FutureNanoNeeds – Pioneering Hazard Assessment

Growing Importance of Emerging Nanomaterials: The last decade has seen the emergence of numerous nano-enabled devices (NED). Nano and small submicron particles are becoming more common in consumer goods as well as in industrial and public large-scale use. Industries impacted range from cosmetics and food to aerospace engineering. An example of this trend is the global nano-enabled packaging market that in 2015 was valued at USD 23 billion and is forecast to possibly double in the next decade according to a Grand View Research forecast report. While it is too early to tell, many believe that the major advantages in functionality and economy will come from ‘materials of the future’, far removed from those legacy materials in common use today. Applications in nano-energy harvesting, nano-enabled batteries, telecommunications, structural materials, and others will also be important. The parameters describing new nanomaterials are typically complex in many aspects, including, for example, their shape, composition, and surfaces. The role of FutureNanoNeeds (FNN) has been to explore various new kinds of nanomaterials, to see if there are unexpected risks associated with them.

From Research to Use: Exploring Value Chains: The FutureNanoNeeds framework is pursuing two parallel strategies in trying to understand the behaviour of novel materials. In the first approach we explore ‘value chains’ for specific industry applications, concentrating on potential materials that by virtue of their commercial promise seem most likely to be widely used. The value chains follow a material from R&D to manufacture through use and disposal and evaluate potential hazards and exposure scenarios. Candidate value chains, which include solar energy, batteries, and lubricants among others, were identified in part by an extensive exploration of possible materials and applications, a process driven by the project value chain advisory committee.

Systematic Research on Promising Materials: In the second approach, we explore model materials with properties likely to appear in future materials important in consumer and industrial applications. Given the limited range of materials that have been explored in the nanosafety community until now, it is considered important to go far beyond typical parameters and deal with wide variations in shape and composition. Special emphasis is placed on understanding how these parameters impact the biological interactions of new materials.

Merging the Approaches: Overall the first approach has the advantage in directly studying the most promising materials (for example perovskites that are of intense interest right now because of their potential in solar energy applications). The second approach has the advantage of being systematic and providing complete information about a homologous series of materials with key parameters varied. The drawback here is that one loses the immediacy and familiarity of real applications. In practice, the best solution in exploring the space of possibilities is in balancing both lines of enquiry. During the first phase of the project, the proportionating between these approaches was investigated, with emphasis on identifying potential hazards not previously explored. Several instances of new and subtle effects requiring further consideration have been observed, and are now being pursued in more depth.

Research Highlights: In the project’s first phase, we systematically addressed uncertainty related to the toxicity of well-known nanomaterials. Much of the uncertainty was explained by artefacts related to experimental conditions or to dissolution of the tested material into known toxic compounds. In the remainder of cases, toxicity observations were a product of known processes such as photo-toxicity. A consensus has been reached on the absence of acute toxicity effects caused by the nano-scale of material on its own. A summary review of the whole arena of acute toxicity of nanomaterials is under way, in which it is suggested that for the most part, short term toxicity, where it is found, is associated with effects such as nanoparticle dissolution and release of materials for which toxicity parameters are already established. This is in line with what has been reported for previous nanomaterials of all types.

In the second phase, the project focus has shifted to the search for potential sources of hazard from entirely novel materials as well as a deeper understanding of potentially harmful complex behaviours, including novel shape-specific phenomena and possible new diseases prompted by complex bio-nano interactions (e.g. the Trojan horse effect). In implementing this strategy, we face many challenges related to the synthesis, analysis and classification of novel materials, the presence of contamination impacting hazard studies, and the complication of novel or uncommon biological studies.

The synthesis of new nanomaterials was not previously optimized for biological use and suffered from problems due to the contamination by chemicals, catalysts, and (almost universally) biological substances. Comprehensive analysis of these new materials, anisotropic or composite, presents several hurdles. Most notably there is a lack of consensus in both naming and categorizing, a problem discussed in more detail below. This problem leads to a lack of tools and understanding to assess fundamental physico-chemical properties such as size and shape, properties that are essential to biological and toxicological studies.

Recently we worked on a series of new approaches, for a basis not only for particle classification and accurate assessment of fundamental properties, but also for analysis of anisotropic particles in complex media. A significant amount of attention has been given to developing endotoxin-free and surfactant-free synthesis procedures, or alternatively quantifying endotoxin content in samples so that appropriate conclusions are made.  Even after all of these precautions to avoid confounding contamination have been taken, we have observed several new biological effects that appear to relate to the nature of shape. These effects will be studied in more depth to understand their role in any potential form of toxicity.

Expected Outcomes: The first major outcome is expected to be that, for exemplar composite and other novel materials, we can confirm that no exceptional acute toxicity except what has been observed so far, e.g. toxicity solely based on dissolution to toxic components.

The second outcome is progress on identifying the minimal number of material features and properties needed to characterise and predict the interactions of a nanomaterial with biological entities. This would have significant ramifications for the nanosafety community and possibly broader consequences for regulators and industries.

The third and potentially most promising outcome is expected to be identification of specific material features linked to new biological responses not usually observed in existing studies of conventional nanomaterials. While this project may only begin the process of uncovering those connections, it is hoped the way will be opened for an understanding of what additional testing, if any, will be required to secure safety. Ideally we would be able to connect specific structural features to potential downstream hazard effects and begin to understand how to group materials by the features that cause novel effects.

Author: Delyan Hristov, John Rumble, and Kenneth Dawson