A recent critical perspective argues that nanomaterials should be regulated as biological rather than chemical entities. The researchers emphasise the importance of using existing knowledge about the biological interactions of nanomaterials and their impact on human health and the environment. The authors list various well-known challenges regarding the safety assessment of nanomaterials. However, they do not provide sufficient justification to consider nanomaterials as biological entities, nor do they offer a clear strategy for addressing the long-standing regulatory challenges in this area.

Nanomaterials can act like biological entities in safety research

In a recent critical perspective on safety research and regulation for nanomaterials, two scientists argue that nanomaterials behave like biological entities within an exposed organism and that this should be reflected in relevant regulations. Their argument is based on recent studies showing specific nanomaterial interactions with biological systems. These interactions include coronation, which is the formation of a layer of biomolecules on the surface of nanomaterials. This layer influences how cells recognise nanomaterials and affects how these materials transform through processes like dissolution and degradation.

Challenges in assessing the safety of nanomaterials

The perspective mentions several challenges and difficulties related to  safety assessment of nanomaterials. One example given is that the functionalisation type of multi-walled carbon nanotubes (MWCNT) can affect their toxicity and behaviour within an exposed organism. The authors emphasise the importance of material characterisation and point out that the choice of an in vivo test system will influence the outcome. They also stress that when using in vitro methods to test the toxicity of nanomaterials, the effects of chronic or repeated exposure should be considered. Additionally, the authors suggest that studying nanomaterials might reveal new biological mechanisms. However, they note that establishing universal toxicological concepts for all nanomaterials will be challenging.

Nanomaterials: chemical versus biological entities

Given their interactions with biological components (such as coronation) and their behavioural similarities to biological entities (for example, receptor interactions and degradation), the authors argue that it would be more appropriate to regulate nanomaterials as biological entities rather than chemicals.

Reflections by RIVM

There clearly is truth behind the challenges and issues mentioned. However, the rationale behind the main argument - that nanomaterials behave as biological entities and should be regulated as such -  is not coherent or sufficiently developed. The perspective mainly focuses on known difficulties related to nanomaterial testing and regulation without providing a clear way forward.

Receptor interaction is not restricted to biological materials in the body; the body can also recognise and clear foreign materials in this way. Similarly, degradation and dissolution apply to both biological and chemical entities. The authors provide no guidance or detail on how they envision their proposed regulation for nanomaterials as biological entities, instead of their current regulation as chemicals.

Many challenges mentioned in the current article are well-known in the regulatory toxicology community. For instance, corona formation is an established concept in particle toxicology. It has long been understood that particles rapidly become coated with biomolecules such as proteins once they enter an organism. It is extremely difficult to take corona formation into account in regulatory toxicity testing. The composition of the corona changes over time and varies depending on how the particles enter the body, their distribution within the organism, and the direct environment of the nanoparticles (for instance, food, water or ambient air). Similarly, the issues related to dissolution and degradation have been known for decades. Low solubility is commonly considered as a critical factor in particle toxicity.

Nanomaterials indeed present specific challenges that should be addressed in their regulatory safety assessment. However, the perspective does not offer a clear regulatory strategy, or elements thereof, that could improve on the shortcomings of the current system. In addition, the author’s assertion that nanomaterials behave like biological entities is not convincing. While we agree that the regulation of nanomaterials could benefit from considering factors beyond their chemical properties, it may be more appropriate to focus on their physical properties rather than regulating them as biological entities. It should be noted in this regard that since the 1st of January 2020, specific REACH requirements apply to registrants that produce or import nanoforms of substances.

Read the Dutch summary: Nanomaterialen in regelgeving: biologisch of chemisch