New Study Expresses ‘Significant Concern’ for Work with Carbon Nanotubes Due to Risk of Mesothelioma

Nanomaterials have 1 or more of dimensions the size of a few nanometers (nm), where 1,000,000,000nm = 1m. Carbon nanotubes (CNTs) are among the most promising type of nanomaterial in the field of nanotechnology.

CNTs are composed of graphene sheets, consisting of a series of carbon rings rolled into cylindrical fibres, with an external measurement between 1 and 100nm.

In layman’s terms, they are very long, thin tubes made up of carbon atoms and are used to manufacture exceptionally small, strong, lightweight materials, e.g. bicycles, helmets, aircraft, automobiles, medicines, textiles, water filters and computer motherboards.

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[Source: Wikimedia Commons – The Commonwealth Scientific and Industrial Research Organisation (2 November 2005)  ‘Carbon nanotubes being spun to form a yarn’]

However, in the past, we have pointed towards the potential dangers of exposure to carbon nanotubes, as they share some physico-chemical properties with asbestos fibres. For instance, they both have high aspect ratios (length is far greater than diameter) and are both biopersistent (unlikely to be expelled from the lungs once inhaled).

In edition 208 of BCDN (here), we revealed that 10% to 25% of mice, which had been exposed to CNTs in an experimental animal study, went on to develop mesothelioma, with long-term inflammation visible in pleural spaces, leading to the inactivation of tumour suppressing genes. Months later, (here), we went on to divulge that workers involved in the production of multi-walled CNTs displayed elevated signs of inflammation and damage to blood vessel linings – an early indicator of cardiovascular disease.

That being said, we professed (here), in our feature article on non-asbestos-related causes of mesothelioma, that there is still little epidemiological evidence, let alone definitive proof, that they are hazardous to humans. Further, that it could take several decades of intense research to discover this, potentially once latency periods have begun to elapse.

In an immense world of nanomaterials, CNTs constitute a diverse, or heterogenous, sub-group and it not yet understood which characteristics [e.g. length, size (surface areas), diameter (mass concentrations), impurities, the method used for synthesis/dispersion of the final product, or a combination of these properties], whether separately or in combination, influence their carcinogenic potential. It is therefore recognised that generalised conclusions on CNT toxicity should not be drawn.

However, scholars affiliated with non-profit charity, the Sbarro Health Research Organization, and the Department of Medical Biotechnology at the University of Siena, Italy, have, in the journal, Cancers, highlighted evidence of CNTs having a strong inflammatory impact on the respiratory system (similar to that of asbestos) and correlating with molecular alterations known to have a key role in mesothelioma onset.[i]

Giordano and Barbarino (2021) were particularly interested in studies published after the International Agency for Research on Cancer’s (IARC) classification of long, rigid, needle-shaped Mitsui-7 carbon nanotubes as ‘possibly carcinogenic to humans’ (class 2B), in 2014.

Adhering to the IARC’s protocol for defining an agent as a human carcinogen, this latest review was structured to assess the potential adverse respiratory effects of CNTs (paying particular attention to pleural membranes), in line with a prescriptive list of parameters:

  • Induces oxidative stress;
  • Induces chronic inflammation;
  • Induces epigenetic alterations;
  • Is genotoxic;
  • Alters DNA repair or causes genomic instability;
  • Causes immortalization;
  • Alters cell proliferation, cell death, or nutrient supply;
  • Acts as an electrophile either directly or after metabolic activation;
  • Is immunosuppressive; and
  • Modulates receptor-mediated effects.

Work environments (e.g. laboratory handling and packaging of the final product) are thought to be the principal source of human exposure (through pulmonary inhalation), and between 2015 and 2020, there were 9 studies performed on humans exposed to CNTs in the workplace, which indicated that exposure can stimulate sustained inflammatory responses, oxidative stress, fibrosis, histological alterations, mesothelial hyperplasia, mesothelioma, and lung tumours.

Ultimately, the authors concluded that a ‘global improvement of studies on exposed human populations’ is urgently needed, as well as a need to address the ‘non-applicability of disproportionate precautionary measures of exposure control’.

They offered ‘strong support’ for the creation of a repository of biological samples pertaining to exposed workers, in order to monitor ‘biologically relevant changes over time’; for less variability among instruments used for sampling and analysing exposure, and for the foundation of criteria (regarding ‘preparation and dispersion, concentrations, models and methods to use’) that will ensure the reliability, reproducibility and comparability of clinical data.

By introducing some of these changes and simply conducting more studies, it is hoped that the principal obstacles to reaching a consensus on the dangers of CNT exposures (CNT heterogeneity, varied use of CNT types across companies over time, a lack of specific legislation addressing nanomaterial manufacturing processes and low numbers of participants in extant scientific literature) can be overcome.

It was deemed ‘fortunate’ that the ‘CNT era’ is only just beginning. Though data on CNTs carcinogenicity is sparse, there is an ‘opportunity’, now, to establish safe management of these materials:

‘While we cannot precisely assess which modifications in the genome or in the epigenome will lead to mesothelioma onset, we do know that the long latency of malignant mesothelioma is sustained by decades of chronic inflammation in an aberrant microenvironment rich in ROS [reactive oxygen species] and the resulting oxidative DNA damage. We must carefully reflect on the data supporting the strong inflammatory potential of CNTs, similar to that of asbestos, as well as the data correlating CNT exposure with molecular alterations known to have a key role in mesothelioma onset’.

N.B. As was eluded to above, even though occupational exposure during CNT synthesis is an issue of ‘significant concern’, there is still no common standard for defining worker risk levels.

Exposures in the course of employment in a nanotechnology setting can be monitored by measuring levels of elemental carbon (EC) and typically range from 2.6 micrograms per cubic metre (μg/m3) to 45 µg/m3, depending on the particular workplace (handling facilities, production areas, construction sites, offices, etc.).

To date, EC limits are only regulated within the EU and the UK as a quasi measure of diesel exhaust emissions (DEE), at a threshold level of 50 μg/m3 – see the latest version of the Carcinogens and Mutagens Directive (2004/37/EC).

 

[i] Barbarino M and Giordano A, Assessment of the Carcinogenicity of Carbon Nanotubes in the Respiratory System. Cancers (Basel). 2021 Mar; 13(6): 1318. <https://www.mdpi.com/2072-6694/13/6/1318/pdf> accessed 8 April 2021.

Sbarro Health Research Organization (SHRO), ‘Like Asbestos, Do Carbon Nanotubes Have Potential Health Risks?’ (Newswise) <https://www.newswise.com/articles/like-asbestos-do-carbon-nanotubes-have-potential-health-risks> accessed 8 April 2021.