Genotoxicity in the absence of inflammation after tungsten inhalation in mice

Jorid B. Sørli*, Alexander C.Ø. Jensen, Alicja Mortensen, Józef Szarek, Eleni Chatzigianelli, Claudia A.T. Gutierrez, Nicklas R. Jacobsen, Sarah S. Poulsen, Iosif Hafez, Charis Loizides, George Biskos, Karin S. Hougaard, Ulla Vogel, Niels Hadrup*

*Corresponding author for this work

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Abstract

Tungsten is used in several applications and human exposure may occur. To assess its pulmonary toxicity, we exposed male mice to nose-only inhalation of tungsten particles at 9, 23 or 132 mg/m3 (Low, Mid and High exposure) (45 min/day, 5 days/week for 2 weeks). Increased genotoxicity (assessed by comet assay) was seen in bronchoalveolar (BAL) fluid cells at Low and High exposure. We measured acellular ROS production, and cannot exclude that ROS contributed to the observed genotoxicity. We saw no effects on body weight gain, pulmonary inflammation, lactate dehydrogenase or protein in BAL fluid, pathology of liver or kidney, or on sperm counts. In conclusion, tungsten showed non-dose dependent genotoxicity in the absence of inflammation and therefore interpreted to be primary genotoxicity. Based on genotoxicity, a Lowest Observed Adverse Effect Concentration (LOAEC) could be set at 9 mg/m3. It was not possible to establish a No Adverse Effect Concentration (NOAEC).
Original languageEnglish
Article number104074
JournalEnvironmental Toxicology and Pharmacology
Volume98
Number of pages9
ISSN1382-6689
DOIs
Publication statusPublished - 2023

Bibliographical note

This work was supported by a grant from the Danish Working Environment Research Fund [grant number Sikker-Motor 29-2019-09] and FFIKA, Focused Research Effort on Chemicals in the Working Environment, from the Danish Government.

Keywords

  • Comet assay
  • Wolfram
  • Pulmonary
  • Toxicity
  • Toxicology

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