2020 journal article

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

PARTICLE AND FIBRE TOXICOLOGY, 17(1).

By: A. Taylor-Just n, M. Ihrie n, K. Duke n, H. Lee n, D. You n, S. Hussain*, V. Kodali*, C. Ziemann* ...

co-author countries: Belgium 🇧🇪 Germany 🇩🇪 Romania 🇷🇴 United States of America 🇺🇸
author keywords: Carbon nanotubes; Purification; Functionalization; Lung injury; Fibrosis
MeSH headings : Administration, Inhalation; Air Pollutants / toxicity; Animals; Bronchoalveolar Lavage Fluid / chemistry; Cytokines / metabolism; Inhalation Exposure; Lung / drug effects; Lung Injury; Mice; Mice, Inbred C57BL; Nanotubes, Carbon / toxicity; Transforming Growth Factor beta1 / metabolism
Source: Web Of Science
Added: December 21, 2020

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.