Convergent mechanistic actions of emerging food contaminants.
| Contaminant class | Example compounds | Dominant food/food-contact sources (illustrative) | Primary Mode of Action (MoA) | Target pathway | Specific mechanism (evidence-based) | Supporting evidence (key citations) |
|---|---|---|---|---|---|---|
| PFAS | PFOS, PFOA, PFHxS | Dietary intake via the food chain (e.g., seafood/animal products) and drinking water | Chemical/structural mimicry of thyroid-hormone transport | Thyroid axis (transport and clearance) | PFAS bind transthyretin (TTR) and can displace T4, lowering effective TH availability; some PFAS promote TH clearance, reproducing thyroid-disrupting patterns in experimental models. | [28–30] |
| PFAS | PFOS, PFOA, mixed-chain PFAS | Dietary intake via the food chain and drinking water (mixtures in population exposure) | Receptor-mediated activation (PPAR-centric) | Metabolic/nuclear-receptor signaling | PFAS activate PPARα/γ and related lipid–glucose program consistent with the metabolism-disrupting profile described for endocrine-active chemicals. | [72] |
| Bisphenol analogues | BPS, BPF, BPAF | Food-contact materials and packaging migration (e.g., linings/plastics) contributing to dietary exposure | Hormone mimicry/substitution | ER/AR-linked nuclear-receptor signaling | BPS and BPF show ER-agonist activity comparable to BPA and exhibit anti-androgenic interference, explaining obesogenic and reproductive signals in newer cohorts. | [31] |
| Phthalates | DEHP, DBP, monoester metabolites | Food-contact plastics and packaging migration; dietary exposure via contact with plastic surfaces | Enzyme-level interference in steroidogenesis | Gonadal/adrenal steroidogenic pathway (StAR, CYP11A1) | Environmentally relevant phthalate mixtures downregulate key steroidogenic genes/proteins and reduce steroid output, matching recent animal and in vitro data. | [73–75] |
| Micro- and nanoplastic (MNPs) | Polystyrene | Food processing/contact surfaces and packaged foods; ingestion via contaminated foods and drinking water | Physical barrier injury and inflammation | Gut-barrier integrity and gut–liver axis | PS-MPs induce gut microbiota dysbiosis, disrupt tight junctions, and cause metabolic disorders in mice, creating secondary endocrine–metabolic disturbance. | [76] |
| MNPs as chemical vectors | PS, PE, PP particles detected in foods/water | Particles present in foods and drinking water; packaging/processing as entry routes with co-migrants | Vector-mediated co-exposure amplification | Cross-cutting endocrine pathways (thyroid, metabolic, reproductive) | MNP surfaces adsorb legacy EDCs (BPA, phthalates, PCBs) and can desorb them in the GI tract, effectively turning particle exposure into an EDC-mixture exposure, which current EFSA mixture guidance can already handle. | [77] |
This table organizes three major food-relevant contaminant groups into a mechanistic grid, showing that PFAS, bisphenol/phthalate plasticizers, and MNPs converge on a small number of endocrine, metabolic, and barrier pathways. BPA: bisphenol A; BPAF: bisphenol AF; BPF: bisphenol F; BPS: bisphenol S; EDCs: endocrine-disrupting chemicals; EFSA: European Food Safety Authority; MNPs: micro- and nanoplastics; PCBs: polychlorinated biphenyls; PE: polyethylene; PFAS: per- and polyfluoroalkyl substances; PFHxS: perfluorohexanesulfonic acid; PFOA: perfluorooctanoic acid; PFOS: perfluorooctanesulfonic acid; PP: polypropylene; PS: polystyrene; PS-MPs: polystyrene-microplastics; TH: thyroid hormone; TTR: transthyretin.