Toxicological evaluations and risk of hum an exposure to m ixtures - - PowerPoint PPT Presentation

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Toxicological evaluations and risk of hum an exposure to m ixtures - - PowerPoint PPT Presentation

Toxicological evaluations and risk of hum an exposure to m ixtures of chem icals Anne Marie Vinggaard Technical University of Denmark National Food I nstitute, Technical University of Denm ark National Food I nstitute, Technical University of


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Toxicological evaluations and risk of hum an exposure to m ixtures of chem icals

Anne Marie Vinggaard Technical University of Denmark

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National Food I nstitute, Technical University of Denm ark

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National Food I nstitute, Technical University of Denm ark

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Exposure to FCM chem icals contribute to hum an health effects

Fluor chem icals Bisphenol A Phthalates

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Risk assessm ent should take into account m ixture effects

Mixture effects have been documented in experimen- tal studies for decades ⇒Chemicals can ‘join forces’ to cause an effect even at low doses

Ref: Svingen & Vinggaard, The risk

  • f chemical cocktail effects and how

to deal with the issue. Editorial, JECH, Nov 2015

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It doesn’t take into account: 1 ) m ixture effects of chem icals 2 ) adverse effects like endocrine disruption, im m unotoxicity etc. 3 ) FCMs m ade of paper & board

The current paradigm for evaluation

  • f safety of FCMs is insufficient
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National Food I nstitute, Technical University of Denm ark

How do w e address the challenge of risk assessing FCMs in the future?

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Know n chemicals in food packaging with unknow n effects Toxicological profiling in silico, in vitro & in vivo Effect-directed analysis & analytical chemistry Unknow ns in food packaging

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I n vitro tests for assessing integrated m ixture effects in FCM

Potential endocrine disruption Cytotoxicity Genotoxicity Potential carcinogenicity Estrogen receptor Androgen receptor PPARs GR, PR, TR etc Steroidogenesis Cell organelle health Cell proliferation & death Indicator assays for genotoxicity Mutagenecity tests Potential carcinogenecity

Ref.: ILSI report Europe, 2015 (modification of figure)

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Effect-directed analysis

Quantification of active ID compounds

FCM FCM extraction In vitro toxicity tests

Fractionation of active extracts Tentative ID of compounds in fractions Expert evaluation of tentatively ID compounds

2 3 4 1 5 6 7 8 9 Calculation of EQs 10

Migration tests

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AR ↑ AR ↓ ER AhR PPARγ RAR Nrf2 p5 3 Am es Sandwich wrapper Muffin forms Baking paper Flour bag Pizza box White pizza box Microwave pizza box Popcorn bag 1 Popcorn bag 2 Sausage tray Fish tray Tomato tray Cereal box Nordic paper Basis paper Chinese paper 1 Chinese paper 2 Board w UV print Board w watersol print Board w offset print

Unpublished data

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Take hom e m essages

  • More focus on FCM is needed as it can be a

significant source of human exposure to chemicals

  • Mixture effects of chemicals have to be taken into

account (also) when risk assessing FCMs

  • Our effect-directed analysis covering endocrine

disruption, cyto- and genotoxicity is quantitative and valuable for identification of emerging chemicals (reduces uncertainty)

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National Food I nstitute, Technical University of Denm ark

Thanks!

Anna Rosenm ai Camilla Taxvig Marianne Dybdahl Terje Svingen Xenia Trier Linda Bengtström Jens Højslev Petersen Gitte Alsing Pedersen Colleagues & technicians at DTU Food Funding The Ministry of Food, Agriculture, and Fisheries of Denmark Barbara van Vugt-Lussenburg Peter Benisch BioDetection Systems, NL Laurianne Lesné Bernard Jégou Rennes University, FR