Keeping it real: The importance of material characterization in nanotoxicology

Highlights

• More coherence is needed in the way that nanotoxicology is conducted.

• Thorough physicochemical characterization is necessary in nanotoxicology.

• The biological ‘identity’ of nanomaterials in a living system is also important.

• Material characterization should be fit-for-purpose, and relevant for the study.

• Categorization of nanomaterials based on functionality may support regulation.

Abstract

Nanomaterials are small and the small size and corresponding large surface area of nanomaterials confers specific properties, making these materials desirable for various applications, not least in medicine. However, it is pertinent to ask whether size is the only property that matters for the desirable or detrimental effects of nanomaterials? Indeed, it is important to know not only what the material looks like, but also what it is made of, as well as how the material interacts with its biological surroundings. It has been suggested that guidelines should be implemented on the types of information required in terms of physicochemical characterization of nanomaterials for toxicological studies in order to improve the quality and relevance of the published results. This is certainly a key issue, but it is important to keep in mind that material characterization should be fit-for-purpose, that is, the information gathered should be relevant for the end-points being studied.

Introduction

Engineered nanomaterials have become the focus of extensive research in many areas including biomedical applications due to the novel and unique properties arising at the nanoscale. In addition, during the past decade, there has been an exponential increase in the number of papers on the toxicological effects of nanomaterials. However, while this certainly shows that the potential risks of nanomaterials are being considered, it has been argued that numerous poorly controlled studies have been published, offering little insight into any ‘nanospecific’ effects [1]. Indeed, Krug concluded in a recent overview of the field that while 10.000 papers have been produced on environmental and health effects of nanomaterials in the last 15 years, we are left with “a plethora of low-value results” due to the lack of harmonized experimental protocols, poor or nonexistent characterization of the nanomaterials, a lack of reference materials, the frequent reliance on unrealistically high doses both for in vitro and in vivo studies, and so on [1]. Others have also complained, on the basis of a meta-analysis of several dozen papers focused on silica particles, that “after over a decade of research, answers for the most basic questions are still lacking” and suggested that more coherence in the experimental methods and materials used is needed [2].

Ten years have passed since the review by Oberdörster et al. defining and outlining the emerging discipline of nanotoxicology [3]; in their review, which is now a ‘citation classic’, the authors defined nanotoxicology as a “science of engineered nanodevices and nanostructures that deals with their effects in living organisms” and they pointed out that nanotoxicology research also will advance the field of nanomedicine by providing information on the undesirable properties of nanomaterials and means to avoid them. Indeed, this is sometimes referred to as ‘safe-by-design’ [4].

In another very pertinent review, also published in 2005, Oberdörster et al. summarized the views of an international expert group convened to develop a screening strategy for the hazard identification of engineered nanomaterials [5]. Hence, the authors stated that “there is a strong likelihood that biological activity of nanoparticles will depend on physicochemical parameters not routinely considered in toxicity screening [of chemicals]” and put forward a list of physicochemical properties that may be important in understanding the toxicity of nanomaterials namely: particle size and size distribution, agglomeration state, particle shape, crystal structure, chemical composition, surface area, surface chemistry, surface charge, and porosity [5]. Similar suggestions for minimal material characterization requirements in nanotoxicology have been proposed in recent years, as we shall discuss in the present essay. The question is: are we ready to adopt such requirements as an international standard(s)? Indeed, can we afford not to do so? Furthermore, are there any examples of ‘good’ nanotoxicological studies, or has all been for naught?