In Vitro Toxicity Testing of Food Contact Materials: State-of-the-Art and Future Challenges.

Currently, toxicological testing of food contact materials (FCMs) is focused on single substances and their genotoxicity. However, people are exposed to mixtures of chemicals migrating from food contact articles (FCAs) into food, and toxic effects other than genotoxic damage may also be relevant. Since FCMs can be made of more than 8 thousand substances, assessing them one-by-one is very resource-consuming. Moreover, finished FCAs usually contain non-intentionally added substances (NIAS). NIAS toxicity can only be tested if a substance's chemical identity is known and if it is available as a pure chemical. Often, this is not the case. Nonetheless, regulations require safety assessments for all substances migrating from FCAs, including NIAS, hence new approaches to meet this legal obligation are needed. Testing the overall migrate or extract from an FCM/FCA is an option. Ideally, such an assessment would be performed by means of in vitro bioassays, as they are rapid and cost-effective. Here, we review the studies using in vitro bioassays to test toxicity of FCMs/FCAs. Three main categories of in vitro assays that have been applied include assays for cytotoxicity, genotoxicity, and endocrine disruption potential. In addition, we reviewed studies with small multicellular animal-based bioassays. Our overview shows that in vitro testing of FCMs is in principle feasible. We discuss future research needs and FCM-specific challenges. Sample preparation procedures need to be optimized and standardized. Further, the array of in vitro tests should be expanded to include those of highest relevance for the most prevalent human diseases of concern.