Prioritisation of potentially genotoxic substances migrating from printed paper and board food contact materials using in silico tools

Introduction: The occurrence of several recent food contamination issues due to leakage of food packaging substances into food have raised concerns towards potential adverse health effects caused by exposure to these chemicals (e.g. bisphenol A). A new EU list of authorised chemicals to manufacture plastics intended to come into contact with food was adopted in 2011 by means of Commission Regulation 10/2011. On the contrary, no such EU regulation exists on chemicals used in other types of food contact materials (FCM). Therefore, non-plastic FCM are only covered by national legislation or by the general recommendations of the Council of Europe, containing ‘inventory lists’ of additives, monomers and other compounds that might be present in non-plastic FCM. Since no (recent) safety evaluation has been carried out for thousands of substances present in these inventory lists, identification of substances requiring further safety data is urgently needed. This study attempts to identify substances of highest concern used in printed paper and board FCM.
Materials and methods: First, information on substances present in the inventory lists of the Council of Europe or from national legislation was assembled in one database. Next, the non-evaluated single substances were selected for further prioritisation. Their genotoxic potential was analysed in silico using multiple (quantitative) structure-activity relationship [(Q)SAR] models (ToxTree, VEGA Consensus, Derek Nexus, Sarah Nexus). The initial focus was on mutagenicity and the applicability domain tools available within the in silico tools were applied to ensure fitting of the test compounds in the models.
Results and conclusions: Among the 6068 unique compounds of the database, 4699 or 77% have not been officially evaluated. Focusing on the non-evaluated single substances reveals that over 75% have physicochemical characteristics in favour of both migration to food and bioavailability (required to exert toxic effects). Furthermore, 106 were found positive in all 4 tools (substances of highest concern), whereas 1107 were negative in all 4 tools (lowest concern). Another 515 were either positive in at least one tool, or could not be analysed in one or several tools (medium concern). The above findings indicate that several hundreds of non-evaluated single substances used in printed paper and board are predicted genotoxicants by multiple in silico tools. Moreover, inspection of their physicochemical properties shows considerable migration and toxicity potential. The substances containing a structural alert for genotoxicity were selected for further more in depth study. To this extent, both literature review and in vitro genotoxicity testing are being performed.