THE HIDDEN HAZARDS - EngineeringNet.be

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Pathways in cell and tissue damage (part 1)
The hidden hazards
of nanomaterials
Wat volgt is het eerste deel van een
uitzonderlijke Engelstalige bijdrage van
onze columnist Frank Moerman (KULeuven). Wetenschappelijke artikels over
de veiligheidsrisico's verbonden aan
nanomaterialen zijn eerder zeldzaam,
en bovendien ontbreekt enig regelgevend kader. «Beter vroeg dan laat», een
waarschuwing aan het adres van de
preventie-adviseurs!
O
ndanks het feit dat de eerste wetenschappelijke onderzoeksresultaten
aantonen dat veel nanomaterialen
toxisch zijn voor levende organismen,
worden ze toch met ongeziene snelheid
in allerlei applicaties gebruikt. Nanomaterialen zijn een klasse materialen waarbij
minstens één dimensie zich in de nanometer-range (10-9 m) bevindt. Koolstof nanobuisjes hebben dezelfde analoge structuur
als asbest, en er zijn indicaties dat zij
vele jaren na blootstelling (bv. inademen)
dezelfde gezondheidsproblemen zullen
veroorzaken, meer specifiek long- en buikvlieskanker. Zonder richtlijnen en wetgeving die beschrijven hoe deze materialen
moeten behandeld worden tijdens productie, verwerking, toepassing en afvalverwerking, zullen verwerkers en gebruikers op
korte of lange termijn mogelijks ernstige
gezondheidsschade ondervinden. Er is dus
dringend meer onderzoek vereist om per
type nanomateriaal de schadelijke gezondheids- en milieu-effecten te bepalen, te
meer omdat men niet zomaar de toxiciteit
kan bepalen op basis van de eigenschappen die hetzelfde corresponderende
materiaal in de millimeter-range bezit. Men
moet de gezondheids- en milieurisico’s
van nanomaterialen dus geval per geval
onderzoeken.
Frank Moerman,
Catholic University of Leuven
M
any countries have developed programs to promote
nanotechnology. Nanomaterials are all materials with a structural component smaller than 100 nm
in at least one dimension. Besides
nanoparticles that have three dimensions in the 1-100 nm range, there
are also nanorods or nanotubes that
have two dimensions in this range,
and nanosheets or nanomembranes
that have one dimension in this range.
Nanoparticles of a specific material exhibit quite different physical
(optical, electromagnetic), chemical
(catalytic with increased chemical
reactivity as result) and mechanical
properties as compared to their larger
counterparts, mainly due to surface
and quantum effects. Because of these
properties, nano-materials have the
potential to alter physicochemical and
biological characteristics. So, a material that is considered nontoxic in its
larger-sized form might be extremely
toxic at the nanoscale.
Cntpolymermatrix. Engineered
nanoparticles are materials
engineered to create novel
functionality or properties
different from those of their
larger counterparts of the same
chemical composition.
Safety concerns
Safety concerns about nanomaterials
are mainly driven by the accumulated
knowledge of the health effects of
inhaled anthropogenic nanoparticles,
which are man-made in contrary to
the nanoparticles commonly found in
nature. Well-known natural nanoparticles are ash of volcanic eruptions,
dust from desert storms, dust particles
due to physical and chemical weathering of rocks, soot due to incomplete
combustion during forest fires, extraterrestrial dust, etc. Anthropogenic
nanoparticles (e.g., pollution due
to vehicle and automobile exhaust,
smoke and ash formed when burning
wood, combustion of coal and petroleum for heating and power generation, waste incineration, occupational
activities such as building demolition
and welding, etc.) have shown to be
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ENGINEERINGNET.BE & NL
IN THE FIELD
Fig. 1 Lung lesions in rats after inhalation of nanomaterials: saline (A, F, K), carbon black (B, G, L), asbestos (C,
H, M), multiwall carbon nanotubes (D, I, N), and grounded
multiwall carbon nanotubes (E, J, O) (Buzea et al., 2007).
Fig. 2 Diseases associated with nanoparticle exposure
(Buzea et al., 2007)
Fig. 3 At the cellular level, nanomaterials can interact with
cells by various means. (1) Nanotubes can bind to receptors,
(2) block the pores on the cell membrane and (3) damage the
cell membrane. (4) Nanowire can puncture the entire cell
responsible for the increase in cardiovascular, airway and pulmonary diseases,
often resulting in death. The adverse
health effects of pathogenic fibres, such
as asbestos and silicates are well-known.
Asbestos is responsible for lung and peritoneum mesothelioma (asbestos cancer),
and because of their similar morphology,
nanofibres and nanorods (e.g., single- and
multiwalled carbon nanotubes) are suspected to exert the same damaging effects
as asbestos after inhalation (Fig. 1).
So, concerns have arisen that engineered nanoparticles, another category of
man-made nanoparticles, might be toxic.
Engineered nanoparticles are materials
engineered at the nanoscale to create
novel functionality or properties different
from those of their larger counterparts of
the same chemical composition. At present, the health effects of the long-term
use of engineered nanomaterials and their
interaction with other components such
as proteins, lipids, carbohydrates and
nucleic acids are not sufficiently known.
Hence, before nanomaterials are largely
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membrane and (5) nanoparticles can physically rupture the cell membrane
due to hyperthermic effects. Nanoparticles can be internalized into the cell
(6) and the production of reactive oxygen species (ROS) (7) can be induced
due to the high surface-to-volume ratio and the increased surface reactivity
of these nanomaterials. High ROS concentrations are often associated with
severe protein, DNA (8) and membrane (9) damage via excessive oxidation,
resulting in induced programmed cell death in a vast number of cell types.
The internalized nanomaterials can also damage subcellular organelles such
as the mitochondria (10) and lysosomes (11), and stop their functions. All of
these effects can disrupt cellular processes resulting in cell death (apoptosis
and/or necrosis), chronic inflammation and fibrosis (Han et al., 2011).
used in a wide range of applications,
risk assessments must be performed
to identify and quantify their potential
toxicity. Notice that it is virtually impossible to extrapolate the adverse effects of
nanoparticles from their bulk properties
(Buzea et al., 2007; Pacheco-Blandino et
al., 2012; Moerman, 2014).
Nanomaterials in the body
Nanomaterials can be absorbed by
inhalation of free nanomaterials present
in the air, by ingestion from food and
water, and by penetration through the
skin (Fig. 2). Once nanoparticles enter
the body, they can penetrate the mucosal
barriers of the gut and airways and travel
through the circulatory systems, to finally
deposit in various organs including the
liver, kidneys and brain, where they can
remain for weeks and months. Biostable nanomaterials (e.g., nanoparticles
made of metal, such as quantum dots
and silver; TiO2 nanoparticles; carbonbased nanomaterials such as fullerenes,
carbon nanotubes, carbon soot; and
silicon-based nanoparticles) have proven
to exhibit long tissue retention times, in
particular in the liver, spleen, and lymph
nodes. Biopersistence, being the ability
to penetrate into body tissues and to
resist solubilization and normal clearance
mechanisms (macrophage engulfment or
renal/fecal excretion), is the main property of nanoparticles that may induce
its longer term toxicity (Moerman, 2014).
Adverse health effects
of nanomaterials
Some nanomaterials have been found to
exhibit negative effects on tissues (Stone
et al., 2009; Becker et al., 2011) (Fig. 3),
as they may:
• mobilize tissue macrophages eliciting
sustained local inflammatory reactions,
generally mediated by macrophage generated reactive oxygen species (ROS) and
inflammatory cytokines;
• cross membrane barriers, preventing
entry of larger particles to the systemic
circulation;
• penetrate cell membranes, after which
ENGINEERINGnet.BE & NL
IN THE FIELD
References
they may initiate the formation of ROS
that may cause oxidative damage to cells
and impair cellular functional pathways.
Oxidative stress at the cellular level may
evoke acute and chronic inflammation,
and also plays a significant role in the
etiopathogenesis of several diseases,
such as cardiovascular diseases, cancer
as the consequence of uncontrolled cell
proliferation, and neurodegenerative
diseases as the consequence of premature
cell death (apoptosis).
Cytotoxicity of several
nanomaterials
Soto et al. (2005) performed comparative
cytotoxicological assessment of several
nanomaterials utilizing a murine lung
macrophage cell line. Considering chrysotile asbestos as the positive control, and
assigning it a relative cytotoxicity index
of unity 1.0, relative cytotoxicities (relative cell viability (RCV) values) for the
corresponding nanoparticulate materials
Becker, H., Herzberg, F., Schulte, A.
and Kolossa-Gehring, M. (2011), ‘The
carcinogenic potential of nanomaterials,
their release from products and options for
regulating them’, International Journal of
Hygiene and Environmental Health, 214 (3),
231-238.
Buzea, C., Pacheco, I.I. & Robbie, K.
(2007),’Nanomaterials and nanoparticles:
sources and toxicity’, Biointerphases, 2,
MR17-MR712.
Han, Z.J., Levchenko, I., Kumar, S.,
Yajadda, M.M.A., Yick, S., Seo, D.H.,
Martin, P.J., Peel, S., Kuncic, Z. & Ostrikov,
K. (2011), ‘Plasma nanofabrication and
nanomaterials safety’, Journal of physics D:
applied physics, 44 (17),174019-1 - 17409-8.
2014, 22-23 April, Ohrid, Macedonia, Journal
of Hygienic Engineering & Design, 7, 8-29.
Pacheco-Blandino, I., Vanner, R. & Buzea,
C. (2012), ‘Toxicity of nanoparticles’, Ch.
14, in Pacheco-Torgal, F., Jalali, S. & Fucic,
A. (eds.), Toxicity of Building Materials,
Cambridge, United Kingdom, Woodhead
Publishing, pp. 427-475.
Soto, K.F., Carrasco, A., Powell, T.G.,
Garza, K.M. & Murr, L.E. (2005),
‘Comparative in vitro toxicity assessment
of some manufactured nanoparticulate
materials characterized by transmission
electron microscopy’, Journal of Nanoparticle
Research, 7 (2-3), 145-169.
Moerman, F. (2014), ‘Antimicrobial
materials, coatings and biomimetic surfaces
with modified microtopography to control
microbial fouling of product contact surfaces
within food processing equipment: legislation,
requirements, effectiveness and challenges’,
Lecture at Central European Food Congress
Stone, V., Hankin, S., Aitken, R., Aschberger,
K., Baun, A., Christensen, F., Fernandes,
T., Hansen, F., Hartmann, B., Hutchison,
H., Johnston, H., Micheletti, C., Peters, S.,
Ross, B., Sokull-Kluettgen, B., Stark, D. &
Tran, L. (2009), ‘Engineered Nanoparticles:
Review of Health and Environmental Safety’,
Final Report of the European 7th Framework
Program ENRHES, Edinburgh Napier
University, United Kingdom, 408 p.
in the concentration range of 5-10 µg/ml
were referenced to this substance (see
table below). <<
In the next issue:
«Toxicity of nanoparticles
in current applications»
Table: nanomaterials, morphologies and relative Cytotoxicity Index (Soto et al., 2005)
Material
Ag (silver; 99,99 %) (25 nm grade)
Ag (silver; 99,99 %)
A2O3 (-alumina)
Component particle size
Relative cytotoxicity* index
(at 5 µg/ml)
Relative cytotoxicity* index
(at 10 µg/ml)
3-100 nm spherules; 30 nm (mean)
1.5
0.8
5-65 nm spherules; 30 nm (mean)
1.8
0.1
4-115 nm spherules; 50 nm (mean)
0.7
0.4
Fe2O3 (-iron oxide)
5-140 nm spherules; 50 nm (mean)
0.9
0.1
ZrO2 (zirconia)
7-120 nm spherules; 20 nm (mean)
0.7
0.6
TiO2 (80% anastase)
5-100 nm spherules; 40 nm (mean)
0.4
0.2
5-40 nm spherules; 20 nm (mean)
0.4
0.1
Irregular, short fibres
5-15 nm (diameter); 20-60 nm (length)
0.3
0.05
10-150 nm spherules; 60 nm (mean)
0.4
0.06
15-40 nm fibre diameter; 20 nm (mean)
0.5 - 15 µm length ; ~ 5.:1 – 500:1 aspect ratio
1.0
1.0
2-50 nm spherules; 20 nm (mean)
0.8
0.6
Nanoropes/bundles
10-200 nm diameter
1.1
0.9
Multi wall carbon nanotube
powder (MWCNT)
~ 50 % nanotubes; 10-30 nm (diameter)
50 nm - 1 µm fibre (length)
~ 50 nm fullerene diameters
1.1
0.8
Multi wall carbon nanotube
powder (MWCNT)
~ 85 % nanotubes; 3-5 nm (diameter)
15 nm (mean); 20 nm - 1 µm lengths
0.9
0.8
TiO2 (anastase)
TiO2 (rutile)
Si3N4 (silicon nitride)
Chrysotile Asbestos Mg3Si2O5(OH)4
Carbon black powder
Single wall carbon nanotube
powder (SWCNT)
* Referenced to asbestos, an index less than 1 represents lower toxicities, while higher values reveal higher cytotoxicity
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