Peer-reviewed papers

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.

Modern societies synthesize, distribute, and utilize thousands of chemicals, but their contribution to the global burden of non-communicable diseases remains insufficiently characterized. Improved availability of robust hazard data would enable more systematic assessment, prioritization, and management of chemical-related health risks. New Approach Methodologies (NAM) are promising because they provide high-throughput, mechanistically informative, and animal-free testing that improves current regulatory toxicity testing. However, selecting biologically relevant in-vitro assays capable of predicting chemical-induced effects remains a challenge. Here, we present a systematic strategy for assembling relevant in-vitro assays. We identified critical molecular and cellular key events of Adverse Outcome Pathways (AOPs) across six clusters of diseases that can be triggered by chemical exposure. Curation and filtering of 487 AOPs resulted in 266 AOPs, which were manually mapped to the AOP networks of disease clusters containing 25–84 AOPs each. The three most frequently occurring key events across all clusters were cytotoxicity (6/6 clusters), oxidative stress (5/6 clusters), and mitochondrial dysfunction (4/6 clusters). This prioritization aligns with oxidative stress as an overarching “key characteristic of toxicants”. Receptor-mediated key events were also frequent, with aryl hydrocarbon and estrogen receptor activation in multiple clusters. Other key events were cluster-specific, such as triglyceride accumulation in metabolic diseases. Building on this analysis, we propose high-throughput cell-based assays covering critical endpoints by integrating the key characteristics of toxicants framework to ensure coverage beyond current AOP limitations. A panel of 15 multiplexed assays meeting criteria for simplicity, robustness, and high-throughput could enable efficient screening of single chemicals or chemical mixtures.

Microplastics and nanoplastics (MNPs) are everywhere. These tiny particles—formed by abrasion, fragmentation, and open burning of plastics—are found in the ocean, the Arctic, Himalayan glaciers, air, food, and drinking water. More recently, they have been reported in human lung and faeces, reflecting exposures via inhalation and ingestion, as well as in blood, carotid arteries, heart, brain, liver, ovaries, testes, and placenta. Early clinical and epidemiological reports suggest associations between MNPs and health effects, notably cardiovascular disease, adverse reproductive outcomes, and immune modulation. These findings are supported by experimental models showing that MNPs, especially smaller particles, can cross epithelial barriers to induce inflammation, oxidative stress, and metabolic disruption. These reports have received considerable attention.

Background
The normal and intended use of plastic food packaging and other food contact articles (FCAs) leads to the migration of micro- and nanoplastics (MNPs) into food and beverages, resulting in human exposure. In 2022, we systematically assessed the state of science on this topic. However, at the time, reliable data on MNP release from FCAs into food were scarce, and since then, research has expanded significantly.

Objectives
We aim to update our dataset with the latest evidence of MNPs detected in foodstuffs in contact with plastic FCAs. To achieve this, we will systematically map the literature based on a Population, and Outcomes (PO) framework.

Search strategy and eligibility criteria
We will search Web of Science, PubMed, and Science Direct for combinations of search terms related to FCAs, packaging, foodstuffs/food simulants, plastic particles, and abrasion/release. Cited references from relevant reports will also be included. In a two-step screening process, we will apply predefined eligibility criteria to titles and abstracts of all references, followed by a screening of full texts.

Data extraction
According to defined data categories, we will collect information on types and characteristics of the FCAs, MNPs, food/food simulant, and the experimental design.

Synthesis and visualization
Results will be published as a narrative summary, and data in the freely accessible, filterable FCMiNo dashboard.

Objective
This narrative review examines the potential role of plastic-derived chemicals and micro- and nanoplastics in metabolic diseases. It applies the recently proposed key characteristics (KCs) for metabolism-disrupting agents to evaluate chemicals commonly found in plastics and microplastic and nanoplastic particles.

Methods
The KC framework, adapted from the KCs of toxicants originally developed for the identification of carcinogens, was applied to evaluate evidence from epidemiological, animal, and cellular studies. The review specifically evaluates compounds such as perfluorooctanoic acid (PFOA), bisphenol-S (BPS), and diisonyl phthalate (DINP), as well as emerging evidence relating to microplastics and nanoplastics (MNPs).

Results
Evidence shows that exposure to chemicals derived from plastics, including PFOA, BPA substitutes (eg, BPS) and phthalate substitutes, is linked to metabolic dysfunction, obesity, diabetes, and MASLD. BPS and DINP exhibit properties consistent with metabolism-disrupting agents, suggesting they are “regrettable substitutes.” Although human data on MNPs are limited, animal and cellular studies indicate they may also contribute to metabolic diseases, though mechanisms remain unclear.

Conclusion
Rising exposure to chemicals in plastics poses significant risks to metabolic health. Identifying metabolic disruptors among thousands of plastic-associated chemicals is urgently needed. Increasing awareness and promoting the use of safer, inert, and reusable materials are essential steps to reduce health risks associated with plastic-derived pollutants and support more sustainable consumption.

Antimony (Sb) is a group 15 metalloid that is used as a catalyst in the production of polyethylene terephthalate (PET) plastic, a common food contact material (FCM). PET accounts for over 44% of single-use beverage packaging units and is also used in the production of food trays, storage containers, and other items. Due to its frequent co-occurrence with other metals, Sb is also a common contaminant in crystalware, ceramics, and metal FCMs. In light of the increasing use of Sb-containing FCMs in modern society, a thorough evaluation of Sb’s potential effect on public health is warranted since burgeoning evidence suggests it is linked to common cardiometabolic conditions, including dyslipidemia, obesity, diabetes, hypertension, heart failure, and atherosclerotic cardiovascular disease. Thus, this review aims to (i) perform a comprehensive systematic assessment of Sb migration from FCMs into foodstuffs and food simulants, (ii) obtain an overview of antimony-related health risks, and (iii) inform the generation of harm reduction guidelines at the individual and systems levels.

Background
Food contact chemicals (FCCs) are known to migrate from food packaging and other food contact articles into food. This leads to human exposure to FCCs, and some FCCs have been linked to human health effects such as chronic and non-communicable diseases. However, a systematic overview of the health effects of FCCs is missing.

Objectives
The objective of this study is to systematically map the relations between exposure to FCCs and human health effects within the Population, Exposure, Comparator, Outcomes, and Study Design (PECOS) framework.

Search strategy and eligibility criteria
We will search PubMed for combinations of search terms related to the identity of the chemical and the epidemiological study design. The references will be screened at the title-and-abstract level, followed by the full-text level. Eligible references will be included according to predefined criteria, further specifying the elements of the applied PECOS framework.

Data extraction and coding
Information on human exposure to FCCs will be collected and linked to human health effects according to previously defined data categories and standardized terms. The human health effects will be classified based on the Six Clusters of Disease (SCOD) framework.

Synthesis and visualization
Results will be published in a narrative summary, and data will be made available in a freely accessible interactive dashboard, the Food Contact Chemicals Health Effect Matrix (FCChelix).

• Reporting of micro- and nanoplastics (MNPs) originating from food contact materials should follow guidelines for chemicals.
• MNP amounts should relate to surface area of plastic food contact material, not to volume of beverage.
• Determining sources of MNPs in foodstuffs requires specific study designs.
• All possible origins of MNPs must be considered, including processing equipment and contamination of raw ingredients.

Plastics are a grave, growing, and under-recognised danger to human and planetary health. Plastics cause disease and death from infancy to old age and are responsible for health-related economic losses exceeding US$1·5 trillion annually. These impacts fall disproportionately upon low-income and at-risk populations. The principal driver of this crisis is accelerating growth in plastic production—from 2 megatonnes (Mt) in 1950, to 475 Mt in 2022 that is projected to be 1200 Mt by 2060. Plastic pollution has also worsened, and 8000 Mt of plastic waste now pollute the planet. Less than 10% of plastic is recycled. Yet, continued worsening of plastics’ harms is not inevitable. Similar to air pollution and lead, plastics’ harms can be mitigated cost-effectively by evidence-based, transparently tracked, effectively implemented, and adequately financed laws and policies. To address plastics’ harms globally, UN member states unanimously resolved in 2022 to develop a comprehensive, legally binding instrument on plastic pollution, namely the Global Plastics Treaty covering the full lifecycle of plastic. Coincident with the expected finalisation of this treaty, we are launching an independent, indicator-based global monitoring system: the Lancet Countdown on health and plastics. This Countdown will identify, track, and regularly report on a suite of geographically and temporally representative indicators that monitor progress toward reducing plastic exposures and mitigating plastics’ harms to human and planetary health.

Plastics are composed of complex chemical mixtures, resulting in many chemicals being released during plastic’s life cycle, alongside a range of actual or potential impacts on human health and the environment. Many plastic chemicals also hinder technological solutions toward a safe and sustainable circular economy. Hence, there is broad agreement to address so-called plastic chemicals of concern, including under the Global Plastics Treaty. However, debate on how to identify such chemicals of concern is ongoing, particularly around whether their risk (and by extension, exposure) should be considered. In this perspective, we provide a review of the difficulties associated with understanding human and ecosystem exposure to and risks from plastic chemicals. Based on this, we highlight benefits of applying a hazard-based approach for identifying plastic chemicals of concern in a timely manner, and argue that additional consideration of exposure/risk would result in unjustified and costly delays, complications, and uncertainties, and therefore should not be required. A hazard-based approach to identifying plastic chemicals of concern would enable efficient action toward mitigating the impacts of plastics on human health and the environment, and facilitate a transition to a safe and sustainable plastics economy.