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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.

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Acknowledgments

We thank Ms. Susanne Lindemann and Ms. Silke Hankinson for valuable bibliographic support.

Conflict of interest

Heidi Foth has already performed research on safety aspects of nanoparticles and is corresponding author of the manuscript ‘Vorsorgestrategien für Nanomaterialien’. Alexius Freyberger is employed as a toxicologist by Bayer Pharma AG, Wuppertal, Germany. Pharmaceuticals are explicitly not considered in this article. A. F. previously participated in toxicological studies on other nanomaterials as a contributing scientist. Currently, he is not involved in the assessment of hazard or risk of nanomaterials. Thomas Gebel is working at the German Federal Institute for Occupational Safety and Health (BAuA) which conducts research and development in the field of safety and health at work. BAuA is a governmental research institution within the purview of the Federal Ministry of Labour and Social Affairs. T. G. is involved in the toxicological evaluation of workplace chemicals both with respect to hazard classification and occupational exposure limit setting in Germany. This includes nanomaterials. Results of such evaluations are partly published as scientific or regulatory papers or in text books. T. G. is further involved in funding extramural research on nanomaterials by BAuA. Peter-Jürgen Kramer certifies that as co-author he has no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript. He has some stock ownership at the chemical-pharmaceutical company Merck KGaA, but has no knowledge, to which extend Merck is involved in the nanochemical business. In the past, until June 2008, he was an employee at Merck (Merck Pharma/Merck Serono) and worked as Ombudsman for Merck Serono R&D from August 2008 until July 2012. Today he receives standard company pension payment from Merck. Werner Lilienblum is a former official at the authority for the environment and occupational safety and health in Lower Saxony, Germany. After his retirement, he worked as a consultant in toxicology until 2012. Since 2013, he is a member of the Scientific Committee on Consumer Safety (SCCS) and of its working group on nanomaterials at the European Commission. He also contributed as an associated scientific advisor to the SCCS Guidance on Safety Assessment of Nanomaterials in Cosmetics. Working as a member or scientific advisor in the scientific committees of the European Commission requires a commitment to scientific activity only in the public interest. Claudia Röhl has been involved in research projects on nanomaterials funded by the Christiana Albertina University Kiel and the ‘Deutsche Forschungsgesellschaft’ (DFG). She has published scientific papers in this area and is working at the German Federal Institute for Risk Assessment (BfR) since August 2013, where she is not involved in risk assessment of nanomaterials. The present article exclusively represents the authors’ opinion. Thomas Schupp was employed by BASF Polyurethanes GmbH, Germany, until August 2012. Working in the product safety group, he received some general questions concerning the risk of nanomaterial from researchers of the R&D department (who were anxious about a new asbestos case). These questions were forwarded to the central product stewardship department of BASF. Thomas Schupp left the company before a reply was received and did not deal with that issue in detail. Currently, Thomas Schupp is not involved in projects dealing with nanoparticles. Carsten Weiss is an independent research group leader at the Institute of Toxicology and Genetics at KIT. C. W. studies the mechanisms of action and physico-chemical properties of nanomaterials in several model systems such as cell lines, zebrafish embryos and mice. C. W. is and has been funded by the European Commission in various projects (framework programme), German research foundation (DFG) and the German Federal Institute for Risk Assessment (BfR). C. W. is currently the deputy coordinator of the EU consortium NanoMILE (2013–2017) and published more than 10 papers on nanotoxicology and nanosafety. Klaus-Michael Wollin, Georg Damm and Jan G. Hengstler declare no conflict of interest.

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The authors are members of the Advisory Committee of the German Society of Toxicology (GT), elected by the members of the Society. The Committee consists of scientists from academia, industry and administration in order to guarantee a broad range of toxicological competence. The German Society of Toxicology is the largest scientific toxicological organization in Europe, with more than 1,200 members. The annual plenary meeting had asked the advisory committee to work on a position on the safety of nanomaterials. While all members were invited to contribute to this, the authors are solely responsible for the content of the published manuscript. The advisory committee invited Dr. Carsten Weiss to join the authors as a guest expert.

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Gebel, T., Foth, H., Damm, G. et al. Manufactured nanomaterials: categorization and approaches to hazard assessment. Arch Toxicol 88, 2191–2211 (2014). https://doi.org/10.1007/s00204-014-1383-7

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Keywords

  • Nanoparticles
  • Nanotoxicology
  • Fibrous nanomaterials
  • Granular biodurable nanoparticles
  • Biodistribution
  • Genotoxicity