Two recent reports reviewed existing New Approach Methodologies (NAMs). One focussed on the purpose of regulatory risk assessment and the other on in silico methods for the Safe-and-Sustainable-by-Design (SSbD) of nanomaterials. The reviews concluded that while NAMs are beneficial for developing nanomaterials, most still require validation for regulatory risk assessment purposes. Investment in validating test methods specifically for nanomaterials and proper data management are needed to achieve widespread use and regulatory acceptance of NAMs.

Why are NAMs important for nanomaterials?

NAMs are innovative technologies used in hazard and risk assessment. They aim to reduce or replace traditional animal testing by providing alternative methods to gather the necessary data. NAMs are essential for evaluating the safety of the numerous nanomaterial variants, both for regulatory risk assessment purposes and for SSbD.

NAMs for regulatory risk assessment of nanomaterials

The need for NAMs to reduce animal testing and improve the efficiency of nanomaterial risk assessment was emphasized in a recent report(PDF/) commissioned by the European Chemicals Agency (ECHA) and the European Union Observatory for Nanomaterials (EUON). In the report, researchers conducted a literature review of existing NAMs and categorized the 221 NAMs they found into nanospecific and non-nanospecific. They also determined whether the NAMs were regulatory accepted, under validation, or in development. Among the nanospecific NAMs, the researchers identified eight that were regulatory accepted and 120 that were in development. Industry uses these methods most commonly to assess nanomaterial effects on the skin. The report underscored the need for validated nanospecific NAMs, especially for complex endpoints. These include genotoxicity, carcinogenicity, dermal and oral absorption, inhalation toxicity, neurotoxicity, and toxicokinetics. Additionally, it emphasized the importance of collaboration between regulatory bodies, industry, and academia to advance the development and regulatory acceptance of these methods.

NAMs for SSbD

Another study commissioned by EUON evaluated 190 computer models and methods for developing nanomaterials that are SSbD. These so-called in silico methods were evaluated by 36 experts based on their validation, transparency of data, ease of use, and precise definition of their scope (applicability domain). Most NAMs demonstrated reliable workflows, algorithms, and methodologies. However, there are challenges to their widespread use. These included the need for standardized nanomaterial-related data and the scattered, inaccessible nature of data across different sources and formats. To address these issues and increase confidence in the models, managing data according to the FAIR (Findable, Accessible, Interoperable, and Reusable) principles and using standardized databases such as eNanoMapper, NanoPharos, NanoCommons Knowledgebase, and caNanoLab can play a key role.

Reflections by RIVM

The reviews offer a valuable overview of the state of the art of NAMs for risk assessment and SSbD. They adequately outline the challenges that should be addressed. Most NAMs still require validation, which demands a considerable investment of resources. Proper FAIR data management is another crucial step towards validation, regulatory acceptance, and widespread use of NAMs.

It would also be helpful to compare the existing NAMs and those in development with the priorities for test method development set forth by the Malta Initiative and those proposed by Bleeker et al. (2023). This could provide a clearer view on the regulatory needs for NAMs. Research projects like PARC could provide valuable input in validation of NAMs, but for their regulatory acceptance more is needed. NAMs should preferably be included in standardised methods from bodies like ISO and OECD, which requires more extensive validation, coordination and prioritisation, as well as funding.

Such activities could be part of a European Test Method and Validation Strategy that the European Council called for and was also recently advocated by the Germany and the Netherlands in the context of REACH.

For nanospecific NAMs, (validation) guidance should consider the unique characteristics of nanomaterials that may require tailored NAMs and validation processes. OECD is currently updating its Guidance Document on the validation and international acceptance of new or updated test methods for hazard assessment. As emphasized in these reviews, further initiatives in the field should involve dialogue with all relevant stakeholders. Relevant stakeholders include developers and users of NAMs (e.g. scientists and industry), as well as users of the data that NAMs can provide (e.g risk assessors and regulators).