NAM journal最新文献

{"title":"Awareness and perspectives of translational assessment tools in preclinical research: insights from a survey.","authors":"Francesca Pistollato, Ignacio J Tripodi, Fabia Furtmann, Marco Straccia, Helder Constantino","doi":"10.1016/j.namjnl.2026.100146","DOIUrl":"https://doi.org/10.1016/j.namjnl.2026.100146","url":null,"abstract":"<p><p>Insufficient translation of preclinical findings into clinical benefit continues to undermine drug development, contributing to high attrition rates and avoidable ethical and economic costs. In response, a range of tools and frameworks has emerged to support structured evaluation of translational relevance, including assessment of animal model performance, study validity, bias and harm-benefit considerations. How widely these approaches are recognised and applied in practice remains poorly understood. To address this gap, the Biomedical Research for the 21st Century (BioMed21) Collaboration conducted an exploratory online survey targeting key preclinical research stakeholders across different countries and professional backgrounds. The survey collected responses from 105 self-selected participants across academia, industry, governmental and public institutions, and other organisations, focusing on awareness of existing tools, perceived value and obstacles to their implementation. While respondents overwhelmingly acknowledged the importance of structured assessment approaches, familiarity with the available tools and frameworks was limited, with more than one-third-reporting no prior exposure. Perceived barriers to broader adoption included insufficient standardisation and reproducibility, limited availability of robust comparative human data, uncertainty regarding the validity of assessment outcomes and reliance on subjective expert opinion. Despite these challenges, participants recognised the potential of such tools to support more informed model selection, improve preclinical decision-making and increase research robustness. Relevance to human biology emerged as a particularly important criterion for evaluating translational value. Building on these findings, we discuss potential future strategies to improve accessibility and application of translational assessment frameworks, and support more human-relevant biomedical research.</p>","PeriodicalId":520522,"journal":{"name":"NAM journal","volume":"2 ","pages":"100146"},"PeriodicalIF":0.0,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13696333/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149280594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Understanding the relationship between percentage and actual amount absorbed in topical formulations under finite and infinite dose scenarios.","authors":"Sébastien Grégoire, Clive Roper","doi":"10.1016/j.namjnl.2026.100143","DOIUrl":"https://doi.org/10.1016/j.namjnl.2026.100143","url":null,"abstract":"<p><p>Risk assessment is the product of hazard and exposure. The exposure itself is the product of two components: the percent absorbed and the applied dose. For a topical application, the absorbed dose includes the fraction of a chemical able to enter the skin. It can be expressed in different units, <i>i.e.</i>, amount absorbed per exposure area, and percentage absorbed. The way it is expressed is related to the protocol used and the context of use. The applied dose for a topical product depends on two factors, <i>i.e.</i>, the amount of formulation applied and the concentration of the chemical in the formulation. Calculation of the applied dose is generally well understood. A common misconception in dermal risk assessment is that percent absorbed remains constant across different exposure conditions. The purpose of this review article is to demonstrate that this assumption is not universally valid. The implications of expressing absorption using different units are discussed, together with their impact on chemical risk assessment outcomes.</p>","PeriodicalId":520522,"journal":{"name":"NAM journal","volume":"2 ","pages":"100143"},"PeriodicalIF":0.0,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13691562/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149280612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Critical appraisal of the european commission roadmap towards phasing out animal testing: navigating sociotechnical barriers to the regulatory acceptance of NAMs.","authors":"Aleksandra Čavoški, Laura Holden, Robert G Lee","doi":"10.1016/j.namjnl.2026.100145","DOIUrl":"https://doi.org/10.1016/j.namjnl.2026.100145","url":null,"abstract":"<p><p>The gradual rate of phasing out animal use in regulatory testing has been attracting greater attention from policy makers, the scientific community, and industry. In this paper we analyse the extent to which the strategic 'Roadmap Towards Phasing Out Animal Testing for Chemical Safety Assessments' of the European Commission is able to address sociotechnical barriers that have thus far hindered the greater regulatory acceptance of NAMs, including: the lack of consensus when applying scientific developments to value-laden risk assessments that have inherent uncertainties; the lack of stakeholder participation; regulatory culture; and routes to assurance. The roadmap is predominantly focused on the technical aspects of the transition, leaving the social nature of barriers to be addressed in greater detail in the implementation phase. A review of legal frameworks underpinning the roadmap identifies that more extensive statutory interpretation, particularly regarding the use of Weight-of-Evidence, would aid regulatory acceptance of NAMs. The paper critiques the short-, mid-, and long-term actions of the roadmap, and notes the absence of consideration of the EU judicial system, which plays an important role in providing interpretation to EU chemical law and its enforcement, in particular the obligation to use animal testing as a last resort. Although setting a clear final intention, this paper notes that with the longer-term goal to replace the use of non-protected life stages and invertebrates, and without hard milestone dates by which to indicate progress, the roadmap as a strategy is only able to provide limited clarity that NAM innovators and investors seek.</p>","PeriodicalId":520522,"journal":{"name":"NAM journal","volume":"2 ","pages":"100145"},"PeriodicalIF":0.0,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13694723/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149280600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"On the relevance of genomic approaches to hazard assessment of functionalized nanomaterials in the NAM framework.","authors":"Giulia Motta, Barbara Torsello, Maurizio Gualtieri, Rossella Bengalli, Ilaria Zanoni, Maria Foti, Paride Mantecca","doi":"10.1016/j.namjnl.2026.100144","DOIUrl":"10.1016/j.namjnl.2026.100144","url":null,"abstract":"<p><p>New approach methodologies (NAMs) are changing the ways by which alternative toxicology, in vitro mainly, is approaching the evaluation of hazard of novel materials or compounds. Engineered nanoparticles (NPs) are a typical class of compounds where NAMs found an important area of application. The number of novel NPs and NPs-based products are increasing at a pace that classical in vivo toxicology has difficult to keep. NAMs on the other hand are faster and may provide more human relevant outcomes. According to the Safe and Sustainable by design (SSbD) framework, we report here the comparison of silver NPs (AgNPs) with different functionalization (naked, with curcumin or with hydroxyethyl cellulose). A lung in vitro model (A549 cells with THP-1-derived macrophages) is exposed with a NAM at the air-liquid interface (ALI). The outcomes are explored with a genomic approach followed by RT-PCR. The results show the relevance of combining two de facto NAM to obtain data relevant to human expected exposure and to mine the plethora of hazard information in vitro model can provide. The combination of these approaches should be considered as a reference approach also to pave the road for regulatory acceptance.</p>","PeriodicalId":520522,"journal":{"name":"NAM journal","volume":"2 ","pages":"100144"},"PeriodicalIF":0.0,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13683860/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149240902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Static or microfluidic? A comparative pilot study of an <i>in vivo-in vitro</i> validated human iPSC-derived blood-brain barrier model for neurotoxicity hazard assessment.","authors":"Paul Kurtenbach, Maria Hahn, Mario Thevis, Marc Lamshöft","doi":"10.1016/j.namjnl.2026.100142","DOIUrl":"10.1016/j.namjnl.2026.100142","url":null,"abstract":"<p><p>Blood-brain barrier (BBB) permeation determines human brain exposure to chemicals and is therefore a prerequisite for neurotoxicity. However, the lack of toxicokinetic BBB models remains a critical uncertainty in regulatory <i>in vitro</i> risk assessment, which was highlighted in the new EU roadmap towards phasing out animal testing. Human induced pluripotent stem cell (hiPSC)-derived BBB models combined with clinical positron emission tomography (PET) data provide translational benchmarks for evaluating whether <i>in vitro</i> permeability data predict human brain exposure. Microphysiological systems (MPS) may better emulate physiological flow than static transwell® systems. Nonetheless, it remains unclear whether additional complexity introduced by flow improves fitness-for-purpose, reproducibility, and regulatory utility of BBB new approach methodologies (NAMs). Therefore, we directly compared our static hiPSC-derived BBB model, which was previously validated with human clinical PET brain-penetration data, with its microfluidic counterpart to determine whether flow translates into measurable added value for human brain exposure assessment. The comparative pilot study demonstrated that microfluidic implementation of the static model was technically feasible and maintained key BBB functionality in terms of barrier integrity, efflux capacity, and permeability. However, the MPS displayed reduced <i>in vivo</i>-like barrier characteristics and lower brain-penetration predictive performance than the static counterpart within the tested compound set, which is relevant for regulatory neurotoxicity assessment. In addition, the static model offered advantages in standardization, robustness, and throughput that are important for future regulatory implementation. Finally, this study identified technical limitations of the selected microfluidic transwell®-in-chip implementation that may guide the future development of standardized, commercially available BBB systems.</p>","PeriodicalId":520522,"journal":{"name":"NAM journal","volume":"2 ","pages":"100142"},"PeriodicalIF":0.0,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13683853/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149240893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Current knowledge of xenobiotic metabolism in the skin, associated <i>in vitro</i> and in silico models and their application to Next Generation Risk Assessments.","authors":"Nazanin Golbamaki, Sebastien Gregoire, Nicola J Hewitt, Daniela Lange, Ans Punt, Sandrine Spriggs, Sara Sepehri, Nadia Heramvand, Andreea Cuciureanu, Dave Allen, Abdulkarim Najjar","doi":"10.1016/j.namjnl.2026.100141","DOIUrl":"10.1016/j.namjnl.2026.100141","url":null,"abstract":"<p><p>In Next Generation Risk Assessments (NGRAs) of cosmetic ingredients, evaluations of systemic exposure after topical application range from conservative screening estimates to higher tier kinetic models. The latter need robust and predictive <i>in silico</i> and <i>in vitro</i> skin absorption and metabolism models to ensure regulatory confidence. This review provides an update on skin xenobiotic metabolizing enzymes (XMEs) and <i>in vitro</i> skin metabolism models of varying complexities. It is intended primarily for safety assessors and study planners who need to select and interpret skin-metabolism NGRA approaches for cosmetic ingredients. Qualitative information helps to inform subsequent tiers of the NGRA workflow by identifying potential reactive intermediates, while structural and SAR information helps assess bioactivation and detoxification pathways. Quantitative data should be of good quality, correctly interpreted and extrapolated to <i>in vivo</i> using appropriate equations and scaling factors to provide a relevant indication of first-pass skin metabolism. This can be influenced by access to XMEs, extrinsic and intrinsic factors. Challenges and open questions remain regarding standardized metabolism assays and related guidelines, as well as the development of <i>in silico</i> models to predict skin metabolites and skin bioavailability for integration into Physiologically Based Kinetic (PBK) models. Despite advances in technologies, efforts are still needed to improve our understanding of skin XMEs and their location, and to develop suitable models to predict and measure metabolic pathways. There are increasing efforts to integrate skin metabolism data into PBK models for dermal exposure. Further research into skin metabolism is needed for NGRAs of topically applied cosmetic ingredients.</p>","PeriodicalId":520522,"journal":{"name":"NAM journal","volume":"2 ","pages":"100141"},"PeriodicalIF":0.0,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13677243/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149220818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Technical challenges of testing polymer materials in OECD test guideline methods addressing effects on human health, biotic systems and analytics.","authors":"Susanne N Kolle, Friederike Lünne, Denis Botin, Nora Melchin, Naveed Honarvar, Simon Lüderwald, Dorothee Funk-Weyer, David Schaffert, Robert Landsiedel","doi":"10.1016/j.namjnl.2026.100140","DOIUrl":"10.1016/j.namjnl.2026.100140","url":null,"abstract":"<p><p>Polymers are substances composed of molecules containing repeating monomer units and exhibiting a distribution of molecular weights due to differences in chain length. This inherent heterogeneity distinguishes them from discrete molecules and may complicate the application and interpretation of standardized hazard assessment procedures. Polymers have been exempt from REACH registration since its inception. While a formal revision of the REACH Regulation is currently no longer anticipated, discussions on introducing additional information requirements for certain polymers remain ongoing through implementing measures and comitology processes. These may include analytical, ecotoxicological, and toxicological data. Standardized regulatory testing typically relies on OECD test guidelines (TGs), which were primarily developed for well-defined chemical substances. Their applicability to polymers, with their molecular weight distribution, heterogenous composition and often challenging physiochemical properties, remains uncertain. The present study evaluates the technical applicability of four guidelines (OECD TG 120 (solution/extraction behavior of polymers in water), OECD TG 202 (Daphnia sp. acute immobilization), OECD TG 439 (in vitro skin irritation using reconstructed human epidermis), and OECD TG 487 (in vitro mammalian cell micronucleus test)) to 17 polymer materials. Testing was conducted in water, cell-culture media, and at the air-liquid interface. Results show that TG 120's sample preparation methods were not universally applicable. TG 202 is generally suitable for water-soluble polymers, however, reactive and poorly soluble polymers present challenges. TG 487 is only applicable to water-soluble polymers, and TG 439 is technically broadly applicable if the test material is pipettable or spoon-applicable. Our findings highlight the limitations of current OECD TGs for polymers and emphasize the need for adapted, standardized methods. This work cautions against indiscriminate use of existing TGs tailored for small molecules and supports the development of polymer-specific testing strategies to ensure reliable and accurate regulatory evaluation.</p>","PeriodicalId":520522,"journal":{"name":"NAM journal","volume":"2 ","pages":"100140"},"PeriodicalIF":0.0,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13683867/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149240841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessing <i>in vitro</i> long-term liver metabolism models to characterize intrinsic clearance determination in NGRAs.","authors":"Jaqueline Meinhardt, Abdulkarim Najjar, Nicola J Hewitt, Andreas Schepky, Daniela Lange","doi":"10.1016/j.namjnl.2026.100139","DOIUrl":"10.1016/j.namjnl.2026.100139","url":null,"abstract":"<p><p>In Next Generation Risk Assessments, measurements of hepatic intrinsic clearance (CL_int <i>, _{in vitro}</i> ) and metabolite(s) formation can markedly impact <i>in vitro</i> to <i>in vivo</i> extrapolations and subsequent testing of parent and/or metabolites in <i>in vitro</i> bioassays. It is especially important for slowly metabolized chemicals to use the most suitable model and experimental design to ensure that the IVIVE is accurate. We evaluated four long-term hepatic models (sandwich cultures of primary human hepatocytes (PHH), HepatoPac, HµREL and TruVivo), as well as PHH suspensions, using salicylic acid, 1-methyl-2-pyrrolidinone (NMP) and valproic acid. Assay designs differed in terms of positive and negative controls, cell densities and incubation durations. All models generated a measurable CL_int <i>, _{in vitro}</i> value for salicylic acid i.e. depletion >20%. Differences may be due to donor differences and the cell number. HepatoPac generally resulted in higher values compared with the other models. NMP was not metabolized by HµREL and TruVivo models and a reliable value was only possible using HepatoPac. NMP was metabolized by sandwich cultures; however, the half-life was much longer than the incubation duration. To derive a more robust value, follow up testing could include longer incubation times. Valproic acid was only metabolized in one of the three models in which it was detected, namely sandwich cultures. In conclusion, PHH sandwich cultures, HepatoPac, HµREL and TruVivo models are superior to PHH suspensions with respect to maintaining XME activities over days and for measuring CL_int, <i>_{in vitro}</i> values for slowly metabolized chemicals. To gain regulatory acceptance and better interpret data from different labs, we recommend increasing the number of chemicals tested and harmonization of protocols.</p>","PeriodicalId":520522,"journal":{"name":"NAM journal","volume":"2 ","pages":"100139"},"PeriodicalIF":0.0,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13677246/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149220793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Engineering 3D neural models of neurodegeneration: the Neural Microenvironment Design Code (NMDC), design principles, and emerging new approach methodologies.","authors":"Alp Deniz Yuzbasic, Begum Yagmur Yesil, Damla Arslantunali Sahin, Bugra Ayan","doi":"10.1016/j.namjnl.2026.100138","DOIUrl":"https://doi.org/10.1016/j.namjnl.2026.100138","url":null,"abstract":"<p><p>Neurodegenerative diseases are characterized by progressive neuronal loss driven not only by intrinsic cellular dysfunction but also by complex interactions within the neural microenvironment, including extracellular matrix (ECM) composition, neuroimmune signaling, and neurovascular dynamics. Conventional two-dimensional systems and animal models fail to recapitulate this complexity, limiting their predictive value. Recent advances in three-dimensional (3D) neural platforms, particularly 3D bioprinting and organoid technologies, have enabled the development of more physiologically relevant models that better reproduce brain architecture and multicellular organization. These systems enable the investigation of key pathological processes, including neuroinflammation, protein aggregation, and synaptic dysfunction, while aligning with emerging New Approach Methodologies (NAMs) aimed at improving human-relevant disease modeling. However, current platforms remain constrained by limited maturation, insufficient vascularization, incomplete immune integration, and experimental variability. A central premise of this review is that effective disease modeling requires not only biological complexity but also precise engineering of the neural microenvironment. To organize this engineering effort, we introduce the Neural Microenvironment Design Code (NMDC), a framework encompassing mechanical, biochemical, electrophysiological, and immune-barrier design codes that collectively define the neural microenvironment. Using the NMDC as an organizing framework, we synthesize recent advances across major neurodegenerative diseases and identify key design principles governing biomaterial selection, spatial organization, cellular integration, and biofabrication. Collectively, these approaches position 3D neural models as programmable, human-relevant systems for predictive drug screening and personalized therapeutic development.</p>","PeriodicalId":520522,"journal":{"name":"NAM journal","volume":"2 ","pages":"100138"},"PeriodicalIF":0.0,"publicationDate":"2026-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13659680/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149186887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Replacing HaCaT keratinocytes with 3D reconstructed human epidermis in a THP-1 coculture dendritic cell activation assay: quantitative skin sensitization potency assessment and structure-potency relationships.","authors":"Brunhilde Blömeke, Niklas Peter, Udo Bock, Boris Peter Müller, Peter Griem, Rüdiger Wittlake, Johannes Panten","doi":"10.1016/j.namjnl.2026.100137","DOIUrl":"https://doi.org/10.1016/j.namjnl.2026.100137","url":null,"abstract":"<p><p>Reliable assessment of skin sensitization hazard and potency remains challenging for fragrance and other substances. Although current in chemico and in vitro assays perform well within their respective applicability domains, challenges remain for highly lipophilic, poorly water-soluble, cytotoxic chemicals and substances requiring metabolic or abiotic activation. To address these challenges, the established 2D Cocultured Activation Test (COCAT), combining HaCaT keratinocytes with THP-1 cells as surrogate dendritic cells, was modified by incorporating a reconstructed human epidermis (RHE). The resulting 3D RHE/THP-1 coculture model was evaluated using chemicals that presented challenges for quantitative assessment in the 2D COCAT method. Results were compared with previously published 2D COCAT data and human and animal weight-of-evidence (WoE)-derived skin sensitization potency values (PVs). Incorporation of the RHE substantially expanded the applicability domain by enabling quantitative potency assessment of substances for which robust concentration-response relationships could not previously be established. The 3D RHE/THP-1 model differentiated all sixteen substances over more than three orders of magnitude in skin sensitization potency and enabled systematic comparison of structurally related substances. Alcohol-aldehyde potency relationships were highly structure dependent, ranging from minor differences between benzyl alcohol and benzaldehyde to approximately 15-fold differences between hydroxycitronellol and hydroxycitronellal. Potency estimates showed good overall agreement with published PVs. These findings demonstrate that incorporation of RHE extends the applicability domain of the COCAT method, provides a more physiologically relevant in vitro approach for quantitative skin sensitization potency assessment, and supports the further development of human-relevant, animal-free next-generation risk assessment strategies.</p>","PeriodicalId":520522,"journal":{"name":"NAM journal","volume":"2 ","pages":"100137"},"PeriodicalIF":0.0,"publicationDate":"2026-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13659607/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149187346","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}