The rise of new approach methodologies (NAMs) for environmental safety assessment of chemicals: A systematic review of the current status, challenges and strategies for broader adoption of NAMs.

Traditional ecotoxicity testing relies heavily on vertebrate animal models, which are resource-intensive, low-throughput, and raise ethical concerns under the principle of the 3Rs (Reduction, Refinement, Replacement). New Approach Methodologies (NAMs), including in silico, in chemico, in vitro and ex vivo, offer promising alternatives for environmental chemical hazard assessment. While NAMs have gained traction in human health risk assessment, their regulatory acceptance for environmental safety remains limited due to technical, scientific and policy barriers. This paper presents an overview of a literature review related to the status, challenges and future strategies for broader adoption of NAMs for environmental safety assessment of chemicals. The review´s objectives were to: (1) systematically review the current state of NAMs for aquatic toxicity assessment, (2) identify gaps in NAM readiness and endpoint coverage, and (3) provide recommendations to accelerate regulatory acceptance and integration of NAMs into environmental safety frameworks. A systematic literature review was conducted using PubMed followed by the SWIFT-Active Screener tool, focusing on NAMs applicable to aquatic organisms (fish, amphibians, marine mammals). The review excluded terrestrial and invertebrate models. Search terms considered within the scope of the review included in silico, in chemico, in vitro and ex vivo. While embryo assays may not be considered a NAM by all geographical regions and stakeholders, information from existing embryo assays was also reviewed to reduce the reliance on protected vertebrate life stages. The screening identified 4275 unique articles and 1310 were selected for full-text review. A database containing all the reviewed information is freely available and contains 18 metadata fields including for example the captured assay type, species, endpoints, and readiness level. This review provides a comprehensive roadmap for transitioning toward animal-free environmental safety assessment. By addressing gaps in readiness, standardization, and mechanistic integration, NAMs can become central to next-generation risk assessment, supporting global initiatives to phase out vertebrate testing.