Risk assessment of chemicals occurring in our diet is commonly performed for single chemicals without considering exposure to other chemicals. We performed a case study on risk assessment of combined dietary exposure to chemicals from different regulatory silos, i.e. pesticides (PPRs), persistent organic pollutants (POPs) and food additives (FAs). Chemicals were grouped into the cumulative assessment group (CAG) liver steatosis using a component-based approach. Based on literature, the CAG included 144 PPRs, 49 POPS and 7 FAs for which concentration data were available. For each silo, chronic combined dietary exposure was assessed for adults and children of nine European countries following the most commonly used exposure methodologies in Europe and by using a relative potency factor approach. For risk characterization, a Margin of Exposure (MOE) was calculated. To overarch the risk across silos, a normalised combined margin of exposure (nMOET) approach was proposed. This case study demonstrated that risk assessment of combined exposure to chemicals can be performed within regulatory silos. It also highlighted important differences in the conservatism of exposure scenarios, the derivation of point of departures and the subsequent acceptable MOEs between the silos. To overarch the risk despite these differences, a nMOET approach can be used.

ANSES French Agency for Food Environmental and Occupational Health and Safety Risk Assessment Department Methodology and Studies Unit 947001 Maisons Alfort France

Benaki Phytopathological Institute Department of Pesticide Control and Phytopharmacy Laboratory of Pesticide Residues 8 Stefanou Delta Street Kifissia Athens 14561 Greece

Fera Science Ltd Sand Hutton York YO41 1LZ United Kingdom

ICPS International Centre for PPRs and Health Risk Prevention ASST Fatebenefratelli Sacco Ospedale L Sacco Via GB Grassi 74 20157 Milano Italy

ICPS International Centre for PPRs and Health Risk Prevention ASST Fatebenefratelli Sacco Ospedale L Sacco Via GB Grassi 74 20157 Milano Italy; Department of Biomedical and Clinical Sciences Università Degli Studi di Milano Milan Italy

Laboratory of Toxicology and Environmental Health School of Medecine IISPV Universitat Rovira 1 Virgili Reus Catalonia Spain

National Institute of Public Health Environmental Health Centre Trubarjeva 2 Ljubljana Slovenia

National Institute of Public Health Prague Centre for Health Nutrition and Food Brno Czech Republic

RIVM National Institute for Public Health and the Environment PO Box 1 3720 BA Bilthoven the Netherlands

State General Laboratory Ministry of Health Nicosia Cyprus

Technical University of Denmark National Food Institute Division of Risk Assessment and Nutrition Kemitorvet Building 201 DK 2800 Lyngby Denmark

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Advancing tools for human early lifecourse exposome research and translation (ATHLETE): Project overview