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Index Potential Risks of Nanomaterials
and How to Safely Handle Materials of Uncertain Toxicity
“It is a mistake for someone to say
nanoparticles are safe, and it is a mistake to say nanoparticles
are dangerous. They are probably going to be somewhere in the middle.
And it will depend very much on the specifics.”
V. Colvin, Director of Center for Biological
and Environmental Nanotechnolgy at Rice University, quoted in Technology
Review
Summary
In the last year and a half, there have been a number of research
articles on the toxicity of different types of nanomaterials. These
studies have suggested effects at the cellular level and in short-term
animal tests. The effects seen depend on the base material of the
nanoparticle, its size and structure, and its substituents and
coatings. Additional toxicology testing is being funded or planned
by the National Science Foundation (NSF), the National Toxicology
Program, and other research organizations in the US and in Europe.
Nanomaterials of uncertain toxicity can be handled using the same
precautions currently used at MIT to handle toxic materials: use
of exhaust ventilation (such as fume hoods and vented enclosures)
to prevent inhalation exposure during procedures that may release
aerosols or fibers and use of gloves to prevent dermal exposure.
The EHS Office will continue to review health and safety information
about nanomaterials as it becomes available and distribute it to
the MIT community.
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What are
nanomaterials?
The ASTM Committee on Nanotechnology has defined a nanoparticle
as a particle with lengths in 2 or 3 dimensions between 1 to 100
nm that may or may not have a size related intensive properties.
Nanomaterials are generally in the 1-100 nm range and can be composed
of many different base materials (carbon, silicon, and metals such
as gold, cadmium, and selenium). Nanomaterials also have different
shapes: referred to by terms such as nanotubes, nanowires, crystalline
structures such as quantum dots, and fullerenes. Nanomaterials
often exhibit very different properties from their respective bulk
materials: greater strength, conductivity, and fluorescence, among
other properties. For many types of nanoparticles, 50-100% of the
atoms may be on the surface, resulting in greater reactivity than
bulk materials.
Particles in the nanometer size range do occur both in nature
and as an incidental byproduct of existing industrial processes.
Nanosized particles are part of the range of atmospheric particles
generated by natural events such as volcanic eruptions and forest
fires. They also form part of the fumes generated during welding,
metal smelting, automobile exhaust, and other industrial processes.
One concern about small particles that are less than 10 um is that
they are respirable and reach the alveolar spaces of the lungs
The current nanotechnology revolution differs from past industrial
processes because nanomaterials are being engineered and fabricated
from the “bottom up”, rather than occurring as a byproduct
of other activities. The nanomaterials being engineered have different
and unexpected properties compared to those of the parent compounds.
Since their properties are different when they are small, it is
expected that they will have different effects on the body and
will need to be evaluated separately from the parent compounds
for toxicity.
Currently nanomaterials have a limited commercial market. Some
nanmoaterials are used as catalyst supports in catalytic converters;
nanosized titanium dioxide particles are used as a component of
sunscreens; carbon nanotubes have been used to strengthen tennis
rackets; components in silicon chips are reaching the 45 to 65
nm range. Research and industrial labs are working at the intersection
of engineering and biology to extend uses to medicine as well as
all areas of engineering. The impact is expected to revolutionize
these areas. Government agencies in the US and Europe are beginning
to fund toxicology research to understand the hazards of these
materials before they become widely available.
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What are
the toxic effects of nanomaterials tested to date?
This article will give an overview of the testing done to date.
A list of review articles and research citations are given at the
end for further information.
Any toxic effects of nanomaterials will be very specific to the
type of base material, size, ligands, and coatings. One of the
earliest observations was that nanomaterials, also called ultrafine
particles (<100 nm), showed greater toxicity than fine particulates
(<2.5 um) of the same material on a mass basis. This has been
observed with different types of nanomaterials, including titanium
dioxide, aluminum trioxide, carbon black, cobalt, and nickel. For
example, Oberdorster et al. (1994) found that 21 nm titanium dioxide
particles produced 43 fold more inflammation (as measured by the
influx of polymorphonuclear leucocytes, a type of white blood cell,
into the lung) than 250 nm particles based on the same mass instilled
into animal lungs. The increase in inflammation is believed to
due to the much greater surface area of the small particles for
the same mass of material. Though multiple studies have shown that
nano-sized particles may be more toxic than micro-sized particles,
this is not always the case. Intrinsic surface reactivity may also
be as important as surface area. Warheit et al. (2007) found that
the toxicity for cytotoxic crystalline quartz did not relate to
particle size, but did relate to surface reactivity as measured
by hemoglobin release from cells in vitro. Warheit et al. (2006)
also found that other types of crystalline anatase titanium dioxide
did not show size intensive toxicity for nano sized particles.
Nanoparticles(<0.1 um) are
generally similar in size to proteins in the body. They are considerably
smaller than many cells in the body. Human alveolar macrophages
are 24 um in diameter and red blood cells are 7-8 um in diameter.
Cells growing in tissue culture will pick up most nanoparticles.
The ability to be taken up by cells is being used to develop nanosized
drug delivery systems and does not inherently indicate toxicity.
One study by Goodman et al. (2004) found that cellular toxicity
depended upon cationic charge of side chains substituted onto nanoparticles
with a 2 nm gold core. Gold nanoparticles are being investigated
as transfection agents, DNA-binding agents, protein inhibitors
and other biomedical applications. Goldman et al. found that positively
charged gold particles with quaternary ammonium substituted side
chains were toxic to two types of mammalian cells (red blood cells
and Cos-1 cells) and E coli. bacteria, causing 50% of the cell
to die at 1-3 uM concentrations. Negatively charged cells with
carboxylate substituted side chains did not show cellular toxicity
even when tested at much higher concentrations. The researchers
attributed the cell lysis to binding by cationic particles to negatively
charged cell membranes and subsequent membrane leakage. They are
currently designing nanoparticles with different properties to
prevent this type of toxicity.
Translocation in the Body Once in the body,
some types of nanoparticles may have the ability to translocate
and be distributed to other organs, including the central nervous
system. Silver, albumin, and carbon nanoparticles all showed systemic
availability after inhalation exposure. Significant amounts of
13C labeled carbon particles (22-30 nm in diameter) were found
in the livers of rats after 6 hours of inhalation exposure to 80
or 180 ug/m3 (Oberdorster et al. 2002). In contrast, only very
small amounts of 192Ir particles (15 nm) were found systemically.
Oberdorster et al. (2004) also found that inhaled 13 C labeled
carbon particles reached the olfactory bulb and also the cerebrum
and cerebellum, suggesting that translocation to the brain occurred
through the nasal mucosa along the olfactory nerve to the brain.
The ability of nanomaterials to move about the body may depend
on their chemical reactivity, surface characteristics, and ability
to bind to body proteins.
Titanium Dioxide Nanoparticles As noted above, nanoscale
titanium dioxide has shown very different properties from the micron
scale material in tests of lung toxicity. In
addition 14 to 40 nm titanium dioxide produced lung cancer in rats
at doses of 10 mg/m3; micron sized dust produced cancer only
at very high doses (250 mg/m3). Based on these results the
National Institute of Occupational Safety and Health (NIOSH) issued
a recommended safe occupational exposure limit of 0.1 mg/m3 for
nanoscale material and 1.5 mg/m3 for micron size material. The
International Agency for Research on Cancer (IARC) has also determined
that titanium dioxide is a category 2B carcinogen: possibly carcinogenic
to humans. Last year Wang et al (2008) showed that nanoscale
titanium dioxide when inhaled could travel to the brain by way
of olfactory neurons. Once in the brain, it caused oxidative
stress and neuronal degeneration in several areas, including the
hippocampus which is involved with short-term memory. Nanoscale
titanium dioxide joins several other types of nanomaterials (manganese
oxide, nano carbon, and some viruses) that can enter the brain
directly by means of the olfactory pathway from the nose.
Skin Penetration There is currently no consensus about the
ability of nanoparticles to penetrate through the skin. Particles
in the micrometer range are generally thought to be unable to penetrate
through the skin. The outer skin consists of a 10 um thick, tough
layer of dead keratinized cells (stratum corneum) that is difficult
to pass for particles, ionic compounds, and water soluble compounds.
Tinkle et al. (2003) found that 0.5 and 1 um dextran spheres penetrated “flexed” human
skin in an in vitro experiment. Particles penetrated into the epidermis
and a few entered the dermis only during flexing of the skin. Particles
2 and 4 um in diameter did not penetrate. Rymen-Rasmussen et al.
(2006) also found that quantum dots penetrated through pig skin
and into living dermis using an in vitro pig skin bioassay which
is considered a good model for human skin.
Micronized titanium dioxide (40 nm) is currently being used in
sunscreens and cosmetics as sun protection. The nm particles are
transparent and do not give the cosmetics the white, chalky appearance
that coarser preparations did. The nm particles have been found
to penetrate into the stratum corneum and more deeply into hair
follicles and sweat glands than um particles though they did not
reach the epidermis layer and dermis layers (Laddeman et al., 1999).
There is also a concern that nm titanium dioxide particles have
higher photo-reactivity than coarser particles and may generate
free radicals that can cause cell damage. Some manufacturers have
addressed this issue by coating the particles to prevent free radical
formation. The FDA has reviewed available information and determined
that nm titanium dioxide particles are not a new ingredient but
a specific grade of the original product (Luther, 2004).
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Quantum dots (QD) are nanocrystals
containing 1000 to 100,000 atoms and exhibiting unusual “quantum
effects” such as prolonged fluorescence. They are being investigated
for use in immunostaining as alternatives to fluorescent dyes.
The most commonly used material for the core crystal is cadmium-selenium,
which exhibits bright fluorescence and high photostability. Both
bulk cadmium and selenium are toxic to cells. One of the primary
sites of cadmium toxicity in vivo is the liver.
Early studies found that Cd-Se quantum dots were not toxic to
immortalized cell lines used for these studies. Recently Shiohara
et al. (2004) found that three types mercapto-undecanoic acid (MUA)
substituted Cd-Se quantum dots decrease viability in three types
of cells in vitro (monkey kidney, HeLA cells, and human hepatocytes)
and caused cell death after 4-6 hours of incubation. One type of
MUA-QD was less toxic than the other two. Derfus et al. (2004)
also found that Cd-Se QDs were toxic to liver hepatocytes if exposed
to air or UV light, as a result of oxygen combining with Se and
releasing free Cd+2 from the crystal lattice. They found that coating
the Cd-Se QDs with ZnS, polyethylene glycol, or other coatings
prevented toxicity during a two week incubation with hepatocytes.
They concluded that Cd-Se QDs can be made nontoxic with appropriate
surface coatings but future use in vivo must be carefully evaluated
to rule out release of Cd+2 over time.
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Carbon nanotubes (CNT) can have
either single or multiple layers of carbon atoms arranged in a
cylinder. The dimensions of typical single wall carbon nanotubes
(SWCNT) are about 1-2 nm in diameter by 0.1 um in length. Multiple
wall carbon nanotubes (MWCNT) are 20 nm in diameter and 1 mm long.
CNT may behave like fibers in the lung. They have properties very
different from bulk carbon or graphite. They have great tensile
strength and are potentially the strongest, smallest fibers known.
CNT have been tested in short term animal tests of pulmonary toxicity
and the results suggest the potential for lung toxicity though
there are questions about the nature of the toxicity observed and
the doses used.
Lam et al. (2004) instilled three types of SWCNT into rat lungs
and found granulomas, a type of cellular accumulation in the lung
in which clumps of fibers were surrounded by mononuclear macrophages.
Quartz, a dust known to be very toxic to human lungs, also produced
lung damage but carbon black did not. Warheit et al. (2004), using
a different type of SWCNT, also found granulomas but did not see
increases in other markers of pulmonary inflammation whereas quartz
produced both macrophage accumulation and increased pulmonary inflammation.
Warheit et al. interpreted their SWCNT results as possibly of limited
physiological relevance but requiring further inhalation studies.
Shvedova et al. (2005) using more physiologically relevant doses,
found granulomas, fibrosis, and increased markers of inflammation
from both SWCNT. SWCNT also affected lung function: breathing rate
and the ability to clear bacteria were decreased. More extensive
inhalation studies are currently underway in several research centers.
One mitigating factor regarding lung toxicity is that CNTs have
a tendency to clump together to form nanoropes, which are large,
non-respirable clumps, and may prevent inhalation exposure in many
instances (see discussion below Maynard et al. [2004] study).
In 2008 the first inhalation study was published. Shvedova
et al (2008), in both a single -dose aspiration study and a four
day inhalation study, found an initial inflammatory response followed
by granulomas, fibrosis and decreased rates of respiration. The
dose administered by inhalation produced greater respiratory toxicity
than the same dose administered by aspiration. They also found
activation of a gene that produces lung cancer. The SWCNTs
tested were about 1 nm in diameter and between 100 to 1000 nm in
length. The dose administered was 5 mg/m3 for 5 hours per
day for 4 days, with a calculated final lung burden of 5 ug per
mouse. A dust level of 5 mg/m3 would be considered a very
dusty industrial environment and was chosen because it is the OSHA
permissible exposure limit [PEL] (i.e. safe level) for graphite
in humans. This study demonstrated that the OSHA PEL for graphite
would not be a safe level of exposure for CNTs. It did not
determine a No Observed Adverse Effect Level (NOAEL) or safe level
of exposure. Additional inhalation tests at different doses
are needed to answer what the safe level of pulmonary exposure
is. Until toxicologists determine what the safe level is,
best laboratory practice would be to prevent all inhalation exposure.
Two other studies last year reported mesotheliomas and mesothelioma-like
effects using high doses of MWCNT that were longer than 5 um or
20 um (Takagi et al 2008, Poland et al 2008). These studies
used what are considered very high single doses which were injected
directly into the pleural cavity. We don’t know yet
whether lower doses will make their way from the lungs to the pleura
and produce such effects. We need further studies to know
what levels will be safe (as we know with asbestos).
The addition of functional groups such as phenyl-sulfite and phenyl-carboxylic
acid onto CNTs can decrease toxicity, as demonstrated using in
vitro tests by Sayes et al. (2006). Other in vitro tests have found
inhibited cell growth and viability. Good recent reviews of CNT
toxicity which cover pulmonary toxicity and also in vitro testing
and environmental considerations are provided by Donaldson et al.
(2006) and Helland et al. (2007). A recent report by Zheng Li et
al. (2007) found that instillation of CNTs produced cardiovascular
effects in transgenic artherogenesis prone mice; the mice developed
accelerated plaque formation after four doses of CNTs over an 8
week period.
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Fullerenesare another category
of carbon based nanoparticles. The most common type has a molecular
structure of C60 which take the shape of a ball shaped cage of
carbon particles arranged in pentagons and hexagons. Fullerenes
have many potential medical applications as well as applications
in industrial coatings and fuel cells, so a number of preliminary
toxicology studies have been done with them. In cell culture, different
types of fullerenes produced cell death at concentrations of 1
to 15 ppm in different mammalian cells when activated by light
(as discussed in Colvin, 2003). Sayes et al. (2004) found that
toxicity could be eliminated when carboxyl groups were substituted
on the fullerene surface to increase water solubility. Cell death
in this study appeared to be a function of damage to the cell membranes.
In an in vivo study, Chen et al. (2004) found that water soluble
polyalkylsulfonated C60 produced no deaths in rats when given orally
but was moderately toxic when administered intraperitoneally (LD50=600
mg/kg). Doses of 100 to 600 mg/kg also produced an unusual form
of kidney toxicity. Finally, in the first study investigating aquatic
toxicology, Oberdorster (2004) found that 48 hours of exposure
to 0.5 and 1.0 ppm of uncoated pure C60 produced cell membrane
lipid peroxidation in the brains of fish (juvenile large mouth
bass). The changes in the brain as a result of the short exposure
did not appear to affect the behavior of the fish but were an indication
of oxidative stress. An additional concern generated by this study
is the effects of release of durable carbon nanomaterials into
the environment.
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How
to Work Safely with Nanomaterials
The preliminary conclusions to be drawn from the toxicology studies
to date is that some types of nanomaterials can be toxic, if they
are not bound up in a substrate and they are available to the body.
Multiple government organizations are working to fund and assemble
toxicology information on these materials. In the interim, MIT
researchers must use procedures that prevent inhalation and dermal
exposures because at this time nanotoxicology information is limited.
Based on particles physics and studies of fine atmospheric pollutants,
nanoparticles are in the size range that remains suspended for
days to weeks if released into air. Nanoparticles can be inhaled
and will be collected in all regions of the respiratory tract;
about 35% will deposit in the deep alveolar region of the lungs.
Because they are so small, nanoparticles follow airstreams more
easily than larger particles, so they will be easily collected
and retained in standard ventilated enclosures such as fume hoods.
In addition, nanoparticles are readily collected by HEPA filters.
Respirators with HEPA filters will be adequate protection for nanoparticles
in case of spills of large amounts of material.
Working safely with nanomaterials involves following standard
procedures that would be followed for any particulate material
with known or uncertain toxicity: preventing inhalation, dermal,
and ingestion exposure. Many nanomaterials are synthesized in enclosed
reactors or glove boxes. The enclosures are under vacuum or exhaust
ventilation, which prevent exposure during the actual synthesis.
Inhalation exposure can occur during additional processing of materials
removed from reactors, and this processing should be done in fume
hoods. In addition, maintenance on reactor parts that may release
residual particles in the air should be done in fume hoods. Another
process, the synthesis of particles using sol-gel chemistry, should
be carried out in ventilated fume hoods or glove boxes.
The type of surface coating on nanoparticles often causes them
to clump together so that few particles are actually released when
particles are removed from reactors. In one of the few workplace
industrial hygiene studies of nanoparticles, Maynard et al. (2004)
found almost no release of fibers when carbon nanotubes were removed
from a reactor and transferred into a secondary container. The
SWCNT clumped together into nanoropes and remained attached to
the substrate as it was removed from the reactor. Maynard et al.
(2004) also found that it took considerable energy to break up
the nanoropes and release them into air: the highest settings on
a fluidized bed vortex shaker were needed to produce aerosol release.
The type of SWCNT investigated in this study were uncoated with
about 30% Fe catalyst remaining as part of the nanoropes. Researchers
are attempting to coat CNT and other nanoparticles with materials
that make them less sticky and more easily dispersed; if successful,
this would make them more easily aerosolized and require additional
care when handling.
Concerning skin contact, Maynard et al. found clumps of nanoropes
on the gloves of workers removing the synthesized materials from
the reactors. Since the ability of nanoparticles to penetrate the
skin is uncertain at this point, gloves should be worn when handling
particulate and solutions containing particles. A glove having
good chemical resistance to any solution the particles are suspended
in should be used. If working with dry particulate, a sturdy glove
with good integrity should be used. Disposable nitrile gloves commonly
used in many labs would provide good protection from nanoparticles
for most procedures that don’t involve extensive skin contact.
Two pairs of gloves can be worn if extensive skin contact is anticipated,
as well as gloves with gauntlets or extended sleeve nitrile gloves,
to prevent contamination of lab coats or clothing.
One potential safety concern with nanoparticles is fires and explosions
if large quantities of dust are generated during reactions or production.
This is expected to become more of a concern when reactions are
scaled up to pilot plant or production levels. Both carbonaceous
and metal dusts can burn and explode if an oxidant such as air
and an ignition source are present. Nanodusts can be anticipated
to have a greater potential for explosivity than larger particles.
Determination of lower flammability limits using standard test
bomb protocols is being planned in Europe.
There currently no government occupational exposure standards
for nanomaterials. When they are eventually developed, different
standards for different types of nanomaterials will be needed.
One should also be aware that Material Safety Data Sheets (MSDS)
may not have accurate information at this point in time. For example,
the MSDSs that are accompanying some commercially available carbon
nanotubes are referring to the graphite Permissible Exposure Limit
as a relevant exposure standard. Both graphite and carbon nanotubes
are composed of carbon arranged in a honeycomb pattern. However
CNTs have very different tensile and conductive properties than
graphite. Additionally CNTs are much more toxic in the short-term
animal tests that have been performed to date. Consequently, the
graphite PEL and toxicity information is not appropriate for MSDSs
of CNTs. CNTs should be treated as potentially toxic fibers, if
capable of being released into the air and not bound up in a substrate,
and should be handled with appropriate controls as described previously.
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Nanomaterial
Waste Management
As nanotechnology emerges and evolves, potential environmental
applications and human health and environmental implications are
under consideration by the EPA and local regulators.
EPA has a number of different offices coordinating their review
of this rapidly evolving technology. The EPA is currently trying
a voluntary approach to testing and developing a stewardship program.
There are currently no guidelines from the EPA specifically addressing
disposal of waste nanomaterials. It seems that regulation at some
level is inevitable. Some political subdivisions, including the
City of Cambridge, are already evaluating local regulation.
MIT is taking a cautious approach to nano waste management. It
is our belief that regulation is inevitable. In order to better
understand the potential volumes and characteristics of these waste
streams we are advising that all waste materials potentially contaminated
with nano materials be identified and evaluated or collected for
special waste disposal. On the content section note that it contains
nano sized particles and indicate what they are.
The following waste management guidance applies to nanomaterial-bearing
waste streams consisting of:
- Pure nanomaterials (e.g., carbon nanotubes)
- Items contaminated with nanomaterials (e.g., wipes/PPE)
- Liquid suspensions containing nanomaterials
- Solid matrixes with nanomaterials that are friable or have a
nanostructure loosely attached to the surface such that they can
reasonably be expected to break free or leach out when in contact
with air or water, or when subjected to reasonably foreseeable
mechanical forces.
The guidance does not apply to nanomaterials embedded in a solid
matrix that cannot reasonably be expected to break free or leach
out when they contact air or water, but would apply to dusts and
fines generated when cuttting or milling such materials.
DO NOT put material from nanomaterial – bearing waste streams
into the regular trash or down the drain. Before disposal of any
waste contaminated with nanomaterial, call the EHS Office (452-3477)
for a waste determination.
Collect paper, wipes, PPE and other items with loose contamination
in a plastic bag or other sealing container stored in the laboratory
hood. When the bag is full, close it, take it out of the hood and
place it into a second plastic bag or other sealing container. Label
the outer bag with the laboratory’s proper waste label. On
the content section note that it contains nano sized particles and
indicate what they are.
Currently the disposal requirements for the base materials should
be considered first when characterizing these materials. If the
base material is toxic, such as silver or cadmium, or the carrier
is a hazardous waste, such as a flammable solvent or acid, clearly
they should carry those identifiers. Many nanoparticles may also
be otherwise joined with toxic metals of chemicals. Bulk carbon
is considered a flammable solid, so even carbon based nanomaterials
should be collected for determination as hazardous waste characteristics.
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Additional
Sources of Information
Below are additional information sources for nanomaterials (web
sites, review articles, and individual research articles). The EHS
Office plans to screen new information regularly and alert the MIT
community about additional toxicology studies as they become available.
We also request that MIT researchers alert us about studies that
they learn of so we can distribute them to the MIT community. We
would like to observe handling procedures in different labs so we
can share good practice information within the MIT community. Many
of the articles listed below can be accessed electronically through
the MIT Libraries if an electronic subscription is available. Web
sites are also provided where available.
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Additional MIT Guidance
Best Practices for Handling Nanomaterials in Laboratories, at:
http://web.mit.edu/environment/pdf/University_Best_Practices.pdf
Checklist for Nanomaterials Standard Operating Procedures, at:
http://web.mit.edu/environment/pdf/Checklist_Developing_
Nanomaterials_SOP.pdf
Web Sites that Post Current Information about
Nanotoxicology
Gradient Corp. Monthly EH&S Nano News at www.gradient.com
International Council on Nanotechnology at: http://icon.rice.edu.
Up-to-date postings on nanotoxicology worldwide.
National Institute for Occupational Safety and Health (NIOSH) Nanotechnology
Topic Page at www.cdc.gov/niosh/topics/nanotech
National Nanotechnology Infrastructure Network (NNIN) at: http://www.nnin.org/
National Center for Biotechnology Information (NCBI) Pub Med at:
http://www.ncbi.nlm.nih.gov/entrez.
[Can search for articles on nanoparticle toxicity.]
Safe Nano (UK) [excellent regularly updated site on health and
safety risks of nanotechnology with comments by toxicologists and
regulators]
http://www.safenano.org/
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Review
Articles or Reports About Nanotoxicology
Borm P JA, Robbins D, Haubold S et al. The potential risks of nanomaterials:
a review carried out for ECETOC. Part Fiber Toxicol 3:11-35 2006.
Colvin VL. The potential environmental impact of engineered nanmoaterials.
Nature Biotechnology 21:1166-1170 2003. [Note: Excellent and succinct
overview of nanotoxicology.
Oberdorster G, Oberdorster E, Oberdorster J. Nanotoxicology: An
Emrging Discipline Evolving from Studies of Ultrafine Particles.
Environmental Health Perspectives 113:823-839 2005.
Health and Safety Executive (UK). Health effects of particles produced
for nanotechnologies. Document EH75/6. 35 pp. December 2004. Available
at: www.hse.gov.uk. [Search
for EH75/6]
Health and Safety Executive (UK). Nanoparticles: an occupational
hygiene review. Research Report 274. 100 pp. 2004. Available at:
www.hse.gov.uk. [Search for
RR274]
BIA. Workshop on ultrafine aerosols at workplaces. Held August
2002 in Germany. 208 pp. Available at: http://www.cdc.gov/niosh/topics/nanotech.
[Go to Nanotechnology Topic Page. Report is listed in section Non-US
Governmental Resources]
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Research
Articles on Nanotoxicology
[Many articles are available electronically through MIT
Libraries]
Chen HH, Yu C, Ueng TH, Chen S et al. Acute and subacute toxicity
study of water soluble polyalkylsulfonated C60 in rats. Toxicol
Pathol 26:143-151 1998.
Cui D, Tian F, Ozkan CS, Wang M, Gao H. Effect of single wall
carbon nanotubes on human HEK293 cells. Toxicol Lett 155:73-85
2005.
Derfus AM, Chan WC, Bhatia SN. Probing the cytotoxicity of semiconductor
quantum dots. Nano Lett 4:11-18 2004.
Donaldson K, Aitken R, Tran L, et al. Carbon nanotubes: a review
of their properties in relation to pulmonary toxicology and workplace
safety. Toxicol Sci 92:5-22 2006.
Goodman CM, McCusker CD, Yilmaz T, Rotello VM. Toxicity of gold
nanoparticles functionalized with cationic and anionic side chains.
Bioconjugate Chem 15:897-900 2004.
Helland A, Wick, P, Koehler A, Schmid K, Som, C. Reviewing the
Environmental and Human Health Knowledge Base of Carbon Nanotubes.
Env Hlth Perspec 115:1125-1131 2007
Lademann J, Weigmann HJ, Rickmeyer C, Barthelmes H et al. Penetration
of titanium dioxide microparticles in a sunscreen formulation into
the horny layer and the follicular orifice. Skin Parmacol Appl
Skin Physiol 12:247-256 1999.
Lam CW, James JT, McCluskey R, Hunter RL Pulmonary toxicity of
single-wall carbon nanotubes in mice 7 and 90 days after intratracheal
instillation. Toxicol Sci 77:126-134 2004.
Li Z, Hulderman T, Salmen R, Chapman R, et al. Cardiovascular
effects of pulmonary exposure to single-wall carbon nanotubes.
Environ Hlth Perspec 115:377-382 2007.
Maynard AD, Baron PA, Foley M, Shvedova AA et al. Exposure to
carbon nanotube material: aerosol release during the handling of
unrefined single-walled carbon nanotube material. J Toxicol Environ
Hlth, Part A, 67:87-107 2004.
Monteiro-Riviere NA, Nemanich RJ, Inman AO, Wang YY et al. Multi-walled
carbon nanotube interactions with human epidermal keratinocytes.
Toxicol Lett 155:377-384 2005.
Oberdorster E. Manufactured nanomaterials (fullerenes) induce
oxidative stress in the brain of juvenile largemouth bass. Enn
Hlth Perspec 112:1058-1062 2004.
Oberdorster G, Ferin J, Lehnert BE. Correlation between particle
size, in vivo particle persistence and lung injury. Env Hlth Perspec
102 (suppl 5):173-179 2004a.
Oberdorster G, Sharp Z, Atudorei V, Elder A et al. Extrapulmonary
translocation of ultrafine carbon particles following whole-body
inhalation exposure of rats. J Toxicol Environ Hlth Part A 65:1531-1543
2002.
Oberdorster G, Sharp Z, Atudonrei V, Elder A et al. Translocation
of inhaled ultrafine particles to the brain. Inhal Toxicol 16:453-459
2004b.
Poland CA et al. Carbon nanotubes introduced into the abdominal
cabiety of mice show asbesotos-like pathogenicity in a pilot study. Nat
Nanotech 3:423-428 2008.
Rymen-Rasmussen JP, Riviere JE, Monteiro-Riviere NA. Penetration
of intact skin by quantum dots with diverse physicochemical properties.
Toxicol Sci 91:159-165 2006.
Sayes CM, Fortner JD, Guo W, Lyon D et al. The differential cytotoxicity
of water-soluble fullerenes. Nano Lett 4:1881-1887 2004
Sayes CM, Liang F, Hudson JL et al. Functionalization density
dependence of single-walled carbon nanotubes cytotoxicity in vitro.
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