Manufactured nanomaterials: categorization and approaches to hazard assessment

Abstract

Nanotechnology offers enormous potential for technological progress. Fortunately, early and intensive efforts have been invested in investigating toxicology and safety aspects of this new technology. However, despite there being more than 6,000 publications on nanotoxicology, some key questions still have to be answered and paradigms need to be challenged. Here, we present a view on the field of nanotoxicology to stimulate the discussion on major knowledge gaps and the critical appraisal of concepts or dogma. First, in the ongoing debate as to whether nanoparticles may harbour a specific toxicity due to their size, we support the view that there is at present no evidence of 'nanospecific' mechanisms of action; no step-change in hazard was observed so far for particles below 100 nm in one dimension. Therefore, it seems unjustified to consider all consumer products containing nanoparticles a priori as hazardous. Second, there is no evidence so far that fundamentally different biokinetics of nanoparticles would trigger toxicity. However, data are sparse whether nanoparticles may accumulate to an extent high enough to cause chronic adverse effects. To facilitate hazard assessment, we propose to group nanomaterials into three categories according to the route of exposure and mode of action, respectively: Category 1 comprises nanomaterials for which toxicity is mediated by the specific chemical properties of its components, such as released ions or functional groups on the surface. Nanomaterials belonging to this category have to be evaluated on a case-by-case basis, depending on their chemical identity. Category 2 focuses on rigid biopersistent respirable fibrous nanomaterials with a specific geometry and high aspect ratio (so-called WHO fibres). For these fibres, hazard assessment can be based on the experiences with asbestos. Category 3 focuses on respirable granular biodurable particles (GBP) which, after inhalation, may cause inflammation and secondary mutagenicity that may finally lead to lung cancer. After intravenous, oral or dermal exposure, nanoscaled GBPs investigated apparently did not show 'nanospecific' effects so far. Hazard assessment of GBPs may be based on the knowledge available for granular particles. In conclusion, we believe the proposed categorization system will facilitate future hazard assessments.

Frameworks and tools for risk assessment of manufactured nanomaterials

“…This has become a dynamic area of research and several frameworks for grouping and read-across of MNs have been proposed (Arts et al, 2015a, RIVM, 2015, ECHA, JRC and RIVM, 2016, Gebel et al, 2014, Walser and Studer, 2015. These approaches are still rather conceptual and are not based on sufficient understanding of the interdependencies among the intrinsic and extrinsic properties of MNs and their observed adverse biological effects .…”

Release and toxicity comparison between industrial- and sunscreen-derived nano-ZnO particles

“…The extent of toxicity has recently been reported to depend on size, shape, and surface area (BystrzejewskaPiotrowska et al 2009;Gebel et al 2014). A smaller size, which offers a larger surface area, could increase toxicity possibly due to faster adherence to the cells (Bystrzejewska-Piotrowska et al 2009;Gebel et al 2014).…”

Grouping of nanomaterials for risk assessment

“…However, because of the high number of different materials and the difficulty to interpret many of the in vitro studies with respect to their in vivo relevance, the present categorization concept proposed by Gebel et al (2014) will contribute to a better overview and a more straightforward hazard identification. When novel nanomaterials have to be evaluated, it seems reasonable to check initially whether they fulfill one of the three "Gebel-criteria."…”

“…All molecular mechanisms described for nanomaterials have already been identified for chemicals or described in conventional particle toxicology. The present article (Gebel et al 2014) is of high interest to anyone working in the field of nanotoxicity, because it introduces a straightforward concept and gives the risk evaluator a better overview.…”

“…In this issue of the archives of toxicology, Gebel and colleagues introduce a practical guide how to group nanomaterials for risk assessment (Gebel et al 2014). To establish categories, the authors analyzed exposure scenarios where nanoparticles have been shown to cause adverse health effects.…”