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

Springer Science and Business Media LLC - Tập 17 - Trang 1-18 - 2020
Alexia J. Taylor-Just1, Mark D. Ihrie1, Katherine S. Duke1, Ho Young Lee1, Dorothy J. You1, Salik Hussain2, Vamsi K. Kodali2, Christina Ziemann3, Otto Creutzenberg3, Adriana Vulpoi4, Flaviu Turcu4, Monica Potara4, Milica Todea4,5, Sybille van den Brule6, Dominique Lison6, James C. Bonner1
1Toxicology Program, Department of Biological Sciences, North Carolina State University, Raleigh, USA
2Department of Physiology and Pharmacology, School of Medicine, West Virginia University, Morgantown, USA
3Fraunhofer Institute for Toxicology and Experimental Medicine ITEM, Hannover, Germany
4Interdisciplinary Research Institute in Bio-Nano-Sciences, Babes Bolyai University, Cluj-Napoca, Romania
5Department of Molecular Sciences, Faculty of Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
6Louvain centre for Toxicology and Applied Pharmacology (LTAP), Institut de Recherche Expérimentale et Clinique (IREC), Université catholique de Louvain (UCL), Brussels, Belgium

Tóm tắt

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). 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. 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. These data demonstrate that the purification method is an important determinant of lung toxicity induced by carboxyl- and amine-functionalized MWCNTs.

Tài liệu tham khảo

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