Prioritizing and Grouping Food Contact Chemicals: From Chaos to Clarity.

At least 2,160 food contact chemicals (FCCs) are known to migrate into foodstuffs, and some of them, such as certain bisphenols and ortho-phthalates, have been partially regulated in a few geographic regions due to health risks. However, the current approach to chemicals management is slow and can lead to regrettable substitutions, as seen with bisphenol A (BPA, CAS 80-05-7) being replaced by bisphenol S (BPS, CAS 80-09-1). To help address these issues and provide evidence-based guidance, we systematically prioritized the currently known 15,159 FCCs based on their well-known human health hazards and exposure potential from food contact materials (FCMs). Overall, 1,222 FCCs make up the FCCprio List. These FCCs are carcinogenic, mutagenic, toxic for reproduction, toxic for specific target organs, endocrine disrupting, persistent, bioaccumulative, and/or mobile, based on GHS-aligned hazard data. 94 FCCs are assigned to the highest tier (Tier 1) because of evidence for migration into food and presence in humans from human biomonitoring programs. We then grouped all known FCCs by chemical structure and identified 38 priority structural groups with a particularly high fraction of known hazardous chemicals, including well-known priority groups such as ortho-phthalates and PFASs as well as less-discussed groups (e.g., primary aromatic amines, organophosphates, isocyanates). Importantly, 4,222 FCCs fall into priority groups, meaning they are structurally closely related to hazardous FCCs, and 70% of these FCCs lack adequate hazard data─indicating significant knowledge gaps and the potential for regrettable substitutions. While these results highlight potential for prioritizing data-poor FCCs through grouping, ultimately more holistic strategies, including mixture toxicity assessment or testing finished FCMs for biological activity, are needed to reduce the overall human exposure to hazardous or untested FCCs migrating from FCMs.