Safety Assessment of Food Contact Materials: The Role of High-resolution Mass Spectrometry in the Comprehensive Analysis of the Total Migrate

Significance of the Topic

Food contact materials (FCMs) such as packaging, containers and processing equipment play a crucial role in safeguarding food quality and preventing waste. However, chemicals used in FCMs can migrate into food, raising safety concerns. Non-intentionally added substances (NIAS), including impurities, oligomers and degradation products, are of particular interest because they are not always covered by existing regulations and may pose unforeseen risks. High-resolution mass spectrometry (HRMS) has emerged as a vital tool for comprehensive detection, identification and quantification of all migrants, thereby enabling robust safety assessments for consumer protection.

Objectives and Study Overview

This white paper aims to review the safety assessment workflow for FCMs, with emphasis on the role of high-resolution mass spectrometry in non-targeted analysis of total migrants. Key goals include:

• Describing the classes of substances in FCMs and their migration pathways.
• Outlining a structured eight-step risk assessment process for NIAS.
• Demonstrating an analytical example involving LC-HRMS to investigate polyester can coatings.

Methodology

The assessment framework consists of eight sequential steps:

1. Prediction of possible NIAS based on starting materials, additives and degradation pathways.
2. Detection through non-targeted screening using GC-MS (volatile and semi-volatile), LC-MS (polar/non-volatile) and ICP-MS (trace elements).
3. Identification via library matching, accurate mass measurement, isotope pattern analysis and user-compiled databases of expected substances.
4. Migration quantification using internal standards, universal detectors (e.g., FID), UV/fluorescence features or fractionation/GPC approaches.
5. Exposure estimation employing migration data, consumption statistics and tools such as FACET to model dietary intake.
6. Hazard characterisation via established health-based thresholds and the Threshold of Toxicological Concern (TTC) concept, categorised by Cramer classes and genotoxic alerts.
7. Risk assessment by comparing estimated exposure with toxicological reference values, considering combined effects of related substances.
8. Overall conclusion on compliance and safety, highlighting gaps and uncertainties.

Used Instrumentation

Analysis typically employs a combination of techniques:

• Gas chromatography-mass spectrometry (GC-MS) with headspace or purge-trap for volatiles and solvent extracts for semi-volatiles.
• Liquid chromatography-high-resolution mass spectrometry (LC-HRMS) with electrospray or APCI in both positive and negative modes for non-volatiles.
• Inductively coupled plasma-mass spectrometry (ICP-MS) for elemental analysis.
• Gel permeation chromatography (GPC) for molecular weight fractionation when quantitating total extractables.

Key Results and Discussion

An LC-HRMS case study of a polyester-coated tinplate can revealed over 200 distinct molecular features below 1 000 Da. Accurate mass data, adduct patterns and comparison with a user-compiled formulation database enabled structural proposals for many NIAS, exemplified by elucidation of a 426.1303 Da polyester oligomer. Quantification employed comparison of extracted ion chromatogram peak areas against an overspiked oligomer standard, acknowledging uncertainties in ionisation efficiency.

Benefits and Practical Applications

The integration of HRMS into FCM analysis offers:

• Enhanced detection sensitivity down to parts-per-billion levels.
• Comprehensive coverage of known and unknown migrants.
• Data supporting regulatory compliance with EU Regulation 10/2011 and Framework Regulation 1935/2004.
• Evidence to guide material selection and formulation improvements by industry.

Future Trends and Potential Applications

Advances are likely in:

• Automated data processing algorithms for faster NIAS identification.
• Expanded open-access libraries of accurate mass spectra for FCM substances.
• Integration of HRMS data with in silico toxicology and TTC frameworks.
• Cross-sector sharing of analytical strategies among food, pharmaceutical and water contact materials.

Conclusion

High-resolution mass spectrometry has become indispensable for the comprehensive safety assessment of FCMs. By coupling non-targeted detection with accurate mass identification, migration quantitation and toxicological evaluation, HRMS supports robust risk assessments, ensuring consumer safety and regulatory compliance. Ongoing collaboration between industry, instrument vendors and regulatory bodies will enhance capabilities and streamline workflows.

Reference

• Katan L.L. Multiplicity of Migrants. Nature, 1992, 358, 183–183.
• Brands B. et al. Guidance for exposure assessment of substances migrating from food packaging materials. ILSI Europe, 2007.
• Oldring P.K.T. et al. Exposure to substances from food contact materials: introduction to FACET. Deutsche Lebensmittel-Rundschau, 2009, 105, 501–507.
• Oldring P.K.T. et al. Development of the FACET exposure tool. Food Additives and Contaminants A, 2014, 31, 444–465.
• EFSA Scientific Committee. Opinion on Threshold of Toxicological Concern. EFSA Journal, 2012, 10(7):2750.
• Kroes R. et al. Structure-based thresholds of toxicological concern: guidance. Food Chem. Toxicol., 2004, 42, 65–83.
• Cheeseman M.A. et al. A tiered approach to threshold of regulation. Food Chem. Toxicol., 1999, 37, 387–412.
• Nerin C. et al. Identifying non-intentionally added substances from packaging: review. Anal. Chim. Acta, 2013, 775, 14–24.