Increased surface area of halloysite nanotubes due to surface modification predicts lung inflammation and acute phase response after pulmonary exposure in mice

Kenneth Klingenberg Barfod, Katja Maria Bendtsen, Trine Berthing, Antti Joonas Koivisto, Sarah Søs Poulsen, Ester Segal, Eveline Verleysen, Jan Mast, Andreas Holländer, Keld Alstrup Jensen, Karin Sørig Hougaard, Ulla Vogel*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

The toxicological potential of halloysite nanotubes (HNTs) and variants after functional alterations to surface area are not clear. We assessed the toxicological response to HNTs (NaturalNano (NN)) before and after surface etching (NN-etched). Potential cytotoxicity of the two HNTs was screened in vitro in MutaTMMouse lung epithelial cells. Lung inflammation, acute phase response and genotoxicity were assessed 1, 3, and 28 days after a single intratracheal instillation of adult female C57BL/6 J BomTac mice. The doses were 6, 18 or 54 μg of HNTs, compared to vehicle controls and the Carbon black NP (Printex 90) of 162 μg/mouse. The cellular composition of bronchoalveolar lavage (BAL) fluid was determined as a measure of lung inflammation. The pulmonary and hepatic acute phase responses were assessed by Serumamyloida mRNA levels in lung and liver tissue by real-time quantitative PCR. Pulmonary and systemic genotoxicity were analyzed by the alkaline comet assay as DNA strand breaks in BAL cells, lung and liver tissue. The etched HNT (NN-etched) had 4–5 times larger BET surface area than the unmodified HNT (NN). Instillation of NN-etched at the highest dose induced influx of neutrophils into the lungs at all time points and increased Saa3 mRNA levels in lung tissue on day 1 and 3 after exposure. No genotoxicity was observed at any time point. In conclusion, functionalization by etching increased BET surface area of the studied NN and enhanced pulmonary inflammatory toxicity in mice.
Original languageEnglish
Article number103266
JournalENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY
Volume73
Number of pages14
ISSN1382-6689
DOIs
Publication statusPublished - 2020

Keywords

  • Halloysite nanotubes
  • Airway exposure
  • High aspect ratio nanomaterial (HARN)
  • Acute phase response
  • Comet assay

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