A critical review of the biological mechanisms underlying thein vivoandin vitrotoxicity of carbon nanotubes: The contribution of physico-chemical characteristics

Abstract

This critical review of the available human health safety data, relating to carbon nanotubes (CNTs), was conducted in order to assess the risks associated with CNT exposure. Determining the toxicity related to CNT exploitation is of great relevance and importance due to the increased potential for human exposure to CNTs within occupational, environmental and consumer settings. When this information is combined with knowledge on the likely exposure levels of humans to CNTs, it will enable risk assessments to be conducted to assess the risks posed to human health. CNTs are a diverse group of materials and vary with regards to their wall number (single and multi-walled CNTs are evident), length, composition, and surface chemistry. The attributes of CNTs that were identified as being most likely to drive the observed toxicity have been considered, and include CNT length, metal content, tendency to aggregate/agglomerate and surface chemistry. Of particular importance, is the contribution of the fibre paradigm to CNT toxicity, whereby the length of CNTs appears to be critical to their toxic potential. Mechanistic processes that are critical to CNT toxicity will also be discussed, with the findings insinuating that CNTs can exert an oxidative response that stimulates inflammatory, genotoxic and cytotoxic consequences. Consequently, it may transpire that a common mechanism is responsible for driving CNT toxicity, despite the fact that CNTs are a diverse population of materials. The similarity of the structure of CNTs to that of asbestos has prompted concern surrounding the exposure of humans, and so the applicability of the fibre paradigm to CNTs will be evaluated. It is also necessary to determine the systemic availability of CNTs following exposure, to determine where potential targets of toxicity are, and to thereby direct in vitro investigations within the most appropriate target cells. CNTs are therefore a group of materials whose useful exploitable properties prompts their increased production and utilization within diverse applications, so that ensuring their safety is of vital importance.

Investigating the Interaction of Cellulose Nanofibers Derived from Cotton with a Sophisticated 3D Human Lung Cell Coculture

“…2 Therefore, due to the increased strength and durability of MWCNTs renders them a more specific comparison than SWCNTs. Due to their ability to induce relatively low adverse biological effects, 7 however, and in-line with the data presented in the current study, a comparison between cellulose nanowhiskers and SWCNTs would be of interest to further understand how the specific material may contribute to the interaction of nanofibers with biological systems.…”

Assessing the impact of the physical properties of industrially produced carbon nanotubes on their interaction with human primary macrophages in vitro

“…At sub-lethal concentrations CNTs have been shown to induce the production of ROS which leads in an inflammatory response via the release of pro-inflammatory cytokines in vitro [13,32]; thus fitting the oxidative stress paradigm -the most widely accepted paradigm concerning the potential for nano-objects to cause adverse biological effects [10]. ROS are produced from the respiratory chain in the mitochondria by generating adenosine tri-phosphate (ATP) and can induce, even at low concentrations, TNF-α release from the cell.…”

“…Equivocal results regarding their (potential) hazard however, have been reported. In 2010, Johnston and colleagues published an extensive overview of the literature associated with CNT-cell interactions/effects, highlighting that CNTs can cause a range of biological effects [e.g., cytotoxicity, oxidative stress and (pro-)inflammatory reactions] both in vitro and in vivo [13]. Yet, despite such an exhaustive review of the literature, no clear correlation between CNT physical characteristics and a specific biological response -apart from those CNTs fitting the fiber paradigm [i.e., long ( > 15 µm), high aspect ratio ( ≥ 1:3) and biopersistent] [24-27] -was noted.…”

“…In terms of hazard assessment, a plethora of studies, from both an in vitro and in vivo perspective have investigated how a variety of different CNT types (predominantly single-walled and multi-walled CNTs (MWCNTs) may elicit an adverse biological effect [13]. Due to their increased strength and durability owing to the multiple graphene layers, and thus high applicability towards industrial exploitation within a range of applications, the main focus of this research has been towards MWCNTs [3]).…”

“…Over the past few years, in an aid to try and understand the potential risk posed by these advantageous materials towards human health, a growing literature base has produced a vast array of risk assessment (hazard × exposure) [11] studies of the CNT-cell interaction and the subsequent biochemical effects caused [12,13].…”