Polyester based coatings are one of the technologies used in can coatings following the suspension of the intentional use of Bisphenol A (BPA) in food packaging in France. The aim of this study was to identify volatile and semi-volatile non-intentionally added substances (NIAS) from a single polyester-based formulation (5 batches) to evaluate their health risks in order to provide consumer's safety regarding consumption of canned food. Extractions and migration tests of coated metal plates were performed with acetonitrile (ACN) (incubation at 40°C for 1 day) and ethanol (EtOH) 95% (incubation at 60 °C for 10 days) in Calipack migration cells. Antioxidant degradation product 3-(3,5-di-tert-butyl-4-hydroxyphenyl) propionic acid (CAS RN 20170-32-5), or fenozan, was identified as a NIAS and confirmed by reference standard in both ACN and EtOH 95% samples using gas chromatography–high-resolution mass spectrometry. To evaluate the toxicity of fenozan, several toxicity endpoints were investigated using different in silico quantitative structure-activity relationship predictive tools, such as Derek Nexus, Sarah Nexus, VEGAHUB software and Danish (Q)SAR Database. Positive predictions for carcinogenicity in mice, developmental toxicity, as well as several endpoints of mutagenicity, endocrine disrupting activity, and organ toxicity (hepatotoxicity and thyroid toxicity) resulted from used in silico tools. To confirm positive in silico mutagenicity alerts, fenozan was subjected to the in vitro Ames test (to test point mutation) in accordance with OECD 471 guideline, using three strains of Salmonella Typhimurium (TA100, TA98, and TA1535) and one strain of Escherichia coli (WP2) with and without metabolic activation system. A negative response was obtained in the Ames test for the four strains tested with and without metabolic activation system using direct incorporation and pre-incubation methods. Further, bioassays are required to verify the positive predictive outcomes for other toxicological endpoints to ensure the safety of polyester coatings.