Editorial for the Special Issue “Risk Assessment of Food Contact Materials/Articles”

Food packaging is made of four main materials, namely plastic, cardboard, glass and metals (aluminium and steel), as well as many other materials (wood, waxes, corks, etc [...].

issue, accentuated by these new regulations on the circularity of packaging and the end of single-use plastic packaging.
However, unlike IAS, and even though plastic Regulation (EU) No 10/2011 requires a risk assessment of NIAS in the same way as IAS, this remains difficult. There is no harmonised guideline for an appropriate risk assessment, and the classical approach based on the identification and quantification of substances present in a migrate and their toxicological assessment is not conceivable due to time and cost constraints. Furthermore, technically, the chemical analysis of an extract/migrate is rarely exhaustive [12][13][14].
Professional associations (Food Packaging Forum [15], ILSI Europe [16] and management agencies [17][18][19] encourage global safety assessment for chemically complex mixtures containing unknown substances such as FCA by combining physical-chemical methods with reliable bioassays as a quick and cost-effective strategy. The European Commission also supported a proactive evolution of the regulation to include bioassays along with analytical testing and migration modelling techniques. They have already demonstrated their efficiency in identifying hazards and the mode of action of pure substances. Chemical analyses cannot assess the cocktail effect of FCA, whereas testing the whole migrate with bioassays can [20][21][22]. Bioassay methodology for the risk assessment of FCM/FCA, NIAS has already been reviewed by ILSI (2016) [12].
It is therefore essential to develop protocols to ensure the safety of future packaging by identifying the unknown substances or by testing the toxicity of the complex mixture of substances migrating from FCMs/FCAs. This is the challenge taken up by the following articles published in this Special Issue.
Miralles et al. developed a fast and automated approach to tentatively identify and assess the risk of unknown substances in plastic FCMs using gas chromatography-highresolution mass spectrometry (GC-HRMS). They applied this approach to recycled low density polyethylene (LDPE) and identified 83 substances, most of which were additives used in various plastic applications. Based on the threshold of toxicological concern approach, the authors found that the release of the identified substances did not pose a risk. Furthermore, further studies on unidentified substances and potential mixture toxicity are needed [23].
Plant fiber/plastic composites (PPCs) are considered as an economical and environmentally friendly alternative to traditional petrochemical-based plastics for food contact products. However, Zhang and Weng pointed out that PPCs may pose food safety risks due to the migration of hazardous substances during the production process. The authors recommended that systematic research on migration methods and safety assessments are needed to address the potential safety risks of PPCs [24].
To evaluate the safety of FCMs, it is important to exclude mutagenicity and genotoxicity in migrates but current genotoxicity assays were not enough sensitive in terms of the biological positive threshold. Rainer et al. compared two commonly used formats of the Ames test, the standard preincubation Ames test and the liquid-based Ames MPF TM , to identify DNA-reactive genotoxic substances. They found that both formats showed high concordance for mutagenic versus non-mutagenic compound classification, but the lowest effect concentrations (LEC) of the Ames MPF TM format were lower for 17 of the 21 tested known substances, indicating that this format could be preferable for the detection of complex mixtures of substances from FCM/FCA [25].
Debon et al. proposed the high-performance thin-layer chromatography (HPTLC) coupled with the planar SOS umu-C (p-Umu-C) bioassay as a promising rapid test to detect low levels of mutagens/genotoxins in complex mixtures. An effective bioactivation protocol was developed, and all tested known mutagens could be detected at low concentrations. The threshold of detection was very low compared to regulatory bioassays currently performed, such the Ames test. The p-Umu-C bioassay may become instrumental in the genotoxicity testing of mixture, such as food packaging migrates [26].
Finally, Marin-Kuan et al. combined both identification and testing and present a protocol combining data from analytics and bioassays for the risk assessment of packaging materials. This protocol includes guidance on sample preparation, migrant simulation, chemical analysis using liquid chromatography (LC-MS) and validated bioassays covering endocrine activity, genotoxicity and metabolism-related targets and it was tested through an inter-laboratory study on coating metal packaging materials [27].
To conclude, these five studies illustrate the great challenges facing FCM/FCA research currently and they can be used by regulators, industry and other stakeholders to improve the safety of FCM/FCAs. I would like to express my gratitude to all authors for submitting their original contributions to this Special Issue and to the reviewers for their essential role in assessing the suitability of the manuscripts and improving their quality. I would like also to thank the editors of Toxics for their kind invitation, and in particular Evelyn Ning and, previously, Doris Sun of the Toxics Editorial Office for their valuable and tireless support.

Conflicts of Interest:
The author declares no conflict of interest.