Identification of potential genotoxicants in food contact materials using in silico tools

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 authorized 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, solvents 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. After plastics, these FCM are most widespread. First, information on substances present in the inventory lists of the Council of Europe or from national legislation was assembled in a database. Among the 6068 unique compounds, 4699 or 77% have not been officially evaluated. Next, the non-evaluated single substances were selected for further prioritisation. Over 75% of them have physicochemical characteristics in favour of both migration to food and bioavailability (required to exert toxic effects). The genotoxic potential of the non-evaluated single substances was then analysed in silico using multiple (Q)SAR models (ToxTree, VEGA Consensus, Derek NexusTM, Sarah NexusTM). 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. As a result, 106 substances were found positive in all 4 tools (substances of highest concern), whereas 1107 substances were negative in all 4 tools (lowest concern). Another 515 substances 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.