Recent Trends and Challenges on the Non-Targeted Analysis and Risk Assessment of Migrant Non-Intentionally Added Substances from Plastic Food Contact Materials.

Non-intentionally added substances (NIAS) in plastic food contact materials represent a critical undercharacterized chemical safety concern, caused by their inherent diversity, potential toxicity, and regulatory challenges. This review synthesizes recent advances and persistent gaps in NIAS analysis, with a primary focus on analytical workflows for non-targeted analysis, alongside a consideration of risk assessment and toxicological prioritization frameworks. Conventional plastics (e.g., polyethylene, polypropylene, or polyethylene terephthalate) as well as emerging materials (e.g., bioplastics and recycled polymers) exhibit different NIAS profiles, including oligomers, degradation products, additives, and contaminants, requiring specific approaches for migration testing, extraction, and detection. Advanced techniques, such as ultra-high-performance liquid chromatography or two-dimensional gas chromatography coupled with high-resolution mass spectrometry, have enabled non-targeted analysis approaches. However, the field remains constrained by spectral library gaps, limited reference standards, and inconsistent data processing protocols, resulting in heavy reliance on tentative identifications. Risk assessment procedures mainly employ the Threshold of Toxicological Concern and classification by Cramer's rules. Nevertheless, addressing genotoxicity, mixture effects, and novel hazards from recycled or bio-based polymers remains challenging with these approaches. Future priorities and efforts may include expanding spectral databases, harmonizing analytical protocols, and integrating in vitro bioassays with computational toxicology to refine hazard characterization.