Department Environmental Toxicology

Bisphenol A alternatives are manufactured as potentially less harmful substitutes of bisphenol A (BPA) that offer similar functionality. These alternatives are already in the market, entering the environment and thus raising ecological concerns. However, it can be expected that levels of BPA alternatives will dominate in the future, they are limited information on their environmental safety. The EU PARC project highlights BPA alternatives as priority chemicals and consolidates information on BPA alternatives, with a focus on environmental relevance and on the identification of the research gaps. The review highlighted aspects and future perspectives. In brief, an extension of environmental monitoring is crucial, extending it to cover BPA alternatives to track their levels and facilitate the timely implementation of mitigation measures. The biological activity has been studied for BPA alternatives, but in a non-systematic way and prioritized a limited number of chemicals. For several BPA alternatives, the data has already provided substantial evidence regarding their potential harm to the environment. We stress the importance of conducting more comprehensive assessments that go beyond the traditional reproductive studies and focus on overlooked relevant endpoints. Future research should also consider mixture effects, realistic environmental concentrations, and the long-term consequences on biota and ecosystems.

The ubiquitous and global ecological footprint arising from the rapidly increasing rates of plastic production, use, and release into the environment is an important modern environmental issue. Of increasing concern are the risks associated with at least 16,000 chemicals present in plastics, some of which are known to be toxic, and which may leach out both during use and once exposed to environmental conditions, leading to environmental and human exposure. In response, the United Nations member states agreed to establish an international legally binding instrument on plastic pollution, the global plastics treaty. The resolution acknowledges that the treaty should prevent plastic pollution and its related impacts, that effective prevention requires consideration of the transboundary nature of plastic production, use and pollution, and that the full life cycle of plastics must be addressed. As a group of scientific experts and members of the Scientists' Coalition for an Effective Plastics Treaty, we concur that there are six essential “pillars” necessary to truly reduce plastic pollution and allow for chemical detoxification across the full life cycle of plastics. These include a plastic chemical reduction and simplification, safe and sustainable design of plastic chemicals, incentives for change, holistic approaches for alternatives, just transition and equitable interventions, and centering human rights. There is a critical need for scientifically informed and globally harmonized information, transparency, and traceability criteria to protect the environment and public health. The right to a clean, healthy, and sustainable environment must be upheld, and thus it is crucial that scientists, industry, and policy makers work in concert to create a future free from hazardous plastic contamination.

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.
Objective: To close this important knowledge gap, we conducted a systematic overview of FCCs that have been monitored and detected in human biomonitoring studies according to a previously published protocol. Methods: 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.
Results: 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 the presence in humans for 63 of the 175 prioritized FCCs included in the systematic evidence map, and 59 of the prioritized FCCs lack hazard data.
Significance: Notwithstanding that there are also other sources of exposure for many FCCs, these data will help to prioritize 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.
Impact statement: We present systematically compiled evidence on human exposure to 3601 food contact chemicals (FCCs) and highlight FCCs that are of concern because of their known hazard properties. Further, we identify relevant data gaps for FCCs found in food contact materials and foods. This article improves the understanding of food contact materials' contribution to chemical exposure for the human population and highlights opportunities for improving public health.

If a problem has exponential features, its solution asks for counter-exponential approaches. Chemical pollution appears to be such a problem. Analyses of chemical hazards to human health, biodiversity, and ecosystem services and estimates of the cost of inaction suggest the potential for adverse impacts, and analyses of trends in the chemical economy appear exponential in kind. Here, we argue that we need and can develop an exponential and application-focused mindset in thinking about solutions.

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.

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.

Polymers are the main constituents of many materials and products in our modern world. However, their environmental safety is not assessed with the same level of detail as done for non-polymeric chemical substances. Moreover, the fundamentals of contemporary regulatory approaches for polymers were developed in the early 1990s, with little change occurring since then. Currently, the European Commission is working on a proposal to initiate registration of polymers under the European Union's (EU) chemicals legislation REACH. This provides a unique opportunity for regulation to catch up on recent scientific advances. To inform this process, we here critically appraise the suggested regulatory approaches to the environmental assessment and management of polymers against the latest scientific findings regarding their environmental fate, exposure, and effects, and identify the remaining critical knowledge gaps. While we use the EU draft proposal as an example, our findings are broadly applicable to other polymer legislations worldwide, due to the similarity of polymer assessment criteria being used. We emphasize four major aspects that require more attention in the regulation of polymers: (i) increased transparency about chemical identities, physical characteristics and grouping approaches for in-use polymers; (ii) improved understanding of the environmental fate of polymers and materials composed of polymers across size and density categories and exposure profiles; (iii) comprehensive assessment of the environmental hazards of polymers, considering the effects of degradation and weathering and taking into account the actual uptake, long-term toxicity, and geophysical impacts; and (iv) consideration of the production volume and use/release patterns in determining regulatory data and testing requirements. Transitioning toward a toxic-free and sustainable circular economy will likely require additional policy instruments that will reduce the overall complexity and diversity of in-use polymers and polymeric materials.

Chemical pollution poses a threat to biodiversity on a global scale. This has been acknowledged in the Post-2020 Biological Diversity Framework which proposes to regulate the release of chemicals to the environment and names specific indicators focusing on pesticides, nutrients and plastic waste. We fully endorse the inclusion of these substances but argue that in order to protect biodiversity from hazardous chemicals, the scope of Target 7 should feature other groups of pollutants with potential to contribute to biodiversity loss. We propose the inclusion of non-agricultural biocides, per- and polyfluoroalkyl substances (PFASs), toxic metal(loid)s, and endocrine disrupting chemcials (EDCs). Furthermore, data on emerging pollutants (e.g., rare earth elements, industrial chemicals, liquid crystal monomers, pharmaceuticals, personal care products) need to be regularly scanned and these pollutants added to Target 7 in case of biodiversity risk. We suggest to amend Target 7 to postulate the aim for the overall reduction of chemical production and emissions, as well as the addition of the described substance groups of high concern to biodiversity for discussion and implementation in the Post-2020 Biodiversity Framework. We further elaborate on different strategies for the reduction of emissions of hazardous chemicals through chemical simplification and grouping, reduction of chemicals with non-essential use, and innovative synthesis strategies ("benign by design"). In this context the full life cycle of chemicals, i.e., production, use, end of life needs to be considered. Lastly, we propose to set up data inventories that transparently inform about production, transport and emissions of chemicals in cooperation with industry, that can serve as basis for indicators related to monitoring the effectiveness of the goals set under Target 7.

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.

Through its membership in the High-Level Round Table (HLRT) for the implementation of the Chemicals Strategy for Sustainability (CSS) under the EU Green Deal, and with the support of a sounding board, SETAC Europe tracks the landscape on chemicals regulations closely. The HLRT convened on 1 February to discuss the broad implementation of the CSS and specifically transition pathways for industry, including investment matters. Interesting opportunities have arisen for Society members to support these swift transitions with their scientific expertise.

Pollution by chemicals and waste impacts human and ecosystem health on regional, national, and global scales, resulting, together with climate change and biodiversity loss, in a triple planetary crisis. Consequently, in 2022, countries agreed to establish an intergovernmental science-policy panel (SPP) on chemicals, waste, and pollution prevention, complementary to the existing intergovernmental science-policy bodies on climate change and biodiversity. To ensure the SPP’s success, it is imperative to protect it from conflicts of interest (COI). Here, we (i) define and review the implications of COI, and its relevance for the management of chemicals, waste, and pollution; (ii) summarize established tactics to manufacture doubt in favor of vested interests, i.e., to counter scientific evidence and/or to promote misleading narratives favorable to financial interests; and (iii) illustrate these with selected examples. This analysis leads to a review of arguments for and against chemical industry representation in the SPP’s work. We further (iv) rebut an assertion voiced by some that the chemical industry should be directly involved in the panel’s work because it possesses data on chemicals essential for the panel’s activities. Finally, (v) we present steps that should be taken to prevent the detrimental impacts of COI in the work of the SPP. In particular, we propose to include an independent auditor’s role in the SPP to ensure that participation and processes follow clear COI rules. Among others, the auditor should evaluate the content of the assessments produced to ensure unbiased representation of information that underpins the SPP’s activities.

Climate change, biodiversity loss, and chemical pollution are planetary-scale emergencies requiring urgent mitigation actions. As these "triple crises" are deeply interlinked, they need to be tackled in an integrative manner. However, while climate change and biodiversity are often studied together, chemical pollution as a global change factor contributing to worldwide biodiversity loss has received much less attention in biodiversity research so far. Here, we review evidence showing that the multifaceted effects of anthropogenic chemicals in the environment are posing a growing threat to biodiversity and ecosystems. Therefore, failure to account for pollution effects may significantly undermine the success of biodiversity protection efforts. We argue that progress in understanding and counteracting the negative impact of chemical pollution on biodiversity requires collective efforts of scientists from different disciplines, including but not limited to ecology, ecotoxicology, and environmental chemistry. Importantly, recent developments in these fields have now enabled comprehensive studies that could efficiently address the manifold interactions between chemicals and ecosystems. Based on their experience with intricate studies of biodiversity, ecologists are well equipped to embrace the additional challenge of chemical complexity through interdisciplinary collaborations. This offers a unique opportunity to jointly advance a seminal frontier in pollution ecology and facilitate the development of innovative solutions for environmental protection.

Chemical pollution research should be better integrated with other drivers of biodiversity loss and the assessment of human impacts on ecosystems, to more effectively guide management strategies for biodiversity loss mitigation.

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.

Background: 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/).

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.

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.