Establishing a NexGen, mechanism‐based environmental risk assessment paradigm shift: Are we ready yet?

Traditional (eco)toxicology has reached a tipping point, with the historical reliance on animal tests for assessing safety being rapidly superseded by the quest for alternative approaches that take advantage of the latest science. These new approaches offer a huge opportunity for increased relevance, biological coverage, and throughput to improve environmental and human health safety assessments, while in parallel addressing growing regulatory and societal calls for increased ethical considerations in the conduct of these assessments. Such public awareness is exemplified by over 1.2 million signatures on the European citizens' initiative (ECI) “Save Cruelty Free Cosmetics—Commit to a Europe Without Animal Testing” (Cruelty Free Europe, 2022; Cruelty Free International, 2023). This demonstration of a clear and strong ethical desire to move away from animal‐based testing has galvanized thinking on how to make best use of the latest scientific knowledge anchoring the development of new state‐of‐the‐art science‐based approaches to better inform both environmental and human safety decisions. Furthermore, designing products that society trusts, built upon scientific knowledge, is a key pillar of any relevant sustainable innovation program. It is, therefore, ever more important to keep evolving the science to facilitate safe decision‐making at pace to fully meet societal and economic needs. Recent developments in New Approach Methodologies, commonly referred to as NAMs, mean that non‐animal alternative options, including in chemico, in silico, and in vitro, are becoming readily available to support this change in paradigm (Carmichael et al., 2022). Nevertheless, there is a disconnect between scientific development and regulatory acceptance in some spaces. In actual fact, although the use of recent developments in NAMs has been recognized by the European Commission's Scientific Committee on Consumer Safety (2021), their permitted use within chemicals regulation is restricted. For instance, while the EU Chemicals Regulation (REACH) Annex XI lists several non‐animal‐based approaches as suitable alternatives, there is in practice limited evidence of their acceptance. In the context of the EU Green Deal, the Chemicals Strategy for Sustainability (CSS) sets further ambitious goals to transform the EU's economy for a more sustainable future by tackling chemical pollution across sources and product life‐cycles (European Commission, 2020). Under this scheme, the European Commission is proposing the revision of REACH requirements; introduction of new hazard classes in the regulation on Classification, Labeling, and Packaging of chemicals; and a new framework for the development of chemicals that are safe and sustainable by design (Caldeira et al., 2022). Yet, full implementation of this agenda is very reliant on data availability or generation to fill its requirements. The need to reduce the reliance on animal testing is highlighted as an intrinsic element of the EU CSS, alongside the need to improve the quality, efficiency, and speed of chemical safety assessments. However, if the CSS is implemented within its present hazard‐focused regulatory frameworks, it will lead to an increase in the number of animal tests being required, as pointed out by academics, industry bodies, non‐governamental organizations, and the European Parliament (Barile et al., 2021; Bridges et al., 2023; Cruelty Free Europe & CEFIC, 2021; Euractiv, 2020), with potentially limited environmental and human health quality gains. It becomes evident that to avoid this dichotomy, the transition to a new way of ensuring chemical safety in the environment requires scientists, eco‐toxicologists, risk assessors, regulators, and policy makers to embrace an