Size and end-group chemistry of linear polyethylene terephthalate oligomers matter in chemical risk assessment

Cyclic and linear oligomers, formed as side-products during PET polymerization, are poorly characterized non-intentionally added substances (NIAS) in food. Risk assessment of PET oligomers is challenging due to their size, number, isomerism, complexity in structure, and lack of analytical standards. The great heterogeneity in size and structure of PET oligomers calls for a systematic approach in risk assessment and hazard identification. The aim of our study was to synthesize and characterize physicochemical properties, protein, DNA and cellular interactions of a series of linear methylated and non-methylated PET oligomers (monomer, dimer and trimer). Our results show striking differences in the properties of PET oligomers in relation to size and end-group chemistry (methylated vs. free carboxyl-vs. free hydroxyl-). Solubility in food simulants decreases with increase in methylation and the number of aromatic rings. Linear PET oligomers show little to no toxicity in a wide range of concentrations tested in primary cells and are taken up by human monocyte derived dendritic cells. All linear PET oligomers tested readily interact with food and serum proteins resulting in large protein/plastic oligomer aggregates. Methylated PET trimers bind to salmon sperm DNA, leading to significant destabilization of the DNA. Our results point to the importance of size and end-group of PET oligomers in chemical risk assessment: size and methylation of the oligomer strongly contribute to the observed cellular and molecular effects of tested compounds. Larger methylated PET oligomer binding to DNA prompts further research on the toxicological relevance of the observed interactions.