The pulmonary toxicity of carboxylated or aminated multi-walled carbon nanotubes in mice is determined by the prior purification method

Abstract

Background Inhalation of multi-walled carbon nanotubes (MWCNTs) poses a potential risk to human health. In order to safeguard workers and consumers, the toxic properties of MWCNTs need to be identified. Functionalization has been shown to either decrease or increase MWCNT-related pulmonary injury, depending on the type of modification. We, therefore, investigated both acute and chronic pulmonary toxicity of a library of MWCNTs derived from a common pristine parent compound (NC7000). Methods MWCNTs were thermally or chemically purified and subsequently surface functionalized by carboxylation or amination. To evaluate pulmonary toxicity, male C57BL6 mice were dosed via oropharyngeal aspiration with either 1.6 or 4 mg/kg of each MWCNT type. Mitsui-7 MWCNT was used as a positive control. Necropsy was performed at days 3 and 60 post-exposure to collect bronchoalveolar lavage fluid (BALF) and lungs. Results At day 3 all MWCNTs increased the number of neutrophils in BALF. Chemical purification had a greater effect on pro-inflammatory cytokines (IL-1β, IL-6, CXCL1) in BALF, while thermal purification had a greater effect on pro-fibrotic cytokines (CCL2, OPN, TGF-β1). At day 60, thermally purified, carboxylated MWCNTs had the strongest effect on lymphocyte numbers in BALF. Thermally purified MWCNTs caused the greatest increase in LDH and total protein in BALF. Furthermore, the thermally purified and carboxyl- or amine-functionalized MWCNTs caused the greatest number of granulomatous lesions in the lungs. The physicochemical characteristics mainly associated with increased toxicity of the thermally purified derivatives were decreased surface defects and decreased amorphous content as indicated by Raman spectroscopy. Conclusions These data demonstrate that the purification method is an important determinant of lung toxicity induced by carboxyl- and amine-functionalized MWCNTs.

Innate but Not Adaptive Immunity Regulates Lung Recovery from Chronic Exposure to Graphene Oxide Nanosheets

“…Nevertheless, such assessment is difficult since the use of purification methods also alters the physicochemical characteristics of the materials. [ 34 ]…”

“…For enhanced comparison, reference, multi-walled CNTs (MWCNTs; Mitsui-7) were used as positive control due to their well-known pulmonary adverse effects. [33,34] The MWCNTs were depyrogenated prior to administration in mice. A recovery time of 2 weeks between each exposure was chosen to evaluate a potential activation of the adaptive immunity (Figure 1b).…”

Femtosecond pulsed laser microscopy: a new tool to assess the in vitro delivered dose of carbon nanotubes in cell culture experiments

“…A panel of custom-synthesized, purified and functionalized multi-walled CNTs was obtained from Nanocyl (Sambreville, Belgium). The physicochemical characteristics of the 7 samples (the parent sample NC-7000, the chemically-purified (CP) CP-7000, CP-COOH and CP-NH2, and thermally purified (TP) TP-7000, TP-COOH and TP-NH2) were already reported in detail by Taylor-Just et al [ 31 ] and are summarized in Table S 1 .…”

Multi-Walled Carbon Nanotubes (MWCNTs) Cause Cellular Senescence in TGF-β Stimulated Lung Epithelial Cells

“…Many reports indicate that exposure to MWCNTs can lead to the development of pulmonary fibrosis in vivo [ 4 , 11 , 12 ] and drive pro-fibrotic epithelial-mesenchymal transition (EMT), and myofibroblast differentiation and activation in vitro [ 13 , 14 ]. Previous studies also indicate that certain MWCNTs can result in increased oxidative stress and inflammation which play vital roles in PF.…”