O: Making technological advancement safer by defining the specific attributes of carbon nanofibres that are detrimental to human health
Submitting InstitutionUniversity of Edinburgh
Unit of AssessmentClinical Medicine
Summary Impact TypePolitical
Research Subject Area(s)
Medical and Health Sciences: Cardiorespiratory Medicine and Haematology, Oncology and Carcinogenesis, Other Medical and Health Sciences
Summary of the impact
Impact: Influencing industry, governmental policy, insurance
industry policy and public
Significance: By establishing the actual risks posed by specific
carbon nanotubes (CNT), UK
Health and Safety Executive (HSE) guidance and workplace guidance and
Beneficiaries: CNT industry and users, governments and
policy-makers, the HSE and its
international equivalents, the public.
Attribution: Donaldson and colleagues (UoE) published the first
demonstrations of potential CNT
Reach: Global media coverage, encompassing UK, Europe, USA and
India. Results considered by
national and international policy-making bodies, for example, House of
Lords Science and
Technology committee, US National Institute for Occupational Safety and
Over the last decade, there has been a great deal of investment in
R&D and increasing production
of nanoparticles including nanofibres; however, despite concerns over
health effects, relatively
little effort or funding had been directed towards assessing their safety.
Responding to this deficit,
and based on his experience with asbestos and coalmine dust, Professor Ken
(Professor of Respiratory Toxicology, UoE, 2002-2013; now Emeritus)
established a programme
in 2006 to address the possible dangers of these new materials.
Donaldson's intention was to relate structure to toxicity, and was
therefore relevant to both known
and untested nanofibres. Drawing on the comparison with asbestos, the
focus was on pleural
effects because mesothelioma, a pleural cancer, is uniquely associated
with asbestos exposure.
Fibre length plays a crucial role in the harmfulness of a fibre so, to
investigate whether length was
related to toxicity, Donaldson compared different lengths of carbon
nanotubes (CNT) in a mouse
peritoneal model. Only those CNT that comprised long (>~10 µm)
individual fibres were
pathogenic, whilst those that were compact (agglomerated) and short were
rapidly cleared and did
not cause appreciable inflammation or fibrosis. At the same mass dose, the
effects seen were
significantly greater that those observed with long asbestos fibres; thus,
long-fibre CNT could
cause mesothelioma. With internal and external collaborators, Donaldson
published the findings in
Nature Nanotechnology (impact factor 31.17) in 2008 [3.1].
In subsequent studies, Donaldson demonstrated the same length dependence
and fibrosis for nickel nanowires [3.2], and also, following direct
delivery of CNT into the pleural
cavity of mice, the most common site of mesothelioma development [3.3].
Long, but not short CNT
introduced into the airways caused pleural inflammation; thus, the same
effects were seen using a
physiological route of delivery [3.4].
These early results led to the publication by Donaldson of a highly
accessed article (15,775 times)
outlining the potential risks of fibrous nanomaterials and routes of
safe-by-design particles [3.5].
By fully exploiting nanomaterials' variety and ability to generate
materials to exacting
specifications, Donaldson investigated a large panel of different fibres,
demonstrating that the
length-dependent effect was not material-specific. Silver nanowires in
well-defined length classes,
plus a wide range of nanofibres, were used to show that the threshold
length for retention and
pathogenesis in the pleural space was 5 µm [3.6]. This has great
significance for understanding
and controlling the risk from asbestos and other existing fibres, and for
development of new nanofibres.
References to the research
3.1 Poland C, Duffin R, Kinloch I,...Donaldson K. Carbon nanotubes
introduced into the
abdominal cavity of mice show asbestos-like pathogenicity in a pilot
study. Nat Nanotechnol.
2008;3:423-8. DOI: 10.1038/nnano.2008.111.
3.2 Poland C, Byrne F, Cho W,...Donaldson K. Length dependent
pathogenic effects of nickel
oxide nanowires in the lungs and the peritoneal cavity. Nanotoxicology.
3.3 Murphy F, Poland C, Duffin R,...Donaldson K. Length-dependent
retention of carbon
nanotubes in the pleural space of mice initiates sustained inflammation
and progressive fibrosis
on the parietal pleura. Am J Pathol. 2011;178:2587-600. DOI:
3.4 Murphy F, Poland C, Duffin R, Donaldson K. Length-dependent pleural
parietal pleural responses after deposition of carbon nanotubes in the
pulmonary airspaces of
mice. Nanotoxicology. 2013;7:1157-67. DOI: 10.3109/17435390.2012.713527.
3.5 Donaldson K, Murphy F, Duffin R, Poland C. Asbestos, carbon nanotubes
and the pleural
mesothelium: a review and the hypothesis regarding the role of long fibre
retention in the parietal
pleura, inflammation and mesothelioma. Part Fibre Toxicol. 2010;7:5. DOI:
3.6 Schinwald A, Murphy F, Prina-Mello A,...Donaldson K. The threshold
length for fiber-induced
acute pleural inflammation: shedding light on the early events in
Toxicol Sci. 2012;128:461-70. DOI: 10.1093/toxsci/kfs171.
Details of the impact
Pathways to impact
It was clear that the linkage of a new widely-used material to a mechanism
of toxicity might spark
an unbalanced response and result in damage to UK and worldwide industry
and wealth creation.
Therefore, Donaldson took a considered and multi-faceted approach to
dissemination of the
findings to government, industry and the public. He and colleagues
informed and presented the
findings to the UK Health and Safety Executive (HSE), the UK Department
for Environment, Food
and Rural Affairs and the Nanotechnology Industry Association (NIA) prior
to publication of the
Nature Nanotechnology paper [3.1]; consequently the NIA informed its
members and developed a
proportionate public response.
In collaboration with the Science Media Centre (London), Donaldson gave a
press conference in
May 2008 that was attended by top UK and international science journalists
(including the BBC,
Times and Guardian). Accompanying statements were provided by the British
and UK academic leaders in the field [5.1]. Craig Poland (technician then
PhD candidate, UoE,
2004-2009) presented the findings as an invited speaker at the American
Annual meeting in Toronto (2008).
Impact on society: public engagement and awareness
Donaldson's study achieved widespread global coverage in multiple media
(e.g., Financial Times, New York Times, Agence France Press and Indo-Asian
magazines (e.g., Scientific American), television and internet forums
(e.g. BBC News, CBC News
Canada, NHS Choices). These increased public awareness and stimulated
debate on the risks of
CNT, as evidenced by news interest and by prominent citations of the work
documents discussing the human health risks of CNT, such as those produced
by the US National
Institute for Occupational Safety and Health (NIOSH) [5.2] and by Safe
Work Australia [5.3].The
practical impact of the work is illustrated by the HSE Nanosafety
Partnership Group's health and
safety guidance document [5.4].
Impact on public policy
In September 2008, an HSE guidance document entitled "Risk Management of
Nanotubes" [5.5], which specifically and solely cited Donaldson's study,
was provided to all UK
nanotube-related researchers and industries. Later that year, the US
Agency (EPA) formally put manufacturers on notice that it considered CNT
to be chemically
different from conventional carbon compounds, and potentially subject to
regulation as "new"
chemicals under the Toxic Substances Control Act [5.6]. Donaldson has
frequently been, and
continues to be, consulted as an expert in the field of toxicity of
nanoparticles: for example, in
2010 to the Science and Technology Committee of the House of Lords [5.7].
Impact on industry/commerce
The results of Donaldson's research were noted by industry with interests
in CNT (see NIA
response noted above): for example, specifically addressed in a statement
submitted to the US
Technology Sciences Group by Bayer Material Science AG [5.8]. There have
been at least two
publications from the legal profession considering the ramifications of
the Donaldson study alone
[5.9], and its importance was recognised by the insurance company Lloyds
of London, which
awarded Poland a "Science of Risk" prize in November 2010. Concerns within
the key insurance
industry on the risks of nanotechnology are reflected in the impact of
Donaldson's work; the work
assisted with actuarial decisions that resulted in the withdrawal of
insurance provision for CNT from
November 2008 by Continental Western Insurance Group [5.10].
Sources to corroborate the impact
5.1 NIA news item "Carbon Nanotube News Travels Fast" (2008)
5.2 US National Institute for Occupational Safety and Health,
"Occupational Exposure to Carbon
Nanotubes and Nanofibers" Publication No. 2013-145 Current Intelligence
Bulletin 65 (2013).
5.3 Australian Government Department of Health and Ageing.
Health Hazard Assessment and Classification of Carbon Nanotubes" (2012). [Available
5.4 The UK NanoSafety Partnership Group. "Working Safely with
Nanomaterials in Research
and Development" (2012). [Available on request.]
5.5 HSE "Risk management of carbon nanotubes" (2009). [Available on
request.] This was
reported by The Scotsman on 13 Mar 2009 under the headline "Safety body
acts on city experts'
5.6 Goodwin Proctor Client Alert "EPA Takes First-Ever Regulatory Actions
Aimed at Potential
Nanomaterial Risks" (2008).
5.7 House of Lords Science and Technology Committee Minutes of Evidence
[Memorandum by Donaldson to the Science and Technology Committee
5.8 Technology Science Group Inc. "Multiwalled Carbon Nanotube Toxicity
5.9 (a) Stimers P. The implications of recent nanomaterials toxicity
studies for the nanotech
community"; Nanotechnology Law and Business. 2008;5(3):313-8.
(b) Monica J Jnr and Monica J. A Nano-Mesothelioma False Alarm.
Nanotechnology Law and
Business. 2008;5(3):319-33. http://www.nanolawreport.com/5_3_Policy_Ethics_254_1__pdf.pdf.
5.10 Cozzens S and Wetmore J (eds). Nanotechnology and the Challenges of
and Development. Springer London Limited, 2011.
[Available on request.]