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 × 10(4) to 2.32 × 10(4) particles/cm(3) with ∼80% of the particles <100 nm in diameter. Mass concentration varied between 0.40 and 0.65 mg/m(3). 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.

b Institute of Chemical Process Fundamentals of the CAS Prague Czech Republic

c Institute of Chemical Technology Prague Prague Czech Republic

Department of Methodology Faculty of Physical Education and Sport Charles University Prague Prague Czech Republic e 1st Faculty of Medicine Institute of Informatics Charles University Prague and General University Hospital Prague Prague Czech Republic

Department of Occupational Medicine 1st Faculty of Medicine Charles University Prague and General University Hospital Prague Prague Czech Republic

f J Heyrovský Institute of Physical Chemistry of the CAS Prague Czech Republic

g Department of Chemistry G Scansetti Interdepartmental Centre and NIS Interdepartmental Centre University of Torino Torino Italy

h UMass Lowell Department of Public Health College of Health Sciences Lowell MA USA