Peer-reviewed papers

Many nations have food contact material (FCM) legislation purporting to protect citizens from hazardous chemicals, often specifically by regulating genotoxic carcinogens. Despite such regulations, cancers that are associated with harmful chemical exposures are highly prevalent, especially breast cancer. Using the novel Key Characteristics of Toxicants framework, Kay et al. found 921 substances that are potential mammary carcinogens. By comparing Kay et al.‘s chemicals list with our own Database on migrating and extractable food contact chemicals (FCCmigex), we found that 189 (21%) of the potential mammary carcinogens have been measured in FCMs. When limiting these results to migration studies published in 2020–2022, 76 potential mammary carcinogens have been detected to migrate from FCMs sold in markets across the globe, under realistic conditions of use. This implies that chronic exposure of the entire population to potential mammary carcinogens from FCMs is the norm and highlights an important, but currently underappreciated opportunity for prevention. Reducing population-wide exposure to potential mammary carcinogens can be achieved by science-based policy amendments addressing the assessment and management of food contact chemicals.

Background: Over 1800 food contact chemicals (FCCs) are known to migrate from food contact articles used to store, process, package, and serve foodstuffs. Many of these FCCs have hazard properties of concern, and still others have never been tested for toxicity. Humans are known to be exposed to FCCs via foods, but the full extent of human exposure to all FCCs is unknown. To close this important knowledge gap, we conducted a systema􀆟c overview of FCCs that have been monitored and detected in human biomonitoring studies according to a previously published protocol. We first compared the more than 14,000 known FCCs to five biomonitoring programs and three metabolome/exposome databases. In a second step, we prioritized FCCs that have been frequently detected in food contact materials and systematically mapped the available evidence for their presence in humans. For 25% of the known FCCs (3601), we found evidence for their presence in humans. This includes 194 FCCs from human biomonitoring programs, with 80 of these having hazard properties of high concern. Of the 3528 FCCs included in metabolome/exposome databases, most are from the Blood Exposome Database. We found evidence for presence in humans for 63 of the 175 prioritized FCCs included in the systema􀆟c evidence map, and 59 of the prioritized FCCs lack hazard data. Notwithstanding that there are also other sources of exposure for many FCCs, these data will help to priori􀆟ze FCCs of concern by linking information on migration and biomonitoring. Our results on FCCs monitored in humans are available as an interactive dashboard (FCChumon) to enable policymakers, public health researchers, and food industry decision makers to make food contact materials and articles safer, reduce human exposure to hazardous FCCs and improve public health.

PFASs are linked to serious health and environmental concerns. Among their widespread applications, PFASs are known to be used in food packaging and directly contribute to human exposure. However, information about PFASs in food packaging is scattered. Therefore, we systematically map the evidence on PFASs detected in migrates and extracts of food contact materials and provide an overview of available hazard and biomonitoring data. Based on the FCCmigex database, 68 PFASs have been identified in various food contact materials, including paper, plastic, and coated metal, by targeted and untargeted analyses. 87% of these PFASs belong to the perfluorocarboxylic acids and fluorotelomer-based compounds. Trends in chain length demonstrate that long-chain perfluoroalkyl acids continue to be found, despite years of global efforts to reduce the use of these substances. We utilized ToxPi to illustrate that hazard data are available for only 57% of the PFASs that have been detected in food packaging. For those PFASs for which toxicity testing has been performed, many adverse outcomes have been reported. The data and knowledge gaps presented here support international proposals to restrict PFASs as a group, including their use in food contact materials, to protect human and environmental health.

Food contact materials (FCMs) and food contact articles are ubiquitous in today’s globalized food system. Chemicals migrate from FCMs into foodstuffs, so called food contact chemicals (FCCs), but current regulatory requirements do not sufficiently protect public health from hazardous FCCs because only individual substances used to make FCMs are tested and mostly only for genotoxicity while endocrine disruption and other hazard properties are disregarded. Indeed, FCMs are a known source of a wide range of hazardous chemicals, and they likely contribute to highly prevalent non-communicable diseases. FCMs can also include non-intentionally added substances (NIAS), which often are unknown and therefore not subject to risk assessment. To address these important shortcomings, we outline how the safety of FCMs may be improved by (1) testing the overall migrate, including (unknown) NIAS, of finished food contact articles, and (2) expanding toxicological testing beyond genotoxicity to multiple endpoints associated with non-communicable diseases relevant to human health. To identify mechanistic endpoints for testing, we group chronic health outcomes associated with chemical exposure into Six Clusters of Disease (SCOD) and we propose that finished food contact articles should be tested for their impacts on these SCOD. Research should focus on developing robust, relevant, and sensitive in-vitro assays based on mechanistic information linked to the SCOD, e.g., through Adverse Outcome Pathways (AOPs) or Key Characteristics of Toxicants. Implementing this vision will improve prevention of chronic diseases that are associated with hazardous chemical exposures, including from FCMs.

In the battle against plastic pollution many efforts are being undertaken to reduce, reuse, and recycle plastics. If tackled in the right way, these efforts have the potential to contribute to reducing plastic waste and plastic’s spread in the environment. However, reusing and recycling plastics can also lead to unintended negative impacts, because hazardous chemicals, like endocrine disrupters and carcinogens, can be released during reuse and accumulate during recycling. In this way, plastic reuse and recycling become vectors for spreading chemicals of concern. This is especially concerning when plastics are reused for food packaging, or when food packaging is made with recycled plastics. Therefore, it is of utmost importance that care is taken to avoid hazardous chemicals in plastic food contact materials, and to ensure that plastic packaging that is reused or made with recycled content is safe for human health and the environment. The data presented in this review are obtained from the Database on Migrating and Extractable Food Contact Chemicals (FCCmigex), which is based on over 700 scientific publications on plastic food contact materials. We provide systematic evidence for migrating and extractable food contact chemicals (FCCs) in plastic polymers that are typically reused, such as polyamide (PA), melamine resin (MelRes), polycarbonate (PC), and polypropylene (PP), or that contain recycled content, such as polyethylene terephthalate (PET). 1332 entries in the FCCmigex database refer to the detection of 509 FCCs in repeat-use food contact materials made of plastic. 853 FCCs are found in recycled PET, of which 57.6% have been detected only once. Here, we compile information on the origin, function, and hazards of FCCs that have been frequently detected, such as melamine, 2,4-di-tert-butylphenol, 2,6-di-tert-butylbenzoquinone, caprolactam and PA oligomers, and highlight key knowledge gaps that are relevant for the assessment of chemical safety.

Background: The presence of polyethylene terephthalate (PET) oligomers in food contact materials (FCMs) is well-documented. Consumers are exposed through their migration into foods and beverages; however, there is no specific guidance for their safety evaluation.
Objectives: This systematic evidence map (SEM) aims to identify and organize existing knowledge and associated gaps in hazard and exposure information on 34 PET oligomers to support regulatory decision-making.
Methods: The methodology for this SEM was recently registered. A systematic search in bibliographic and gray literature sources was conducted and studies evaluated for inclusion according to the Populations, Exposures, Comparators, Outcomes, and Study type (PECOS) framework. Inclusion criteria were designed to record hazard and exposure information for all 34 PET oligomers and coded into the following evidence streams: human, animal, organism (non-animal), ex vivo, in vitro, in silico, migration, hydrolysis, and absorption, distribution, metabolism, excretion/toxicokinetics/pharmacokinetics (ADME/TK/PK) studies. Relevant information was extracted from eligible studies and synthesized according to the protocol.
Results: Literature searches yielded 7445 unique records, of which 96 were included. Data comprised migration (560 entries), ADME/TK/PK-related (253 entries), health/bioactivity (98 entries) and very few hydrolysis studies (7 entries). Cyclic oligomers were studied more frequently than linear PET oligomers. In vitro results indicated that hydrolysis of cyclic oligomers generated a mixture of linear oligomers, but not monomers, potentially allowing their absorption in the gastrointestinal tract. Cyclic dimers, linear trimers and the respective smaller oligomers exhibit physico-chemical properties making oral absorption more likely. Information on health/ bioactivity effects of oligomers was almost non-existent, except for limited data on mutagenicity.
Conclusions: This SEM revealed substantial deficiencies in the available evidence on ADME/TK/PK, hydrolysis, and health/bioactivity effects of PET oligomers, currently preventing appropriate risk assessment. It is essential to develop more systematic and tiered approaches to address the identified research needs and assess the risks of PET oligomers.

Polyethylene (PE) is the most widely used type of plastic food packaging, in which chemicals can potentially migrate into packaged foods. The implications of using and recycling PE from a chemical perspective remain underexplored. This study is a systematic evidence map of 116 studies looking at the migration of food contact chemicals (FCCs) across the lifecycle of PE food packaging. It identified a total of 377 FCCs, of which 211 were detected to migrate from PE articles into food or food simulants at least once. These 211 FCCs were checked against the inventory FCCs databases and EU regulatory lists. Only 25% of the detected FCCs are authorized by EU regulation for the manufacture of food contact materials. Furthermore, a quarter of authorized FCCs exceeded the specific migration limit (SML) at least once, while one-third (53) of non-authorised FCCs exceeded the threshold value of 10 μg/kg. Overall, evidence on FCCs migration across the PE food packaging lifecycle is incomplete, especially at the reprocessing stage. Considering the EU’s commitment to increase packaging recycling, a better understanding and monitoring of PE food packaging quality from a chemical perspective across the entire lifecycle will enable the transition towards a sustainable plastics value chain.

The NORMAN Association (https://www.norman-network.com/) initiated the NORMAN Suspect List Exchange (NORMAN-SLE; https://www.norman-network.com/nds/SLE/) in 2015, following the NORMAN collaborative trial on non-target screening of environmental water samples by mass spectrometry. Since then, this exchange of information on chemicals that are expected to occur in the environment, along with the accompanying expert knowledge and references, has become a valuable knowledge base for “suspect screening” lists. The NORMAN-SLE now serves as a FAIR (Findable, Accessible, Interoperable, Reusable) chemical information resource worldwide.
Results
The NORMAN-SLE contains 99 separate suspect list collections (as of May 2022) from over 70 contributors around the world, totalling over 100,000 unique substances. The substance classes include per- and polyfluoroalkyl substances (PFAS), pharmaceuticals, pesticides, natural toxins, high production volume substances covered under the European REACH regulation (EC: 1272/2008), priority contaminants of emerging concern (CECs) and regulatory lists from NORMAN partners. Several lists focus on transformation products (TPs) and complex features detected in the environment with various levels of provenance and structural information. Each list is available for separate download. The merged, curated collection is also available as the NORMAN Substance Database (NORMAN SusDat). Both the NORMAN-SLE and NORMAN SusDat are integrated within the NORMAN Database System (NDS). The individual NORMAN-SLE lists receive digital object identifiers (DOIs) and traceable versioning via a Zenodo community (https://zenodo.org/communities/norman-sle), with a total of > 40,000 unique views, > 50,000 unique downloads and 40 citations (May 2022). NORMAN-SLE content is progressively integrated into large open chemical databases such as PubChem (https://pubchem.ncbi.nlm.nih.gov/) and the US EPA’s CompTox Chemicals Dashboard (https://comptox.epa.gov/dashboard/), enabling further access to these lists, along with the additional functionality and calculated properties these resources offer. PubChem has also integrated significant annotation content from the NORMAN-SLE, including a classification browser (https://pubchem.ncbi.nlm.nih.gov/classification/#hid=101).
Conclusions
The NORMAN-SLE offers a specialized service for hosting suspect screening lists of relevance for the environmental community in an open, FAIR manner that allows integration with other major chemical resources. These efforts foster the exchange of information between scientists and regulators, supporting the paradigm shift to the “one substance, one assessment” approach. New submissions are welcome via the contacts provided on the NORMAN-SLE website (https://www.norman-network.com/nds/SLE/).

Background
Polyethylene terephthalate (PET) oligomers are ubiquitous in PET used in food contact applications. Consumer exposure by migration of PET oligomers into food and beverages is documented. However, no specific risk assessment framework or guidance for the safety evaluating of PET oligomers exist to date.

Aim
The aim of this systematic evidence map (SEM) is to identify and organize existing knowledge clusters and associated gaps in hazard and exposure information of PET oligomers. Research needs will be identified as an input for chemical risk assessment, and to support future toxicity testing strategies of PET oligomers and regulatory decision-making.

Search strategy and eligibility criteria
Multiple bibliographic databases (incl. Embase, Medline, Scopus, and Web of Science Core Collection), chemistry databases (SciFinder-n, Reaxys), and gray literature sources will be searched, and the search results will be supplemented by backward and forward citation tracking on eligible records. The search will be based on a single-concept PET oligomer-focused strategy to ensure sensitive and unbiased coverage of all evidence related to hazard and exposure in a data-poor environment. A scoping exercise conducted during planning identified 34 relevant PET oligomers. Eligible work of any study type must include primary research data on at least one relevant PET oligomer with regard to exposure, health, or toxicological outcomes.

Study selection
For indexed scientific literature, title and abstract screening will be performed by one reviewer. Selected studies will be screened in full-text by two independent reviewers. Gray literature will be screened by two independent reviewers for inclusion and exclusion.

Study quality assessment
Risk of bias analysis will not be conducted as part of this SEM.

Data extraction and coding
Will be performed by one reviewer and peer-checked by a second reviewer for indexed scientific literature or by two independent reviewers for gray literature.

Synthesis and visualization
The extracted and coded information will be synthesized in different formats, including narrative synthesis, tables, and heat maps.

Systematic map protocol registry and registration number
Zenodo: https://doi.org/10.5281/zenodo.6224302.

The EU Chemicals Strategy for Sustainability (CSS) aims at removing the most harmful chemicals from consumer products, including from food contact materials (FCMs). If implemented as intended, the CSS has the potential to significantly improve the protection of public health by banning the use of chemicals of concern that are carcinogenic, mutagenic, or toxic to reproduction (CMRs), or persistent and bioaccumulative, or endocrine-disrupting chemicals (EDCs) in FCMs. However, until now an overview of such food contact chemicals of concern (FCCoCs) has not been available, because the CSS is fairly recent. Therefore, we here systematically analyze the food contact chemicals listed for intentional use in FCMs and identify known FCCoCs. We present a list of 388 FCCoCs that should be phased-out from use. Of these, 352 are CMRs, four are per- and polyfluoroalkyl substances (PFAS), and 127 have empirical evidence for presence in FCMs. Importantly, 30 FCCoCs with evidence for presence are monomers of which 22 have evidence for migration into foodstuff showing that monomers in FCMs indeed become relevant for human exposure. Our findings justify moving away from a risk- towards a hazard-based approach to regulation of chemicals in FCMs.