In Vivo Toxicity Assessment of Occupational Components of the Carbon Nanotube Life Cycle To Provide Context to Potential Health Effects

Abstract

Pulmonary toxicity studies on carbon nanotubes focus primarily on as-produced materials and rarely are guided by a life cycle perspective or integration with exposure assessment. Understanding toxicity beyond the as-produced, or pure native material, is critical, due to modifications needed to overcome barriers to commercialization of applications. In the first series of studies, the toxicity of as-produced carbon nanotubes and their polymer-coated counterparts was evaluated in reference to exposure assessment, material characterization, and stability of the polymer coating in biological fluids. The second series of studies examined the toxicity of aerosols generated from sanding polymer-coated carbon-nanotube-embedded or neat composites. Postproduction modification by polymer coating did not enhance pulmonary injury, inflammation, and pathology or in vitro genotoxicity of as-produced carbon nanotubes, and for a particular coating, toxicity was significantly attenuated. The aerosols generated from sanding composites embedded with polymer-coated carbon nanotubes contained no evidence of free nanotubes. The percent weight incorporation of polymer-coated carbon nanotubes, 0.15% or 3% by mass, and composite matrix utilized altered the particle size distribution and, in certain circumstances, influenced acute in vivo toxicity. Our study provides perspective that, while the number of workers and consumers increases along the life cycle, toxicity and/or potential for exposure to the as-produced material may greatly diminish.

Three-dimensional printing with nano-enabled filaments releases polymer particles containing carbon nanotubes into air

“…However, discrete CNTs and bundles of CNTs are known to induce numerous toxicological and pathological effects in experimental animals and may induce alterations in respiratory and cardiovascular function in workers, though epidemiology studies are not consistent . This observed toxicity of native CNTs raises concern about the potential toxicity of inhaling polymer‐associated CNT particles . To date, most studies of CNT release from polymer composites have focused on low‐energy processes (eg, environmental degradation from UV light) or high‐energy processes (eg, drilling and sanding) .…”

“…[13][14][15][16] This observed toxicity of native CNTs raises concern about the potential toxicity of inhaling polymer-associated CNT particles. 17 To date, most studies of CNT release from polymer composites have focused on low-energy processes (eg, environmental degradation from UV light) or high-energy processes (eg, drilling and sanding). 18 It is currently unknown whether CNTs are released during thermal degradation of polymer composite filaments used for material extrusion 3-D printing or is there understanding of potential lung deposition if emitted particles are inhaled by workers or members of the general public in schools, libraries, or homes who use or are in proximity to the 3-D printer.…”

Sparse Supervised Classification Methods Predict and Characterize Nanomaterial Exposures: Independent Markers of MWCNT Exposures

“…In this study, protein levels in the lung lavage fluid were used to discriminate between NP exposed and unexposed controls using male C57BL6 mice exposed by oropharyngeal aspiration to subtoxic and toxic doses of various MWCNT relevant to nano-enabled manufacturing processes. This study was designed and conducted based on the results from several previous and ongoing studies (Bishop et al 2017;Kodali et al 2016;Roberts et al 2016), albeit all using MWCNT particles, but having different physicochemical characteristics and/or PCs (Table S1), by independent investigators at NIOSH. We constructed sparse SVM-based classification models to determine or select proteins in the lung lavage fluid that allow prediction of exposure and/or pulmonary responses to MWCNT as a material group (Figure 1) as well as those that can discriminate between the different forms of MWCNT investigated (Table 5).…”

“…The lungs from a separate set of mice were referenced for pathological outcomes at 84-day postexposure to each type of MWCNT investigated as part of this study. The detailed quantification of various pulmonary pathological outcomes using morphometry techniques and/or severity-based scoring/grading is and/or will be provided as part of the main pulmonary toxicity assessment studies (Bishop et al 2017;Kodali et al 2016;Roberts et al 2016), and only a qualitative analysis describing pulmonary pathology is provided as part of this study. For all the referenced histopathology, at sacrifice, lungs were inflated with buffered formalin, processed into paraffin blocks, sectioned at 5 microns, and stained with hematoxylin and eosin (H&E) for routing histopathology or picrosirius red (PSR) for fibrosis.…”

“…The details corresponding to the various training and test data sets employed in this study are reported in Table 1. In this study, we specifically chose data sets from materials relevant to nano-enabled manufacturing, that is, toxicological evaluation of pristine MWCNT and their PC counterparts (Bishop et al 2017). Several strategies have been used to improve dispersion quality of NPs, including chemical and PCs, for various nano-enabled applications.…”