Linear polyethylene terephthalate oligomers toxicity in human primary cells and interactions with biomolecules

Side-products of PET polymerization reactions are cyclic and linear oligomers of PET, recently recognized as novel non-intentionally added substances in food (NIAS) and classified as poor data chemicals. 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, to investigate solubility in common solvents and food simulants, as well as 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. 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. All linear PET oligomers tested readily interact with food and serum proteins, and with salmon sperm 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. PET oligomers binding to DNA prompts further research on the toxicological relevance of the observed interactions.