationHealth Implications of AcrylamideFAO/WHO ConsultationHealth Implications of Acrylamide• June 2002• Confirmed presence of acrylamide in foods• Estimated average intake, 0.3 to 0.8 ug/kg bw/d• No neurotoxic effects expected at these levels• Carcinogenic potency of acrylamide in animals• Similar to other carcinogens in human diet• Likely overall human intake is higher• No evidence on carcinogenesis in humans• Major concern based on induction of cancer and heritable mutations in animalsFAO/WHO Recommendations on Acrylamide in FoodFAO/WHO Recommendations on Acrylamide in Food• Interim advice• Food should not be cooked excessively<But must be cooked thoroughly to destroy pathogens• Eat a balanced and varied diet<Plenty of fruits and vegetables<Moderate consumption of fried and fatty foods• Investigate possibilities for reducing acrylamide in foods• Establish an international network to share data and ongoing workFDA Estimate of Mean Acrylamide IntakeCFSII 1994-96, 1998; Ages 2 and OlderFDA Estimate of Mean Acrylamide IntakeCFSII 1994-96, 1998; Ages 2 and Older7070.027Brewed Coffee100180.070Other Foods Tested8250.020Soft Bread0.370.0230.0400.0410.0440.0490.056Mean acrylamide intake(ug/kg bw/d)100776252285415Cumulative percent100Total6Toast10Cookies10Potato Chips11Breakfast Cereal13French Fries (OB)14French Fries (RF)FoodPercent of total intakeOther Tested Foods Contributing to FDA’s Estimate of Acrylamide IntakeOther Tested Foods Contributing to FDA’s Estimate of Acrylamide IntakeSoup mixPeanut butterBreaded chickenBaked beansPopcornPretzelsCrackersCorn snacksBreaded fishTortillaChocolateBagelsInstant coffeeCrisp bread, matzoCocoaTested Foods Providing the Remaining 18% of Estimated Mean Acrylamide IntakeMalted drinksPork rindsSoy proteinTaroNuts & seedsAlmondsDoughnutsFDA Preliminary Exposure Assessment ImplicationsFDA Preliminary Exposure Assessment Implications• Estimated average US exposure• Similar to international estimates• 1000 x below animal neurotoxic or carcinogen levels• Exposure of small children• 2-3 times greater per kg body weight• Expected based on body size and food intakeWorkers Exposed to AA in Three U.S. & One Dutch Chemical Plants Workers Exposed to AA in Three U.S. & One Dutch Chemical Plants • Cohort of 8508 workers potentially exposed to AA at 3 U.S. chemical plants & one plant in Netherlands 1925-89 (Collins et al, 1989)• Data on cohort updated covering 11 yrs. (Marsh et al., 1999)• “Most definitive study of the human carcinogenic potential of exposure to AA conducted to date.”AA Worker Study (cont’d.)AA Worker Study (cont’d.)• Authors of study found increased SMRs of rectal, esophageal, pancreatic & kidney cancers for some categories of exposure to AA, but little evidence of exposure-response relations• 2.26-fold risk (95% CI 1.03 – 4.29) found for pancreatic cancer among workers with cumulative exposure to AA >0.30 mg/m3yrs, but no consistent exposure-response relationWorker AA Study (cont’d.)Worker AA Study (cont’d.)• Authors noted limitations of study to be a large proportion of short term workers, low AA exposure, incomplete smoking data• Low statistical power to detect cancers of brain & CNS, thyroid gland, testis & other male genital organs• Good statistical power to detect respiratory cancers• Authors concluded little evidence for a causal relation between exposure to AA and mortality from any cancer siteEpidemiology Study on Dietary Acrylamide and Cancer RiskEpidemiology Study on Dietary Acrylamide and Cancer Risk• Case-control study, January, 2003• Men and women in Stockholm, Sweden• Aged 51 to 77• Found no positive association between dietary acrylamide and incidence of cancer of large bowel, bladder, kidneyEvaluations of Workers StudiesEvaluations of Workers Studies• In addition to evaluations by original authors, this chemical plant study has been evaluated by Sobel et al (1986), Hogan & Scott (1990) with reply by Collins et al. (1990). Also Granathet al. (2001) with reply by Marsh et al. (2001)• Various authors disagree on conclusions, statistical power and limitations of original studyEpidemiology Study on Dietary Acrylamide and Cancer RiskEpidemiology Study on Dietary Acrylamide and Cancer Risk• Dietary acrylamide• Food frequency questionnaire • Swedish acrylamide food data• Various fried and baked potatoes, crisp breads, soft breads, breakfast cereals, biscuits• Did not include coffee or toasting of soft breads• Subjects• 538 controls• 591 large bowel cancer• 263 bladder cancer• 133 kidney cancer•Source: Mucci et al., 2003Study EvaluationStudy Evaluation• Authors concluded that“Acrylamide intake through dietary sources may thus be effectively detoxified within the range of human exposure.”• StrengthsThis was a well-conducted study with strengths that