Department Environmental Toxicology

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.

The number of new psychoactive substances (NPS) increases rapidly, harming society and fuelling the need for alternative testing strategies. These should allow the everincreasing number of drugs to be tested more effectively for their toxicity and psychoactive effects. One proposed strategy is to complement rodent models with zebrafish (Danio rerio) larvae. Yet, our understanding of the toxicokinetics in this model, owing to the waterborne drug exposure and the distinct physiology of the fish, is incomplete. We here explore the toxicokinetics and behavioral effects of an NPS, meta-chlorophenylpiperazine (mCPP), in zebrafish larvae. Uptake kinetics of mCPP, supported by toxicokinetic modeling, strongly suggested the existence of active transport processes. Internal distribution showed a dominant accumulation in the eye, implying that in zebrafish, like in mammals, melanin could serve as a binding site for basic drugs. We confirmed this by demonstrating significantly lower drug accumulation in two types of hypo-pigmented fish. Comparison of the elimination kinetics between mCPP and previously characterized cocaine demonstrated that drug affinities to melanin in zebrafish vary depending on the structure of the test compound. As expected from mCPP-elicited responses in rodents and humans, zebrafish larvae displayed hypoactive behavior. However, significant differences were seen between zebrafish and rodents with regard to the concentration-dependency of the behavioral response and the comparability of tissue levels, corroborating the need to consider the organism-internal distribution of the chemical to allow appropriate dose modeling while evaluating effects and concordance between zebrafish and mammals. Our results highlight commonalities and differences of mammalian versus the fish model in need of further exploration.

Zebrafish is a widely used animal model in biomedical sciences and toxicology. Although evidence for the presence of phases I and II xenobiotic defense mechanisms in zebrafish exists on the transcriptional and enzyme activity level, little is known about the protein expression of xenobiotic metabolizing enzymes. Given the important role of glutathione S-transferases (GSTs) in phase II biotransformation, we analyzed cytosolic GST proteins in zebrafish early life stages and different organs of adult male and female fish, using a targeted proteomics approach. The established multiple reaction monitoring-based assays enable the measurement of the relative abundance of specific GST isoenzymes and GST classes in zebrafish through a combination of proteotypic peptides and peptides shared within the same class. GSTs of the classes alpha, mu, pi and rho are expressed in zebrafish embryo as early as 4 h postfertilization (hpf). The majority of GST enzymes are present at 72 hpf followed by a continuous increase in expression thereafter. In adult zebrafish, GST expression is organ dependent, with most of the GST classes showing the highest expression in the liver. The expression of a wide range of cytosolic GST isoenzymes and classes in zebrafish early life stages and adulthood supports the use of zebrafish as a model organism in chemical-related investigations.

The United Nations' Sustainable Development Goals have been established to end poverty, protect the planet, and ensure prosperity for all. Delivery of the Sustainable Development Goals will require a healthy and productive environment. An understanding of the impacts of chemicals which can negatively impact environmental health is therefore essential to the delivery of the Sustainable Development Goals. However, current research on and regulation of chemicals in the environment tend to take a simplistic view and do not account for the complexity of the real world, which inhibits the way we manage chemicals. There is therefore an urgent need for a step change in the way we study and communicate the impacts and control of chemicals in the natural environment. To do this requires the major research questions to be identified so that resources are focused on questions that really matter. We present the findings of a horizon‐scanning exercise to identify research priorities of the European environmental science community around chemicals in the environment. Using the key questions approach, we identified 22 questions of priority. These questions covered overarching questions about which chemicals we should be most concerned about and where, impacts of global megatrends, protection goals, and sustainability of chemicals; the development and parameterization of assessment and management frameworks; and mechanisms to maximize the impact of the research. The research questions identified provide a first‐step in the path forward for the research, regulatory, and business communities to better assess and manage chemicals in the natural environment.