Abstract Environmental Threshold Concentrations (ETCs), such as the Predicted No Effect Concentrations (PNECs) and European Environmental Quality Standards (EQSs), represent the concentration of a chemical in an environmental compartment at or below which no adverse effects are expected. While multiple ETCs may exist for a given substance across regulatory frameworks and scientific literature, selecting the most useful value can be challenging. Even when only one ETC exists, its usefulness must be evaluated. This paper addresses this challenge by providing a systematic and stepwise framework for selecting and interpreting ETCs, with a focus on human pharmaceuticals and European regulatory frameworks. However, the ideas behind this may be applied more broadly. The proposed approach begins by defining the context of the assessment and the associated protection goals. It then requires a systematic evaluation of all available ETCs, regarding their relevance and reliability. This includes the use of the most appropriate methodology and underlying data, as well as newly published information. It also considers overall uncertainties, the need to address chronic or short-term peak exposures, and whether the ETCs have been independently reviewed. We apply the framework to metoprolol to demonstrate its usefulness in ensuring that ETCs used in environmental assessments and management decisions are robust and fit for purpose.

Novel entities are diverse and complex; hence, defining their Planetary Boundary through control variables, indicators, and acceptable limits is challenging. Here, we highlight shortcomings of the current quantitative boundary, which applies a purely precautionary interpretation of safety that defines the safe operating space as zero novel entities that are not fully characterized. In practice, the zero limit is unattainable and undesirable for human societies that rely on services provided by novel entities. Furthermore, it is not operational within the framework of other boundaries, which have risk-based thresholds. We therefore propose a reboot of the Planetary Boundary for Novel Entities and recommend governance and monitoring strategies based on: (a) clarification of the "safe operating space" for novel entities, distinguishing pure precaution ("safe from the unknown") from operational precaution that tolerates a workable, non-zero level of uncertainty; (b) complementary, multilayer control variables spanning pressures, states, and impacts; (c) extensions to existing monitoring systems to provide quantitative indicators of distribution, accumulation, exposure, and impacts for subsets of novel entities to communicate the status and trends of stress from novel entities on the Earth system; and (d) recognition of regulatory and policy-related success stories that illustrate comprehensive, protective, and operational governance of novel entities.

The One Health concept strongly brings into focus the important connections for human and ecosystem health. However, the incorporation of behavior method guidelines in risk assessment and regulation/policy is not equal between human and ecological disciplines. A survey was conducted on the perceptions and role of behavioral (eco)toxicology in the protection of human and ecosystem health. Those surveyed include scientists working in the field of environmental toxicology and behavioral ecology, representing industry, government, nongovernment organizations, and academia/research centers. The respondents (N = 166) agreed that contaminants "can impact" and "are impacting" wildlife (97% and 77%) and humans (84% and 62%, respectively). Overall respondents believed behavioral experiments to be repeatable (60%), reliable (61%), and relevant (84%), although those not studying behavior (43%) were more cautious in their answers. Respondents were more likely to be neutral when asked whether behavioral endpoints are more sensitive (43%), but they agreed (80%) that behavioral endpoints provide important alternative information to standard endpoints. The largest group disagreed (42%) with the statement that behavioral endpoints are currently used in risk assessment but agreed that they were essential (55%). The majority of respondents disagreed (63%) that we understood the risks of contaminants to human and ecosystem health, but they agreed (68%) that regulatory authorities should consider behavioral endpoints. When answers were compared among sectors (academia, government, or industry), industry scientists were more likely to be negative or neutral in their responses to the application of behavioral toxicology. We discuss how these data could be used to support our understanding of and confidence in the effects of contaminants on human and ecosystem health.

The United Nations Outer Space Treaty states that the exploration of celestial bodies must avoid "harmful contamination" which may impede scientific exploration by other parties to the treaty. To guide treaty compliance, Planetary Protection regulations promulgated by the Committee on Space Research set limits for microbial contamination of celestial bodies, particularly those that may harbor extant life (e.g., Mars). However, anthropogenically introduced chemicals and materials are not regulated but may cause "harmful contamination" and thus pose a potential threat to scientific exploration. On Earth, threats from anthropogenic chemicals and materials are often managed by considering both potential exposure to the substances and their hazardous properties. The lack of knowledge around hazards to possible extant life on Mars means that chemicals and materials should be designed and used so that their exposure concentrations are minimized. Here, we review possible emission, partitioning, persistence, and transport processes on Mars for anthropogenically introduced chemicals and materials and identify key knowledge gaps. We highlight difficulties and lessons learned from pollution policy development on Earth that could inform interplanetary chemical and material management. This work aims to support the expansion of the Planetary Protection guidelines to include a "No- or Low-Exposure by Design" approach to chemicals and materials on Mars.

Revision of the REACH chemical regulation should enable more realistic understanding and management.

Today’s production and consumption are increasingly overusing and polluting natural resources. In response, actors globally are developing circular economy strategies to use resources such as materials and products in a sustainable way. An important but often neglected part of the circular economy is hazardous chemicals. These are part of everyday products and when recycled they become part of the resource cycle. This paper discusses the management of circular non-toxic supply chains, focusing on goal conflicts and synergies in policy and regulation, issues of transparency and traceability in supply chains, and difficult trade-offs and knowledge gaps regarding circularity and end-of-life. The exploratory study builds on semi-structured interviews and reference group discussions with respondents from the chemicals management and circular economy sectors. The results show that the transition to a circular non-toxic economy is impeded by insufficient legislation, policy incoherence and low supply chain transparency and traceability. This leads to the circulation of hazardous chemicals in materials and products, including legacy chemicals, significantly increasing consumer and environmental exposure. The findings illustrate how designing products and materials to be non-toxic from the start creates synergies and opportunities for a sustainable use of resources and how a hazard-based approach to risk management promotes circularity and safer consumer products. It also identifies relevant management and policy steps to achieve a circular, non-toxic economy as part of the transition to a society that meets today’s environmental and resource challenges.

Chemicals in the EU are mainly regulated based on their intended use. Each legal framework consists of requirements and guidance for hazard- and risk assessment, along with the associated decision processes e.g., registration or authorisation of chemicals for market access in the EU. As a single chemical may have multiple uses, it may be assessed under more than one framework, potentially leading to different assessment outcomes. To address this, the European Commission has introduced the 'one substance, one assessment' approach as part of the Chemicals Strategy for Sustainability. The aims of the approach include streamlining risk assessment processes and reducing duplication of work in assessing the same chemical. This study aimed to map the scope of chemicals subject to assessment in multiple legal frameworks and to illustrate the importance of coordination and communication in chemical assessment processes. This was achieved by identifying chemicals that are either registered or have received specific approval for the EU market, and analysing their presence in different legal frameworks. Our findings showed that almost one-tenth of the substances identified were listed under more than one framework. However, there was a notable lack of coherent chemical identifiers available to accurately identify chemicals across the frameworks. Additionally, we identified the presence of phthalates, bisphenols and PFAS in EU frameworks to illustrate how a group-based approach to chemical assessment could be applied across different legal frameworks.

This article provides a qualitative analysis of stakeholder perspectives on the European Commission’s revision of the REACH Regulation, highlighting how these perspectives reveal deeper epistemic and normative tensions in EU risk governance. Beyond summarising stakeholder positions, the paper offers an interpretive reading of how the precautionary principle is invoked to justify competing approaches to scientific uncertainty, risk assessment, and regulatory simplification. The analysis identifies three cross-cutting themes—knowledge and precaution, risk versus hazard, and simplification versus improved protection—and discusses how these reflect divergent legal and epistemological visions of chemical safety in EU. By contextualising stakeholder reasoning within EU regulatory traditions, the study contributes to understanding how precaution continues to shape, and be contested within, contemporary EU chemicals governance.

A substantial body of evidence exists demonstrating that exposure to environmental contaminants can alter animal behavior. Moreover, methodological and technological advancements, as well as increasing standardization, mean that behavioral ecotoxicity studies are more rigorous and reliable than ever before. Despite this, behavioral data are still seldom used in the risk assessment and regulation of chemicals. This is partly due to a lack of clarity among some stakeholders about whether changes in behavior at the individual level result in population-level outcomes. To address this, we first consider the state of evidence within the field of behavioral ecotoxicology linking individual-level behavioral alterations with population-level consequences. We then assess the evidence from behavioral ecology and other neighboring fields that supports this link. Further, we evaluate whether some behavioral endpoints are more easily tied to population-level changes than others. In this regard, we propose combining insights from two complementary ecological frameworks─the functional trait framework and the limiting traits framework─to evaluate which behaviors should be prioritized in ecotoxicological research and regulatory efforts. We contend that the link between behavioral changes and population-level outcomes is evident, with behavioral endpoints representing a highly valuable yet so far underutilized line of evidence in applied environmental protection.

The EU recently introduced four new hazard classes to the Classification, Labelling and Packaging Regulation (CLP) (EC) 1272/2008. The classes are endocrine disruption for human health (ED HH) and the environment (ED ENV), persistent, bioaccumulative and toxic (PBT) or very persistent and very bioaccumulative (vPvB), and persistent, mobile and toxic (PMT) or very persistent and very mobile (vPvM). This action was a direct consequence of the EU’s Chemicals Strategy for Sustainability, which aims at strengthening the protection of human health and the environment, as well as reinforcing the CLP Regulation as the central piece of the chemicals legislation. This study examined the regulatory obligations triggered by these new hazard classes, as well as the existing obligations for endocrine disrupters and PBT/vPvB substances identified in other EU regulations. In addition, we compared the CLP criteria for endocrine disruption and PBT/vPvB to criteria existing in other EU regulations and investigated how these criteria are used in the EU chemicals legislation. We found that the implementation of the new hazard classes under the CLP into existing EU chemicals legislation will require the revision of all regulations that rely on the CLP hazard criteria for risk management. Without revision, the immediate impact of the new hazard classes will only extend to six regulations and the regulatory obligations they contain, all of which apply to substances classified under any of the CLP hazard classes. Meanwhile, substances with endocrine disrupting and PBT/vPvB properties are already being identified and regulated using criteria from regulations other than the CLP. When comparing the criteria for identification of endocrine disrupters and PBT/vPvB substances across the chemicals legislation, we found that the criteria differed between regulations. The findings aim to support the efficient implementation of the new CLP hazard classes and harmonization of criteria across regulations, in line with the Chemicals Strategy for Sustainability.

This work presents a case study in applying a systematic review framework (SYRINA) to the identification of chemicals as endocrine disruptors. The suitability and performance of the framework is tested with regard to the widely accepted World Health Organization definition of an endocrine disruptor (ED). The endocrine disrupting potential of triphenyl phosphate (TPP), a well-studied flame retardant reported to exhibit various endocrine related effects was assessed. We followed the 7 steps of the SYRINA framework, articulating the research objective via Populations, Exposures, Comparators, Outcomes (PECO) statements, performed literature search and screening, conducted study evaluation, performed data extraction and summarized and integrated the evidence. Overall, 66 studies, consisting of in vivo, in vitro and epidemiological data, were included. We concluded that triphenyl phosphate could be identified as an ED based on metabolic disruption and reproductive function. We found that the tools used in this case study and the optimizations performed on the framework were suitable to assess properties of EDs. A number of challenges and areas for methodological development in systematic appraisal of evidence relating to endocrine disrupting potential were identified; significant time and effort were needed for the analysis of in vitro mechanistic data in this case study, thus increasing the workload and time needed to perform the systematic review process. Further research and development of this framework with regards to grey literature (non-peer-reviewed literature) search, harmonization of study evaluation methods, more consistent evidence integration approaches and a pre-defined method to assess links between adverse effect and endocrine activity are recommended. It would also be advantageous to conduct more case studies for a chemical with less data than TPP.

The CLP mandates manufacturers and importers to classify substances and mixtures according to hazard criteria, with notifications submitted to the European Chemicals Agency (ECHA). Substances meeting hazard criteria must be appropriately labelled and packaged to communicate hazards effectively. The CLP establishes hazard classification criteria but does not independently prohibit or restrict the use of hazardous chemicals. Instead, it serves as a basis for regulatory obligations in other specific regulations. This study investigates the regulatory implications of meeting hazard criteria under the CLP across EU regulations and directives listed in EU Chemicals Legislation Finder (EUCLEF). The results show that fulfilling criteria for human health hazard classes trigger regulatory obligations in the highest number of regulations/directives, with carcinogenicity, mutagenicity, and reproductive toxicity (CMR) leading to obligations in 19 of 20 pieces of legislation linked to the CLP. Conversely, physical, environmental, and ozone layer hazards are associated with fewer regulations and directives, and lead to fewer prohibitions. The study underscores the pivotal role of the CLP in EU chemical legislation and the need for coherence and consistency across regulations. While regulatory obligations are primarily aimed at substances meeting hazard criteria, the variability in self-classification notifications and limitations in harmonized classification processes were observed. Moreover, the complexity of the regulatory structure poses challenges for stakeholders and policymakers, including inconsistencies, compliance difficulties, and the need for frequent revisions. Addressing these challenges is critical for enhancing regulatory effectiveness and ensuring a more coherent and harmonized approach to chemical management in the EU.