Dear readers,

A new year always carries the promise of new challenges and experiences. The ALTEX Events page is already filling up with webinars and meetings, especially the MPS World Summit in Brussels on June 9 - 13 and the World Congress on Alternatives and Animal Use in the Life Sciences in Rio de Janeiro on August 31 - September 4. Make sure to submit your abstracts for your opportunity to share your achievements and connect with the 3Rs community.

In this issue’s Food for Thought …, Thomas Hartung and Nicole Kleinstreuer outline their vision of artificial intelligence-based new approach methods for chemical safety testing. They discuss the challenges of validating such AI-based methods, especially ensuring data quality and that decisions are understandable and transparent, and the benefits ongoing monitoring and refinement of such methods will have. AI can be harnessed to expedite validation, but stakeholders must work together to ensure it is reliable and trustworthy.

In Europe, the safety information on chemicals that must be submitted to the European Chemicals Agency (ECHA) depends on the amount of chemical produced or imported. If such information is not already available and it cannot be obtained with a guideline non-animal method, registrants can propose filling the data gap by extrapolating information from similar substances instead of performing the standard animal test. Hannah Roe et al. investigate how successful such read-across proposals have been in the past 15 years, what arguments accepted or rejected proposals contain, and what arguments are made by ECHA to support decisions on proposals. This information can guide companies in building better read-across justifications and avoiding animal testing.

Acute systemic toxicity testing is employed to determine the dose of a chemical that results in the death of 50% of test animals. Thomas Ward and colleagues challenge an animal-free test method (AcutoX), which includes a function that mimics liver metabolism, with a set of 67 test chemicals that that were previously tested in animals. They report that AcutoX predicts the correct or a higher EPA or GHS hazard category in 90 or 93% of cases, respectively.

Although the bioavailability of parenteral drugs is extensively tested, we often do not know how well non-pharmaceuticals are absorbed from the gut after oral exposure. Gregory Honda and colleagues test gut absorption for 400 chemicals using a human cell-based assay and use their results and other available data to develop a machine learning model to predict this property. Both models predict human bioavailability better than previous animal tests, suggesting that such data can be used to prioritize chemicals for more extensive risk assessment.

Replacing the Draize eye test with defined approaches, which are based on fixed combinations of non-animal OECD guideline tests, is a major recent achievement in the 3Rs field. A new defined approach specifically for surfactants was recently published as an OECD case study. Nathalie Alépée et al. show that the new defined approach reliably predicts the eye irritation potential of 50 surfactants, but that there is currently not sufficient data available to assess whether other combinations of OECD guideline tests could do so as well.

Exposure to chemicals that affect the hormone system in a human fetus may disturb its brain development. Andrea Cediel-Ulloa et al. propose a cell-based test system to identify such endocrine disruptors that cause developmental neurotoxicity without the use of animals. They show proof of principle that some hormones and their antagonists affect the length and branching of neurites during the maturation of a mouse nerve cell line, indicating that this test system may be suitable to identify chemicals that affect the hormone system during development.

In their Concept Article, Anne Kienhuis and colleagues introduce the Virtual Human Platform for Safety Assessment (VHP4Safety) project and call on interested parties to collaborate in building this platform to shape the transition to safety assessment of drugs and chemicals without animal testing.

Susan Debad and colleagues report on a workshop hosted by US FDA on the transition of developmental neurotoxicity testing (DNT) from animal methods to new approach methods. The state of the science as well as ongoing challenges and critical next steps are discussed in the form of presentations and panel discussions.

In their BenchMarks contribution, Cathalijn Leenaars and colleagues compare four software tools used for systematic review and advise which is suitable in which scenario. In a second BenchMarks contribution, Jonathan Blum et al. explore the different data layers and data processing steps required to turn raw measurement values into NAM-based information and explain the importance of careful data management and the potential impact of modifying set data processing procedures.

Meeting Reports, a Book Review and the Corners fill you in on recent activities in the 3Rs field.

Wishing all our readers an inspiring 2025,

Sonja von Aulock
Editor-in-chief