Ensuring safety: research on the health impacts of nanomaterials

A vast array of nanomaterials is generated by industry. These nanomaterials possess many remarkable properties which make them useful in a wide variety of products ranging from medicines to cosmetics, food additives and electronics. Understanding their potential hazards is of paramount importance for human and environmental health.

Industries in Europe are required to provide specific information to the European Chemicals Authority (ECHA) and other regulators regarding the risks of any nanomaterials that it manufactures and markets. Each unique form of a nanomaterial requires detailed information about its chemical composition and physical characteristics (e.g. shape), its potential for release leading to human or environmental exposure, as well as information on its potential hazards. To test the hazards of every nanomaterial form is impossible due to the cost, time and the number of animals required.

The GRACIOUS project aimed to find a solution to this challenge. An EU H2020 project coordinated by Heriot-Watt (2018-2021), it united 23 partners from leading institutions across the EU and US, encompassing academia, industry, regulators, and policymakers. It aimed to develop a science-based framework that could streamline the assessment of hazard posed by the ever-increasing array of nanomaterials, with a focus on reducing animal use.

Creating an innovative risk assessment framework

GRACIOUS developed a framework to support the logical, evidence-based grouping of similar forms of nanomaterials. Grouping allows data to be shared between nanomaterials within the same group. For example, if one group member has animal data demonstrating a specific toxicity (e.g. lung tumour formation) then this hazard data can be shared (read-across) to other group members. This reduces the need to generate animal data for the remaining group members.

The GRACIOUS framework supports industry to meet the needs of regulators.

Regulators require industry to generate a grouping hypothesis that explains the relationship between nanomaterial physicochemical characteristics, route of exposure and mechanism of toxicity. To support the user, the framework includes 40 pre-defined grouping hypotheses (17 for human hazard, 23 for environmental hazards). The user can choose the most appropriate hypothesis, or if necessary, design their own via application of the framework’s hypothesis template.

Regulators require industry to provide evidence that their nanomaterials are sufficiently similar to each other to be grouped and therefore share data. The framework provides tailored Integrated Approaches to Testing and Assessment (IATA; decision trees) that support the user to gather evidence to test their grouping hypothesis for all group members.

Regulators require the evidence to be supported by a data matrix. The framework combines the outputs of the IATA into a data matrix, and then uses machine learning (artificial intelligence) to demonstrate similarity to support non-biased evidence-based grouping and therefore read-across of data.

The Framework is delivered as an open access E-tool blueprint for incorporation into risk assessment tools and decision support systems. It is also provided as a Guidance Document with example case studies to support the user.

Delivering long-term impact in the nanotechnology field

GRACIOUS has addressed important gaps in knowledge about nanotechnology including safety testing, influenced the content of international regulation guidance, and promoted the responsible and sustainable development of nanotechnology.

Its framework is being used by the Organisation for Economic Cooperation and Development (OECD) and is aligned with the requirements of the European Chemicals Agency (ECHA) in relation to Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH). It has been used in case studies by the European Commission (Joint Research Centre), and national authorities such as the German Federal Institute for Risk Assessment (BfR), as well as in the USA by the US Environment Protection Agency (EPA) and the National Institute for Occupational Safety and Health (NIOSH).

The framework has also been used by industry including BASF, Blue Frog Scientific, and Yordas.

It is also listed on the Innovation Radar, a European Commission initiative to identify high potential innovations and innovators in EU-funded research and innovation projects.

Expanding access and impact

At an international level the GRACIOUS Framework is being developed further by a wide range of EU projects that are developing solutions for the safe and sustainable design of new multicomponent and advanced materials (SUNSHINE, HARMLESS, DIAGONAL, SUNRISE, CHIASMA).

The framework has been published in NanoToday and the data gathered through GRACIOUS is publicly available via the GRACIOUS eNanoMapper database, which is extending the project’s impact globally.

Reducing the financial burden and requirements for animal testing, GRACIOUS is enabling more ethical and easier pathways to market for nano-products. By streamlining innovation, it is supporting the wider application of nanotechnologies which underpin some of the most exciting and most significant developments in the modern world.