Markers of lipid oxidative damage in the exhaled breath condensate of nano TiO₂ production workers

Abstract

Nanoscale titanium dioxide (nanoTiO₂) is a commercially important nanomaterial. Animal studies have documented lung injury and inflammation, oxidative stress, cytotoxicity and genotoxicity. Yet, human health data are scarce and quantitative risk assessments and biomonitoring of exposure are lacking. NanoTiO₂ is classified by IARC as a group 2B, possible human carcinogen. In our earlier studies we documented an increase in markers of inflammation, as well as DNA and protein oxidative damage, in exhaled breath condensate (EBC) of workers exposed nanoTiO₂. This study focuses on biomarkers of lipid oxidation. Several established lipid oxidative markers (malondialdehyde, 4-hydroxy-trans-hexenal, 4-hydroxy-trans-nonenal, 8-isoProstaglandin F2α and aldehydes C₆–C₁₂) were studied in EBC and urine of 34 workers and 45 comparable controls. The median particle number concentration in the production line ranged from 1.98 × 10⁴ to 2.32 × 10⁴ particles/cm³ with ∼80% of the particles <100 nm in diameter. Mass concentration varied between 0.40 and 0.65 mg/m³. All 11 markers of lipid oxidation were elevated in production workers relative to the controls (p < 0.001). A significant dose-dependent association was found between exposure to TiO₂ and markers of lipid oxidation in the EBC. These markers were not elevated in the urine samples. Lipid oxidation in the EBC of workers exposed to (nano)TiO₂ complements our earlier findings on DNA and protein damage. These results are consistent with the oxidative stress hypothesis and suggest lung injury at the molecular level. Further studies should focus on clinical markers of potential disease progression. EBC has reemerged as a sensitive technique for noninvasive monitoring of workers exposed to engineered nanoparticles.

Keywords:

• Nanoparticles
• TiO₂
• exhaled breath condensate
• aldehydes
• oxidative stress
• occupational exposure
• monitoring

Funding

This research was supported by the project of the Charles University P25/1LF/2, P28/1LF/6 and EU Project “Material - technical Research Base for the Diagnostics and Treatment of Environmentally-caused and Oncological Disorders and their Risks, in the General University Hospital in Prague” (reg. No. CZ.2.16/3.1.00/24.12) and Czech Science Foundation project P503/12/G147, and project No. 44/16/RPZP of the Czech Ministry of Health.

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.