NAM journal最新文献

The use of non-animal, new approach methodologies (NAMs) is increasing but there has been no associated decrease in animal use. Reasons may include the focus on phasing-in NAMs over phasing-out animal use and the focus on transition within the regulatory sphere, although most animals are used in basic research. The transition to NAMs is often viewed as a technical matter, without acknowledging that scientific knowledge and practices are socially produced and that scientists may be motivated - like all social beings - by interests and power relationships. This paper employs the insights of French sociologist, Pierre Bourdieu, to explore the persistence of animal research within academia. Several of Bourdieu's concepts are applied, including field and habitus, but perhaps it is his concept of capital that is most valuable in this context, providing a valuable shorthand for discussing the system of rewards and penalties within academia, clarifying how animal research converts into symbolic as well as social and economic capital and elucidating what scientists risk if they attempt to transition from animal research to NAMs. Bourdieu reminds us to attend to power relationships, particularly the relationship between the animal research field and the field of power. Importantly, he argued that scientific change does not occur simply as a result of paradigm shifts, but because of struggles between scientists for capital and for the power to define their science as 'legitimate'. Bourdieu's concepts bring clarity and sensitivity to discussions about the transition as these gather momentum.

The development of in vitro developmental and reproductive toxicity (DART) models is challenging. We made a brief review of in silico models and an in-depth review of 17 established in vitro New Approach Methodologies (NAMs) used to assess the DART potential of cosmetic-related ingredients. We investigated their coverage of the stages of male and female fertility and embryo-fetal development and related biomarkers to identify potential gaps. There are multiple in silico tools for early screening to flag DART potential, design subsequent testing, use in a weight of evidence approach or to fill data gaps. All stages of male and female fertility and embryo-fetal development are covered by at least one of the 17 NAMs evaluated, with most focusing on late organogenesis. Many NAMs measure specific receptors, enzymes and pathways involved in teratogenicity, highlighting the increased understanding of the pathways involved. Cellular endpoint assays are being refined by incorporating biomarker measurements. These can be combined in integrated and WoE approaches across different tiers in a testing strategy to cover different pathways to provide good confidence in the outcome of the testing. The most cited NAM in the literature was the zebrafish embryotoxicity test. This is not generally used for cosmetic-related ingredients, which are mainly evaluated using molecular and cellular assays related to steroidogenesis. The predictivity of several NAMs is increased when the measured or predicted plasma concentration is considered. In conclusion, this analysis indicates that currently available NAMs enable an analysis of the different stages of male and female fertility and embryo-fetal development.

With increasingly stringent regulatory requirements, the cosmetics industry is confronted with the growing expectation to assess the environmental fate of its ingredients (Persistence, Bioaccumulation, and Mobility). However, this assessment is often hampered by data gaps, a challenge exacerbated by the EU's ban on animal testing. In response to these limitations, in silico predictive tools, such as (Quantitative) Structure-Activity Relationship ((Q)SAR) models, are being promoted to provide essential data for environmental risk assessment. The objective of this study was to identify the most suitable freeware tools for predicting Persistence, Ready Biodegradation, Log Kow, BCF and Log Koc. Models integrated into VEGA, EPI Suite™, T.E.S.T., ADMETLab 3.0, and Danish QSAR Models were selected, and their performances were compared by using cosmetic ingredients dataset. Regarding the persistence property, Ready Biodegradability IRFMN (VEGA), Leadscope model (Danish QSAR Model) and BIOWIN (EPISUITE) models showed the highest performance. Moreover, higher performance for bioaccumulation assessment was observed in the ALogP (VEGA), ADMETLab 3.0 and KOWWIN (EPISUITE) models for the Log Kow parameter, as well as in Arnot-Gobas (VEGA) and KNN-Read Across (VEGA) models for BCF prediction. Finally, VEGA's OPERA and KOCWIN-Log Kow estimation models were identified as relevant models for predicting mobility. These results suggest that qualitative predictions are more reliable than quantitative ones when evaluated against REACH and CLP regulatory criteria. The study also highlighted the significant role of the Applicability Domain (AD) in assessing the reliability of (Q)SAR models. These (Q)SAR models showed promising results for assessing the environmental fate of cosmetic ingredients; however, further investigations are needed to confirm these findings.

[This corrects the article DOI: 10.1016/j.namjnl.2025.100009.].

In recent years, there has been a significant push towards the development of animal-free methods in toxicology. Despite this progress, the adoption of such methods in safety assessment practices remains limited, particularly in the context of gonadal and placental toxicity. This paper reviews current in vitro models relevant to gonadal (gametogenesis and steroidogenesis) and placental biology, and potentially applicable in developmental and reproductive toxicology (DART). Additionally, we present the results of a survey conducted among DART experts (n = 16), examining current practices and perceptions in industry regarding these in vitro methodologies. The findings indicate a predominant reliance on animal models, largely driven by regulatory requirements, despite concerns about their ability to reliably predict human outcomes. Respondents reported limited familiarity with and confidence in available in vitro models for gonadal and placental toxicity, yet expressed optimism about their future integration. These findings underscore the need for increased awareness of gonadal and placental in vitro models, particularly among DART risk assessors, to facilitate a shift toward more reliable and human relevant risk assessments.

Inflammatory bowel disease (IBD), encompassing ulcerative colitis and Crohn's disease, is a chronic and relapsing inflammatory condition of the gastrointestinal tract resulting from a complex interplay of oxidative stress, immune dysregulation, microbial imbalance, and epithelial dysfunction. While animal models have primarily contributed to our understanding of IBD pathogenesis, their limited translational relevance and ethical concerns have led to the accelerated adoption of New Approach Methodologies (NAMs). This review highlights the increasing importance of in vitro platforms, including intestinal epithelial cell lines, 3D organoids, and microfluidic gut-on-chip models, which offer physiologically relevant and ethically sustainable solutions. In silico strategies, such as molecular docking, network pharmacology, toxicogenomics, artificial intelligence, and machine learning, enhance these models by enabling predictive simulations of drug interactions and molecular targets. Emerging mechanisms, such as barrier modulation and multi-targeted inflammatory regulation, are being explored using NAMs. Despite significant progress, challenges remain in standardization, integrating the immune and microbiome systems, and achieving regulatory acceptance. The combination of NAMs, multi-omics, and real-world data represents a promising avenue for mechanistic research, therapeutic screening, and precision medicine in IBD.

New Approach Methodologies (NAMs) for risk assessment of chemicals and pharmaceuticals are widely regarded as essential for phasing out animal testing and advancing next-generation risk assessment. However, despite substantial public investments in research and development (R&D) to develop these NAMs, concerns persist about the limited societal impact of these projects. This study addresses this concern by examining how societal impact is pursued in sixteen large-scale, publicly-funded European R&D projects focused on developing NAMs that integrate in silico and in vitro methods. Drawing on an in-depth analysis of 197 publicly available documents and seven semi-structured interviews, we identify 25 impact activities typically pursued in these projects, which vary in the stakeholders targeted as well as levels of engagement ranging from one-way communication to more interactive approaches such as deliberation and co-production. From these findings, we derive five routes to impact focused on community and capacity building, changing policy and regulation, advancing scientific developments, commercialization and industrial partnerships, and mobilizing civil society. We then analyze how these routes function within projects with a focus on perceived barriers and trade-offs between them. Based on this we offer practical and strategic recommendations for pursuing impact in NAM R&D projects. In particular, we recommend that project coordinators and partners be more reflexive on the pursuit of multiple impact routes in a single project and adopt more co-productionist approaches to stakeholder engagement, beyond those already used in case-study development. We also recommend a stronger focus on engaging civil society, which remains underrepresented in NAM R&D projects.

Fetal bovine serum (FBS) is widely used as a supplement in cell culture due to its complex composition, which supports cell growth, and metabolism for conducting experiments with mammalian cells in vitro. However, concerns regarding reproducibility, ethical considerations, and batch variability have prompted efforts to investigate its biochemical composition and potential alternatives, to subsidize the development of chemically defined alternatives. This study aimed to analyze the qualitative and quantitative composition of different FBS samples, including growth factors, vitamins, hormones, lipids, proteins, ions, and organic compounds. Additionally, mycoplasma contamination was assessed. FBS samples from different suppliers (Brazil, USA, and Paraguay) were evaluated before and after inactivation at 56 °C for 30 min. Results demonstrated the absence of mycoplasma in all samples. Among the 58 biochemical parameters analyzed, 20 exhibited significant variability (16-102 %) in non-inactivated samples, while 19 parameters showed variations (16-84 %) after inactivation. The highest variability was observed for luteinizing hormone and transferrin. Growth factor analysis revealed that epidermal growth factor, and insulin-like growth factor type 1 concentrations were below detection limits, whereas basic Fibroblast Growth Factor, and vascular endothelial growth factor A concentrations considerably reduced after the heat inactivation process for most of the evaluated samples. These findings highlight the heterogeneity of FBS composition, which may impact reproducibility in cell-based assays. Despite being considered a universal cell culture supplement, our results demonstrate that alternatives to FBS should be explored to improve the in vitro data quality and move towards a more ethical science in the field of new approach methodologies.

Cell-based in vitro bioassays are essential New Approach Methodologies (NAMs) that allow the bioactivity screening for thousands of chemicals in a time- and cost-efficient manner. One major obstacle for the widespread acceptance of in vitro bioassays is the undefined exposure in these tests. The present study aimed to complement in vitro testing of cytotoxicity as well as specific endpoints, such as the activation of oxidative stress response, with measured exposure concentrations as additional readout. Freely dissolved concentrations (C _free) of 24 test chemicals in four different cell-based in vitro bioassays were measured in 96-well plate format at the time point of dosing and after 24 h of exposure in the assay plates for all tested concentrations of the chemicals. Freely dissolved fractions (f _free) in the medium decreased with increasing hydrophobicity. Hydrophilic chemicals like atenolol had f _free of >90 %, while the most hydrophobic test chemical chrysene had an f _free of only 1.4 % at the beginning of the test and 0.7 % after 24 h of exposure to the cells. For 12 of the 24 chemicals C _free decreased >20 % during the bioassays. Depending on the chemical, the loss may be due to sorption to well plate plastic, cellular metabolism or abiotic degradation (e.g., hydrolysis). The simultaneous measurement of toxicity and exposure allows the identification of chemicals with unstable exposure concentrations and/or low bioavailability and provides a quantitative measure of bioactivity that can directly be applied for in vitro-to-in vivo extrapolation (IVIVE).