Genotoxic substances in printed paper and board food contact materials: A prioritisation strategy based on non-animal methods

Over the past decades, several food contamination crises caused by the migration of substances from food contact materials (FCM) into food and drinks have been reported. As a result, concerns have been raised regarding the potential adverse health effects for consumers following exposure to these substances. Printing inks and paper(board), two FCM types that are often used in combination, have already been the subject of multiple food contamination issues. Nevertheless, as for the majority of FCM types, no specific harmonised European legislation is in place for printed paper and board. Since thousands of printed paper and board substances have not been officially evaluated for their safe use, identification of those of highest concern is required. In the present work, a prioritisation strategy based on the substances’ genotoxic potential was developed, since this toxicological endpoint is related to serious adverse human health effects, including cancer. The developed strategy was solely based on non-animal test methods such as in silico tools, literature consultation and in vitro experiments. Importantly, within the strategy, most emphasis was put on the substances’ potential to induce gene mutations as for this endpoint, in silico models are most advanced. By using a battery of 4 in silico tools, a first selection was obtained consisting of 106 non-evaluated single substances that were predicted to induce gene mutations in all 4 tools. For these substances, publically available experimental genotoxicity data (including information on the induction of gene mutations) were collected. For the substances lacking (adequate) genotoxicity data, a bacterial reverse gene mutation test was performed. Ultimately, the prioritisation strategy identified a large number of substances of concern, out of which five are of very high concern based on their confirmed in vivo genotoxicity, current use, high migration and bioavailability potential and inclusion in European lists with substances of concern. Interestingly, the developed prioritisation strategy can also be applied in numerous other domains with a high need for substance prioritisation.