Human exposure and internal dose assessments of acrylamide in food E. Dybing a , P.B. Farmer b , M. Andersen c , T.R. Fennell d , S.P.D. Lalljie e , D.J.G. Mu ¨ ller f , S. Olin g , B.J. Petersen h , J. Schlatter i , G. Scholz j , J.A. Scimeca k , N. Slimani l , M. To ¨ rnqvist m , S. Tuijtelaars n, * , P. Verger o a Norwegian Institute of Public Health, Division of Environmental Medicine, P.O. Box 4404, Nydalen, NO-0403 Oslo, Norway b University of Leicester, Biocentre, University Road, LE1 7RH Leicester, UK c CIIT Centers for Health Research, Six Davis Drive, P.O. Box 12137, Research Triangle Park, NC 27709-2137, USA d RTI International, 3040 Cornwallis Road, P.O. Box 12194, Research Triangle Park, US-27709-2194 Raleigh, NC, USA e Safety and Environmental Assurance Centre, Unilever, Colworth House, Sharnbrook, Bedford MK44 1LQ, UK f Procter & Gamble Service GmbH, Sulzbacher Strasse 40, DE-65824 Schwalbach Am Taunus, Germany g International Life Sciences Institute, Risk Science Institute, One Thomas Circle, Ninth Floor, Washington, DC 20005-5802, USA h Food and Chemicals Practice Exponent, Inc., 1730 Rhode Island Avenue, Suite 1100, US-20036 Washington, DC, USA i Swiss Federal Office of Public Health, Food Toxicology Section, Stauffacherstrasse 101, CH-8004 Zu ¨ rich, Switzerland j Nestle ´ Research Center Lausanne, Nestec Ltd., P.O. Box 44, Vers-Chez-les-Blanc, 1000 Lausanne 26, Switzerland k Cargill, 15407 McGinty Road, West, MS #56, US-55391 Wayzata, MN, USA l International Agency for Research on Cancer, Nutrition and Hormones Group, Cours Albert Thomas, 150, FR-69008 Lyon, France m University of Stockholm, Department of Environmental Chemistry, SE-106 91 Stockholm, Sweden n ILSI Europe, 83, Av. E. Mounier, Box 6, B-1200 Brussels, Belgium o Institut National Agronomique de Paris Grignon, Unite ´ Me ´ tarisk, 16, rue Claude Bernard, FR-75231 Paris Cedex 05, France Received 2 September 2004; accepted 9 November 2004 Abstract This review provides a framework contributing to the risk assessment of acrylamide in food. It is based on the outcome of the ILSI Europe FOSIE process, a risk assessment framework for chemicals in foods and adds to the overall framework by focusing especially on exposure assessment and internal dose assessment of acrylamide in food. Since the finding that acrylamide is formed in food during heat processing and preparation of food, much effort has been (and still is being) put into understanding its mechanism of formation, on developing analytical methods and determination of levels in food, and on evaluation of its toxicity and potential toxicity and potential human health consequences. Although several exposure estimations have been proposed, a systematic review of key information relevant to exposure assessment is currently lacking. The European and North American branches of the International Life Sciences Institute, ILSI, discussed critical aspects of exposure assessment, parameters influencing the outcome of exposure assessment and summarised data relevant to the acrylamide exposure assessment to aid the risk characterisation process. This paper reviews the data on acrylamide levels in food including its formation and analytical methods, the determination of human consumption patterns, dietary intake of the general population, estimation of maximum intake levels and identification of groups of potentially high intakes. Possible options and consequences of mitigation efforts to reduce exposure are discussed. Furthermore the association of intake levels with biomarkers of exposure and internal dose, considering aspects of bioavailability, is reviewed, and a physiologically-based toxicokinetic (PBTK) model is described that pro- vides a good description of the kinetics of acrylamide in the rat. Each of the sections concludes with a summary of remaining gaps and uncertainties. Ó 2004 ILSI. Published by Elsevier Ltd. All rights reserved. 0278-6915/$ - see front matter Ó 2004 ILSI. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.fct.2004.11.004 * Corresponding author. Tel.: +32 2 771 00 14; fax: +32 2 762 00 44. E-mail address: publications@ilsieurope.be (S. Tuijtelaars). www.elsevier.com/locate/foodchemtox Food and Chemical Toxicology 43 (2005) 365–410