4 research outputs found
Inhalation and Oropharyngeal Aspiration Exposure to Rod-Like Carbon Nanotubes Induce Similar Airway Inflammation and Biological Responses in Mouse Lungs
Carbon
nanotubes (CNTs) have the potential to impact technological
and industrial progress, but their production and use may, in some
cases, cause serious health problems. Certain rod-shaped multiwalled
CNTs (rCNTs) can, in fact, induce severe asbestos-like pathogenicity
in mice, including granuloma formation, fibrosis, and even cancer.
Evaluating the comparability between alternative hazard assessment
methods is needed to ensure fast and reliable evaluation of the potentially
adverse effects of these materials. To compare two alternative airway
exposure methods, C57BL/6 mice were exposed to rCNTs by a state-of-the-art
but laborious and expensive inhalation method (6.2–8.2 mg/m<sup>3</sup>, 4 h/day for 4 days) or by oropharyngeal aspiration (10 or
40 μg/day for 4 days), which is cheaper and easier to perform.
In addition to histological and cytological studies, transcriptome
analysis was also carried out on the lung tissue samples. Both inhalation
and low-dose (10 μg/day) aspiration exposure to rCNTs promoted
strong accumulation of eosinophils in the lungs and recruited also
a few neutrophils and lymphocytes. In contrast, the aspiration of
a high-dose (40 μg/day) rCNT caused only a mild pulmonary eosinophilia
but enhanced accumulation of neutrophils in the airways. Inhalation
and low-dose aspiration exposure promoted comparable giant cell formation,
mucus production, and IL-13 expression in the lungs. Both exposure
methods also exacerbated similar expression alterations with 154 (56.4%)
differentially expressed, overlapping genes in microarray analyses.
Of all differentially expressed genes, up to 80% of the activated
biological functions were shared according to pathway enrichment analyses.
Inhalation and low-dose aspiration elicited very similar pulmonary
inflammation providing evidence that oropharyngeal aspiration is a
valid approach and a convenient alternative to the inhalation exposure
for the hazard assessment of nanomaterials
<i>In vitro</i> and <i>in vivo</i> genotoxic effects of straight versus tangled multi-walled carbon nanotubes
<p>Some multi-walled carbon nanotubes (MWCNTs) induce mesothelioma in rodents, straight MWCNTs showing a more pronounced effect than tangled MWCNTs. As primary and secondary genotoxicity may play a role in MWCNT carcinogenesis, we used a battery of assays for DNA damage and micronuclei to compare the genotoxicity of straight (MWCNT-S) and tangled MWCNTs (MWCNT-T) <i>in vitro</i> (primary genotoxicity) and <i>in vivo</i> (primary or secondary genotoxicity). C57Bl/6 mice showed a dose-dependent increase in DNA strand breaks, as measured by the comet assay, in lung cells 24 h after a single pharyngeal aspiration of MWCNT-S (1–200 μg/mouse). An increase was also observed for DNA strand breaks in lung and bronchoalveolar lavage (BAL) cells and for micronucleated alveolar type II cells in mice exposed to aerosolized MWCNT-S (8.2–10.8 mg/m<sup>3</sup>) for 4 d, 4 h/d. No systemic genotoxic effects, assessed by the γ-H2AX assay in blood mononuclear leukocytes or by micronucleated polychromatic erythrocytes (MNPCEs) in bone marrow or blood, were observed for MWCNT-S by either exposure technique. MWCNT-T showed a dose-related <i>decrease</i> in DNA damage in BAL and lung cells of mice after a single pharyngeal aspiration (1–200 μg/mouse) and in MNPCEs after inhalation exposure (17.5 mg/m<sup>3</sup>). <i>In vitro</i> in human bronchial epithelial BEAS-2B cells, MWCNT-S induced DNA strand breaks at low doses (5 and 10 μg/cm<sup>2</sup>), while MWCNT-T increased strand breakage only at 200 μg/cm<sup>2</sup>. Neither of the MWCNTs was able to induce micronuclei <i>in vitro</i>. Our findings suggest that both primary and secondary mechanisms may be involved in the genotoxicity of straight MWCNTs.</p
The EU chemicals strategy for sustainability: in support of the BfR position
The EU chemicals strategy for sustainability (CSS) asserts that both human health and the environment are presently threatened and that further regulation is necessary. In a recent Guest Editorial, members of the German competent authority for risk assessment, the BfR, raised concerns about the scientific justification for this strategy. The complexity and interdependence of the networks of regulation of chemical substances have ensured that public health and wellbeing in the EU have continuously improved. A continuous process of improvement in consumer protection is clearly desirable but any initiative directed towards this objective must be based on scientific knowledge. It must not confound risk with other factors in determining policy. This conclusion is fully supported in the present Commentary including the request to improve both, data collection and the time-consuming and bureaucratic procedures that delay the publication of regulations