NAM journal最新文献

The European Commission (EC) developed a Roadmap to phase out animal testing, with milestones and practical steps across 15 different European chemical legislations (EC 2026). Currently though, the number of animals used for compliance testing in the EU remains high, particularly for high-volume chemicals such as Petroleum Substances, and is expected to increase with the introduction of new hazard classes under Regulation (EC) 1272/2008 (CLP). A reduction in animal testing for these substances can be achieved today by grouping, read-across and composition-activity models leveraging historical data and an in-depth understanding of substance composition and manufacturing processes. However, full replacement with New Approach Methodologies (NAM) remains challenging due to the complexity and physico-chemical properties of hydrocarbon substances from conventional and renewable feedstocks which are UVCB substances (Unknown, Variable composition, Complex reaction products or Biological materials). This manuscript outlines the current efforts to reduce animal testing in environmental and human health assessment of hydrocarbon UVCB and highlights key challenges limiting broader application of in silico and in vitro approaches. To address these challenges, we propose a pragmatic and readily implementable roadmap for the transition to animal-free UVCB assessment, adapting the different elements of NAM frameworks including analytical characterization, in silico predictions, in vitro testing, and in vitro-in vivo extrapolation. Short-term actions focus on enhancing read-across and increasing regulatory acceptance of existing approaches, mid-term priorities include improving technical readiness of in vitro testing and in silico approaches and the long-term goal aims at integrating predictive models and the development of an animal-free UVCB framework for regulatory acceptance. This transition will require tailored approaches and is expected to follow a different timeline compared to other industrial chemicals.

Obesity is a global health issue and risk factor for various diseases. Given its systemic nature, multi-organ-on-a-chip (MOC) models have been proposed to model human organ interactions in vitro. Obesity MOC models are still in an early stage of development. Early stakeholder engagement may provide insights into societal, scientific, and ethical aspects of obesity MOC models, and incorporating these dimensions can support their development and implementation. Therefore, we conducted an explorative qualitative study focusing on academic and industrial biomedical researchers' views on MOC models for obesity, based on a hypothetical model incorporating adipose tissue, kidney, and liver organ systems. Analysis of the semi-structured interview transcripts identified six themes that consistently emerged across all participants. Our results show that participants perceived obesity as a global health issue requiring prevention efforts. However, researchers argued that obesity MOC models should mimic human (patho)physiology, rather than focus on prevention. Moreover, tensions between capturing human system complexity and maintaining manageable technical setup were identified. Perceived hurdles, including finding universal culture medium, limited affordability, and inadequate high-throughput capacity, may hamper obesity MOC model development. Clear research objectives and model validity were considered crucial, and explicitly defining context of use may facilitate progress. Divergent views on obesity MOC model validation, ranging from animal replacement to animal benchmarking, highlight tensions in scientific practice. In conclusion, consensus on the value and validation of obesity MOC models requires engagement among scientists, institutions, and society. Our findings can inform design and communication of obesity-related MOC experiments, supporting their development and use.

Definitions for new approach methodologies (NAMs) are highly varied. We argue that current efforts to clarify and harmonize these definitions have paid insufficient attention to their ethical and social significance. Because the choice of definitions influences which methods receive the most policy attention and funding, these definitions are ethically and socially value-laden. To address this issue, we propose three strategies: (1) employing broad definitions that are compatible with multiple values in contexts where the most important values have not been specified; (2) promoting deliberation among stakeholders in an effort to clarify which values should guide future NAM definitions; and (3) aligning NAM definitions with the values of particular initiatives and organizations when their values are clear.

Political, Regulatory and Scientific developments are propelling the use of New Approach Methodologies (NAMs) across regulatory toxicology and drug development, creating challenges for organisations operating animal-testing facilities. High clinical attrition rates driven by lack of efficacy and toxicity continue to stimulate interest in more human-predictive approaches. The FDA Modernization Acts and UK and EU initiatives to phase out animal testing are also influencing future testing strategies. Universities, pharmaceutical companies and contract research organisations (CROs) have made substantial investments in facilities, equipment, support services and highly skilled personnel. Increasing adoption of NAMs forces existing infrastructure redevelopment, whilst preserving capital investment and retaining/repurposing scientific expertise. A practical framework is presented for organisations transitioning from animal-based testing towards NAM-centred operations, addressing infrastructure redevelopment, workforce transition, expertise retention and capital investment preservation. Infrastructure requirements, support services, workforce development, business sustainability and role-specific staff retraining are examined. Retaining institutional knowledge and recognising the continuing value of technical, scientific and regulatory expertise developed through animal-testing programmes as organisations transition towards NAMs are prioritised. Contexts of Use (CoUs) and Adverse Outcome Pathways (AOPs) help connect historical animal-study knowledge with future NAM applications. Successful transition is presented as a managed organisational process involving people, infrastructure, knowledge and investment rather than simply the replacement of one experimental model with another.

While a comprehensive revision of the REACh regulation is currently no longer under consideration, regulatory requirements potentially covering analytical, ecotoxicological, and toxicological aspects of polymers may still evolve. Regulatory testing typically relies on OECD test guidelines (TGs), which are generally designed for small molecules. According to REACh and following the 3R principles, non-animal methods, also described as new approach methods (NAMs) are the first choice for testing. The applicability of NAMs for polymers, substances with high molecular weights and varying solubility, is limited and test substance application in aqueous media presents a challenge. Standards described for the biological evaluation of medical devices (DIN EN ISO 10993) and food contact materials (DIN EN 13130) offer test substance preparation methods for finished articles including polymer materials. In this study, preparations of seven non-water soluble (pre)polymer materials were selected for testing with four different NAMs: basal cytotoxicity assay, an estrogen receptor transcriptional activation assay (OECD TG 455), in vitro micronucleus test (OECD TG 487) and in vitro skin irritation test (OECD TG 439/ DIN EN ISO 10993). Although the test substance preparation steps developed for finished medical device or food contact products technically allowed testing of all seven (pre)polymers across the four NAMs, this approach is fundamentally limited. Applying standard methods designed for small molecules (e.g., OECD TGs) or finished articles (e.g., ISO standards) to (pre)polymers does not necessarily produce data that realistically reflect bioavailable fractions under intended use conditions. Development of standardized methods for analytical, ecotoxicological and toxicological evaluations is essential for complex test materials such as polymers.

Reducing reliance on animal studies while improving human relevance requires new approach methodologies (NAMs) that reproduce dynamic biological interactions and metabolism-dependent drug exposure. Microphysiological systems (MPSs) are promising NAMs that can recapitulate selected human organ functions in vitro. However, the advantages of multi-organ MPSs over conventional culture methods have not been sufficiently validated because direct comparisons between these systems are difficult. Here, we constructed a liver-cancer MPS using a Kinetic-pump integrated microfluidic plate (KIM-Plate) containing two open, standard-well-compatible culture chambers connected by recirculating microchannels. PXB human hepatocytes and MCF7 breast cancer cells were evaluated using well-plate monoculture, conditioned-medium transfer, KIM-Plate monoculture, and dynamic KIM-Plate coculture. Dynamic coculture significantly increased MCF7 proliferation relative to KIM-Plate monoculture, whereas conditioned-medium transfer did not significantly increase proliferation relative to well-plate monoculture. PXB cells produced the active CPT-11 metabolite SN-38 and SN-38 glucuronide under both static and perfusion conditions, demonstrating sequential CPT-11-metabolizing activity in the MPS. MCF7 cells showed greater apparent sensitivity to SN-38 under perfusion than under static conditions. During CPT-11 exposure, the dynamic liver-cancer coculture was estimated to generate a gradually increasing SN-38 exposure profile and a lower SN-38 area under the concentration-time curve than conditioned-medium exposure. Nevertheless, observed MCF7 viability was higher than predicted from cumulative SN-38 exposure alone, suggesting that the temporal exposure profile may also have contributed to the drug response. The KIM-Plate therefore provides a tractable human cell-based NAM for investigating how continuous intercellular interactions, perfusion, and time-dependent metabolism collectively influence drug responses, thereby providing mechanistically informative evidence for metabolism-dependent drug assessment.