Genotoxicity in the absence of inflammation after tungsten inhalation in mice

Environ Toxicol Pharmacol. 2023 Mar:98:104074. doi: 10.1016/j.etap.2023.104074. Epub 2023 Jan 29.

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).

Keywords: Comet assay; Pulmonary; Toxicity; Toxicology; Wolfram.

MeSH terms

  • Animals
  • Bronchoalveolar Lavage Fluid
  • DNA Damage
  • Humans
  • Inflammation / pathology
  • Inhalation Exposure / adverse effects
  • Lung
  • Male
  • Mice
  • Reactive Oxygen Species / metabolism
  • Semen* / metabolism
  • Tungsten* / metabolism
  • Tungsten* / pharmacology

Substances

  • Tungsten
  • Reactive Oxygen Species