- Evaluation of a high-throughput in-vitro-to-in-vivo extrapolation (IVIVE) workflow for the prioritization of potential developmental toxicity of chemicals
Linakis et al. - From cellular perturbation to probabilistic risk assessments
Maertens et al. - Determination of U-SENS™ borderline range thresholds to address uncertainty for skin sensitization assessment in a regulatory context
Nardelli et al.
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Editorial
Dear readers,
In an Open Letter published in parallel across various European toxicology journals, including ALTEX, the respective editors-in-chief jointly voice their concerns about the impact of recently announced changes at U.S. governmental institutes and warn of their implications for public health and environmental protection in the U.S. and beyond.
Thomas Hartung and Lena Smirnova give us Food for Thought … on the transformative potential of microphysiological systems (MPS) in drug development and personalized medicine. They discuss the challenges of MPS standardization, validation, and regulatory integration, and propose solutions for the path forward.
In their 3rd t4 Workshop Report, Uwe Marx and colleagues assess developments and trends in the field of MPS in academia, industry, and the regulatory environment over the past five years. They review to what extent their previous recommendations have been implemented and update their long-term roadmap towards overcoming barriers to trust and acceptance of MPS-derived data.
A review by Shekh Rahman et al. explores potential applications of liver, gut, lung and heart microphysiological systems in drug development and discusses challenges and approaches towards harnessing them to augment the predictivity and reliability of nonclinical testing.
Laure-Alix Clerbaux argues for organizing evidence on detrimental effects of food additives on gut microbiota and their consequences to human health outcomes into adverse outcome pathways. This would provide a basis for human-based tests to be developed for the safety assessment of food additives.
The GARDskin Dose-Response assay is a quantitative in vitro test for skin sensitization potency intended to determine safe concentrations of ingredients for use in consumer products. Isabelle Lee et al. explore how well the test predicts the sensitization potency category of a set of one hundred fragrance ingredients in comparison to historical data from the mouse local lymph node assay.
Three in vitro approaches covering different mechanisms are used by Laure Asselin et al. to assess the potential effects of ten chemicals on thyroid hormone regulation and to identify possible differences between the human and the rat system. The assay is proposed to identify endocrine-disrupting chemicals ahead of testing them in animal experiments.
Bernard Staumont et al. introduce the concept of physiological maps to visually represent biological processes and interactions within organs and cells. This systems biology approach could complement new approach methodologies, including adverse outcome pathways, by providing a better understanding of the relevant biological mechanisms.
Eike Cöllen et al. develop the results of a brainstorming session at the DNT5 meeting into a strategy towards implementing the DNT-IVB, a set of in vitro tests that assess developmental neurotoxicity concern, in a regulatory context. This includes how to combine DNT-IVB results with other toxicity data or with signaling assay results, how the tests can be applied as soon as possible, what the decision framework could look like, and how validation of the DNT-IVB can be achieved.
The DNT5 meeting and its outcomes are summarized in an extensive Conference Report by Ivana Celardo et al. The report covers the application and further development of the DNT-IVB and the potential contributions of embryonic zebrafish tests, computational approaches, and brain organoids. It is complemented by Thomas Hartung’s after-dinner speech “Devil-mental neurotoxicity”.
Meeting Reports on work towards a global education hub for animal-free innovation, the SCAHT AOP_HUB to support AOP development, efforts towards adopting new approach methodologies in Argentina, and applications of new approach methodologies in ecotoxicology and the Corners complete this issue of ALTEX.
Be sure to consult our website for current international 3Rs-related news and upcoming events such as the 4th MPS World Summit in Brussels and the 13th World Congress on Alternatives and Animal Use in the Life Sciences in Rio de Janeiro.
Sonja von Aulock
Editor-in-chief