Although numerous in vitro studies on the effect of carbon nanotubes (CNTs) have been performed so far, a final statement about their toxicity is not possible due to the very controversial discussion about the observed effects in the literature. A frequently mentioned reason for this is the contamination of the materials and not the carbon nanotubes themselves.

Brightfield image of A549 cells treated with single-walled carbon nanotubes (SWCNTs, highlighted with white arrows). Brightfield image of A549 cells treated with single-walled carbon nanotubes (SWCNTs, highlighted with white arrows).

 

As an alternative to in vivo animal tests, the effects of carbon nanotubes (CNTs) are often investigated in cell culture systems (in vitro). Here the CNTs are transferred into a liquid (suspension), then added to the cell culture medium thus bringing the cells into contact with the CNTs (exposure). Despite the plethora of such performed in vitro studies over the last decade, it is not possible to make a final statement on the toxicity of carbon nanotubes due to the differences of the tested CNT materials and applied test methods.

 

However, some conclusions can be drawn from the published work: bundling (agglomeration) of the carbon nanotubes potentially increases their toxicity [1]. Nevertheless, inhaling of such long or agglomerated CNTs is very limited and due to their large size, they cannot reach the deeper regions of the lung. Furthermore, many of the reported toxic events of carbon nanotubes can be attributed to the high-applied doses, which in reality will not even be achieved with malfunctions during the production.

TEM picture of carbon nanotubes (CNTs).TEM picture of carbon nanotubes (CNTs).

Even after production, CNTs are often contaminated with various residues like catalyst metals (in most cases iron, but also nickel, cobalt or molybdenum), amorphous carbon (similar to its appearance in fine dust) or other additives. It has been proven that the observed acute effects were mainly caused by the contaminants [2,3,4].

 

Carbon nanotubes are considered as very stable and biopersistent. However, experiments demonstrated that an enzymatic degradation of functionalised and non-functionalised single-walled CNTs is possible [5,6]. Likewise, scavenger cells (macrophages) were able to degrade single-walled carbon nanotubes in vitro[7].

 

Using carbon nanotubes in medical applications, e.g. as vehicle for active substances or drugs, requires often some chemical modifications (cross cutting – coatings for nanomaterials). Such modified carbon nanotubes are then e.g. water-soluble and therefore cause no acute toxicity [1,8].

 

In order to deduce reliable conclusions on the toxicity of carbon nanotubes it is necessary to not only thoroughly characterise the materials but also to apply environmentally relevant doses and to use adjusted pharmaceutical dosage forms together with realistic and suitable testing methods [9].

For the future it is essential to develop suitable models, which on the one hand will analyse the results of comparative in vitro and in vivo studies and which on the other hand will help to measure and characterise the genetic answer (switching-on and –off of genes or genetic programmes) of cells or even the whole organism. With these models in hand, it should be possible to predict the toxicity of a substance or a nanomaterial [10]. Equally, the usage of standardised operating procedures (SOPs) together with internationally accepted reference materials will significantly improve the quality and comparability of in vitro studies.

 

Literature arrow down

  1. Kaiser, JP et al. (2011), Curr Med Chem, 18(14): 2115-2128.
  2. Donaldson, K et al. (2006), Toxicol Sci, 92(1): 5-22.
  3. Kagan, VE et al. (2006), Toxicol Lett, 165(1): 88-100.
  4. Pulskamp, K et al. (2007), Toxicol Lett, 168(1): 58-74.
  5. Allen, BL et al. (2008), Nano Lett, 8(11): 3899-3903.
  6. Allen, BL et al. (2009), J Am Chem Soc, 131(47): 17194-17205.
  7. Kagan, VE et al. (2010), Nat Nanotechnol, 5(5): 354-359.
  8. Sayes, CM et al. (2006), Toxicol Lett, 161(2): 135-142.
  9. Wick, P et al. (2011), ChemSusChem, 4(7): 905-911.
  10. Snyder-Talkington, BN et al. (2012), J Toxicol Environ Health B Crit Rev, 15(7): 468-492.
  11. Woerle-Knirsch, JM et al. (2006), Nano Lett, 6(6): 1261-1268.

 

 

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