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 Denm ark

Exposure to FCM chem icals contribute to hum an health effects Bisphenol A Fluor Phthalates chem icals

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 of chemical cocktail effects and how to deal with the issue. Editorial, JECH, Nov 2015

The current paradigm for evaluation of safety of FCMs is insufficient 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

How do w e address the challenge of risk assessing FCMs in the future? National Food I nstitute, Technical University of Denm ark

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

I n vitro tests for assessing integrated m ixture effects in FCM Potential Cytotoxicity Genotoxicity endocrine Potential disruption carcinogenicity Estrogen receptor Cell organelle health Indicator assays for Androgen receptor Cell proliferation & genotoxicity PPARs death GR, PR, TR Mutagenecity tests etc Potential Steroidogenesis carcinogenecity Ref.: ILSI report Europe, 2015 (modification of figure)

Effect-directed analysis FCM Calculation of EQs Tentative ID of compounds in fractions 9 Migration 1 tests FCM extraction 10 5 2 6 Quantification of active Expert evaluation of In vitro toxicity tests ID compounds tentatively ID 8 compounds 7 3 4 Fractionation of active extracts

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AhR Nrf2 p5 3 Am es Sandwich wrapper Muffin forms Baking paper Flour bag Pizza box White pizza box Microwave pizza box Unpublished data Popcorn bag 1 Popcorn bag 2 Sausage tray Fish tray Tomato tray Cereal box Nordic paper Basis paper Chinese paper 1 Chinese paper 2 Board w UV print Board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

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)

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