The gradual build up of political and societal pressures over the past few decades has led to a considerable momentum for moving away from animal testing for chemical risk assessments towards alternative non-animal methods (NAMs). However, despite a lot of progress made in this field, the true potential of NAMs to replace animal tests has yet to be realised. This is because of the structure and practice of the current risk assessment paradigm, and the uncertainties and lack of standardised frameworks for 'weighting' NAMs data when integrating to the overall weight of evidence for use in risk assessment. This Editorial highlights the key issues to focus attention in regard to the mismatch between general expectations and true ranking of the data generated by NAMs for use in regulatory risk assessment of chemicals.

Under the European Cosmetic Regulation, safety assessments of cosmetics and their ingredients must be conducted without the use of animals. This regulatory requirement poses a number of challenges, as validated alternative methods are only available for some of the toxicological endpoints that are typically considered in standard human health risk assessments. Despite significant progress since the ban in 2013, particularly in the development of New Approach Methodologies (NAMs) for local and acute toxicity, and for mutagenicity/genotoxicity, there remains an urgent need for non-animal test methods to assess systemic toxicity, which often becomes evident after repeated or long-term exposure. Currently, no validated animal-free alternatives are available for assessing sub-acute, sub-chronic and chronic toxicity, carcinogenicity, developmental/reproductive toxicity, or for a major part of toxicokinetics. In response to these challenges, the Methodology Working Group of the Scientific Committee on Consumer Safety organised a dedicated workshop in December 2024 to discuss advances in the application of Next Generation Risk Assessment (NGRA) as a strategic animal-free approach for the safety assessment of cosmetic ingredients. The workshop focused on a number of important key issues for the practical application of NAMs and NGRA, their regulatory acceptance and identification of possible (partial) solutions to overcome existing limitations.

New Approach Methodologies (NAMs) are increasingly used across industrial sectors to assess chemicals for endocrine activity and support endocrine disruption assessment. The European Partnership for Alternative Approaches to Animal Testing (EPAA) conducted a strategic, cross-sector review of NAM-based frameworks within the EU regulatory context to capture lessons learned, identify scientific gaps, and explore opportunities for collaboration. A key challenge is that most current in vitro NAMs cannot, by design, demonstrate endocrine-mediated adversity in an intact organism. Because evidence of adversity is required to define an endocrine disruptor, this limits the ability of NAMs to replace animal-based endocrine disruptor tests unless clear links between endocrine activity and adverse outcomes are established. Refocusing adverse outcome pathways (AOPs) on improving the predictive capacity of endocrine activity assays, rather than directly demonstrating adversity, could enhance NAM development and application. Additional gaps include limited information on internal exposure, the role of potency, and adequate coverage of sensitive life stages—an issue relevant to both NAMs and in vivo studies. Building regulatory trust in existing and emerging in vitro and in silico methods is essential and will require agreement on acceptable levels of uncertainty and confidence that NAM-based predictions are equivalent to or better than current approaches. Developing robust validation frameworks, enabling cross-sector data sharing, and strengthening dialogue among regulators, academia, and industry are critical to accelerating the regulatory integration of NAMs in endocrine disruption assessment.

Read-across is a method used in chemical risk assessment to predict the toxicological properties of a target substance by using data from structurally and mechanistically similar substances, known as source substances. EFSA's Scientific Committee has developed an approach for using read-across in food and feed risk assessment. This method provides a step-by-step guide to applying read-across as part of a weight-of-evidence evaluation for individual substances. It includes an explanation of the key aspects to consider at each step of the read-across workflow, i.e. problem formulation, target substance characterisation, source substance identification, source substance evaluation, data gap filling, uncertainty assessment, conclusion and reporting. It highlights the importance of clarity, impartiality and quality to derive transparent and reliable read-across conclusions. A particular emphasis is placed on the analysis of uncertainty and whether the overall uncertainty can be lowered to tolerable levels by using standardised approaches, and/or additional data from new approach methodologies (NAMs). The guidance outlines methods to integrate data from NAMs to support read-across in the relevant steps, improving the robustness of the assessment. The ultimate goal is to equip risk assessors and applicants with a comprehensive framework to carry out read-across assessments systematically and transparently, thereby supporting the safety evaluation of chemicals in the food and feed chain.

•BZP-4 is safe when used as UV filter up to a max. conc. of 5 % in sunscreen, all leave-on products (tot. dermal aggregate).•BZP-4 is safe when used as UV filter up to a max. conc. of 5 % in sunscreen, all rinse-off products (tot. dermal aggregate).•Same for lipstick, sunscreen propellant and pump spray (separately or in combination based on determ. aggregated exposure).•BZP-4 use as stabiliser when the product is exposed to light should remain within the conc. of. 5 %, incl. UV-filter use.•This assessment did not cover the safety of Benzophenone-4 for the environment.

[This corrects the article DOI: 10.1016/j.namjnl.2025.100035.].

•o-Phenylphenol (OPP) is safe when used as preservative up to a maximum concentration of 0.2 % in rinse-off cosmetic products.•o-Phenylphenol (OPP) is safe when used as preservative up to a maximum concentration of 0.15 % in leave-on cosmetic products.•Sodium o-Phenylphenate is safe when used as preservative up to a maximum concentration of 0.2 % in rinse-off cosmetic products.•Sodium o-Phenylphenate is safe when used as preservative up to a maximum concentration of 0.15 % in leave-on cosmetic products.•OPP and Sodium o-Phenylphenate, when used together, should not exceed the maximum concentration 0.15 % in leave-on cosmetic products.•OPP and Sodium o-Phenylphenate, when used together, should not exceed the maximum concentration 0.2 % in rinse-off cosmetic products.•Since this safety dossier related to dermally applied products only, the SCCS did not consider oral and inhalation routes.•This assessment did not cover the safety of O-Phenylphenol and Sodium o-Phenylphenate for the environment.

Growing restrictions and bans on animal testing for chemical safety assessment under different regulations have led to an increasing use of alternative methods. Read-across is one of the major approaches used for this purpose, which relies on the identification of toxicological hazards of a data-poor or untested (target) chemical from data on other already-tested (source) similar chemicals. This requires the target substance to be first assigned to a group or category of ‘similar’ chemicals. The ‘similarity’ may be in terms of structural features alone, or in combination with certain rules that are based on mechanistic and/or toxicological aspects. In this regard, the OECD QSAR Toolbox - a major free-access in silico platform - is widely used to derive toxicity predictions for a range of (eco) toxicological endpoints. The Toolbox allows the user to identify a set of similar chemicals (analogues) by computational ‘profilers’ that incorporate different structural alerts, or a combination of structural alerts and physicochemical and/or toxicokinetic rules relevant to a specific toxicological endpoint. The overall aim of this study was to assess the performance of the in silico profilers provided in the OECD QSAR Toolbox for reliability for identifying chemical analogues for category formation in a number of high-quality databases on mutagenicity, carcinogenicity, and skin sensitisation. The study also aimed to identify the reasons for any limitations in the performance of the profilers, and propose ways to improve their overall accuracy. The results showed that whilst some structural alerts are fit-for-purpose as such within the acceptable limits, others need refinement or a consideration for their possible exclusion from the profiler. Such refinements are imperative for a reliable use of the profilers in read-across and grouping/categorisation for classification, labelling and risk assessment of chemicals.

Background: The risk assessment of small particles (including nanoparticles) in products used in the food chain in the EU falls within the remit of the European Food Safety Authority (EFSA) and has been under thorough sci-entific considerations for over a decade. Now that more experience is gained with evaluating novel foods, food contact materials, food/feed additives and pesticides, the outlines for regulatory safety assessments and data requirements are established. Scope and approach: This paper reviews the principles underlying safety testing of small particles, referring to two recently published EFSA guidance documents. Examples and observations from assessing existing materials are provided to facilitate to a wider readership adequate implementation of the regulatory requirements. Main findings and conclusions: The starting point for safety testing is the physicochemical characterisation of the pristine material, being an engineered nanomaterial, a nanostructured material or a conventional material that contains a fraction of small particles that may retain properties at the nanoscale. Key parameters and threshold values for establishing the presence of small particles, the techniques and methods for characteri-sation in complex matrices, as well as approaches for dietary exposure assessment are outlined. Where there is the likelihood of small particles remaining after gastrointestinal digestion, hazard identification and hazard characterisation are required with special provisions. In particular, certain nano-specific considerations are highlighted that have to be considered during toxicological testing with the aim to demonstrate consumer safety of products to be used in the food chain in Europe.