Iseult Lynch ↗, professor and researcher at the University of Birmingham ↗, has devoted her career to understanding the interactions between nanomaterials and biological systems. Initially focused on nanomaterials in medical devices, Lynch has expanded her research to explore their broader impact on human health, investigating how nanoparticles interact with proteins, cells, and tissues. Her work seeks to maximise beneficial applications of nanomaterials, such as in medicine, while minimising unintended exposure risks, a concept central to safe-and-sustainable-by-design approaches. As PARC’s Chemical Leader on nanomaterials, Lynch is leading efforts to develop innovative testing methods, including in vitro and in silico approaches, to assess health risks and ensure that the rapid advancement of nanotechnology goes hand in hand with robust safety science

You initially focused on nanomaterials in medical devices. What led you to evolve your focus to include the potential impact of nanomaterials on human health in a broader sense?

One of the things that I learned during my PhD was that proteins interacting with man-made materials, such as polymer-coated stents used to treat narrowing of blood vessels or heart attacks, are key to whether the device is accepted or rejected by the body. My PhD focused on developing polymer coatings to control the release of drugs that prevent the body from rejecting stents. As part of that, we developed nanoparticles of the polymer that were loaded with the drug and embedded into a layer of the polymer to achieve sustained drug release into the bloodstream – we called these “plum-pudding coatings ↗”.

We found that proteins from blood interacted differently with the nanoparticles than with flat surfaces of the same polymer, due to curvature effects at the nanoparticle surface. This opened up the whole area of nanomaterial–protein corona research, to understand the initial protein binding and then the exchange of high-abundance but low-affinity proteins by low-abundance but higher-affinity proteins – known as the Vroman effect.

The importance of the nanomaterial’s protein (and more generally, biomolecule) corona is now well established. It is what is “read” by cellular machinery, driving the uptake and transport of nanomaterials in the body. Depending on which proteins bind, nanomaterials can be selectively transported across biological barriers such as the blood–brain barrier, thereby enabling nanomedicine. However, for nanomaterials that were never intended to be internalised by humans, this can lead to unwanted uptake.

Thus, my interest in the broader impact of nanomaterials on human health stems from the desire to maximise beneficial interactions and reduce unintended ones – in part through manipulation of nanomaterial surfaces to “design in” their protein interactions, as part of a safe (and sustainable) by design strategy. 

What makes assessing the health risks of nanomaterials particularly complex compared to conventional chemicals?

Nanomaterials are classified as chemicals and indeed have chemical properties and can undergo chemical reactions at their surfaces. However, they also have physical properties related to their particulate nature, which means we need to consider both physical and chemical-driven modes of action for hazard assessment.

The surfaces of nanomaterials tend to be highly reactive, as they don’t have their full complement of bonds. Therefore, their properties are very responsive to their surroundings – or context dependent – meaning that much more characterisation is needed to understand how nanomaterial physico-chemical properties evolve: when they are dispersed, when they interact with lung lining fluid during inhalation, or when they reach the bloodstream, for example.

One of my major research interests is understanding the interactions of nanomaterials with proteins, lipids, and other biomolecules – forming the protein or biomolecule corona (or the eco-corona for nanomaterials in the environment) – which adsorbs to the nanomaterial surface and provides a biological identity that is recognised by cells.

Do you think that people are aware they are widely exposed to nanomaterials through everyday products or treatments?

Probably not, although there are efforts to explain where and how nanomaterials are used. The European Commission set up the European Union Observatory for Nanomaterials ↗ (EUON) to provide accessible information on their uses. For example, EUON offers interactive explainers on where nanomaterials are found in the home ↗, in the garage ↗, and in cosmetics ↗.

For cosmetics and personal care products, ingredients in nanoform must be indicated on the label, so you can see terms like “(nano) Titanium dioxide (TiO₂)” on many sunscreen bottles. The nanoform of TiO₂ offers the same benefits as the larger form in protecting the skin from UV rays, but without the very white appearance that results from larger particles.

What do we currently know about potential short- and long-term health effects?

The range of compositions and variants of nanomaterials is enormous, so speaking about them as a general class is challenging – like asking “what do we know about chemicals?” That said, we can make some general claims: in general, the toxicities associated with intentionally produced nanomaterials are broadly similar to those that arise from other particles, such as incidental ultrafine particles from diesel exhaust.

It’s always worth remembering that everything (even water) is toxic at a high enough dose. The issues we are exploring in PARC include understanding what safe exposure levels are. In general, nanoscale materials have not exhibited any major acute toxicities beyond those of their constituent elements – for example, the toxicity of silver nanomaterials is driven by the release of silver ions, which are ecotoxic.

Nanomaterials that are persistent, rigid, and long (so-called high aspect ratio nanomaterials) are known to induce persistent inflammation, so much focus has been on understanding the features that drive toxic responses so they can be designed out – for example, by reducing particle rigidity so they can be engulfed by macrophages (white blood cells) and removed.

Longer-term effects are still being explored. A topic of enormous interest to me is whether the evolution of the nanomaterial’s acquired protein corona as the particles move in the body drives new toxicity pathways – for example, by transporting proteins from their normal sites of action to other locations, thus disrupting protein homeostasis and cellular metabolism (see Cai et al., 2022 ↗).

Can the simple use of sunscreen compromise my health due to the behaviour of nanomaterials?

Sunscreens have been extensively tested to ensure safety, and the skin barrier is a very effective defense. For healthy skin, there is very little risk to health from using sunscreens containing nanomaterials. The risk from not using sunscreen is much, much higher, as there is clear evidence showing that excessive UV exposure causes cancer.

The EU’s Scientific Committee on Consumer Safety ↗ (SCCS) confirmed that evaluated titanium dioxide (TiO₂) nanomaterials, used at concentrations up to 25% as a UV filter in sunscreens, can be considered safe for humans after application on healthy, intact, or sunburned skin.

As sunscreen comes in both cream and spray forms, there is a small risk of particles being ingested from spray versions. As TiO₂ was banned in the EU as a food ingredient (formerly E171, used in many foods with white glazing), nanoscale TiO₂ is not recommended for spray versions of sunscreen.

But again, use sunscreen – any chemical risk is much lower than the risk from UV rays!

How is PARC contributing to the development of methods to assess nanomaterial safety for humans (e.g., in vitro, in silico approaches)?

Up to now, PARC has not been actively working on nanomaterials. However, following the second round of chemical prioritisation, nanomaterials were identified as an area of interest. Consequently, Susana Loureiro and I were appointed as Chemical Leads for nanomaterials.

Our first task was to conduct a landscape mapping to identify key gaps that PARC could address. From this, we proposed a dedicated PARC activity on nanomaterials – focusing on developing a test guideline to assess the suitability of PARC’s New Approach Methods (NAMs), originally developed for other chemicals, for use with nanomaterials.

This includes defining standard adaptations needed to account for their dynamic and context-dependent nature – for example, assessing dispersion stability, interactions with biomolecules, exposure setup, and potential interference with assay readouts.

The NanoTox-NAMs project will also develop a set of functional assays – both in vitro and in silico – to assess deviations from baseline toxicity caused by nanomaterials, supporting the grouping of nanomaterials within sets of nanoforms and prioritising testing for those showing specific modes of toxicity.

A clear focus throughout the project will be on making existing nanomaterial toxicity data Findable, Accessible, Interoperable, and Reusable (FAIR). These areas were identified as PARC priorities based on input from the Governance Board and European agencies such as ECHA, EFSA, and EEA.

Are current methods keeping up with the pace of innovation in nanotechnology?

From a regulatory perspective, such as under REACH ↗, nanomaterials are classified based on their core composition – e.g., titanium dioxide, graphene – and their physical and chemical properties, such as shape, morphology, and surface modification. These factors are used to establish a “set of nanoforms” that behave similarly, as described in the REACH Annex on nanoforms ↗.

Currently, it is not possible to use knowledge from one nanomaterial composition (e.g., TiO₂) to predict the toxicity of another (e.g., SiO₂). However, in silico approaches gain power by combining datasets from different compositions and finding patterns or key physico-chemical drivers (e.g. ionization energy, electronegativity).

Thus, regulatory approaches to grouping, read-across, and establishing quantitative structure–activity/toxicity relationships (QSARs/QPARs) also need to evolve. Additionally, since nanomaterials are dynamic and change properties depending on their surroundings, testing based only on their pristine (as-synthesised) state may miss critical aspects or incorrectly identify materials as toxic or safe.

Do you think regulators currently have sufficient tools and knowledge to assess nanomaterial risks in healthcare or consumer products?

A huge amount of progress has been made, and regulations are adapting to the specific challenges of nanomaterials (e.g., the inclusion of “nanoforms and sets of nanoforms ↗” under REACH). Agencies such as EFSA and EMA are also advancing, with EFSA’s report on NAMs for nanomaterials ↗ and EMA’s horizon scanning on nanotechnology-based medicinal products ↗.

The forthcoming transition to “One Substance, One Assessment ↗” will be game-changing, ensuring harmonised definitions of nanomaterials and streamlined testing approaches. It will also make it easier for validated NAMs to be accepted across sectors.

That said, the gap between science and regulation remains significant. “Omics” technologies are a key example, where enormous mechanistic insights are not yet fully integrated into regulatory approaches, though steps are being made – for example, ECHA’s proposed “omics-enhanced in vivo studies.”

How can research more effectively support evidence-based policymaking in this area?

This remains a challenge. Researchers aim to continuously push the boundaries of knowledge, while policymakers – limited by “bounded rationality” – must make quick decisions using limited information, often relying on emotion, belief, and familiarity (see Cairney & Oliver, 2017 ↗).

Recognising that policymaking and science-based advocacy are both value-driven means researchers must adapt: focusing on storytelling, simplifying messages, aligning with initiatives like PARC, and maintaining persistence, since policy change is gradual.

Training researchers in effective and responsible data communication, especially in the age of misinformation and generative AI, is also critical.

Nanotechnology has been one of the few fields with an explicit commitment to responsible communication, through the 2008 European Commission Code of Conduct for Responsible Research in Nanosciences and Nanotechnologies ↗, emphasising accountability and balanced reporting.

An interesting development is EMA’s proposal for a European Platform for Regulatory Science Research ↗, which aims to foster collaboration among academia, regulators, and research organisations. This could provide a blueprint for a broader platform under the One Substance, One Assessment initiative.

What should be the top priorities over the next five years to ensure that innovation in nanomaterials goes hand in hand with protecting human health?

Major knowledge gaps include: 

• the need for chronic studies in human-relevant model species and cell lines, or organ-on-a-chip approaches;
• a shift to grouping and read-across approaches that consider nanomaterial transformations and corona composition during exposure, uptake, and localisation;
• extending knowledge from mono-constituent nanomaterials to advanced multi-component materials; and
• understanding nanomaterials’ roles in chemical mixtures and their influence on toxicokinetics and toxicodynamics of other substances.

All of these issues are equally relevant to environmental nanomaterials and complement the priorities identified by my co-chemical leader, Susana Loureiro.

How do you see your role as a Chemical Leader, and what are PARC’s priorities?

For me, the role of Chemical Leader is to champion the specific chemical class – in this case, nanomaterials – and ensure it is visible within PARC as a priority area. It’s also about making PARC’s nanomaterials activities visible externally – to other research projects, regulators, member states, and materials developers – supporting safe and sustainable by design approaches.

While we cannot address all identified priorities due to time constraints, having a roadmap of needs and gaps helps funding agencies prioritise future topics and provides researchers with strategic directions for upcoming proposals.

PARC’s priorities are regulatory-focused, and our NanoTox-NAMs project will deliver concrete outputs applicable across nanomaterial compositions and types, supporting the regulatory risk assessment of advanced materials in the long term.