Display omitted •Plastic food packaging leaches chemicals and toxicity into food simulants.•Probable transfer of toxic chemicals to food, including endocrine disruptors.•Similar toxicity in methanol extracts and water–ethanol food simulant.•LDPE, PUR and PVC migrates induce most receptor activity.•Between 8 and 10 631 chemical features migrate into food simulants. Plastics constitute a vast array of substances, with over 16000 known plastic chemicals, including intentionally and non-intentionally added substances. Thousands of chemicals, including toxic ones, are extractable from plastics, however, the extent to which these compounds migrate from everyday products into food or water remains poorly understood. This study aims to characterize the endocrine and metabolism disrupting activity, as well as the chemical composition of migrates from plastic food contact articles (FCAs) from four countries as significant sources of human exposure. Fourteen plastic FCAs covering seven polymer types with high global market shares were migrated into water and a water–ethanol mixture as food simulants according to European regulations. The migrates were analyzed using reporter gene assays for nuclear receptors relevant to human health and non-target chemical analysis to characterize the chemical composition. Chemicals migrating from each FCA interfered with at least two nuclear receptors, predominantly targeting pregnane X receptor (24/28 migrates). Moreover, peroxisome proliferator receptor gamma was activated by 19 out of 28 migrates, though mostly with lower potencies. Estrogenic and antiandrogenic activity was detected in eight and seven migrates, respectively. Fewer chemicals and less toxicity migrated into water compared to the water–ethanol mixture. However, 73 % of the 15 430 extractable chemical features also transferred into food simulants, and the water–ethanol migrates exhibited a similar toxicity prevalence compared to methanol extracts. The chemical complexity differed largely between FCAs, with 8 to 10631 chemical features migrating into food simulants. Using stepwise partial least squares regressions, we successfully narrowed down the list of potential active chemicals, identified known endocrine disrupting chemicals, such as triphenyl phosphate, and prioritized chemical features for further identification. This study demonstrates the migration of endocrine and metabolism disrupting chemicals from plastic FCAs into food simulants, rendering a migration of these compounds into food and beverages probable.