Prioritizing substances of genotoxic concern for in-depth safety evaluation using non-animal approaches: The example of food contact materials

Due to the exponentially growing number of substances requiring safety evaluation, efficient prioritization strategies are needed to identify those of highest concern. To limit unnecessary animal testing, such strategies should respect the 3R principles (Replacement, Reduction, Refinement). In the present study, a strategy based on non-animal approaches was developed to prioritize non-evaluated printed paper and board food contact material (FCM) substances for further in-depth safety evaluation. Within the strategy, focus was placed on genotoxicity, a key toxicological endpoint when evaluating safety. By combining in silico predictions with existing in vitro and in vivo genotoxicity data from publicly available literature sources and results from in vitro gene mutation experiments, the 106 study substances could all be assigned to one of the four priority classes (ranging from low to very high concern). Importantly, 19 substances were considered of very high concern due to in vivo genotoxicity. Five of these are furthermore listed as substances of very high concern (SVHC) by the European Chemicals Agency (ECHA), in addition to demonstrating physicochemical properties linked to a high migration potential as well as oral bioavailability and being used in primary food packaging materials. The current animal-free strategy proved useful for the priority ranking of printed paper and board FCM substances, but it may also be considered to prioritize other substances of emerging concern.