New Approach Methodologies (NAMs), broadly understood to include in silico, in chemico, in vitro and ex vivo methods, show great potential in advancing risk assessment albeit their regulatory implementation is lagging. The EFSA Guidance on risk assessment of nanomaterials (EFSA Guidance on Nano‐RA) suggests nano‐specific risk assessment is best achieved through Integrated Approaches to Testing and Assessment (IATAs) with NAMs as the first choice to generate new information. Integrating NAMs in risk assessment promises several advantages such as a better human focus, more detailed insights into molecular mechanisms and a higher efficacy. However, applying NAMs to NMs also poses considerable challenges such as issues related to dispersion stability, dosimetry, agglomeration, dissolution, transformations or assay interferences. Significant efforts are being undertaken by standardisation organisations and research projects to establish various NAMs for NMs. Here a thorough review is provided covering NAMs that will be potentially useful for risk assessment of NMs in the food and feed sector. It follows the structure of the EFSA Guidance on Nano‐RA and expands it, where needed, to support decision‐making in selection of NAMs for NM risk assessment. The review begins with an overview on nano‐specific NAM‐frameworks, followed by a description of individual NAMs including those relevant to NM physicochemical characterisation, exposure and hazard assessment covering toxicodynamics and toxicokinetics. The focus is on NAMs concerning NM degradation/dissolution, genotoxicity, cytotoxicity, oxidative stress, (pro‐)inflammation, and barrier integrity as those are important endpoints for initial screening according to the EFSA framework. As a result, in total 267 individual nano‐relevant NAMs, mostly “not validated” (with a few notable exceptions), were included in this review. Validation notwithstanding, NAMs could already prove relevant and reliable for risk assessment of NMs, especially in integrated approaches.
