Nanotoxicology, 2011; Early Online, 1–13 © 2011 Informa UK, Ltd. ISSN: 1743-5390 print / 1743-5404 online DOI: 10.3109/17435390.2011.626535 Length-dependent pathogenic effects of nickel nanowires in the lungs and the peritoneal cavity Craig A. Poland 1,2 , Fiona Byrne 3 , Wan-Seob Cho 2 , Adriele Prina-Mello 4 , Fiona A. Murphy 2 , Gemma Louise Davies 5 , J.M.D. Coey 3 , Yurii Gounko 5 , Rodger Duffin 2 , Yuri Volkov 4 & Ken Donaldson 2,6 1 Safenano, Institute of Occupational Medicine, Research Avenue North, Riccarton, Edinburgh, UK, 2 Centre for Inflammation Research, University of Edinburgh, Edinburgh, UK, 3 School of Physics and Centre for Research on Adaptive Nanostructures and Nanodevices (CRANN), Trinity College, Dublin 2, Ireland, 4 School of Medicine and CRANN, Trinity College, Dublin 2, Ireland, 5 School of Chemistry and CRANN, Trinity College, Dublin 2, Ireland and 6 Institute of Occupational Medicine, University of Edinburgh, Research Avenue North, Riccarton, Edinburgh, UK Abstract The use of fibre-shaped nanomaterials in commercial applications has met with concern that they could cause health effects similar to those seen with pathogenic fibres such as certain forms of asbestos. Of the attributes which form the fibre pathogenicity paradigm, fibre length is thought to be a critical factor in determining fibre toxicity. We have previously shown that carbon nanotubes display such length-dependent pathogenicity but it remains unclear if other forms of fibrous nanomaterials conform to the fibre pathogenicity paradigm. As such, our aim is to determine the generality of this hypothesis by asking whether a radically different form of fibrous nanomaterial, nickel nanowires, show length-dependent pathogenicity. Our results indicate that nickel nanowires synthesised to be predominantly long (>20 mm) show the ability to elicit strong inflammation in the mouse peritoneal model in a dose-dependent manner; inflammation or fibrosis was not seen with the short (<5 mm) nanowires. This length-dependent response was also seen after lung aspiration and within a macrophage in vitro model adding further weight to the contention that fibre length is an important driver of hazard potential. This may have important implications when considering the hazard posed by fibrous nanomaterials and their regulation in workplaces. Keywords: Nanofibres, fibre pathogenicity paradigm, inflammation, structure activity relationship Introduction Fibres have long been used as an industrial material due to commercially advantageous properties such as tensile strength and anisotropic electrical or thermal conductivity. However, the experience with asbestos, a fibrous silicate mineral, engendered a general suspicion that industrial fibres are pathogenic and this suspicion has fallen on new forms of engineered nanofibres currently being developed. However, the large variety of industrial fibres display a wide range of toxicities from, in the majority of cases, harmless fibres to those which cause a variety of diseases including cancer. Knowledge regarding the toxicity of a wide variety of pathogenic and non- pathogenic fibres, such as asbestos, led to the development of a fibre pathogenicity paradigm (FPP) through the work of such luminaries as Stanton (Stanton et al. 1981) and Pott (Pott et al. 1987) and as discussed recently in relation to the organic fibre para-aramid (Donaldson 2009) and in relation to carbon nanotubes (CNTs) (Donaldson et al. 2010). The FPP is based on three essential physicochemical attributes which a fibre must possess to be pathogenic in a fibre-specific manner. These are: diameter less than 3 mm to allow aerodynamic penetration into the lung; a length greater than approximately 15 mm to frustrate macrophage mediated clearance; and resistance to dissolution and/or breakage in the biological environment causing the fibre to persist – biopersistence (Donaldson 2009). The suggestion that fibrous nanomaterials might conform to the FPP was first raised in relation to CNTs (Service 1998; The Royal Society and Royal Academy of Engi- neering 2004). CNTs by virtue of their nano and graphenic nature are thin and biopersistent, but can vary considerably in length. Long CNTs therefore can fulfil all the attributes of a pathogenic fibre, if long, and have been shown to be both highly inflammogenic and fibrogenic in the peritoneal cavity in this form (Poland et al. 2008). This raises the question which forms the basis of this study: do other nanofibres show length- dependent toxicity? Through the commercialisation of nanoparticles (NPs) and their incorporation into an ever more diverse range of products and applications, engineered NPs are increasingly becoming part of today’s world. This has raised the Correspondence: Craig Poland, Safenano, Institute of Occupational Medicine, Research Avenue North, Riccarton, Edinburgh EH14 4AP, Tel: +44(0)131 449 8096. Fax: +44(0)131 449 8084. E-mail: craig.poland@iom-world.org (Received 21 March 2011; accepted 23 August 2011)  Nanotoxicology Downloaded from informahealthcare.com by Trinity College Library on 02/22/12 For personal use only.