MXenes (pronounced maxenes) are a unique family of two-dimensional materials. Current regulatory frameworks struggle to effectively manage MXenes due to their distinct properties and lack of appropriate safety testing methods. The OECD's Early4AdMa methodology highlights the need for improved characterisation, toxicity testing, and greener production processes for titanium carbide MXenes, emphasising the limited data available on their health and environmental impacts. Proactive regulation and interdisciplinary collaboration are essential as MXenes move closer to commercialisation, ensuring that safety and sustainability considerations are incorporated into the development of advanced materials.

Challenges in regulatory frameworks

Current regulatory frameworks may not be adequate for MXenes due to their distinctive physicochemical properties, including variations in lateral size, number of layers, and surface modifications. Appropriate methods for ensuring reliable dispersions and accurate characterisation of MXenes and their transformation products in complex environments—essential for safety testing—may not be available. These conclusions were drawn by the OECD Working Party on Manufactured Nanomaterials (WPMN - Steering Group for Advanced Materials), which evaluated MXenes as a case study using the Early4AdMa methodology.

What are MXenes?

MXenes are a family of two-dimensional carbides and nitrides that are gaining attention for their potential applications in energy storage and biomedicine. The general formula of a MXene is Mn+1XnTx, where M represents an early transition metal atom (such as titanium, chromium or zirconium), X denotes either carbon or nitrogen, and T signifies the surface termination groups. These materials feature ultra-thin layers, high surface area, tuneable surface properties, and exceptional electrical conductivity. A significant focus of MXenes research thus far has been on the first discovered titanium carbide (Ti₃C₂T_x).

Early4AdMa methodology

The Early4AdMa anticipatory regulatory preparedness tool aims to bridge the gap between innovation and regulation. It is designed to foster innovation while ensuring that safety and sustainability considerations can be taken into account. By identifying potential issues early on, the tool supports risk governance and helps formulate appropriate follow-up actions, such as assessing the suitability of safety testing methods. The Early4AdMa tool was applied to systematically identify potential safety and sustainability issues and regulatory challenges associated with titanium carbide MXenes.

Case study findings

The case study findings were presented during an online workshop hosted by the OECD on 28 May 2024, summarised in an OECD report, and followed by a recent publication that dives deeper into the available literature and data and explores follow-up actions. The authors emphasise the limited data on the human health and environmental impacts of titanium carbide MXenes. Existing toxicity studies are inconsistent, and long-term studies are scarce. The synthesis of titanium carbide MXenes comes with a high environmental cost due to the use of hazardous chemicals and energy-intensive processes, underscoring the urgency of developing greener production methods.

Recommendations for future research

To address these gaps, the authors recommend several actions, including the development of harmonised test methods, a review of the adequacy of physicochemical characterisation in regulatory contexts, guidance on sample preparation and compatible analytical methods, and additional comprehensive toxicity and sustainability studies. These measures are intended to ensure the safe and sustainable use of titanium carbide MXenes and similar two-dimensional materials.

Reflections by RIVM

Currently, MXenes are in the late-stage of innovation or pre-market stage, with commercialisation just beginning. Proactive identification of early warning signals at this stage could facilitate targeted actions for regulatory preparedness and the implementation of Safe and Sustainable by Design (SSbD) principles in future material or product development. Although this paper focuses on titanium carbide MXenes, the lessons learned may be relevant to other MXenes and advanced materials.
The most well-known two-dimensional material is graphene, for which the Nobel Prize in physics was awarded in 2010. This recognition sparked a surge in interest and investment in graphene research and development, culminating in the Graphene Flagship research initiative (2013-2023) in Europe. With a budget of €1 billion, this initiative supported the commercialisation of over 100 graphene-based products. However, the human health and environmental impacts of graphene remain a topic of debate.
Moreover, in 2025, the Nobel Prize in Chemistry was awarded for research on Metal-Organic Frameworks (MOFs), a class of porous advanced materials with applications in gas storage, catalysis and drug delivery, among others. With graphene in mind, this may raise questions about regulatory preparedness for the potentially large group of different MOFs, which may not necessarily be restricted to two dimensions.
The lessons learned from the application of Early4AdMa to MXenes, as well as to nanocarriers, serve as a valuable guide for promoting safe and sustainable innovation in other advanced materials like MOFs. To effectively implement the identified actions, interdisciplinary collaboration among researchers, industry, regulators and other stakeholders is required.