The Toxicologist - Society of Toxicology

1798 TESTING OF MWCNT FOR POSSIBLE HEALTH
HAZARDS AND RELEASE FROM COMPOSITE
MATERIALS.
R. Landsiedel 1 , W. Wohlleben 1, 2 , L. Ma-Hock 1 , S. Treumann 1 , K. Wiench 3 and
B. van Ravenzwaay 1 . 1 Department of Experimental Toxicology and Ecology, BASF
SE, Ludwigshafen am Rhein, Germany, 2 Polymer Physics Department, BASF SE,
Ludwigshafen am Rhein, Germany and 3 Product Safety Department, BASF SE,
Ludwigshafen am Rhein, Germany.
MWCNT are of great commercial interest, as they combine high electrical conductivity,
good mechanical strength and excellent thermal conductivity. A sustainable
development of these materials requires a risk assessment of production. The toxicity
of four different MWCNTs was examined by 5- inhalation studies and one
MWCNT was subsequently examined in a 90-day inhalation studies in rats according
to OECD test guideline no. 413. Test concentrations were 0 (control), 0.1,
0.5, or 2.5 mg/m 3 . The exposure to MWCNT resulted in no systemic toxicity, but
a concentration-dependent increase of lung weights and granulomas with histiocytic,
neutrophilic inflammation and intra-alveolar lipoproteinosis in the lung and
lung-associated lymph nodes at 0.5 and 2.5 mg/m 3 . At 0.1 mg/m 3 , there was still
minimal granulomatous inflammation. Obviously, the exposure to the MWCNT
could occur during production and compounding and the toxicity of the
MWCNT demands strict industrial hygiene measures. Consumers and the general
population are unlikely to be exposed to MWCNTs, unless they are bound in
nanocomposites or in other ways incorporated into a product. The concern for
nanocomposites is the release of MWCNT. This may occur due to weathering or by
mechanical shear forces (drilling, sawing, sanding). We examined MWCNT release
from thermoplastic and cementitious nanocomposites and found that the abraded
materials from the nanocomposites were micron-sized hybrids, not naked
MWCNTs. The amount of test substance obtained from the degradation was too
small for inhalation studies. Therefore the sanding powder was instilled into rat
lungs and its toxicity was compared to matrix without MWCNT and to the naked
MWCNT: The naked MWCNT was significantly more toxic than the abraded material;
but there was no difference in toxicity between the hybrid material from
abrasion of composites with MWCNT and the abraded matrix without MWCNT.
1799 EXPERIMENTAL EVIDENCE FROM A 90-DAY MWCNT
INHALATION STUDY IN RATS: ANALYSIS OF
COMMON DENOMINATORS OF MWCNT WITH
SUBMICRONSIZED PARTICLES.
J. Pauluhn. Toxicology, Bayer HealthCare, Wuppertal, Germany.
Multi-walled Carbon Nanotubes (MWCNT, Baytubes®) were examined in a subchronic
13-week inhalation study. The focus of study was to better understand the
cause of toxicological properties of these types of aggregated structures and whether
the density of agglomerates plays the key role in triggering the cascade of events
leading to sustained pulmonary inflammation. There is compelling evidence from
repeated inhalation exposure studies on rats suggesting that the particle displacement
volume is the unifying denominator for pulmonary toxicity. Procedures were
developed to analyze and model the pulmonary toxicokinetics and associated inflammatory
potency of six different types of the following poorly soluble nano-
/submicron dusts: ultrafine and pigmentary TiO2, synthetic iron oxide (Fe3O4,
magnetite), two aluminum oxyhydroxides (AlOOH, Boehmite) with primary isometric
particles of either 10 or 40 nm, and multiwalled carbon nanotubes
(MWCNT, Baytubes®). The specific agglomerate densities of these materials
ranged from 0.1 g/cm3 (MWCNT) to 5 g/cm3 (Fe3O4). Along with all PM, due to
their long retention half-times and associated biopersistence in the lung, even shortterm
inhalation studies may require post¬exposure periods of at least 3 months to
reveal PM-specific dispositional and toxicological characteristics. This analysis provides
strong evidence that pulmonary toxicity (sustained inflammation) corresponds
best with the volume-based cumulative lung exposure dose exceeding the
overload threshold. This analysis supports the conclusion that repeated inhalation
studies on rats should utilize an experimental window resulting in cumulative volume
concentrations of respirable PM from 1 to maximal 10 μl/m3. This data support
a volume-based generic no-adverse-effect mass concentration of respirable PM
at 0.5 μl x agglomerate density/m3, independent whether nano- or submicronsized.
1800 FACTORS AFFECTING THE PULMONARY RESPONSE
TO CARBON NANOTUBES.
V. Castranova. Pathology & Physiology Branch, CDC NIOSH, Morgantown, WV.
Published studies report that pulmonary exposure to single-walled carbon nanotubes
(SWCNT) or multi-walled carbon nanotubes (MWCNT) causes transient
inflammation, granulomatous legions, and persistent fibrosis. Due to the fibrous
386 SOT 2011 ANNUAL MEETING
shape of carbon nanotubes (CNT), questions concerning asbestos-like induction of
lung cancer and mesothelioma have also been raised. Therefore, hazard assessment
for CNT is essential. There are at least three distinct synthesis processes for CNT.
In addition, CNT can exist in the raw (catalytic metals present) or purified (metals
removed) forms. Physical dimensions (both width and length) can vary among
SWCNT and MWCNT. Furthermore, the degree of agglomeration of CNT can
result in a wide range of structure sizes. Lastly, CNT can be functionalized in multiple
ways, resulting in altered surface properties. Thus, hundreds of types of CNT
are possible. Since it will not be feasible to evaluate the toxic potential of each CNT
type, it is critical to determine the relationships between physicochemical characteristics
of CNT and bioactivity. Development of such relationships requires the
collaboration between material scientists and toxicologists. Such a matrix of physicochemical
properties vs. bioactivity is critical for risk analysis. Existing data concerning
the effects of metal contamination, dimension, and agglomeration state on
the pulmonary reactions to CNT exposure will be presented. Another issue for risk
assessment is the relevance of pulmonary responses after a bolus exposure to inhalation
of CNT. In this presentation, pulmonary responses to bolus exposure (pharyngeal
aspiration) will be compared to those after short term inhalation of SWCNT
and MWCNT.
1801 TITANIA-CRYSTALLINITY AND SURFACE REACTIVITY
EFFECTS ON TOXICITY—NOT ALL NANO TITANIUM
DIOXIDE PARTICLES HAVE THE SAME HAZARD
POTENTIAL.
D. B. Warheit. DuPont Haskell Global Centers, Newark, DE.
The lung toxicities of several different well-characterized nanoscale and fine TiO2
particle types were assessed in rats. The experimental design included dose response
and time course characteristics, and benchmark control particulates. Groups of rats
were intratracheally instilled with doses of 1 or 5 mg/kg of two different nano rutile
TiO2 particle-types; a rutile fine-TiO2 particle; an anatase/rutile nano-TiO2 particulate;
or alpha-quartz particles. Phosphate-buffered saline (PBS) solution instilled
rats served as vehicle controls. Following exposures, the lungs of PBS and
particle-exposed rats were evaluated by using bronchoalveolar lavage (BAL) fluid
inflammatory markers, cell proliferation indices, and lung histopathology at postexposure
time points of 24 hrs, 1 week, 1 month, and 3 months. Rigorous physicochemical
characterization of the TiO2 particle-types demonstrated significant differences
in crystal structure, surface area indices, pH effects, and surface reactivity
measurements- using the Vitamin C yellowing assay. The range of lung inflammation/cytotoxicity/cell
proliferation and histopathological responses was alphaquartz
> anatase/rutile nano TiO2 > rutile fine TiO2 = rutile nano TiO2- 1 =rutile
nano TiO2- 2. Exposures to quartz and to a lesser degree, anatase/rutile TiO2 particles
produced pulmonary inflammation, cytotoxicity and adverse lung tissue effects.
These results demonstrated that exposures to TiO2 nanoparticles can produce
differential pulmonary inflammatory and histopathological effects, based upon
their particle composition, surface reactivity, and crystal structure rather than particle
size characteristics. Moreover, the lung toxicity of anatase/rutile TiO2 nanoparticles
clearly is not representative of all TiO2 nanoparticle particle types. Therefore,
the rigorous characterization of the nanoparticle test material is a necessary prerequisite
for the interpretation of hazard studies. Finally, development of OELs for
nano TiO2 particles requires consideration of physicochemical characteristics. Not
all TiO2 particles are alike!
1802 CHARACTERIZING MWCNTS AND TITANIA
NANOSTRUCTURES: DIFFERENT MATERIALS
REQUIRE DIFFERENT TECHNIQUES.
C. Sayes. Texas A&M University, College Station, TX.
Manufactured nanomaterials are beginning to make their way into a variety of industrial
processes and consumer goods. In parallel to the development of nanomaterials
in the workplace, the need for regulatory guidelines is critical to success of
these novel materials and their uses. One important factor within the regulatory
discussion is the need for accurate and relevant nanomaterial characterization of the
physicochemical properties for toxicological evaluations. Some of the most common
properties of nanomaterials in aqueous suspensions are aggregation/agglomeration,
leeching of metal ions, and the production of reactive species. With some
nanomaterials, when designed appropriately, they can generate reactive oxygen
species quite efficiently. In many studies published in the literature, it has been
found that differences in the physicochemical properties of nanomaterials with a
“class” determine the biological activity, including cytotoxicity and inflammation.
While most data follows a dose-dependent and time-dependent trend, other materials
do not. Phase composition, chirality, and surface coating of the nanomatertial
is related to cytotoxicity. Anatase nano-titania, for example, is more than 100 times
more toxic than an equivalent sample of titania in the rutile phase. The observed