Towards harmonisation of testing of nanomaterials for EU regulatory requirements on chemical safety

MACRAMÉ Partners have contributed to the identification of 11 different needs for action to address 22 information requirement needs across different EU regulatory areas concerning the market access of products containing nanomaterials. Experts from RIVM (Dutch National Institute for Public Health and the Environment) and AcumenIST SRL have co-authored a new publication entitled ‘Towards harmonisation of testing of nanomaterials for EU regulatory requirements on chemical safety – A proposal for further actions’, in which the information requirements are categorised into three overarching activities:

resolve issues around nanomaterial dispersion stability and dosing in toxicity testing, in particular for human health endpoints,
further develop tests or guidance on degradation and transformation of organic nanomaterials or nanomaterials with organic components, and
further develop tests and guidance to measure (a)cellular reactivity of nanomaterials.

The authors argue that ‘[e]fforts towards addressing these issues will result in better fit-for-purpose test methods for (EU) regulatory compliance. Moreover, it secures validity of hazard and risk assessments of nanomaterials.’

The Review Methodology

The publication is based on a thorough review of EU regulatory relevant documents pertaining to nanomaterials and/or their specificities; for the identification of information requirements, legislation and guidance documents that were applicable in June 2021 were considered. Due to the lack of specific requirements in some of the EU legislations, the authors also looked at accompanying regulatory guidance documents, notes or reflection papers from ECHA, the Scientific Committee on Consumer Safety (SCCS), the European Food Safety Authority (EFSA), the European Medicines Agency (EMA), and the Scientific Committee on Emerging and Newly Identified Health Risks (SCENIHR) to gather the necessary information.

A group of 22 experts subsequently identified potential needs for further action to accommodate guidance and test guidelines to nanomaterials. To this end, 136 information requirements, grouped into one of 21 categories, were identified. Many of these are general requirements for chemicals that are also relevant for nanomaterials (e.g. toxicological endpoints do not differ, although testing for these endpoints may require nano-specific adaptations).

The results of the study accentuate the need for a structural process of identification of information needs and knowledge generation, preferably as part of risk governance and closely connected to technological innovation policy.

Proposed Prioritisation of further Needs for Actions

[…] priority may be given to issues that are relevant for a range of regulatory requirements and/or a broader range of regulatory areas.
[Towards harmonisation of testing of nanomaterials for EU regulatory requirements on chemical safety – A proposal for further actions. Regulatory Toxicology and Pharmacology, 139 (2023), 105360, https://doi.org/10.1016/j.yrtph.2023.105360]

The authors suggest ‘a prioritisation for future work. […] For example, the importance of guidance on sample preparation, agglomeration and/or dispersion stability is mentioned for several physical-chemical properties (i.e. dispersion stability in relevant media, stability (physical and chemical)) and a human health information requirement (i.e. cell toxicity).’

The publication concludes that focusing on three overarching activities could help to resolve some of the most urgent outstanding scientific and regulatory issues for nanomaterials:

Resolving issues around nanomaterial sample preparation, agglomeration, dispersion stability and dosing in toxicity testing, in particular for human health endpoints.
Further development of tests or guidance on degradation and transformation of organic nanomaterials or nanomaterials with carbon components to better assess environmental fate of this group of nanomaterials.
Further development of tests and guidance to measure (a)cellular reactivity of nanomaterials, which will be critical, e.g. for the development of NAMs and in high-throughput systems needed for assessing the ever increasing diversity of (newly) developed (advanced) nanomaterials.

The MACRAMÉ Project will develop improvements to the following OECD Test Guidelines identified by the publication: