A vision for safer food contact materials: Public health concerns as drivers for improved testing

Muncke, J., Andersson, A.M., Backhaus, T., Belcher, S.M., Boucher, J.M., Almroth, B.C., Collins, T.J., Geueke, B., Groh, K.J., Heindel, J.J., von Hippel, F.A., Legler, J., Maffini, M.V., Martin, O.V., Myers, J.P., Nadal, A., Nerin, C., Soto, A.M., Trasande, L., Vandenberg, L.N., Wagner, M., Zimmermann, L., Zoeller, R.T., Scheringer, M.
2023, Environment Journal
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.

Hazardous chemicals in recycled and reusable plastic food packaging

Geueke, B., Phelps, D.W., Parkinson, L.V., and Muncke, J.
2023, Plastics
  • DOI: //doi.org/10.1017/plc.2023.7
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.

Evaluating the food safety and risk assessment evidence-base of polyethylene terephthalate oligomers: A systematic evidence map

Schreier, V.N., Çörek, E., Appenzeller-Herzog, C., Brüschweiler, B.J., Geueke, B., Wilks, M.F., Schilter, B., Muncke, J., Simat, T.J., Smieško, M. and Roth, N.
2023, Environment International
  • DOI: 10.1016/j.envint.2023.107978

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.

Unpacking the complexity of the polyethylene food contact articles value chain: A chemicals perspective

Gerassimidou, S., Geueke, B., Groh, K.J., Muncke, J., Hahladakis, J.N., Martin, O.V., and Iacovidou, E.
2023, Journal of Hazardous Materials
  • DOI: 10.1016/j.jhazmat.2023.131422
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 Suspect List Exchange (NORMAN-SLE): facilitating European and worldwide collaboration on suspect screening in high resolution mass spectrometry

Taha H.M., Aalizadeh R., Alygizakis N., Antignac J.P., Arp H.P.H., Bade R., Baker N., Belova L., Bijlsma L., Bolton E.E., Brack W., Celma A., Chen W.L., Cheng T.J., Chirsir P., Cirka L., D'Agostino L.A., Feunang Y.D., Dulio V., Fischer S., Gago-Ferrero P., Galani A., Geueke B., Glowacka N., Gluge J., Groh K., Grosse S., Haglund P., Hakkinen P.J., Hale S.E., Hernandez F., Janssen E.M.L., Jonkers T., Kiefer K., Kirchner M., Koschorreck J., Krauss M., Krier J., Lamoree M.H., Letzel M., Letzel T., Li Q.L., Little J., Liu Y.N., Lunderberg D.M., Martin J.W., McEachran A.D., McLean J.A., Meier C., Meijer J., Menger F., Merino C., Muncke J., Muschket M., Neumann M., Neveu V., Ng K., Oberacher H., O'Brien J., Oswald P., Oswaldova M., Picache J.A., Postigo C., Ramirez N., Reemtsma T., Renaud J., Rostkowski P., Rudel H., Salek R.M., Samanipour S., Scheringer M., Schliebner I., Schulz W., Schulze T., Sengl M., Shoemaker B.A., Sims K., Singer H., Singh R.R., Sumarah M., Thiessen P.A., Thomas K.V., Torres S., Trier X., van Wezel A.P., Vermeulen R.C.H., Vlaanderen J.J., von der Ohe P.C., Wang Z.Y., Williams A.J., Willighagen E.L., Wishart D.S., Zhang J., Thomaidis N.S., Hollender J., Slobodnik J., and Schymanski E.L.
2022, Environmental Sciences Europe
  • DOI: 10.1186/s12302-022-00680-6

The NORMAN Association (//www.norman-network.com/) initiated the NORMAN Suspect List Exchange (NORMAN-SLE; //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 (//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 (//pubchem.ncbi.nlm.nih.gov/) and the US EPA’s CompTox Chemicals Dashboard (//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 (//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 (//www.norman-network.com/nds/SLE/).

Evaluating the food safety and risk assessment evidence-base of polyethylene terephthalate oligomers: Protocol for a systematic evidence map

Schreier V.N., Appenzeller-Herzog C., Brüschweiler B., Geueke B., Wilks M.F., Simat T.J., Schilter B., Smieško M., Muncke J., Odermatt A., and Rothab N.
2022, Environment International
  • DOI: 10.1016/j.envint.2022.107387

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: //doi.org/10.5281/zenodo.6224302.

Implementing the EU Chemicals Strategy for Sustainability: The case of Food Contact Chemicals of Concern

Zimmermann L., Scheringer M., Geueke B., Boucher J.M., Parkinson L.V., Groh K.J. and Muncke J.
2022, Journal of Hazardous Materials
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.

Systematic Evidence on migrating and extractable Food Contact Chemicals: Most Chemicals detected in Food Contact Materials are not listed for Use

Geueke B., Groh K.J., Maffini M.V., Martin O.V., Boucher J.M., Chiang Y.T., Gwosdz F., Jieh P., Kassotis C.D., Lanska P., Myers J.P., Odermatt A., Parkinson L.V., Schreier V.N., Srebny V., Zimmermann L., Scheringer M., and Muncke J.
2022, Critical Reviews in Food Science and Nutrition
Food packaging is important for today’s globalized food system, but food contact materials (FCMs) can also be a source of hazardous chemicals migrating into foodstuffs. Assessing the impacts of FCMs on human health requires a comprehensive identification of the chemicals they contain, the food contact chemicals (FCCs). we systematically compiled the “database on migrating and extractable food contact chemicals” (FCCmigex) using information from 1210 studies. we found that to date 2881 FCCs have been detected, in a total of six FCM groups (Plastics, Paper & Board, Metal, Multi-materials, Glass & Ceramic, and Other FCMs). 65% of these detected FCCs were previously not known to be used in FCMs. Conversely, of the more than 12’000 FCCs known to be used, only 1013 are included in the FCCmigex database. Plastic is the most studied FCM with 1975 FCCs detected. Our findings expand the universe of known FCCs to 14,153 chemicals. This knowledge contributes to developing non-hazardous FCMs that lead to safer food and support a circular economy.

Unpacking the complexity of the PET drink bottles value chain: A chemicals perspective

Gerassimidou S., Lanska P., Hahladakis J.N., Lovat E., Vanzetto S., Geueke B., Groh K.J., Muncke J., Maffini M., Martin O.V., and Iacovidou E.
2022, Journal of Hazardous Materials
Chemicals can migrate from polyethylene terephthalate (PET) drink bottles to their content and recycling processes may concentrate or introduce new chemicals to the PET value chain. Therefore, even though recycling PET bottles is key in reducing plastic pollution, it may raise concerns about safety and quality. This study provides a systematic evidence map of the food contact chemicals (FCCs) that migrate from PET drink bottles aiming to identify challenges in closing the plastic packaging loop. The migration potential of 193 FCCs has been investigated across the PET drink bottles lifecycle, of which 150 have been detected to migrate from PET bottles into food simulants/food samples. The study reveals that much research has focused on the migration of antimony (Sb), acetaldehyde and some well-known endocrine-disrupting chemicals (EDCs). It indicates and discusses the key influential factors on FCCs migration, such as physical characteristics and geographical origin of PET bottles, storage conditions, and reprocessing efficiency . Although, safety and quality implications arising from the recycling of PET bottles remain underexplored, the higher migration of Sb and Bishphenol A has been reported in recycled (rPET) compared to virgin PET. This is attributed to multiple contamination sources and the variability in the collection, sorting, and decontamination efficiency. Better collaboration among stakeholders across the entire PET bottles lifecycle is needed to ensure sustainable resource management and food contact safety of rPET.

Role of epidemiology in risk assessment: a case study of five ortho-phthalates

Maffini M.V., Geueke B., Groh K., Carney Almroth B., and Muncke J.
2021, Environmental Health
Background: The association between environmental chemical exposures and chronic diseases is of increasing concern. Chemical risk assessment relies heavily on pre-market toxicity testing to identify safe levels of exposure, often known as reference doses (RfD), expected to be protective of human health. Although some RfDs have been reassessed in light of new hazard information, it is not a common practice. Continuous surveillance of animal and human data, both in terms of exposures and associated health outcomes, could provide valuable information to risk assessors and regulators. Using ortho-phthalates as case study, we asked whether RfDs deduced from male reproductive toxicity studies and set by traditional regulatory toxicology approaches sufficiently protect the population for other health outcomes. Methods: We searched for epidemiological studies on benzyl butyl phthalate (BBP), diisobutyl phthalate (DIBP), dibutyl phthalate (DBP), dicyclohexyl phthalate (DCHP), and bis(2-ethylhexyl) phthalate (DEHP). Data were extracted from studies where any of the five chemicals or their metabolites were measured and showed a statistically significant association with a health outcome; 38 studies met the criteria. We estimated intake for each phthalate from urinary metabolite concentration and compared estimated intake ranges associated with health endpoints to each phthalate’s RfD. Result: For DBP, DIBP, and BBP, the estimated intake ranges significantly associated with health endpoints were all below their individual RfDs. For DEHP, the intake range included associations at levels both below and above its RfD. For DCHP, no relevant studies could be identified. The significantly affected endpoints revealed by our analysis include metabolic, neurodevelopmental and behavioral disorders, obesity, and changes in hormone levels. Most of these conditions are not routinely evaluated in animal testing employed in regulatory toxicology. Conclusion: We conclude that for DBP, DIBP, BBP, and DEHP current RfDs estimated based on male reproductive toxicity may not be sufficiently protective of other health effects. Thus, a new approach is needed where post-market exposures, epidemiological and clinical data are systematically reviewed to ensure adequate health protection.