Genotoxicity mode of action exploration of polyethylene glycol terephthalate (PET) acetic acid migration solution under repeated-dose exposure in rats.

As a commonly used material that contacts food, polyethylene glycol terephthalate (PET) may interact with food, and since certain components can migrate, this has become a food safety concern. This study aims to investigate the genotoxicity of PET acetic acid migration solution and its toxic mode of action using an in vivo multi-endpoint genotoxicity evaluation system and quantitative liver proteomics analysis. Forty-eight male Sprague-Dawley rats were randomly divided into eight groups: the PET acetic acid migration solution group, the acetic acid group, the phosphate-buffered saline (PBS) control group, the N-ethyl-N-nitrosourea (ENU) positive control group, and their corresponding satellite groups. PBS and ENU were administered by gavage, while the PET acetic acid migration solution and acetic acid were administered orally in the drinking water. The exposure duration was 35 days, followed by a recovery period of 15 days. The PET acetic acid migration solution can cause heart, liver, and kidney injury in rats. On the 15th day, mutations were seen in the Pig-a gene test. On the 35th day, DNA damage was observed in peripheral blood and liver cells. Gene ontology (GO) analysis of the liver proteomics revealed enrichment in DNA metabolism and binding processes, while Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis highlighted the DNA replication pathway. Immunohistochemical analysis demonstrated a significant increase in 8-hydroxydeoxyguanosine (8-OHdG) and a decrease in single-stranded-binding (SSB) protein in the PET acetic acid migration solution group. In summary, the PET acetic acid migration solution has the potential to induce DNA damage, possibly by inhibiting DNA replication and DNA repair pathways. However, the likelihood of genetic toxicity is low.