Carbon nanotubes have distinctive characteristics, but their needle-like fibre shape has been compared to asbestos, raising concerns that widespread use of carbon nanotubes may lead to mesothelioma, cancer of the lining of the lungs caused by exposure to asbestos. Here we show that exposing the mesothelial lining of the body cavity of mice, as a surrogate for the mesothelial lining of the chest cavity, to long multiwalled carbon nanotubes results in asbestos-like, length-dependent, pathogenic behaviour. This includes inflammation and the formation of lesions known as granulomas. This is of considerable importance, because research and business communities continue to invest heavily in carbon nanotubes for a wide range of products under the assumption that they are no more hazardous than graphite. Our results suggest the need for further research and great caution before introducing such products into the market if long-term harm is to be avoided.

http://www.appletonlaw.com/files/2009/PDFs/14_CarbonNanotubes.pdf

Carbon nanotubes introduced into the abdominal cavity of mice show asbestos-like pathogenicity in a pilot study.

Carbon nanotubes: a review of their properties in relation to pulmonary toxicology and workplace safety.

The biocompatibility of carbon nanotubes

Interstitial pulmonary fibrosis caused by the inhalation of asbestos fibers or silica particles continues to be an important cause of interstitial lung disease. Although more stringent control of asbestos in the workplace and decreasing industrial use has contributed to declines in the prevalence of asbestosis in the United States (1), new cases continue to be identified. Similarly, silicosis is seen among sandblasters, underground miners, foundry and quarry workers, and in other dust-exposed trades (2). Both diseases, which may have relatively long latency periods, are observed in the clinic today, usually as a result of high occupational exposures in the past, and they are problematic in that treatment with corticosteroids and immunosuppressants, the usual approaches to therapy for fibrotic lung disease, is ineffective (3). Asbestos and silica are complex, naturally occurring minerals that are chemically and physically distinct. Moreover, the pathology of asbestosis and silcosis is dissimilar. However, the pathogenesis of these lesions and the major changes in pulmonary architecture, namely, the laying down of collagen in an interstitial location, appear to be similar to many of the features seen in idiopathic pulmonary fibrosis (IPF). Like IPF and representative animal models of IPF such as bleomycin instillation (4), both asbestosis and silicosis are characterized by a persistent inflammatory response and generation of proinflammatory and profibrotic mediators. Although asbestosis and silicosis have been studied intensely by basic and clinical research scientists, little is known about the crucial cellular mechanisms that initiate and drive the processes of inflammation and fibrogenesis. Many laboratories have developed animal and in vitro models of asbestosis and silicosis to elucidate the cellular events and properties of minerals important in disease causation. Others have explored confounding factors contributing to particulate-induced cell injury as well as cellular and molecular defense mechanisms in response to these minerals. This information has been used to modulate inflammation and fibrosis in expermental animal models in attempts to develop more effective treatment regimens for pulmonary fibroses. This review will briefly address the clinical and pathologic features of asbestosis and silicosis, and consider the mineralogic features of asbestos and silica that may be important in disease causation along with confounding factors such as coexposures to smoking and/or other mineral dusts. The relationship of particle number, type, and size to disease patterns will be reviewed. We will then summarize data published within the past 5 yr on cellular and molecular mechanisms of asbestosis and silicosis and preventive approaches to these diseases in experimental animal models. Lastly, we emphasize in our SUMMARY AND CONCLUSIONS the common mediators and cell types affected in the pathogenesis of both mineral-related and other forms of pulmonary fibrosis and plausible interrelationships between the development of fibrosis and lung cancer, a disease linked to occupational exposures to asbestos and possibly to exposures to silica (1, 5).

Mechanisms in the pathogenesis of asbestosis and silicosis.

Note: This article was originally published with an incorrect version of the Acknowledgments, which appeared on p. 218 of the print version. The correct version of the Acknowledgments appeared on pp. 1–2. The corrected article is available below.

/pdf/human-health-risk-assessment-for-aluminium-aluminium-oxide-5dfetd69xm.pdf

Human Health Risk Assessment for Aluminium, Aluminium Oxide, and Aluminium Hydroxide

Previous studies have shown that long thin asbestos fibres are more pathogenic in in vivo and more active in in vitro assays than short fibre samples. In the present study a long fibre amosite asbestos sample and a short fibre sample prepared from it were tested for ability to cause inflammation in the peritoneal cavity of the mouse; a UICC sample intermediate in fibre size and an inert compact dust, TiO2, were also tested. The ability of the dust samples to cause inflammation, as judged by macrophage and neutrophil recruitment, was ranked in the order long fibre greater than UICC greater than short fibre greater than TiO2. Ability of amosite samples to cause inflammation was therefore related to the proportion of long fibres. The enhanced ability of long fibres to cause inflammation and cause macrophage activation is probably a key factor in the ability of long fibres to cause pulmonary fibrosis and may also be important in fibre carcinogenesis.

https://oem.bmj.com/content/oemed/46/4/271.full.pdf

Inflammation generating potential of long and short fibre amosite asbestos samples.

The kinetics of the bronchoalveolar response was assessed in rats exposed, at equal airborne mass concentration (10 mg/m3), to titanium dioxide--a non-pathogenic dust--and the two pathogenic mineral dusts quartz and chrysotile asbestos. Rats were killed at intervals over a 75 day exposure period and groups of rats exposed for 32 and 75 days after recovery for two months. Bronchoalveolar lavage was carried out and the lavage fluid characterised for cellular content, macrophage activation, and concentrations of free total protein, lactate dehydrogenase, and N-acetyl-beta-D-glucosaminidase. Inhalation exposure to the two pathogenic dusts resulted in an increased number of leucocytes, macrophage activation, and increased levels of free enzymes and total protein. The pattern and magnitude of the responses to quartz and chrysotile differed. Chrysotile caused less inflammation than quartz, and the main cellular response peaked around the middle of the period of dust exposure whereas the highest levels of enzymes occurred towards the end. The difference in timing suggests that macrophages were not available for lavage towards the end of the exposure, owing to their playing a part possibly in deposition of granulation tissue. Quartz caused a greater cellular and enzyme response than chrysotile, particularly towards the end of the dust exposure phase. There was a noticeable progression of inflammation in the quartz exposed groups left to recover for two months, but not in the chrysotile recovery groups.

https://thorax.bmj.com/content/thoraxjnl/43/7/525.full.pdf

Kinetics of the bronchoalveolar leucocyte response in rats during exposure to equal airborne mass concentrations of quartz, chrysotile asbestos, or titanium dioxide.

Fibre length has been shown to be an important factor in the ability of respirable fibres to cause lung fibrosis and cancer. We have reported that a long sample of amosite asbestos is more carcinogenic and fibrogenic than a short sample of similar diameter. These amosite asbestos samples were studied with regard to their ability to stimulate the release of the pro-inflammatory cytokine tumour necrosis factor (TNF) from rat alveolar macrophages in vitro. The long fibre sample was found to stimulate substantially greater release of the cytokine than the short sample. Furthermore, on treatment of the fibres with rat immunoglobulin G (IgG), there was an increase in the ability of both the long and the short sample to stimulate TNF secretion, although the long sample retained by far the greatest activity. Coating of the fibres with a range of other proteins had no substantial effect on their ability to stimulate TNF secretion. Quartz and titanium dioxide (TiO2) were included as control particles and the TNF-stimulating activity of quartz was notably increased by opsonization with IgG. TiO2 showed a similar low activity to that of the short fibre sample of amosite but this again could be modestly increased by opsonization with IgG. The simulation of TNF release caused by treatment with immunoglobulin-opsonized long fibre amosite could be inhibited by treatment of the macrophages with the protein kinase C-inhibitor staurosporine. The study demonstrates a fibre length-related ability to stimulate cytokine secretion by alveolar macrophages, and its enhancement by opsonization with IgG. This is likely to be relevant to the relationship between fibre length and pathogenic potential to the lung.

Asbestos-stimulated tumour necrosis factor release from alveolar macrophages depends on fibre length and opsonization.

Bronchoalveolar leukocyte response in experimental silicosis: Modulation by a soluble aluminum compound

Background Fibrous materials have much to commend them in industrial applications, where they can offer, in varying degree, reinforcement, thermal and electrical insulation, flexibility, and strength. In the first part of this century the fibrous material that was available, cheaply and in bulk, that could provide these properties to industry was the asbestos group of silicate minerals (table 1). The fibrous, crystalline, asbestiform habit, however, also means that during mining and industrial use fibres are released into the air. Some of these are in the respirable size range and may be deposited in the bronchiolar-alveolar region. Subsequently we have come to realise that asbestos inhalation is associated with several different lung diseases-namely, asbestosis (interstitial fibrosis), carcinoma of the lung, mesothelioma, and small airways diseaseand the association is now well documented. This information on the harmful effects of asbestos has led to bans in some countries and considerable litigation and claims for damages throughout the developed world. Regulatory and legal pressures on asbestos have contributed to an increase in the use of alternative materials, both natural and manmade, including some fibrous materials. More importantly, advances in materials science have identified ar, ever widening range of applications in which the fibrous nature of a material offers positive advantages. Thus in addition to their traditional use in thermal insulation new fibre composites have found new uses, such as metal reinforcement, to which asbestos was never suited (table 2). The finding that in at least some biological assays some non-asbestos fibres could cause the same types of effect as asbestos has raised the question of whether all fibres have the same pathogenic potential as asbestos. A major approach in present research on fibres is therefore to compare any fibre under study with asbestos and to gauge the potential for

https://thorax.bmj.com/content/thoraxjnl/48/4/390.full.pdf

G. M. Brown

Papers

Inflammation generating potential of long and short fibre amosite asbestos samples.

Kinetics of the bronchoalveolar leucocyte response in rats during exposure to equal airborne mass concentrations of quartz, chrysotile asbestos, or titanium dioxide.

Asbestos-stimulated tumour necrosis factor release from alveolar macrophages depends on fibre length and opsonization.

Bronchoalveolar leukocyte response in experimental silicosis: Modulation by a soluble aluminum compound

New perspectives on basic mechanisms in lung disease. 5. Respirable industrial fibres: mechanisms of pathogenicity.