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ILSI Europe

Human Exposure and Internal Human Exposure and Internal Dose Assessments Dose Assessments

of Acrylamide in Foodof Acrylamide in Food

ILSI Europe Acrylamide Task Force

Sandra Tuijtelaars

ILSI Europe

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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

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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

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Content

Human exposure and internal dose assessments of acrylamide in food 

1. Formation and levels in food and diet2. Amounts AA containing foods consumed3. Biomarkers of exposure & internal dose4. Bioavailability5. AA target doses & PBTK* modeling

Key messages, uncertainties and data gaps

* Physiologically based toxicokinetic

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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)

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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

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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

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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

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Food consumption surveys

Uncertainties, gaps• Harmonisation of studies

• Identify populations at risk

• Within and between samples variability

• Home cooking and industrial processes

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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 ?

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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

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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

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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

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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

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Bioavailability

Uncertainties, gaps• Oral bioavailability of AA in humans not

known with certainty

• Influence of various food matrices unclear

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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

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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

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Impact

• Framework may be useful for risk assessors involved in evaluation of AA in food

• Submitted to JECFA consultation on acrylamide

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Acknowledgements

ILSI Expert Group on Acrylamide

Erik Dybing Josef SchlatterPeter Farmer Gabriele ScholzMel Andersen Joseph ScimecaTim Fennell Nadia SlimaniSam Lalljie Margareta TörnqvistDetlef Müller Sandra Tuijtelaars Steve Olin Philippe VergerBarbara Petersen

Human exposure and internal dose assessments ofacrylamide in food, Food and Chemical Toxicology,

Accepted November 2004, In Press

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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