Cancer Causes & Control

, Volume 20, Issue 3, pp 269–278 | Cite as

Validation of a food frequency questionnaire measurement of dietary acrylamide intake using hemoglobin adducts of acrylamide and glycidamide

  • Kathryn M. Wilson
  • Hubert W. Vesper
  • Paula Tocco
  • Laura Sampson
  • Johan Rosén
  • Karl-Erik Hellenäs
  • Margareta Törnqvist
  • Walter C. Willett
Original Paper



Acrylamide, a probable human carcinogen, is formed during high-heat cooking of many common foods. The validity of food frequency questionnaire (FFQ) measures of acrylamide intake has not been established. We assessed the validity of acrylamide intake calculated from an FFQ using a biomarker of acrylamide exposure.


We calculated acrylamide intake from an FFQ in the Nurses’ Health Study II. We measured hemoglobin adducts of acrylamide and its metabolite, glycidamide, in a random sample of 342 women. Correlation and regression analyses were used to assess the relationship between acrylamide intakes and adducts.


The correlation between acrylamide intake and the sum of acrylamide and glycidamide adducts was 0.31 (95% CI: 0.20–0.41), adjusted for laboratory batch, energy intake, and age. Further adjustment for BMI, alcohol intake, and correction for random within-person measurement error in adducts gave a correlation of 0.34 (CI: 0.23–0.45). The intraclass correlation coefficient for the sum of adducts was 0.77 in blood samples collected 1–3 years apart in a subset of 45 women. Intake of several foods significantly predicted adducts in multiple regression.


Acrylamide intake and hemoglobin adducts of acrylamide and glycidamide were moderately correlated. Within-person consistency in adducts was high over time.


Acrylamide Glycidamide Diet Hemoglobin adducts 


  1. 1.
    IARC(1994) Monographs on the evaluation of carcinogenic risks to humans, Vol 60Google Scholar
  2. 2.
    International Programme on Chemical Safety. Acrylamide (EHC 49, 1985). Available at:
  3. 3.
    Tareke E, Rydberg P, Karlsson P, Eriksson S, Törnqvist M (2002) Analysis of acrylamide, a carcinogen formed in heated foodstuffs. J Agric Food Chem 50(17):4998–5006. doi:10.1021/jf020302f PubMedCrossRefGoogle Scholar
  4. 4.
    Mucci LA, Dickman PW, Steineck G, Adami HO, Augustsson K (2003) Dietary acrylamide and cancer of the large bowel, kidney, and bladder: absence of an association in a population-based study in Sweden. Br J Cancer 88(1):84–89. doi:10.1038/sj.bjc.6600726 PubMedCrossRefGoogle Scholar
  5. 5.
    Mucci LA, Lindblad P, Steineck G, Adami HO (2004) Dietary acrylamide and risk of renal cell cancer. Int J Cancer 109(5):774–776. doi:10.1002/ijc.20011 PubMedCrossRefGoogle Scholar
  6. 6.
    Mucci LA, Sandin S, Balter K, Adami HO, Magnusson C, Weiderpass E (2005) Acrylamide intake and breast cancer risk in Swedish women. JAMA 293(11):1326–1327. doi:10.1001/jama.293.11.1326 PubMedCrossRefGoogle Scholar
  7. 7.
    Mucci LA, Adami HO, Wolk A (2006) Prospective study of dietary acrylamide and risk of colorectal cancer among women. Int J Cancer 118(1):169–173. doi:10.1002/ijc.21309 PubMedCrossRefGoogle Scholar
  8. 8.
    Pelucchi C, Franceschi S, Levi F, Trichopoulos D, Bosetti C, Negri E et al (2003) Fried potatoes and human cancer. Int J Cancer 105(4):558–560. doi:10.1002/ijc.11118 PubMedCrossRefGoogle Scholar
  9. 9.
    Pelucchi C, Galeone C, Levi F, Negri E, Franceschi S, Talamini R et al (2006) Dietary acrylamide and human cancer. Int J Cancer 118(2):467–471. doi:10.1002/ijc.21336 PubMedCrossRefGoogle Scholar
  10. 10.
    Pelucchi C, Galeone C, Dal Maso L, Talamini R, Montella M, Ramazzotti V et al (2007) Dietary acrylamide and renal cell cancer. Int J Cancer 120(6):1376–1377. doi:10.1002/ijc.22457 PubMedCrossRefGoogle Scholar
  11. 11.
    Hogervorst JG, Schouten LJ, Konings EJ, Goldbohm RA, van den Brandt PA (2007) A prospective study of dietary acrylamide intake and the risk of endometrial, ovarian, and breast cancer. Cancer Epidemiol Biomarkers Prev 16(11):2304–2313. doi:10.1158/1055-9965.EPI-07-0581 PubMedCrossRefGoogle Scholar
  12. 12.
    Stadler RH, Scholz G (2004) Acrylamide: an update on current knowledge in analysis, levels in food, mechanisms of formation, and potential strategies of control. Nutr Rev 62(12):449–467. doi:10.1301/nr.2004.janr.449-467 PubMedCrossRefGoogle Scholar
  13. 13.
    Wirfält E, Paulsson B, Törnqvist M, Axmon A, Hagmar L (2008) Associations between estimated acrylamide intakes, and hemoglobin AA adducts in a sample from the Malmo Diet and Cancer cohort. Eur J Clin Nutr 62(3):314–323PubMedCrossRefGoogle Scholar
  14. 14.
    Bjellaas T, Olesen PT, Frandsen H, Haugen M, Stolen LH, Paulsen JE et al (2007) Comparison of estimated dietary intake of acrylamide with hemoglobin adducts of acrylamide and glycidamide. Toxicol Sci 98(1):110–117. doi:10.1093/toxsci/kfm091 PubMedCrossRefGoogle Scholar
  15. 15.
    Kütting B, Uter W, Drexler H (2008) The association between self-reported acrylamide intake and hemoglobin adducts as biomarkers of exposure. Cancer Causes Control 19(3):273–281PubMedCrossRefGoogle Scholar
  16. 16.
    Bergmark E, Calleman CJ, He F, Costa LG (1993) Determination of hemoglobin adducts in humans occupationally exposed to acrylamide. Toxicol Appl Pharmacol 120(1):45–54. doi:10.1006/taap.1993.1085 PubMedCrossRefGoogle Scholar
  17. 17.
    Törnqvist M, Fred C, Haglund J, Helleberg H, Paulsson B, Rydberg P (2002) Protein adducts: quantitative and qualitative aspects of their formation, analysis and applications. J Chromatogr B Analyt Technol Biomed Life Sci 778(1–2):279–308. doi:10.1016/S1570-0232(02)00172-1 PubMedGoogle Scholar
  18. 18.
    U.S. Food and Drug Administration. Survey Data on Acrylamide in Food: Individual Food Products, 2002–2004. 2006; Available at:
  19. 19.
    U.S. Food and Drug Administration (2006) Survey Data on Acrylamide in Food: Total Diet Study Results, 2003–2006Google Scholar
  20. 20.
    U.S. Food and Drug Administration. The 2006 Exposure Assessment for Acrylamide. 2006; Available at:
  21. 21.
    Rosén J, Nyman A, Hellenäs KE (2007) Retention studies of acrylamide for the design of a robust liquid chromatography-tandem mass spectrometry method for food analysis. J Chromatogr A 1172(1):19–24. doi:10.1016/j.chroma.2007.09.050 PubMedCrossRefGoogle Scholar
  22. 22.
    Wenzl T, Karasek L, Rosen J, Hellenaes KE, Crews C, Castle L et al (2006) Collaborative trial validation study of two methods, one based on high performance liquid chromatography-tandem mass spectrometry and on gas chromatography-mass spectrometry for the determination of acrylamide in bakery and potato products. J Chromatogr A 1132(1–2):211–218. doi:10.1016/j.chroma.2006.07.007 PubMedCrossRefGoogle Scholar
  23. 23.
    Vesper HW, Ospina M, Meyers T, Ingham L, Smith A, Gray JG et al (2006) Automated method for measuring globin adducts of acrylamide and glycidamide at optimized Edman reaction conditions. Rapid Commun Mass Spectrom 20(6):959–964. doi:10.1002/rcm.2396 PubMedCrossRefGoogle Scholar
  24. 24.
    Vesper HW, Bernert JT, Ospina M, Meyers T, Ingham L, Smith A et al (2007) Assessment of the relation between biomarkers for smoking and biomarkers for acrylamide exposure in humans. Cancer Epidemiol Biomarkers Prev 16(11):2471–2478. doi:10.1158/1055-9965.EPI-06-1058 PubMedCrossRefGoogle Scholar
  25. 25.
    Willett WC (1998) Nutritional epidemiology. Oxford University Press, New YorkGoogle Scholar
  26. 26.
    Rosner B, Willett WC (1988) Interval estimates for correlation coefficients corrected for within-person variation: implications for study design and hypothesis testing. Am J Epidemiol 127(2):377–386PubMedGoogle Scholar
  27. 27.
    Bergmark E (1997) Hemoglobin adducts of acrylamide and acrylonitrile in laboratory workers, smokers and nonsmokers. Chem Res Toxicol 10(1):78–84. doi:10.1021/tx960113p PubMedCrossRefGoogle Scholar
  28. 28.
    Hagmar L, Wirfalt E, Paulsson B, Törnqvist M (2005) Differences in hemoglobin adduct levels of acrylamide in the general population with respect to dietary intake, smoking habits and gender. Mutat Res 580(1–2):157–165PubMedGoogle Scholar
  29. 29.
    Schettgen T, Rossbach B, Kutting B, Letzel S, Drexler H, Angerer J (2004) Determination of haemoglobin adducts of acrylamide and glycidamide in smoking and non-smoking persons of the general population. Int J Hyg Environ Health 207(6):531–539. doi:10.1078/1438-4639-00324 PubMedCrossRefGoogle Scholar
  30. 30.
    Schettgen T, Weiss T, Drexler H, Angerer J (2003) A first approach to estimate the internal exposure to acrylamide in smoking and non-smoking adults from Germany. Int J Hyg Environ Health 206(1):9–14. doi:10.1078/1438-4639-00195 PubMedCrossRefGoogle Scholar
  31. 31.
    Aureli F, Di Pasquale M, Lucchetti D, Aureli P, Coni E (2007) An absorption study of dietary administered acrylamide in swine. Food Chem Toxicol 45(7):1202–1209. doi:10.1016/j.fct.2006.12.029 PubMedCrossRefGoogle Scholar
  32. 32.
    Doerge DR, Young JF, McDaniel LP, Twaddle NC, Churchwell MI (2005) Toxicokinetics of acrylamide and glycidamide in Fischer 344 rats. Toxicol Appl Pharmacol 208(3):199–209. doi:10.1016/j.taap.2005.03.003 PubMedCrossRefGoogle Scholar
  33. 33.
    Doerge DR, Young JF, McDaniel LP, Twaddle NC, Churchwell MI (2005) Toxicokinetics of acrylamide and glycidamide in B6C3F1 mice. Toxicol Appl Pharmacol 202(3):258–267. doi:10.1016/j.taap.2004.07.001 PubMedCrossRefGoogle Scholar
  34. 34.
    Besaratinia A, Pfeifer GP (2004) Genotoxicity of acrylamide and glycidamide. J Natl Cancer Inst 96(13):1023–1029PubMedCrossRefGoogle Scholar
  35. 35.
    Manjanatha MG, Aidoo A, Shelton SD, Bishop ME, McDaniel LP, Lyn-Cook LE et al (2006) Genotoxicity of acrylamide and its metabolite glycidamide administered in drinking water to male and female Big Blue mice. Environ Mol Mutagen 47(1):6–17. doi:10.1002/em.20157 PubMedCrossRefGoogle Scholar
  36. 36.
    Calleman CJ, Bergmark E, Stern LG, Costa LG (1993) A nonlinear dosimetric model for hemoglobin adduct formation by the neurotoxic agent acrylamide and its genotoxic metabolite glycidamide. Environ Health Perspect 99:221–223. doi:10.2307/3431486 PubMedCrossRefGoogle Scholar
  37. 37.
    Vesper HW, Licea-Perez H, Meyers T, Ospina M, Myers GL (2005) Pilot study on the impact of potato chips consumption on biomarkers of acrylamide exposure. Adv Exp Med Biol 561:89–96PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2008

Authors and Affiliations

  • Kathryn M. Wilson
    • 1
    • 2
  • Hubert W. Vesper
    • 3
  • Paula Tocco
    • 2
  • Laura Sampson
    • 2
  • Johan Rosén
    • 4
  • Karl-Erik Hellenäs
    • 4
  • Margareta Törnqvist
    • 5
  • Walter C. Willett
    • 1
    • 2
    • 6
  1. 1.Department of EpidemiologyHarvard School of Public HealthBostonUSA
  2. 2.Department of NutritionHarvard School of Public HealthBostonUSA
  3. 3.Division of Laboratory SciencesNational Center for Environmental Health, Centers for Disease Control and PreventionAtlantaUSA
  4. 4.Swedish National Food AdministrationUppsalaSweden
  5. 5.Department Environmental ChemistryStockholm UniversityStockholmSweden
  6. 6.Channing Laboratory, Department of MedicineBrigham and Women’s Hospital and Harvard Medical SchoolBostonUSA

Personalised recommendations