1. 14 January 2005 1 ILSI Europe Human Exposure and Internal Dose Assessments of Acrylamide in Food ILSI Europe Acrylamide Task Force Sandra Tuijtelaars ILSI Europe

2. 14 January 2005 2 Background Large quantity of data on AA exposure Little evaluation of data with respect to exposure assessment Systematic review of key information lacking Important contribution would be to review and collate information on exposure assessment Expert Group on Acrylamide set up –ILSI Europe Acrylamide Task Force –ILSI North America Technical Committee on Food Toxicology and Safety

3. 14 January 2005 3 Objectives Develop framework contributing to risk assessment of AA in food based on the FOSIE* process Focus on exposure assessment and internal dose assessments Provide risk assessor with overview of the current level of knowledge on AA exposure highlighting sources of variability, gaps, uncertainties and research needs relevant to the overall risk assessment of AA in food * FOSIE: Food Safety in Europe – Risk assessment of chemicals in food and diet

4. 14 January 2005 4 Content Human exposure and internal dose assessments of acrylamide in food 1.Formation and levels in food and diet 2.Amounts AA containing foods consumed 3.Biomarkers of exposure & internal dose 4.Bioavailability 5.AA target doses & PBTK* modeling Key messages, uncertainties and data gaps * Physiologically based toxicokinetic

5. 14 January 2005 5 Formation and food levels Main route of formation in foods confirmed Analytical methods sufficiently developed Databases set up in EU and US that collected reliable quality assured data Major food categories contributing to most of the human exposure similar in US and EU (French fries, potato fritter, potato chips, cereals, crispbread, bread, coffee, pies and pastry)

6. 14 January 2005 6 Formation and food levels Uncertainties, gaps Non-European and non-North American foods, i.e. data for Asian and African foods lacking Large between sample variability ‘What if’ scenarios by FDA: 30 % reduction in AA level potato chips, only 4-14 % reduction in overall AA intake Hence options to reduce AA in food may have very little impact on overall dietary exposure Data on AA levels in home cooked food and catering sector unknown Susceptible subgroups have not been identified to date

7. 14 January 2005 7 Food consumption surveys Questionnaire survey on food consumption and AA content data - sent to institutions in 31 countries - not an exhaustive inventory - examples of type of study designs and dietary exposure data - highlights strengths and limitations of current methodology for estimating and interpreting data

8. 14 January 2005 8 Food consumption surveys Used existing available national surveys, not designed for AA exposure assessment Do not necessarily reflect current dietary consumption habits Exhibit other limitations concerning –preparation and cooking method –preparation at home vs. industrial preparation Methods used to record dietary intakes vary considerably

9. 14 January 2005 9 Food consumption surveys Uncertainties, gaps Harmonisation of studies Identify populations at risk Within and between samples variability Home cooking and industrial processes

10. 14 January 2005 10 Exposure assessment Several organisations in NA and Europe have done exposure estimates since 2002 Significantly higher exposure for younger age groups than for the average consumer Overall results of estimates of the average consumer remain consistent with conclusions of first FAO/WHO consultation and following meetings Exposure levels calculated based on measurement biomarkers are around 3-fold exposure calculated from food intake: unknown source of AA ?

11. 14 January 2005 11 Exposure assessment Uncertainties, gaps Data on overall exposure consistent for EU and US, but role of diets and cultural differences on exposure not yet assessed Contribution of industrial, retail, catering and home food preparation unknown Impact of modifications in processing and cooking (risk/benefit) should be assessed Extrapolation of external exposure (from food level) to internal exposure (biomarkers) or vice versa should be improved

12. 14 January 2005 12 Biomarkers AA biomarker in urine and blood Hb adducts as biomarkers of internal dose N7-(2-carbamoyl-2-hydroxyethyl)guanine biomarker of the dose of genotoxically active material that reaches DNA

13. 14 January 2005 13 Biomarkers Uncertainties, gaps Interspecies extrapolation Lack of validation of some methods Need to have comparison of external dietary exposure and validated biomarkers of exposure and internal dose Need for studies on relationship biomarkers of internal dose with biological effects

14. 14 January 2005 14 Bioavailability Bioavailability of AA after oral administration high –68-90% of dose absorbed in rats –73% in dogs –99% in miniature pigs Human volunteer study: 34% of oral dose excreted in urine during first 24h

15. 14 January 2005 15 Bioavailability Uncertainties, gaps Oral bioavailability of AA in humans not known with certainty Influence of various food matrices unclear

16. 14 January 2005 16 PBTK modeling PBTK model for acrylamide and glycidamide (GA) in rats developed Model parameters provide a good description of the kinetics of AA and GA Similar model required for humans A validated human model capable of predicting target doses will reduce the uncertainty in risk assessment

17. 14 January 2005 17 PBTK modeling Uncertainties, gaps Further improvement PBTK model depends on collection key data for refining model parameters Improve understanding of AA toxicokinetics, e.g. kinetic studies linked to mode of action Extension of the model to humans requires measurements of selected parameters in human tissues

18. 14 January 2005 18 Impact Framework may be useful for risk assessors involved in evaluation of AA in food Submitted to JECFA consultation on acrylamide

19. 14 January 2005 19 Acknowledgements ILSI Expert Group on Acrylamide Erik DybingJosef Schlatter Peter FarmerGabriele Scholz Mel AndersenJoseph Scimeca Tim Fennell Nadia Slimani Sam LalljieMargareta Törnqvist Detlef Müller Sandra Tuijtelaars Steve OlinPhilippe Verger Barbara Petersen Human exposure and internal dose assessments of acrylamide in food, Food and Chemical Toxicology, Accepted November 2004, In Press

20. 14 January 2005 20 Support ILSI Europe Acrylamide Task Force Barilla, Cereal Partners, Danisco Sweeteners, Frito Lay, Groupe Danone, Kellogg, Kraft Foods, Masterfoods, Nestlé, Procter & Gamble, RHM Technology, Swiss Quality Testing Services, Unilever